SCE Practicaldiabetes - Elzohry

El-Zohry
StudyPRN
Endocrinology and
Diabetes – SCE
Revision
Khalid Yusuf
Sohag Teaching Hospital
(Egypt)
[email protected] 2017
FB: Sohag Endocrine Group
StudyPRN (Endocrinology and Diabetes – SCE Revision)
https://www.studyprn.com
Endocrinology and Diabetes – SCE

Revision
Category Total From Q - To
Adrenal 30 1-30
Complications of diabetes 45 31-75
Diabetes mellitus (diagnosis and general management,

142 337-478
delivery of diabetes care)
Diabetic emergencies and management during acute

21 76-96
illness/surgery
Gonads 29 97-125
Hypothalamus and Pituitary 46 203-248
Other 88 249-336
Parathyroid/calcium 21 126-146
Thyroid 56 147-202
Total: 478
Page | 2 Dr. Khalid Yusuf (FB: Sohag Endocrine Group)

[ Q: 1 ] Adrenal - Question ID #63 [ Q: 2 ] Question ID #64

A 55 year old male is admitted with abdominal
A 45 year old male is referred for investigation of
pain and vomiting under the surgeons. A CT scan
difficult to treat hypertension. He has a 6 year
is arranged. Gallstones are noted but note is also
history of hypertension and takes amlodipine,
made of a 3cm left adrenal adenoma. The ramipril and bendrofluazide yet his GP reports that
surgeons plan a cholecystectomy but want advice he has a blood pressure consistently between 150-
regarding the adrenal lesion. 170 mmHg systolic.
On examination, the patient is well, temperature
is normal and the pulse is 80 bpm with a blood On examination, he is obese with a BMI of 33.5
pressure of 124/70 mmHg. Routine biochemistry kg/m2, his blood pressure is 160/84 mmHg and no
other abnormalities are noted. His biochemistry
is reported as normal.
reveals:
Which of the following would be the most
appropriate investigation for this patient? Sodium 142 mmol/l (134-144)
(Please select 1 option) Potassium 3.4 mmol/l (3.5 - 5.5)
1- 24hr urine collection for catecholamines Urea 5.5 mmol/l (3-8)

Creatinine 100 micromol/l (50-100)
2- 24hr urine collection for urine free cortisol
3- MRI adrenals Which of the following is the most appropriate
management plan for this patient?
4- No further investigation required
(Please select 1 option)
5- Plasma rennin:aldosterone activity
1- Arrange MIBG scan
Answer & Comments 2- Arrange MRI abdomen
Answer: 1- 24hr urine collection for 3- Check 24 hr urine catecholamines

catecholamines 4- Check Plasma renin activity - aldosterone
ratio (PRA:Aldo) on current therapy
This patient has been admitted with abdominal
5- Stop bendrofluazide and check PRA:Aldo
pain and CT has revealed what at first sight
appears to be an incidentaloma. These occur in up
to 10% of the population with imaging yet it is Answer & Comments
important to investigate thoroughly. The most Answer: 4- Check Plasma renin activity -
important thing to exclude, particularly in view of aldosterone ratio (PRA:Aldo) on current
any further intervention, is a phaeochromocytoma therapy
as catastrophic consequences can ensue following
anaesthesia or surgical intervention. There is little
The resistant hypertension and the hypokalaemia
added benefit of MR over CT in the examination of suggest primary hyperaldosteronism - Conn’s
the adrenals and in this case would not exclude syndrome. Although ACE inhibitors are associated
phaeochromocytoma. with false negative test results, in clinical practice
the PRA:Aldo ratio can be assessed without
Reference: stopping these agents. In fact, ACEi may actually
Investigation of adrenal adenoma improve the sensitivity of the test. The only drugs
to avoid for the initial screening for Conn's
syndrome would be beta blockers (for 2 weeks)
and spironolactone (for 6 weeks). Patients may
require a subsequent confirmatory test if the

initial PRA:Aldo ratio is suggestive of Conn's 230

syndrome (typically above 1000). Confirmatory 24hr Urine free corisol nmol/d
testing may for instance entail selective adrenal (<280)
sampling.
Urine catecholamines normal
9am Cortisol post 1mg overnight 88 nmol/l
[ Q: 3 ] Question ID #65 dexamethasone (<50)
low dose dexamethasone cortisol
A 45 year old male has been noted to have a 5.2
suppression test 110 nmol/l
cm adrenal adenoma after having MRI scan of the
abdomen performed privately due to lower back 10 pmol/l
ACTH
pain. He was referred to endocrinology and urine (20 - 52)
free cortisol, urine catecholamines and plasma Renin activity/Aldosterone ratio 450 (<800)
rennin activity: aldosterone ratios were all normal.
Midnight Salivary Cortisol x3 normal
What is the most appropriate action for this
Which of the following is the most appropriate
patient?
management for this patient?
1- Arrange repeat MRI in 1 year
1- Arrange PET scan
2- Arrange repeat MRI in 3 months
2- Discharge as this is an incidentaloma
3- Arrange repeat MRI in 6 months
3- Refer to surgery for removal of lesion
4- Reassure and discharge
4- Repeat MRI of adrenals in 1 year
5- Refer for surgical removal
5- Repeat MRI of adrenals in 6 months
Answer & Comments

Answer & Comments
Answer: 5- Refer for surgical removal
Answer: 3- Refer to surgery for removal of lesion
Although the investigations would suggest that

This patient appears to have non-suppressible
this patient does not have a functional adenoma,
cortisol on overnight dexamethasone testing and
one must be aware of the possible risk of
has a low ACTH concentration, yet UFC is normal.
carcinoma of the adrenals. The criteria for surgical
This is quite typical of subclinical Cushing’s
removal of an adrenal tumour is a diameter of 4
syndrome and with evidence of functionality,
cm or more as the risk of primary carcinoma with
surgery would be recommended. With the
such size is of the order of 1 in 30.
increasing use of imaging lesions of the adrenal
occur in up to 10% of such scans and of these 10%
[ Q: 4 ] Question ID #72 may be subclinically functional.
A 42 year old female is co-incidentally noted to AACE guidelines: management of adrenal

have a right 2cm adrenal lesion after having an incidentalomas
MRI scan for possible colonic neoplasm. She is a
known patient with type 2 diabetes with poor [ Q: 5 ] Question ID #75
glycaemic control. On examination she has a BMI
of 32 kg/m2, a blood pressure of 146/88 mmHg
A 22 year old male is diagnosed with an extra-
and no abnormalities are otherwise noted. Her
adrenal phaeochromocytoma. There is no family
investigations reveal:
history of note and there are no abnormalities to
note on examination.

Which of the following genetic tests would you 3- Refer for adrenal surgery
request?
4- Repeat MRI scan in 3-6 months
1- BRAC
2- FGF 1 Answer & Comments
3- NF type 1 Answer: 4- Repeat MRI scan in 3-6 months
4- NF type 2
From investigations this mass is measured at 2cm
5- SDH type B/D
in diameter. There is no evidence of functionality
of this tumour from testing either. It does not
Answer & Comments meet the size criteria of >4cm for consideration of
surgical removal. The only concern is that this may
Answer: 5- SDH type B/D
be an adrenal carcinoma and therefore the patient
should be re-scanned in approximately 3 months
Phaeochromocytoma susceptibility genes include looking for significant size changes. If there are no
Succinate dehydrogenase types BCD, VHL and RET size changes in the interval there is no evidence to
protooncogene (MEN II). The phenotypic support further radiological imaging. FNA does not
characteristics are likely to be present for NF 1 and provide any useful differentiating information
so this is not the most appropriate investigation in between carcinoma and benign disease and
this patient. All patients with a phaeo diagnosed should not be undertaken as, if this were a
before 45 years of age should be investigated carcinoma FNA could result in seeding.
further for a potential genetic cause for their
Phaeo.
[ Q: 7 ] Question ID #88
[ Q: 6 ] Question ID #85 A 44 year old female is investigated for

hypertension, weight gain and weakness. Her
A 53 year old female is noted to have a 2 cm right investigations including a low dose
adrenal incidentaloma whilst having an abdominal dexamethasone suppression test confirms the
CT scan by the general surgeons. Further clinical suspicion of Cushing’s syndrome. These are
investigation reveals the following results: the further investigations for this patient:
U+Es Normal Urine free

1020 nmol/d (<250)
Urine Catecholamines Normal cortisol
228 nmol/d ACTH <10 pmol/l (20 - 50)
24hr Urine free cortisol
(<250) Bilateral nodular adrenal
MRI adrenals
plasma rennin enlargment
480 (<850)
activity/aldosterone Pituatary MRI Normal
Cortisol post 1 mg overnight
38 nmol/l Which of the following is the most appropriate for
dexamethasone
this patient?
What is the most appropriate management for (Please select 1 option)
this patient?
1- Refer for bilateral adrenalectomy
2- Refer for pituitary exploration
1- Arrange fine needle aspiration of adrenal
3- Refer for inferior petrosal sinus sampling
2- Arrange PET scan

4- Treat with metyrapone This patient has an adrenal carcinoma which is the
cause of Cushing’s syndrome. Surgery has
5- Treat with mitotane
effectively treated the hyperocrtisolism and the
patient now requires steroid replacement.
Answer & Comments Although at this stage the patient has no evidence
of metastases, further serial scanning will be
Answer: 1- Refer for bilateral adrenalectomy required. The prognosis associated with adrenal
carcinoma is usually very poor although there is
This patient has Cushing’s syndrome due to emerging evidence that the prognosis may be
bilateral adrenal nodular enlargement which is improved with adjuvant mitotane therapy.
independent of ACTH. This could be due to food-
induced Cushing’s and a meal test may be [ Q: 9 ] Question ID #131
appropriate but the condition of ACTH-
independent macronodular adrenal hyperplasia is
described and seems the more probable An 18 year old female who presents with
explanation. The most appropriate treatment oligomenorrhoea is found to have non-classical
would be congenital adrenal hyperplasia. She enquires as to
the risk of any of her future children suffering the
disorder.
Which of the following is correct concerning this
A 55 year old female is confirmed to have adrenal risk?
dependent Cushing’s syndrome following (Please select 1 option)
presentation with a 6 month history of weight
gain, weakness and thinning of the skin. CT 1- Virtually 0%
abdomen has demonstrated a 9cm left adrenal
2- 1%
tumour and no other abnormalities are noted on
this scan. An adrenalectomy is performed and 3- 5%
histology reports an adrenal carcinoma.
4- 25%
Post-operative assessment reveals that the 5- 50%
patient is steroid dependent and is prescribed
10mg of hydrocortisone bd. She then undergoes a
Answer & Comments
1mg overnight dexamethasone test and her 9am
cortisol is measured at 22 nmol/l (150-800). Answer: 2- 1%
Which adjuvant therapy would most likely prolong

The patient has non-classical CAH which is most
the period of remission post radical surgery? likely due to 21 hydroxylase deficiency. It is an
(Please select 1 option) autosomal recessive condition and the gene
1- Cisplatin frequency is approximately 1 in 40 in the general
population. Thus, the chances of this girl meeting
2- Ketoconazole a partner heterozygous for CAH is 1 in 40 yet she
is homozygous for the condition. Therefore, the
3- Metyrapone
chances of her having a child with CAH is 1 in 2
4- Mitotane with this person (50% chance that any children will
be HMZ and 50% chance that they will be
5- No therapy required unaffected HTZ). Thus the overall chance of having
a child with CAH would be 1 in 40 x 1 in 2 = 1 in 80
Answer & Comments or roughly 1%.
Answer: 4- Mitotane

[ Q: 10 ] Question ID #146 [ Q: 11 ] Question ID #160
A 45 year old male is investigated for possible gall A 40-year-old man was referred to the endocrine
stones and undergoes an ultrasound which as well clinic for his resistant hypertension. He is currently
as displaying some gall stones reveals a possible taking atenolol 50 mg od, bendrofluazide 2.5 mg
adrenal lesion. Further imaging with CT confirms od, doxazosin 4 mg od, amlodipine 10 mg od
the presence of gall stones but also reveals a 2cm and ramipril 10 mg od.
right adrenal lesion. On endocrine review, the
patient has no symptoms to suggest functionality On examination, his pulse was 64 beats per
of this lesion but has been taking atenolol 25 mg minute, his blood pressure was 162/96 mmHg,
daily for hypertension. Investigations reveal: heart sounds were normal and there were no
cushingoid features.
24 hour Urine fee
148 nmol/d (<290) Investigations
cortisol
220 nmol/d (120-
Urine Noraderaline Serum Urea 4.4mmol/L (2.5-7.5)
590)
Urine Adrenaline 110 nmol/d (30-190) Serum Creatinine 88 µmol/L (60-110)
Urine Metadrenaline 5.2 micromol/l (0-2) Serum Potassium 3.06 mmol/L(3.5–4.9)
2.1 micromol/l (0-
Urine normetadrenaline Which is the most important medication to be
5.3)
discontinued before testing his
Plasma Renin Activity 1.2 pmol/min (0.5-2) aldosterone:plasma renin activity ratio?
400 pmol/l (150- (Please select 1 option)
Aldosterone
800)
1- Amlodipine
Which of the following is the likely diagnosis? 2- Atenolol
3- Bendrofluazide
1- Adrenal carcinoma
4- Doxazosin
2- Aldosteronoma
5- Ramipril
3- Cushing's syndrome
4- Incidentaloma with factitious results Answer & Comments
5- Phaeochromocytoma Answer: 2- Atenolol
Answer & Comments Beta blockers are well recognised to cause a

decrease in renin concentrations and hence could
Answer: 5- Phaeochromocytoma create a false positive result in a patient suspected
of having Conn's syndrome. Consequently the
Elevated urine free metadrenalines are one of the drug should be stopped at least 2 weeks before
most sensitive measurements indicating testing the patient. Spironolactone would also
phaeochromocytoma and even in the absence of need to be stopped prior to testing
elevated catecholamines suggest underlying PRA/aldosterone ratios as this would result in
phaeochromocytoma. The fact that both urine falsely elevated aldosterone concentrations and
adrenaline and noradrenaline are normal argue should be stopped at least 6 weeks pre-testing.
that there is internal metabolism of the Although one might think that ACEis are
metadrenaline within the tumour. associated with inaccurate results, this is not the
case in primary hyperaldosteronism.

http://www.ncbi.nlm.nih.gov/pubmed/17315030 and low renin. This is unlikely to be essential

hypertension as the renin would be expected to be
[ Q: 12 ] Question ID #163 normal as would aldosterone.
A 22 year old woman was referred to clinic by her [ Q: 13 ] Question ID #345

GP due to tiredness. She was not taking any
medications. On examination, her blood pressure A 33 year old male presents with lethargy and easy
was measured at 180/98 mmHg. Investigations by fatigue. He does not take any medication, has
the GP revealed: generally been well and denies the use of illicit
drugs.
Serum Sodium 140 mmol/l (134 - 144)
On examination, his BMI is 33.2 kg/m2 his blood
Serum Potassium 3.2 mmol/l (3.5 - 5)
pressure is 118/72 mmHg and no abnormalities
Serum Urea 7.0 mmol/l (3 - 8) are otherwise noted. Investigations reveal:
Serum Cretinine 92 µmol/l (50-100)
Sodium 142 mmol/L (135-145)
Further investigations reveal: Potassium 2.8 mmol/L (3.5-5)
Urea 5.8 mmol/L (3-8)
Plasma Renin 5.2
(1.1-2.7) Creatinine 88 µmol/L (50-100)
Activity pmol/ml/h
(135 -
Serum Aldosterone 900 pmol/L Which of the following is the most likely diagnosis?
400)
Which of the following is the correct diagnosis? 1- Apparent mineralocorticoid excess

2- Bartter's syndrome
1- Barrter's Syndrome
3- Conn's syndrome
2- Conn's Syndrome
4- Gitelmann syndrome
3- Essential hypertension
5- Hypokalaemic periodic paralysis
4- Fibromuscular dysplasia
5- Gitelman's syndrome Answer & Comments
Answer: 4- Gitelmann syndrome
Answer & Comments
Answer: 4- Fibromuscular dysplasia The hypokalaemia with normal blood pressure in
a middle aged male without any skeletal
abnormalities or retardation would suggest a
This young woman has hypereninaemic diagnosis of Gitelmann syndrome rather than
hyperaldosteronism, hypertension and Barrter syndrome.
hypokalaemia. Due to her age, of the options
listed, the most likely cause is fibromuscular
dysplasia. The high renin concentration is a [ Q: 14 ] Question ID #346
consequence of the relative renal ischaemia due
to the fibromuscular dysplasia. This is not Barrter's A 33 year old female presents with a three month
syndrome as the patient is hypertensive. history of fatigue, weight loss and is noted to have
Gitelman’s similarly causes a low potassium buccal pigmentation.
concentration but with normal blood pressure.
Conn's is associated with elevated aldosterone

Which of the following antibodies would be the usually used during the preoperative management
most appropriate to check in this patient? of patients awaiting surgery or if surgical
treatment is contraindicated as a palliative
measure. Nausea, hypertension and features of
1- Anti-21-hydroxylase antibody hirsutism are the major associated side effects.
The dose titration of drug is usually based on
2- Anti-intrinsic factor antibody
cortisol day curve. In children Ketoconazole is
3- Anti-peroxidase antibody preferred over Metyrapone as a preoperative
medication (while awaiting adrenal surgery).
4- Anti-rho antibody
5- Anti-TTG antibody [ Q: 16 ] Question ID #643
Answer & Comments A 32 year old female presents with hypokalaemia

Answer: 1- Anti-21-hydroxylase antibody and metabolic alkalosis. She has a blood pressure
of 124/76 mmHg. Her biochemistry shows:
21-hydroxylase is involved in the cholesterol

135 (135-
steroid synthetic pathway and the antibody to this Sodium
mmol/L 145)
enzyme is present in approximately 80% of cases
of Addison's disease. Potassium 3.2 mmol/L (3.5-5.5)
Mg 0.4 mmol/L (0.7-1.0)
[ Q: 15 ] Question ID #642 HCO3 28 mmol/L (18-23)
Plasma renin activity 5.5 nmol/L (0.5-2.2)
A patient with severe Cushing's disease is being (100-
pre-treated with metyrpaone prior to elective Aldosterone 722 pmol/L
500)
surgical intervention.
What is the likely underlying diagnosis?
Upon which of the following enzymes does
Metyrapone act?
(Please select 1 option) 1- Bartter`s syndrome
1- 3 ß HSD 2- Congenital adrenal hyperplasia
2- 11 ß HSD 3- Conn's syndrome
3- 11 ß hydroxylase 4- Gitelman`s syndrome
4- 17 ß hydroxylase 5- Liddle`s syndrome
5- 21 ß hydroxylase
Answer & Comments
Answer & Comments Answer: 4- Gitelman`s syndrome
Answer: 3- 11 ß hydroxylase
Gitelman`s syndrome is characterised by mutation
in the SCL12A3 gene that encodes for a Na-Cl
Metyrapone is a competitive inhibitor of 11 ß transporter at distal convoluted tubule. As a result
hydroxylase enzyme (CYP11B1) which is expressed the affected individuals develop Na loss (salt
in Zona fasciculata and Zona glomerulosa. This wasting), hypovolemia, hypocalciuria,
enzyme is required for conversion of deoxycortisol hypomagnesaemia and metabolic alkalosis. The
to cortisol and its inhibition leads to decrease in fluid loss prompts activation of Renin-Angiotensin
cortisol concentration and an increase in ACTH system leading to increase in both renin and
through feedback mechanism. Metyrapone is

aldosterone levels. The main differential diagnosis [ Q: 18 ] Question ID #646

for Gitelman`s syndrome includes Bartter`s
syndrome which usually affects children (rarely A 45 year old hypertensive undergoes
young adolescents). In contrast to Gitelman`s investigations for her hypertension. She currently
syndrome the primary defect in Bartter`s takes no medication and occasionally chews
syndrome is at Na-K-Cl transporter in ascending liquorice.
limb of loop of Henle, hypomagnesaemia is absent
and patients usually have hypercalciuria.
What is the likely underlying mechanism of her
hypertension?
[ Q: 17 ] Question ID #645 (Please select 1 option)
1- Apparent mineralocorticoid excess

An 18 year old boy presents with hypertension
which is controlled with small dose of 2- Atypical variant of CAH
dexamethasone.
3- Conn's syndrome
What's the likely inheritance of his underlying 4- Glucocorticoid remedial aldosteronism
condition?
5- Pseudohypoaldosteronism
1- Autosomal dominant Answer & Comments

2- Autosomal recessive Answer: 1- Apparent mineralocorticoid excess
3- Polygenetic
4- X linked dominant Liquorice which is used in candies, cough mixtures
and chewing tobacco contains glycyrrhetinic acid
5- X linked recessive which inhibits 11 beta-HSD enzyme. As a result the
conversion of cortisol (which is a more potent
Answer & Comments mineralocorticoid as compared to cortisone) is
hampered locally. This leads to a state of apparent
Answer: 1- Autosomal dominant mineralocorticoid excess, similar to the one seen
with genetic defect in 11 beta-HSD enzyme. The
Glucocorticoid remediable hypertension is a rare patient's eating of liquorice can result in
autosomal dominant condition due to gene hypertension, hypokalaemia and metabolic
duplication resulting in fusion of 11 beta- alkalosis. The diagnosis can be confirmed by
hydroxylase gene to aldosterone synthase gene. measurement of urinary tetrahydrocortisol to
The resultant chimeric gene on activation leads to cortisone ratio (increased levels of
increased ACTH dependent aldosterone synthesis. tetrahydrocortisol as compared to cortisone).
The patients usually present with features of
aldosterone excess (hypertension, hypokalaemia [ Q: 19 ] Question ID #648
and metabolic alkalosis) with suppressed renin
levels. The hypertension is exquisitely responsive A 70 year old male is investigated for a co-
to steroid therapy. The disease usually runs in
incidentally noted Right adrenal adenoma which is
families and clinical suspicion should be raised if undertaken as investigation of iron deficiency. The
primary aldosterone excess is seen in more than patient is referred to endocrinology and
one family members. The diagnosis of this undergoes investigations which reveals that the
condition is based on measurement of 18- adenoma is a functional cortisol secreting tumour
oxycortisol and 18-hydroxycortisol levels and and surgical excision is planned by the endocrine
confirmed by genetic testing. surgeons.

Which of the following concerning peri and post- 124

operative management of this patient is Sodium (135-145)
mmol/L
important? 5.6
Potassium (3.5-5.5)
(Please select 1 option) mmol/L
1- Assessment of cortisol levels post Urea 30 mmol/l (7-20)
operatively and hydrocortisone to be given 104
Creatinine (60-115)
only if cortisol levels are low µmol/L
2- Assessment of 24 hour urinary free cortisol 9 am cortisol 55 nmol/L
secretion preoperatively to guide cortisol 30 min 220 (Post ACTH
dose cortisol nmol/L injection)
3- Fludrocortisone post operatively
The CT image shows the presence of calcification
4- Measurement of intra-operative cortisol within the adrenal gland.
5- Peri and post operative hydrocortisone with
What is the likely aetiology of his adrenal
further assessment of post-operative
insufficiency?
cortisol secretion
Answer & Comments 1- Adrenal leukodystrophy
Answer: 5- Peri and post operative hydrocortisone 2- Adrenal tuberculosis

with further assessment of post-operative 3- Histoplasmosis
cortisol secretion
4- Metastatic disease
The perioperative management of a cortisol 5- Sarcoidosis

producing adenoma includes glucocorticoid cover
(generally hydrocortisone 100 mg IM/IV 6 hourly) Answer & Comments
until the patient is eating and drinking normally in
the post operative period. The dose of steroid Answer: 2- Adrenal tuberculosis
cover is gradually tapered to a maintenance dose
(prednisolone or hydrocortisone). As the contra- Adrenal tuberculosis remains one of the
lateral adrenal gland may be suppressed due to commonest causes of adrenal insufficiency in the
long term excess cortisol production by the developing world with about 5% of the patients
functional adrenal adenoma, reassessment of with disseminated tuberculosis (Miliary Koch's)
cortisol secretion is required and usually first developing significant adrenal insufficiency. A low
performed at 2 week post operative interval. It threshold of suspicion to seek adrenal
may require months or even years for contra- insufficiency is warranted in patients with
lateral adrenal gland to recover its function. tuberculosis as the symptoms and signs are non
Therefore the steroid cover may need to be specific and at times are attributed to underlying
continued. condition (Tuberculosis). Adrenal tuberculosis is
reversible with anti-tuberculosis medications if
[ Q: 20 ] Question ID #649 these are given at an early stage of the disease.
An Asian man is admitted with a history of weight [ Q: 21 ] Question ID #650

loss, lethargy, nausea and vomiting. On
examination he looks dehydrated and pigmented. A 49 year old male presents with abdominal pain
His biochemical profile is as shown below: and swelling. Following investigation, he is found
to have metastatic adrenal carcinoma.

Which of the following is likely to improve the Answer & Comments

prognosis in a patient with adrenal carcinoma?
Answer: 4- SDHB mutation
1- Aminglutethimide The 2004 WHO classification of endocrine

2- Ketoconazole tumours classifies catecholamine secreting
tumours into intra-adrenal paragangliomas
3- Metyrapone (classically known as phaeochromocytomas) and
extra-adrenal paragangliomas. The later are
4- Mitotane
further subdivided into those arising from
5- Sunitinib sympathetic tissue or parasympathetic tissues
(usually located in head and neck, rarely produce
catecholamine). Hereditary catecholamine
Answer & Comments
producing intra or extra- adrenal paragangliomas
Answer: 4- Mitotane can be caused by one of the following germ line
mutations:
Mitotane is an adrenolytic drug which inhibits
1. RET proto-oncogene
several enzymes involved in
2. von Hippel-Lindau gene (vHL)
steroid/mineralocorticoid synthesis including side
3. Neurofibromatosis Type 1 gene (NF-1)
chain cleavage, 11 ? hydroxylase and 3? hydroxy
4. Succinate dehydrogenase subunit B
steroid hydrogenase (3?HSD). It is licensed for
(SDHB)
symptomatic treatment of advanced or inoperable
5. Succinate dehydrogenase subunit D
adrenocortical carcinoma. The limitations with
(SDHD)
Mitotane therapy include delayed response and
frequent side effects such as severe nausea,
vomiting, hypogonadism and neurotoxicity. Patients with SDHB or SDHD are more likely to
Sunitinib has been a break through in the present with extra-adrenal disease, bilateral
treatment of renal cell carcinoma but not adrenal tumours and metastatic disease. According to the
cancer. guidelines issued by The First International
Symposium on Phaeochromocytomas (October
2005), genetic screening should be individualised
Adjuvant Mitotane Chemotherapy for adrenal
and is generally warranted in:
carcinoma NEJM 2007
 Patients aged < 50 years, presenting with
[ Q: 22 ] Question ID #651 catecholamine secreting
 Multiple tumours
A 22 year old has been noticed to have a carotid  Malignant tumours
body tumour. He has a strong family history of  Bilateral tumours
paragangliomas.
What's the underlying etiology for his disease?
(Please select 1 option) A 29 year old woman presents with hypertension
1- Carney complex and palpitations and is diagnosed with a
paraganglioma.
2- MEN- 2 syndrome
3- Neurofibromatosis With which of the following mutations are
paragangliomas associated?
4- SDHB mutation
5- VHL syndrome
1- 21-Hydroxylase deficiency

2- Loss of function of MAX mutation seemingly adequate replacement with

glucocorticoids and mineralocorticoids. The role
3- MENIN mutation
of DHEAS is discussed during the consultation as
4- TMEM127 mutation she has read about this treatment and wondered
if it might help her.
5- VHL mutation
Which of the following would best describe the
Answer & Comments impact of DHEAS from studies?
Answer: 5- VHL mutation (Please select 1 option)
1- Decreased weight
The 2004 WHO classification of endocrine 2- Improved sense of well being
tumours classifies catecholamine secreting
tumours into intra-adrenal paragangliomas 3- Increase in muscle mass
(classically known as phaeochromocytomas) and 4- Increase in fertility
extra-adrenal paragangliomas. The later are
further subdivided into those arising from 5- Maintenance of blood pressure
sympathetic tissue or parasympathetic tissues
(usually located in head and neck, rarely produce Answer & Comments
catecholamine). Hereditary catecholamine
producing intra or extra- adrenal paragangliomas Answer: 2- Improved sense of well being
can be caused by one of the following germ line
mutations:
Dehydroepiandrosterone sulphates (DHEAS) are
the androgens secreted by adrenal glands which
1. RET proto-oncogene decline with age. These were commonly termed as
2. von Hippel-Lindau gene (vHL) elixir of youth with alleged role in general well
3. Neurofibromatosis Type 1 gene (NF-1) being, cognitive and sexual function and as a
4. Succinate dehydrogenase subunit B
weight loss therapy. Randomised controlled trials
(SDHB) have failed to demonstrate any apparent benefit
5. Succinate dehydrogenase subunit D with DHEAS in patients with normal adrenal
(SDHB) function. These may play a role in female patients
with adrenal insufficiency by increasing a sense of
Patients with SDHB or SDHD are more likely to well being by bringing about a modest
present with extra-adrenal disease, bilateral improvement in sexual function.
tumours and metastatic disease. According to the
guidelines issued by The First International
Symposium on Phaeochromocytomas (October [ Q: 25 ] Question ID #655
2005), genetic screening should be individualised
and is generally warranted in: A 65 year old woman is investigated lady for an
assumed secondary hypertension. She has been
 Patients aged < 50 years, presenting with found to have a blood pressure of 165/95mmHg.
catecholamine secreting There is little to find on examination and her BMI
 Multiple tumours is 26.4 kg/m2. Currently she takes amlodipine
 Malignant tumours 10mg daily. Results of her investigations are
 Bilateral tumours shown below.
[ Q: 24 ] Question ID #654 143 (135-

Sodium
mmol/L 145)
A 40 year old woman with a diagnosis of Addison's Potassium 3.8 mmol/L (3.5-5.5)
disease presents with persistent fatigue despite Urea 20 mg/dL (7-20)

Creatinine 72 µmol/L (60-115) PRA:Aldo interpretations and need to be stopped

prior to assessing the ratio:
Plasma Renin Activity 0.5 nmol/L (0.5-2.2)
(100- Aldosterone antagonists - Spironolactone
Aldosterone 782 pmol/L
500)
Beta- blockers - lower PRA increase false positive
An aldosterone suppression test did not results
significantly alter this patient's aldosterone
concentrations. CT abdomen is usually the radiological modality
employed to localise the adrenal adenoma. But as
Which is the next best test for diagnostic the incidence of adrenal incidentalomas rises with
purposes? age, adrenal venous sampling is the technique
most often used to confirm and lateralise the site
of lesion. Considering this lady is 65 years old and
1- Adrenal CT her biochemistry reveals normal potassium and
2- Adrenal venous sampling high sodium along with non usage of any of the
interfering antihypertensive medications, the next
3- Arrange MIBG scan investigation used should be CT abdomen and
adrenal venous sampling used only if there is a
4- Stop amlodipine and repeat the renin
suspected adrenal adenoma. In view of her age
aldosterone ratio group, she is more likely to have adrenal
5- Postural stimulation test hyperplasia.
Answer & Comments [ Q: 26 ] Question ID #656
Answer: 1- Adrenal CT
A 70 year old male has a history of hypertension
which is adequately controlled with doxazosin yet
This patient is likely to have Conn's syndrome. She has persistent hypokalaemia. The patient is
has an elevated PRA:Aldosterone ratio ~1500 but referred to clinic as the potassium is persistently
has a normal potassium that may confound some between 2.6-3.1 mmol/l. Investigations show a
people. About 20% of patients with Conn's Plasma renin activity:aldosterone ratio of 780.
syndrome may have a normal potassium. Primary
Hyperaldosteronism accounts for as much as 10% Which of the following is the most appropriate
of patients diagnosed to have essential management option for him?
hypertension in one secondary care hypertension
clinic. Screening for excess aldosterone
production is warranted in the following group of 1- Switch Doxazosin to an ACE inhibtor
patients:
2- Start a Potassium supplement
1. Young hypertensive (age <40> 3- Switch Doxazosin to Spironlactone
2. Resistant hypertension (unresponsive to 3
or more antihypertensive agents) 4- Switch Doxazosin to a Thiazide diuretic
3. Associated hypokalaemia 5- Stop Doxazosin
4. Incidental adrenal tumour
Answer & Comments
Measurement of aldosterone: renin ratio is the
best initial diagnostic test. Increased aldosterone Answer: 2- Start a Potassium supplement
and suppressed renin levels are highly indicative of
underlying primary aldosteronism. A number of
medications interfere with test results and should The initial screening test for the diagnosis of
ideally be stopped. The following interfere with primary aldosteronism is measurement of a

plasma renin activity to aldosterone ratio. A ratio cortisol levels during an acute illness are not truly
above 1000 is highly suggestive of primary reflective of adrenal hyper-secretion and a
hyperladosteronism. (In the UK this is used in the suspected adrenal excess cortisol values should
states they often quote the other way around, only be evaluated (if clinically warranted) once the
Aldo:renin ratio. ARR. A ratio of >20 is suggestive patient shows clinical improvement.
of diagnosis of primary aldosteronism). However
false positives and negatives can occur. Some
medications can interfere with aldosterone/ renin
levels. Doxazosin has no effect. Also if the patient
is hypokalaemic, aldosterone concentrations can What is the best investigation to monitor a patient
fall and marginal increases in renin can make for a with classic salt wasting congenital adrenal
false negative result. Oral potassium supplements hyperplasia (CAH)?
are given to avoid any false negative test results. A (Please select 1 option)
false negative result can also be obtained in
1- Check 17 hydroxy progesterone (17 OHP)
patients with chronic renal failure due to
persistently elevated renin levels. levels
2- DHEA levels
[ Q: 27 ] Question ID #661 3- Monitor 21 alpha hydroxylase
4- Measure Plasma renin activity
A 38 year old man is admitted after an RTA leading
to head trauma. He is being managed in the 5- USG adrenals
intensive care unit. On day 2 of admission his 24
hour Urinary free cortisol values are noticed to be
Answer & Comments
high. You are asked to give opinion regarding
further assessment for his possible cortisol excess Answer: 1- Check 17 hydroxy progesterone (17
secretion. OHP) levels
What is the most appropriate next step in his

Classic salt wasting congenital adrenal hyperplasia
management?
(CAH) is an autosomal recessive genetic disorder
(Please select 1 option) with a prevalence of 1: 10,000 - 1: 15,000. It is due
1- Check mid night cortisol values to deficiency of 21 α hydroxylase enzyme and
usually presents with acute life threatening illness
2- Low dose DST in a neonate with vomiting, dehydration,
3- Organise ODST circulatory collapse and features of adrenal
insufficiency on biochemistry.
4- No need to evaluate cortisol secretion at this
stage Management includes steroid replacement and
about 3/4th of patients may require
5- Repeat 24 hour UFC
mineralocorticoid replacement in addition.
Monitoring of treatment is based on clinical
Answer & Comments examination (signs of hyper-androgenism and
glucocorticoid excess) and biochemical
Answer: 4- No need to evaluate cortisol secretion
measurement of 17 OHP / renin levels. The aim of
at this stage steroid therapy is usually to keep 17 OHP levels
mildly elevated (to prevent side effects related
In a critically ill patient CRH, ACTH and cortisol with excess steroid replacement) and
levels increase rapidly as a haemostatic response Fludrocortisone dose is titrated with the aim to
to the illness. Low cortisol binding globulin and keep plasma renin levels in mid normal range.
albumin levels during the acute illness can cause
an elevation of free cortisol levels. As a result

A 24 year old presents with hypertension, You are called via the arrest bleep to a 43 year old
hypokalaemia, suppressed renin and aldosterone woman who is on the surgical ward. She had a
values is suspected to have apparent laparoscopic cholecystectomy performed two
mineralocorticoid excess. days ago and has since had nausea and vomiting
and has been receiving IV dextrose. It transpires
Which of the following tests can be used for that she had a fit for which the nursing staff
establishment of her diagnosis? requested the arrest team. She is now drowsy. Her
past medical history is unremarkable.
1- Check 3 β hydroxy steroid dehydrogenase (3 On examination, she is drowsy with a GCS of 13.
β HSD) enzyme levels Her pulse is 88 bpm and blood pressure 132/88
mmHg with oxygen sats of 100% on air. There is no
2- CT abdomen
focal neurology and her plantar responses are
3- Deoxycortisol levels equivocal.
4- Measure urinary cortisol to cortisone ratio
Of note, her blood results reveal:
5- Serum cortisol
Sodium 118 mmol/l (135-144)
Answer & Comments Potassium 3.5 mmol/l (3.5-5)
Answer: 4- Measure urinary cortisol to cortisone Urea 3.8 mmol/l (3-8)
ratio Creatinine 70 micromol/l (50-100)
Glucose 4.1 mmol/l (3.5-6)
Presence of hypertension, hypokalaemia and a
suppressed renin and aldosterone values are Which of the following is the most appropriate
suggestive of apparent mineralocorticoid excess initial treatment for this patient?
seen due to deficiency of 11β hydroxy steroid (Please select 1 option)
dehydrogenase (11β HSD) enzyme in this patient.
This enzyme is mediates the conversion of cortisol 1- 15mg oral Tolvaptan
to cortisone locally to protect mineralocorticoid 2- 100mg IV Hydrocortisone stat
receptor.
3- 150mls of 3% hypertonic saline over 20 mins
Deficiency of 11 β HSD leads to hampered
4- 1litre Normal saline infused over 4 hrs
conversion of cortisol (which is a more potent
mineralocorticoid as compared to cortisone) to 5- Fluid restriction to 500mls per day
cortisone locally, resulting in a state of apparent
mineralocorticoid excess. The patients usually
Answer & Comments
present with hypertension, hypokalaemia and
metabolic alkalosis in presence of suppressed Answer: 3- 150mls of 3% hypertonic saline over 20
levels of aldosterone and renin. The diagnosis can mins
be confirmed by measurement of urinary
tetrahydrocortisol to cortisone ratio (increased
This patient is likely to have hyponatraemic
levels of tetrahydrocortisol as compared to
encephalopathy which is life threatening and has
cortisone).
presented with a fit. Post-operative
hyponatraemia is not uncommon and is likely to
be due to a combination of SIADH which develops
in the post-op period and the infusion of
inappropriate IVIs. The European Endocrine

Society Guidelines on severe hyponatraemic absence of beta cells suggesting an underlying

encephalopathy recommend a rapid correction of mechanism involving programmed beta cell
sodium by approximately 5 mmol/l. This can death/apoptosis as there are no immunological
ameliorate the cerebral oedema that underlies markers.
this disorder.
For more information on how to correct and what
would be the target see the following guidelines:
A 41 year old man with a history of diabetes
European Journal of Endocrinology (2014) secondary to chronic alcohol related pancreatitis
Clinical Practice Guideline on the diagnosis is reviewed in clinic. On examination his BMI is 22
and management of hyponatraemia, kg / m2 , his body weight is 69 kg and his blood
pressure is 124 / 66 mmHg. He has no evidence of
retinopathy on fundoscopy and examination of his
[ Q: 31 ] Complications of DM - Question ID #5 feet reveals no evidence of neuropathy. His
current medication includes humalog mix 25 twice
A 16 year old boy has a 3 year history of type 1 daily at doses of 10 and 6 units respectively. His
diabetes and has an HbA1c of 8.2% (<6), requiring current Hba1c is 7.9% (<6) and his main
his mother to administer his insulin due to his poor complaints are persisting episodes of diarrhea,
eyesight, a consequence of optic atrophy. He also frequent hypoglycaemic episodes with great
has sensorineural deafness and requires a hearing variability in his self monitored blood glucose
aid. His current medication includes basal bolus levels.
insulin regime consisting of Insulin aspart tds and
insulin glargine together with desmopressin bd. Which of the following the likely cause of these
He has an average self monitored glucose profile symptoms for this gentleman?
of 7.6 mmol/l. (Please select 1 option)
Which of the following is the likely diagnosis? 1- Exocrine pancreatic insufficiency, reduced
glucagon and insulin secretion with
increased hepatic glucose production and
1- Alport syndrome increased insulin resistance
2- Alstrom syndrome 2- Exocrine pancreatic insufficiency, reduced
3- Kearns-Sayre syndrome insulin secretion, increased glucagon
secretion with increased insulin resistance
4- MELAS syndrome
3- Exocrine pancreatic insufficiency, reduced
5- Wolfran Syndrome
insulin and glucagon secretion with reduced
hepatic glucose production and increased
Answer & Comments insulin sensitivity
Answer: 5- Wolfran Syndrome 4- Normal pancreatic exocrine function,
reduced insulin secretion, increased
This patient expresses the clinical features of The glucagon secretion with reduced insulin
DIDMOAD or Wolfram syndrome, characterised sensitivity
by, Diabetes Insipidus (the patient takes
Desmopressin), Diabetes Meliitus of juvenile 5- Exocrine pancreatic insufficiency, reduced
onset, Optic Atrophy and Deafness. Diabetes insulin secretion, normal glucagon
occurs in nearly all patients presenting with this secretion, increased hepatic glucose
syndrome. While little is known around the production with reduced insulin sensitivity.
specific cellular mechanisms, pancreatic islets
from such patients demonstrate a selective

Answer & Comments Hba1c 8.6%

Answer: 3- Exocrine pancreatic insufficiency, Total Cholesterol 5.7 mmol/l (<5)
reduced insulin and glucagon secretion with Fasting plasma
9.8 mmol/l (0.9 - 2.2)
reduced hepatic glucose production and triglyceride
increased insulin sensitivity U + Es Normal
AST 78 iu/l (5 - 45)
This patient has minimal insulin requirements (0.2
ALP 138 iu/l (30 - 115)
u / kg) while complaining of recurrent diarrhea
with evidence of glucose instability. The 94 ml/min/1.73 m2 (90
eGFR
pathophysiology of diabetes secondary to - 110)
pancreatic injury results in both exocrine and TSH 1.2 mu/l (0.32 - 5.5)
endocrine pancreatic insufficiency. The exocrine
pancreatic insufficiency results in malabsorption, What is the correct diagnosis for this patient?
diarrhea and contributing to glucose instability.
Endocrine pancreatic insufficiency in such patients
results in reduced insulin and glucagon secretion 1- Alstroms's syndrome
with consequent reduction in hepatic glucose
production resulting in an increase in insulin 2- Bloom syndrome
sensitivity. Furthermore the glucagon deficiency 3- Edwards syndrome
that occurs in such patients also results in
elevations in urea cycle amino acids in particular 4- Glycogen storage disease
alaninie, asparargine, cysteine, glycine, proline 5- MELAS syndrome
and serine. These metabolic features contribute to
the glucose fluctuations that occur in patients with
diabetes secondary to pancreatic injury and Answer & Comments
provide considerable clinical challenges. Answer: 1- Alstroms's syndrome
[ Q: 33 ] Question ID #14 Alström syndrome (AS) is a rare autosomal

recessive disease characterized by multiorgan
A 32 year old man is referred by his GP. He was dysfunction. The key features are childhood
diagnosed with diabetes at the age of 14 and obesity, blindness due to congenital retinal
initially treated with metformin and was dystrophy, and sensorineural hearing loss.
commenced on exogenous insulin at the age of 22. Associated endocrinologic features include
He has a long standing history of obesity and has hyperinsulinemia, early-onset type 2 diabetes, and
difficulty in glucose monitoring due to very poor hypertriglyceridemia. Thus, AS shares several
vision, having had deterioration in vision from the features with the common metabolic syndrome,
age of 8. namely obesity, hyperinsulinemia, and
hypertriglyceridemia. Mutations in the ALMS1
On examination his BMI is 44 kg / m2 , his body gene have been found to be causative for AS with
weight is 132 kg, his blood pressure is 150/78 a total of 79 disease-causing mutations having
mmHg, he has acanthosis nigricans in axillae and been described. Further symptoms described in
nape of neck, reduced vibration sensation in both relation to AS include progressive sensory neural
feet and also evicence of sensorineural deafness. hearing loss, a dilated cardiomyopathy in over 60%
His current medication includes Novomix 30 84 of cases, developmental delays in 50 % of cases
units twice daily, ramipril 5 mg daily and leading to learning difficulties in up to 30% of
atorvastatin 40 mg once daily cases. MELAS syndrome describes a mitochondrial
myopathy associated with type 2 diabetes, lactic
Investigations reveal: acidosis, encephalopathy and stroke like episodes.
Bloom syndrome is another insulin resistant

syndrome being associated with in impaired lipid profile. Increasing the statin dose or
glucose tolerance and IUGR. Glycogen storage commencing a fibrate is not appropriate as
disease is a condition associated with impaired hypothyroidism is a risk factor for lipid lowering
glucose tolerance, hepatomegaly and may be a therapy-associated myotoxicity. Omega-3 fish oils
cause of early hypoglycaemia. are not routinely recommended for use in this
setting.
A 42 year old South Asian man is referred to the
diabetic clinic by his GP. He has a 5 year history of A 33 year old lady with a 10 year history of type 1
type 2 diabetes. He complains of feeling tired and diabetes has been converted from twice daily
has a previous history of ischemic heart disease. Novomix to a basal bolus insulin regimen
On examination his BMI is 34 kg/m2, his pulse is 51 comprising of insulin glargine and novorapid three
bpm and his blood pressure is 148 / 78 mmHg. His months previously at a total daily dose of 72 units.
current medication includes ‘Novomix 30’ 42 units On review in the clinic her glycaemic control has
twice daily, metformin 500 mg twice daily, improved since her insulin regimen change with
simvastatin 20 mg once daily, aspirin 75 mg once her current Hba1c measuring 8.1 % (<6) compared
daily, enalapril 20 mg once daily and atenolol 50 with 8.9% (<6) prior to her regimen change. She is
mg once daily. however unclear as to how to modify her prandial
insulin doses according to her diet.
Investigations reveal:
HbA1c 7.9% (<6) initial advice for this lady with respect to adjusting
Total Cholesterol 5.6 mmol/l (<5) her prandial insulin dose?
LDL-Cholesterol 3.7 mol/l (< 3)
Plasma Triglyceride 2.2 mmol/l (0.9 - 2.2) 1- 0.5 units of insulin per 10 gram of dietary
carbohydrate
TSH 16.8 mu / l (0.32 - 5.5)
Free T4 7.9 pmol/l (9.4 - 23.4) 2- 1 units of insulin per 10 gram of dietary
carbohydrate
Which of the following is the most appropriate 3- 2 units of insulin per 10 grams of dietary
approach to optimise this patient’s lipid profile? carbohydrate
4- 3 units of insulin per 10 grams of dietary
1- Commence fenofibrate carbohydrate
2- Commence Omega-3 fish oil 5- 4 units of insulin per 10 grams of dietary
3- Commence thyroxine carbohydrate
4- Improve glycaemic control

Answer & Comments
5- Increase simvastatin dose
Answer: 2- 1 units of insulin per 10 gram of dietary
carbohydrate
Answer & Comments
Answer: 3- Commence thyroxine The DAFNE patient education program suggests
that patients should initially adjust prandial insulin
This patient is hypothyroid as evidenced by the doses by 1 units according to each 10 gram of
low T4 and elevated TSH. Correction of his thyroid dietary carbohydrate. This initial ratio may
status will contribute to an improvement in his

subsequently be modified according to response His most recent Hba1c is 6.2% (<6). His main
and the influence of other factors such as exercise. complaint is that of feeling continually hungry and
he has experienced pre-syncopal like symptoms
[ Q: 36 ] Question ID #20 associated with capillary blood glucose
measurements of between 2.5 and 3.5mmol/l.
A 40 yr old woman presents to her GP with Which of the following is a feature of

recurrent vaginal thrush. She has a previous hypoglycaemia in patients with type 2 diabetes?
history of hypothyroidism and is receiving long
term thyroxine replacement. On examination, her
BMI is 30 kg / m2 and her blood pressure is
144/85mm Hg. Investigations reveal a fasting
plasma glucose of 13mmol/l (<5.6) and an HbA1c 1- 15% of patients of patients with type 2
of 9% (< 6). diabetes experience disabling
hypoglycaemia within 2 years of initiation
Which of the following would favour a diagnosis of on a basal insulin
type 2 rather than type 1 diabetes for this lady?
2- 2% of patients receiving sulphonylurea
therapy experience severe hypoglycaemia
1- Autoimmune aetiology of hypothyroidism
3- Approximately 10% of patients with type 2
2- High LDL cholesterol level diabetes experience symptomatic
3- High HDL cholesterol level hypoglycaemia
4- Normal albumin/creatinine ratio 4- The prevalence of severe hypoglycaemia is

higher in patients recently commenced on a
5- Presence of background retinopathy
basal insulin than in patients receiving
sulphonylurea therapy.
Answer & Comments
5- The prevalence of severe hypoglycaemia is
Answer: 5- Presence of background retinopathy similar in patients with type 2 diabetes
receiving insulin for more than 5 years to
Type 1 diabetes is associated with the presence of that in patients with type 1 diabetes
islet cell antibodies along with other autoimmune
conditions. HDL-C concentrations are higher in Answer & Comments
patients with type 1 diabetes, while up to 20% of
patients with type 2 diabetes will demonstrate Answer: 5- The prevalence of severe
evidence of microvascular complications at hypoglycaemia is similar in patients with type
diagnosis which will not be the case in patients 2 diabetes receiving insulin for more than 5
with type 1 diabetes. years to that in patients with type 1 diabetes
[ Q: 37 ] Question ID #25 Data from UKPDS and the RECAP-DM studies

suggest that between 30 to 40 % of patients with
A 69 year old man has a 7 year history of type 2 type 2 diabetes experience symptomatic
diabetes is reviewed in clinic. His current hypoglycaemia. The results of the UK
medication includes metformin 1 gram twice daily, hypoglycaemia study demonstrated a similar
glicalzide 160 mg twice daily, simvastatin 20 mg annual prevalence of around 7% of patients with
once daily, ramipril 5 mg once daily and aspirin 75 type 2 diabetes treated with a sulphonylurea
mg once daily. On examination his BMI is 31 kg / experiencing disabling hypoglycaemia, which was
m2 his blood pressure is 145 / 86 mmHg and he has similar in prevalence to that experienced by
no clinical evidence of microvasular complications. patients recently (< 2 years) commenced on basal

insulin therapy. Patients with type 2 diabetes  There must be appropriate blood glucose
receiving insulin for > 5 years, particularly when monitoring.
the regimen contained a prandial insulin element
experienced a similar prevalence of  Must not be regarded as a likely source of
hypoglycaemia to that observed in patients with danger to the public while driving.
type 1 diabetes.
 The visual standards for acuity and visual
[ Q: 38 ] Question ID #26 field must be met.
If meets the medical standard a 1, 2 or 3 year

A 46 year old aircraft engineer with a 22 year licence will be issued.
history of type 1 diabetes is referred by his GP for
review. His current medication includes 'Novomix
30' 44 units in the morning and 46 units in the [ Q: 39 ] Question ID #36
evening.
A 36 year old man with a 21 year history of type 1
On examination his blood pressure is 135/75 diabetes is reviewed in clinic. He feels generally
mmHg, his BMI is 28 kg/m2; his visual acuity is 6/9 well denies any hypoglycaemia, but historically
in the right eye and 6/6 in the left eye. His most has had poor glycaemic control. On examination,
recent HbA1c is 8.1% (< 6) and his main complaint blood pressure is 151 / 77 mmHg, his BMI 29
is that of recurrent problems with hypoglycaemia kg/m2, foot examination reveals no evidence of
with 3 episodes over the last 4 months requiring neuropathy while retinal screening reveals
paramedic assistance along with a reduction in his bilateral background retinopathy. His current
hypoglycaemia warning symptoms. medication includes novomix 30 and 42 units
twice daily.
What advice should be given to this gentleman
with respect to his driving? Investigations reveal:
Hba1c 8.9% (<6)
1- Discontinue driving for 1 month
Total Cholesterol 5.2 mmol/l (<5)
2- Discontinue driving for 3 months
LDL-Cholesterol 3.1 mmol/l (< 3)
3- Discontinue driving for 6 months HDL-Cholesterol 1.3 mmol/l (0.9 - 1.8)
4- Discontinue driving for 1 year Plasma Triglyceride 1.7 mmol/l (0.9 - 2.2)
5- Discontinue driving for 2 years Albumin Creatinine 6.9 mg / mmol creat
ratio (<2.5)
Answer & Comments
Which of the following is the correct approach to
Answer: 4- Discontinue driving for 1 year treating this man’s lipid profile?
According to the most recent DVLA guidelines, 1- Atorvastatin 20 mg od
patients on insulin therapy for diabetes:
2- Atorvastatin 80 mg od
 Must have awareness of hypoglycaemia.
3- Dietary modification only
 Must not have had more than one episode 4- Ezetimibe 10 mg od
of hypoglycaemia requiring the assistance
5- Fenofibrate 150 mg od
of another person in the preceding twelve
months.

Answer & Comments Fibrates are PPAR alpha receptor agonists and
through this route are responsible for reduced
Answer: 1- Atorvastatin 20 mg od hepatic triglyceride secretion, increased
lipoprotein lipase activity and increased clearance
Current NICE lipid lowering guidelines(July 2014) - of remnant LDL particles. These class of drugs are
offer atorvastatin 20 mg for the primary particularly useful in reducing triglycerides and
prevention of CVD to people who have a 10% or increasing HDL – the typical dyslipidaemia
greater 10-year risk of developing CVD. Estimate associated with diabetes.
the level of risk using the QRISK2 assessment tool.
Lipid lowering therapy for patients with diabetes [ Q: 41 ] Question ID #122
under the age of 40 should be considered when
there is an associated adverse cardiovascular risk
factor profile such as co-existing poor glycaemic A 56 year old male is commenced upon
control, the presence of microvascular Vildagliptin.
complications, features of metabolic syndrome
and family history of premature cardiovascular Through which of the following mechanisms does
disease. This patient should thus be considered for Vildagliptin function?
lipid lowering therapy with atorvastatin as he has (Please select 1 option)
evidence of microvascular complications in the
form of microalbuminuria and retinopathy 1- DPP-IV inhibitor
combined with poor glycaemic control. This 2- GIP agonist
guidance is based on data from all of the major
statin studies in which the relative cardiovascular 3- GLP-1 agonist
risk reduction associated with cholesterol 4- Potassium channel blocker
lowering occurs independent of baseline
cardiovascular risk, being related to the order of 5- PPAR-gamma agonist
magnitude of cholesterol reduction.
Answer & Comments
[ Q: 40 ] Question ID #108 Answer: 1- DPP-IV inhibitor
A 55 year old male with a 5 year history of type 2

Vildagliptin, sitagliptin are a class of drugs that
diabetes is receiving fenofibrate therapy for
inhibit the enzyme, dipeptidyl peptidase DPP-IV,
treatment of a hypertriglyceridaemia associated
which is responsible for the breakdown of GLP-1.
with low HDL and normal LDL.
GLP-1 has a very short half-life and is particularly
important in glucose homeostasis producing
Which of the following describes the mechanism of
delayed gastric emptying, suppression of glucagon
action of fibrate therapy? and glucose mediated insulin secretion.
(Please select 1 option) Consequently, the extension of the half-life of
1- 3-HMG-CoA inhibitor endogenous GLP-1 improves glucose homeostasis
in T2DM.
2- Bile sequestrant
3- Inhibits GI reabsorption of cholesterol [ Q: 42 ] Question ID #182
4- PPAR-alpha agonist
A 56 year old woman with a history of type 2
5- PPAR-gamma agonist diabetes, hypertension, retinopathy and
peripheral neuropathy attended her routine
Answer & Comments chiropody clinic and mentioned a 6-week history
of dull aching discomfort of the right foot. Her vital
Answer: 4- PPAR-alpha agonist signs were normal. On foot examination, there

were bounding peripheral pulses and no ulcer was 3- Laser treatment is 90% effective in
observed. A digital foot thermometer preventing loss of vision
measurement showed that the temperature was
20 degree centigrade on the left foot and 26 4- Recurrent laser treatments will not affect her
degree centigrade on the right foot. ability to drive
5- She will need to have her eye immobilised to
Which of the following is the most likely diagnosis undergo laser treatment
for this lady?
Answer & Comments
1- Abscess of the right foot
Answer: 3- Laser treatment is 90% effective in
2- Charcot neuroarthropathy preventing loss of vision
3- Diabetic foot osteomyelitis
According to the Early Treatment of Diabetic
4- Pes planus
Retiopathy study laser treatment is 90% effective
5- Traumatic fracture of the right foot unaware in preventing loss of vision in type 1 diabetes but
by the patient due to neuropathy only 50% in preventing loss of vision if the
predominant type of retinopathy is macular
oedema (mostly seen in type 2 diabetes). Pan-
Answer & Comments retinal treatment is often associated with loss of
Answer: 2- Charcot neuroarthropathy the peripheral visual field which may affect her
ability to drive if both eyes are treated although
this is usually only an issue after several
This patient with diabetic neuropathy presented treatments. She will not need her eye to be
with insidious onset discomfort, mid-foot immobilised but will need to be able to hold it still
deformity and signs of inflammation, which is a during treatment.
common presentation of charcot
neuroarthropathy. Gradual onset and signs of
inflammation is not consistent with a traumatic [ Q: 44 ] Question ID #201
fracture and again is characteristic feature of
charcot neuroarthropathy. A 38 year old lady with 21 year history of type 1
diabetes has a most recent HbA1c of 7.5% (<6).
[ Q: 43 ] Question ID #199 Her current therapy includes Insulin glargine and
humalog via a basal bolus regimen at a total daily
insulin dose of 79 units. She has no clinical
A 28 year old woman with type 1 diabetes for 14 evidence of microvascular complications although
years has poor glycaemic control with an HbA1c of her most recent digital retinal screen
12.4% (< 6). She has pre-proliferative (severe non- demonstrated the presence of background
proliferative) diabetic retinopathy and you are retinopathy in the right eye.
going to refer her to an ophthalmologist for
assessment. Which of the following lesions would be expected
in this retinal image to classify this as mild non-
What advice would you give her when she enquires
proliferativec (background) diabetic retinopathy?
about the likelihood of needing laser treatment?
1- Blot haemorraghes
1- Laser treatment will only be necessary if she
develops proliferative retinopathy 2- Branch retinal vein occlusion
2- Laser treatment is 60% effective in 3- Cotton wool spots

preventing loss of vision

4- Intra-retinal microvascular abnormality Urine Albumin to Creatine 4.7 mg/ mmol

(IRMA) Ratio (ACR) creat (<2.5)
5- Venous beading
Which of the following treatment strategies would
be most appropriate?
Answer & Comments
Answer: 1- Blot haemorraghes 1- Add a third oral agent with the aim of
improving his glycaemic control over several
Cotton wool spots are a pre-proliferative (sight weeks, there is no need to refer to an
threatening) feature and signify retinal ischaemia, ophthalmologist as his blurred vision is likely
however they do not define pre-proliferative due to hyperglycaemia.
retinopathy. If cotton wool spots are present then
other features - any venous bleeding, any venous 2- Do nothing other than refer him to an
reduplication, any IRMA, or blot haemorrhages - ophthalmologist.
should be looked for. Other sight threatening
3- Initiate insulin with the aim of rapidly
features are intra retinal microvascular
abnormalities (early new vessels), new vessels on improving his glycaemic control and refer
the disc or elsewhere, venous beading (retinal him to an optician for new glasses.
ischaemia), multiple deep haemorrhages 4- Initiate insulin and gently titrate the dose to
(ischaemia) and hard exudates near the fovea as
reduce his HbA1c over several weeks and
they are often associated with fluid leakage and
refer him to an ophthalmologist.
macular oedema. Background/mild
nonproliferative retinopathy is described by hard 5- Switch to insulin so as to rapidly improve his
exudates, dot and blot haemorrhages. glycaemic control and refer to an
ophthalmologist.
Grading of retinopathy
Answer & Comments

Answer: 4- Initiate insulin and gently titrate the
A 58 year old man with a 5 year history of type 2 dose to reduce his HbA1c over several weeks
diabetes attends your clinic with blurred central and refer him to an ophthalmologist.
vision. On examination he has moderate
background retinopathy with multiple lesions This man needs better glycaemic control but this
close to the macula centre. His BMI is 33 kg / m2 should be done gently so as not to suddenly drop
and his blood pressure is 168 / 88 mmHg. His the glucose levels as this is associated with retinal
current medication consists of Metformin 850mg artery vasoconstriction which may lead to a rapid
three times a day, Gliclazide 120mg twice daily, deterioration of retinopathy. His blurred vision is
simvastatin 20 mg once daily and lisinopril 20 mg likely due to a maculopathy and macular oedema
once daily. so referral to an ophthalmologist is also required.
Hba1c 8.9% (<6) [ Q: 46 ] Question ID #203

Total Cholesetrol 6.2 mmol/l (<4)
2.2 mmol/l (0.9 - A 39 year old lady with a 28 year history of type 1
Plasma Triglyceride
2.2) diabetes with chronic poor glycaemic control has
59 a most recent Hba1c of 10.1% (<6). Her current
eGFR ml/min/1.73m2; insulin regimen includes twice daily Novomix 30 at
(90 - 110) doses of 34 units in the morning and 38 units in
the evening. On examination, her blood pressure
is 144/68 mmHg, her BMI is 23 kg/m 2 and

examination of her feet reveals reduced vibration, 2- There is a 2 - 3 fold increase risk of Down
proprioception and thermosensation in both feet. syndrome
Retinal screening reveals evidence of
neovascularisation in the left eye. 3- There is a 2 - 4 fold increase risk of neural
tube defects
Which of the following factors has been shown to 4- There is a 2 - 4 fold risk of the baby
have an important role in regulating retinal subsequently developing type 1 diabetes
capillary blood flow?
5- Shoulder dystocia occurs in 15 - 20% of cases
1- Contractile action of endothelial cells. Answer & Comments

2- Contractile action of pericytes.
Answer: 5- Shoulder dystocia occurs in 15 - 20% of
3- Local release of interleukins. cases
4- Local release of nitric oxide.
Macrosomia and neonatal hypoglycaemia are the
5- Release of vascular endothelial growth commonest complications of gestational diabetes,
factor. with the risk of both being significantly increased
with poor glucose control during the 2nd and 3rd
Answer & Comments trimester. Macrosomia defined by a birth weight >
4.5Kg effects up to 45% of babies with shoulder
Answer: 2- Contractile action of pericytes. dystocia being a common delivery problem
occurring in up to 15 - 20% of cases. Still birth
The retinal pericytes regulate retinal capillary occurs in 2 – 3% of the general population and this
blood flow but they are often damaged and is not increased in gestational diabetes, generally
reduced in number in patients with diabetic gestational diabetes does not cause birth defects
retinopathy leading to disordered blood flow since insulin resistance and thus hyperglycaemia
regulation and increased shear stress on the vessel does not become pronounced until second and
walls which drives the pathogenesis of third trimester. Women with pregestational
retinopathy. diabetes, by contrast, have a 3- 5 fold increase risk
of still birth and neural tube defects, but similar to
gestational diabetes, there is no increase risk of
[ Q: 47 ] Question ID #215 chromosome abnormalities. These risks are
augmented with poor glucose control during the
A 24 year old Asian lady attends the Antenatal first trimester. Gestational diabetes does not
clinic following a 75 gram oral glucose tolerance significantly increase the risk of type 1 diabetes in
test at 24 weeks gestation which revealed a fasting the offspring, rather a paternal history of type 1
plasma glucose of 6.9 mmol/l, a 1 hour post diabetes appears to be a more pertinent factor.
challenge plasma glucose level of 11.7 mmol/l and
a 2-hour post challenge plasma glucose of 10.8
mmol/l. On examination her blood pressure is
132/68 mmHg and her BMI is 29 kg/m2.
A 71 year old lady with a 5 year history of type 2
What is the potential impact of the results of her diabetes is referred by her GP for assessment and
glucose tolerance test on the outcome of her management of her possible diabetic
nephropathy. Current medication includes
pregnancy?
Metformin 850 mg three times daily, Rosiglitazone
(Please select 1 option) 4 mg once daily and Perindopril 4 mg once daily.
1- There is a 2 - 3 fold increase risk of still birth On Examination, her blood pressure is 144/86
mmHg, her BMI 31 kg /m2 and there is reduced

vibration and proprioception sensation in both 2.1 mmol/l (0.9 -

feet. Plasma Triglyceride
2.2)
72 ml/min/1.73m2;
Hba1c 7.4% (<6) eGFR
(90-110)
eGFR 55ml/min/1.72m² Urine Albumin to 9.8 mg/mmol creat
Urine Albumin Creatine 14.6 mg/mmol Creatinine Ratio (<3.5)
Ratio (ACR) creat (<3.5)
How many eGFR readings should be obtained over
What level of albumin to creatinine ratio (ACR) 90 days in order to identify progressive CKD?
confirms a diagnosis of proteinuria? (Please select 1 option)
1- One
1- 10 mg/mmol
2- At least 2
2- 30 mg/mol
3- At least 3
3- 40 mg/mmol
4- At least 5
4- 50 mg/mmol
5- At least 7
5- 60 mg/mmol
Answer & Comments
Answer & Comments
Answer: 2- At least 2
Answer: 2- 30 mg/mol
CKD, defined as abnormalities of kidney function
An ACR 30 mg/mmol confirms a diagnosis of or structure present for more than 3 months, with
persistent proteinuria. Microalbuminuria is implications for health. This includes all people
defined as an ACR > 2.5 mg/mmol for men and > with markers of kidney damage and those with a
3.5 mg/mmol for women, these diagnostic criteria glomerular filtration rate (GFR) of less than 60
are used in the NICE CKD clinical guidance ml/min/1.73 m2 on at least 2 occasions separated
(November 2008). Diagnosis can only be by a period of at least 90 days (with or without
confirmed after two samples have been assessed, markers of kidney damage) (NICE 2015)
separated by a few weeks.
NICE CKD Guidance
diabetes is referred by his GP for assessment. A GP colleague contacts you for advice on a
Current medication includes Metformin 1 g twice patient with type 2 diabetes and deteriorating
daily, glicalzide 160 mg twice daily, Ramipril 5 mg renal function. The patient is a 69 year old man
once daily and Simvastatin 20 mg once daily. On with a 6 year history of type 2 diabetes. His current
examination, his blood pressure is 150/77 mmHg, medication includes glicalzide 160 mg once daily,
his BMI is 32 kg /m2 his waist circumference is 98 Metformin 500 mg twice daily lisinopril 20 mg
cm and fundoscopy reveals background diabetic once daily, amlodipine 5 mg once daily and
retinopathy in both eyes. pravastatin 20 mg once daily. His blood pressure is
145/75 mmHg and he has evidence of background
Hba1c 7.7% (<6) retinopathy on retinal screening.

44 blood pressure is 152/90 mmHg. His current

eGFR ml/min/1.72m² medication includes Metformin 1 gram twice
(90-110) daily, Glicalzide 160 mg twice daily, Insulin
Glargine 32 units once daily, Lisinopril 10 mg once
Urine Albunmin:creatinine 10.5 mg/mmol
daily and Simvastatin 40 mg once daily.
Ratio (ACR) (<2.5)
HbA1c 8.1% (<6) HbA1c 7.8% (<6)
At which level of eGFR would you advise the GP to Total Cholesterol 4.4 mmol/l (<5)
discontinue metformin therapy? 2.7 mmol/l (0.9
Plasma Triglyceride
- 2.2)
U+E Normal
1- eGFR ≤ 15 ml/min/1.72m2
Urine Albumin:Creatinine 9.9 mg/mmol
2- eGFR ≤ 30 ml/min/1.72m2 Ratio (ACR) (<2.5)
3- eGFR ≤ 40 ml/min/1.72m2
Which of the following is the following is the most
4- eGFr ≤ 50 ml/min/1.72m2 appropriate blood pressure target for this patient?
5- eGFR ≤ 60 ml/min/1.72m2 (Please select 1 option)
1- 130 / 80 mm/hg
Answer & Comments
2- 140 / 80 mm/hg
Answer: 2- eGFR ≤ 30 ml/min/1.72m2
3- 120 / 80 mm/hg
Product characteristics for metformin state that it 4- 130 / 70 mm/hg

should be discontinued at an eGFR < 50, however 5- 110 / 70 mm/hg
in clinical practice an eGFR < 30 (CKD 4) is
considered to represent an absolute indication for
the discontinuation of metformin. While not a Answer & Comments
contraindication to metformin, an eGFR 30 – 59 Answer: 1- 130 / 80 mm/hg
should alert clinicians to evaluate the need for
possible dose reduction or discontinuation of
metformin particularly if other risk factors for This patient has microalbuminuria as defined by
metformin toxicity are present such as heart an elevated albumin to creatinine ratio. The
failure. Renal function and metformin safety is diagnosis of microalbuminuria is confirmed by two
based on the fact that metformin is renally measurements at least 1 week apart > 2.5
cleared. In the setting of significant renal mg/mmol for males and > 3.5 mg/mmol for
impairment particularly in the presence of an females. The identification of microalbuminuria
inter-current illness resulting in relative tissue identifies patients at an increased risk of
hypoxia, there is a marked increase in the risk of cardiovascular disease and is an indication for
metabolic acidosis (lactic acidosis) in patients with intensive multiple risk factor intervention. Current
renal impairment receiving metformin therapy. NICE guidelines (November 2008) advocate an
optimal target blood pressure for such patients of
< 130 / 80 mm/Hg.
diabetes attends clinic for review. On examination
he has bilateral background retinopathy along A 65 year old man with a 7 year history of type 2
with reduced vibration and 10 g microfilament diabetes is reviewed in clinic. He feels generally
sensation in both feet, his BMI 32 kg / m2 and his well and his glucose control has improved since
commencing insulin 4 months previously with his

current HbA1c measuring 7.4% (< 6). His main disease and numbness progress. Of course, these
complaint is that of burning discomfort in both uncontrolled patients are at great risk for diabetic
feet which is more severe at night. He has foot ulcers and amputation.
experience only minimal relief with co-codamol
and non-steroidal anti-inflammatory based Reference:
analgesia. NICE clinical guidelines 173: Neuropathic pain
On examination his blood pressure is 144 / 77 [ Q: 53 ] Question ID #223

mmHg, his BMI is 32 kg/m2, retinal screening
reveals features of background retinopathy in his
left eye and examination of his feet reveals A 55 year old Asian lady with a 3 year history of
reduced vibration and proprioception sensation in diet controlled type 2 diabetes is reviewed in
both feet. clinic. Her glucose is well controlled with a most
recent HbA1c measuring 6.9 % (<6). On
Which of the following is the most appropriate examination her blood pressure is 134 / 74 mmHg
therapy option for managing this patient’s and her BMI is31 kg / m2. Her main complaint at
present is that of persisting tingling and
symptoms?
discomfort in her feet at night.
1- Capsaicin 0.025 % topically Which of the following apply in the clinical

assessment of diabetic peripheral sensory
2- Citalopram 10 mg daily neuropathy?
3- Duloxetine 60 mg daily (Please select 1 option)
4- Fluoxetine 20 mg daily 1- Small fiber function may be assessed using a

5- Gabapentin 900 mg daily tuning fork
2- Large fiber function may be assessed by
Answer & Comments thermal discrimination
Answer: 3- Duloxetine 60 mg daily 3- Loss of vibration sensation is an early clinical

feature
In accordance with NICE guidelines 173, for people 4- Loss of ankle jerk reflexes is an early clinical
with painful diabetic neuropathy, offer oral feature
duloxetine 60mg, amitriptyline, pregabalin or
gabapentin as first-line treatment. If the initial 5- Medial plantar sensory action potential is
choice fails despite maximum tolerated dose, offer undetectable in patients with neuropathy
other first line agents - oral amitriptyline 10mg,
oral pregabalin 150mg or gabapentin 300mg tds. Answer & Comments
Hence in our scenario the Duloxetine is the correct
choice. If satisfactory pain reduction is still not Answer: 3- Loss of vibration sensation is an early
achieved with second-line treatment, refer the clinical feature
patient to a specialist pain service and/or a
condition specific service. While waiting for Small fiber function may be assessed via
referral, consider oral tramadol or topical evaluation of thermal discrimination, while large
lidocaine. fiber function is a determinant of vibration and
proprioception sensation and may be clinically
Tight control of blood glucose can reverse the evaluated with a tuning fork. Medial plantar
changes of diabetic neuropathy, but only if the sensory action potential is undetectable in
neuropathy and diabetes is recent in onset. subjects with normal vibration and thermal
Conversely, painful symptoms of neuropathy in thresholds. Large fiber dysfunction and thus loss
uncontrolled diabetics tend to subside as the

of vibration and proprioception sensation is the with autonomic nerve dysfucntion. Examination
earliest manifestation of peripheral sensory motor findings include reduced vibration and
neuropathy in diabetes. proprioception sensation, diminished ankle jerks,
muscle wasting and increased blood flow.
[ Q: 54 ] Question ID #224 Reduced light pressure sensation and vibration
sensation are the earliest clinically identifiable
manifestations of large fiber neuropathy.
diabetes is reviewed in clinic. Her main complaint
is of numbness in her feet. Current medication [ Q: 55 ] Question ID #225
includes metformin 1 gram twice daily, Insulin
glargine 32 u at night, perindopril 4 mg once daily, A 39 year old man with a 21 year history of type 1
simvastatin 20 mg once daily and aspirin 75 mg diabetes with chronic poor control has a most
once daily. On examination her blood pressure is recent HbA1c of 9.1% (< 6). His current medication
155 / 56 mmHg, her BMI is 33 kg / m2 peripheral includes Novomix 30 56 units in the morning and
pulses are present but vibration sensation is 64 units in the evening. Retinal screening reveals
reduced in both feet. bilateral background retinopathy and urinalysis
reveals an albumin:creatinine ratio of 4.9 mg /
Investigations reveal: mmol creat (< 2.5). His main complaint is that of
burning discomfort in both feet. Examination of
HbA1c 7.9% (<6) his feet reveals them to be cold but with preserved
peripheral pulses and reduced thermosensation,
Urine vibration and proprioception sensation.
3.9 mg/mmol creat
Albumin:Creatinine
(<3.5)
Ratio
Which of the following would suggest a diagnosis
55 ml/min/1.73m² of short fiber neuropathy?
eGFR
(90-110)
Which of the following is a typical feature of large 1- Muscle wasting

fiber neuropathy? 2- Decreased light pressure sensation
3- Diminished ankle jerks
1- Hyperaesthesia
4- Paraesthesia
2- Impaired thermosensation
5- Reduced thermosensation
3- Paraesthesia
4- PR interval variation Answer & Comments
5- Reduced sweating Answer: 5- Reduced thermosensation
Answer & Comments Short fiber neuropathy is a later manifestation of

diabetic peripheral neuropathy, with symptoms
Answer: 3- Paraesthesia
including hyperasthesia and superficial pain.
Examination findings indicative of short fiber
Large fiber involvement in neuropathy results in neuropathy include impaired thermosensation,
reduced proprioception and vibration sensation reduced sweating and a cold foot although
and is the earliest clinically identifiable feature of reflexes are not involved.
peripheral sensory motor neuropathy. The
primary symptom associated with large fiber
dysfunction is paraesthesia and an increased risk
of charcot arthropathy, particularly in association

[ Q: 56 ] Question ID #226 should be > 1.2. The heart rate response to

standing may also be useful in evaluating possible
A 26 year old lady with a 21 year history of type 1 autonomic neuropathy. During continuous ECG
diabetes is reviewed in clinic. Her current monitoring, the R-R interval is measured at beats
medication includes Insulin glargine and 15 and 30 after standing. Normally, a tachycardia
novorapid via a basal bolus regimen at a total daily is followed by reflex bradycardia. The 30:15 ratio
dose of 74 units. She has had long standing poor is normally > 1.03. Heart rate variability measures
glucose control with a most recent Hba1c of 12.1% predominantly evaluate parasympathetic nervous
system integrity, while blood pressure changes
(<6). She complains of feeling faint on standing
and also has noticed an increasing frequency of predominantly test sympathetic nervous system
diarrhoea. On examination her blood pressure is integrity. A Q-T interval > 440ms is abnormal and
112/68 mmHg when supine and 96/56 mm/hg on suggestive of parasympathetic autonomic
standing, her body weight is 56kg and her BMI is neuropathy. These diagnostic values refer to
20 kg/m2 . Examination of her feet reveals reduced measurements in patients less than 60 years of
vibration and proprioception sensation in both age. It is important to note that autonomic
feet. function tests tend to decline with age.
Which of the following investigations would [ Q: 57 ] Question ID #227

support a diagnosis of autonomic neuropathy?
(Please select 1 option) A 32 year old lady with a 20 year history of type 1
diabetes is reviewed in clinic. Her current
1- 5 mmHg variation in diurnal blood pressure
medication includes Novomix 30 32 units twice
2- 10 mmHg change in systolic blood pressure daily. Her control has historically been poor with
20 minutes after a meal her most recent Hba1c measuring 10.1% (<6).
3- Heart rate variability of < 10 beats per On examination her blood pressure is 105 / 65
minute with respiration mmHg and her body weight is 63 kg. Examination
4- QT - interval of < 440 ms of her feet reveals reduced absent ankle jerks
bilaterally and reduced vibration and
5- Longest R-R to shortest R-R ratio during proprioception in both feet. Her main complaint is
valsalva maneuver > 1.2 that of increasingly frequent episodes of fecal
incontinence.
Answer & Comments
Which of the following clinical features would
Answer: 3- Heart rate variability of < 10 beats per support a diagnosis of autonomic neuropathy?
minute with respiration (Please select 1 option)
1- Heart rate increase on deep breathing > 15

Heart rate variability during breathing of < 10
beats per minute
beats per minute is indicative of autonomic
neuropathy. A change in post-prandial systolic 2- Heart rate increase on standing after 15
blood pressure > 20 mm /hg is considered seconds <12 beats per minute
abnormal, while a variation in diurnal blood
pressure > 15 mm/hg is considered abnormal. 3- Generalized sweating
During the valsalva maneuver the subject forcibly 4- Postural systolic blood pressure drop 2
exhales into the mouthpiece of a manometer to 40 minutes after standing > 15 mm/hg
mmHg for 15 s during ECG monitoring. Healthy
subjects develop tachycardia and peripheral 5- Resting heart rate > 80 beats per minute
vasoconstriction during strain and an overshoot
bradycardia and rise in blood pressure with
release. The ratio of longest R-R to shortest R-R

Answer & Comments Which of the following is the most likely diagnosis
for this gentleman?
Answer: 2- Heart rate increase on standing after
15 seconds <12 beats per minute (Please select 1 option)
1- Atrophic lateral sclerosis

Heart rate increase on standing of < 12 beats per 2- Diabetic amyotraphy
minute is indicative of autonomic neuropathy, a
normal response being > 15 beats per minute. A 3- Polymyositis
postural fall in systolic blood pressure of > 30 4- Polymyalgia
mmHg 2 minutes after standing is suggestive of
autonomic dysfunction as is a resting heart rate > 5- Lumbar degenerative disc disease
100 beats per minute. Clinical features which help
establish a diagnosis of autonomic neuropathy Answer & Comments
include diarrhea, fecal incontinence and post-
gustatory sweating. Answer: 2- Diabetic amyotraphy
[ Q: 58 ] Question ID #228 Diabetic amyotrophy is a disabling neuropathy

that usually occurs in patients with type 2 diabetes
A 54 year old gentleman with a 2 year history of mellitus in middle or later age. Concomitant
type 2 diabetes is reviewed in the clinic weight loss is frequent. Patients usually have not
complaining of difficulty in walking and frequent had diabetes for a long time, and glycemic
episodes of tripping and stumbling particularly dysregulation is often not severe. A diagnosis of
when walking up hill, but denies any pain or diabetic amyotrophy leads to the discovery of
parasthesia. His current medication includes underlying diabetes mellitus in one quarter to one
metformin 500 mg three times a day, simvastatin third of cases. Long-term diabetic complications
40 mg once daily, perindopril 4 mg once daily and such as diabetic retinopathy and nephropathy are
aspirin 75 mg once daily. often absent at the time of diagnosis. The clinical
presentation is characterized by sudden, sharp,
On examination, his blood pressure is 144/74 and asymmetric pain that usually starts in one hip
mmHg, his BMI is 30 kg/m2 examination of his legs and thigh and subsequently spreads to the other
reveals muscle wasting affecting the left thigh with side within weeks to months. Cases of worsening
marked reduction in power and muscle over 18 months are often described. Weakness
fasciculations, plantar flexion and dorsiflexion of starts distally in one third of cases, leading to
both feet are normal and no sensory deficit can be unilateral or bilateral foot drop. As the pain
identified. improves, weakness becomes the major
symptom; it affects both proximal and distal leg
muscles. In about one third of cases, weakness
spreads to proximal arm muscles and is attributed
to cervicobrachial radiculoplexopathy . However,
HbA1c 7.3% (<6) some of these upper extremity deficits result from
Total Cholesterol 4.4 mmol/l (0.9 - 2.2) compression neuropathy from reliance on the
Plasma Triglyceride 1.6 mmol/l (0.9 - 2.2) arms to support body weight. Approximately 12%
of patients develop thoracic radiculopathy,
Creatinine Kinase leading to radiating belt-like chest or abdominal
74 U/L (38 - 174)
(CK) pain and intercostal muscle weakness causing
ESR 11 mm/hr (<10) pseudohernia. Prominent bulbar symptoms have
CRP 4.1 mg/l (<6) been described. Respiratory weakness may also be
the initial manifestation of diabetic proximal
92 ml/min/1.73 m2; (90- neuropathy.
eGFR
110)

Amyotrophic lateral sclerosis (ALS) may occur vibration sensation, thermosensation and
from the teenage years to the late 80s, but peak proprioception sensation in both feet. Dorsalis
age at onset occurs from 55-75 years with mean pedis and posterior tibial pulses are palpable
age of 62 years at diagnosis. Muscle weakness bilaterally. Her current medication includes
usually is asymmetric, and signs of upper and ‘Novomix 30’ 26 units twice daily, Metformin 500
lower motor neuron involvement may be mg twice daily, rosuvastatin 10 mg once daily,
observed. In the initial stages, reflexes should be perindopril 4 mg once daily, amlodipine 5 mg once
normal to increased, but as the disease becomes daily, bisoprolol 2.5 mg once daily and furosemide
more advanced, reflexes may be diminished or 40 mg once daily.
absent. Fasciculations are commonly seen as a
result of lower motor neuron involvement Investigations reveal
Pathologic long-tract signs of upper motor neuron
involvement, such as the extensor plantar Hba1c 7.9% (<6)
response and/or Hoffmann sign, may be present
in patients with hyporeflexia or areflexia, Total Cholesterol 3.6 mmol/l (<5)
depending upon the extent of the upper motor Plasma TG 1.7 mmol/l (0.9 - 2.2)
neuron involvement. In 75-80% of patients, eGFR 47 ml/min/1.73m² (90-110)
symptoms begin with limb involvement, while 19-
25% of patients present with bulbar symptoms. LFT Normal
For those with limb involvement at presentation, TSH 1.21 mu / / (0.32 - 5.5)
incidence of upper limb versus lower limb
involvement is approximately equal. Patients who Which of the following would be the most
have lower limb onset initially may complain of appropriate initial therapy of choice for this lady’s
tripping, stumbling, or awkwardness when symptoms?
running. Those with upper limb onset may have
difficulty with actions such as buttoning clothes,
picking up small objects, or turning a key. With 1- Amitriptyline
bulbar onset, patients note problems such as
2- Carbemazepine
slurred speech, hoarseness, or decreased volume
of speech. 3- Duloxetine
4- Gabapentin
The absence of any sensory symptoms coupled
with preserved reflexes and no prior history of disc 5- Pregabalin
injury or back pain makes a diagnosis of lumbar
radiculopathy unlikely, while the clinical picture
Answer & Comments
coupled with normal inflammatory markers and
CK levels also makes diagnoses of polymyalgia or Answer: 3- Duloxetine
polymyositis unlikely.
In accordance with NICE guidelines 173, for people
[ Q: 59 ] Question ID #230 with painful diabetic neuropathy, offer oral
duloxetine 60mg, serotonin-norepinephrine
A 75 year old lady with a 10 year history of type 2 reuptake inhibitor (SNRI), as first-line treatment. If
diabetes complicated by ischemic heart disease duloxetine is contraindicated or satisfactory pain
and congestive cardiac failure is reviewed in clinic. reduction is not achieved with maximum tolerated
Her main complaint is that of electric shock like dose of duloxetine, offer oral amitriptyline 10mg,
pains in both feet, particularly at night with only a tricyclic antidepressant (TCA), or oral pregabalin
minimal relief from simple analgesia. 150mg, an anti-epileptic, instead/in addition. If
satisfactory pain reduction is still not achieved
On examination her blood pressure is 106/55 with second-line treatment, refer the patient to a
mmHg, her BMI is 31 kg/m2 and examination of specialist pain service and/or a condition specific
her feet reveals bilateral pitting edema, reduced

service. While waiting for referral, consider oral 4- Arrange a routine referral for nephrology
tramadol or topical lidocaine. assessment
Tight control of blood glucose can reverse the 5- Arrange for an urgent nephrology
changes of diabetic neuropathy, but only if the assessment
neuropathy and diabetes is recent in onset.
Conversely, painful symptoms of neuropathy in Answer & Comments
disease and numbness progress. Of course, these Answer: 4- Arrange a routine referral for
uncontrolled patients are at great risk for diabetic nephrology assessment
foot ulcers and amputation.
This gentleman has demonstrated a significant
Reference: progression in kidney disease as defined by the
NICE clinical guidelines 173: Neuropathic pain observed decline in eGFR over a 6 month period.
A decline in eGFR > 5 ml/min/1.72m2within 1 year
[ Q: 60 ] Question ID #231 defines significant progression of kidney disease
and is an indication for further investigation and
intensification of therapy. Initiation of ACE-I
A 64 year old gentleman with a five year history of
therapy of or Angiotensin receptor blocker
type 2 diabetes is reviewed in clinic. On
therapy may result in decline of eGFR of 15 – 25%
examination, his current medication includes
as part of a normal response. A greater decline in
PIoglitazone 30 mg once daily, gliclazide 160 mg
response to the initiation of such agents should
twice daily, simvastatin 40 mg once daily, ramipril
alert the clinician to the possibility of renovascular
5 mg once daily and amlodipine 5 mg once daily.
disease.
On examination, his blood pressure is 145/75
This gentleman may also have early renal anemia.
mmHg and his BMI is 33 kg/m2. He has bilateral
The WHO definition of normal haemoglobin levels
background retinopathy on retinal screening but
for men and post-menopausal women is > 13 g /
has no evidence of peripheral sensory neuropathy.
dl. In patients with diabetic nephropathy renal
His current eGFR is 43 ml/min/1.73m2 compared
anemia develops earlier than in people with non-
with 59 ml/min/1.73m2 when measured 6 months
diabetic kidney disease.(this is likely to have
previously.
diabetic nephropathy since he has evidence of
other microvascular complications in the form of
Further investigations reveal:
retinopathy). In diabetic kidney disease a
threshold eGFR < 60 ml / min / 1.73m2is advocated
Hba1c 8.1% (<6) by the national service framework as the point at
Haemoglobin 11.9 g/ dl (11 - 16) which to begin screening for renal anemia. Using
this threshold around 85% of cases would be
identified.
Urine 8.9 mg/mmol/creat
Albumin:creatinine ratio (<2.5)
approach to the management of this gentleman? A 44 year old Asian lady with a 5 year history of
type 2 diabetes is admitted to hospital with
progressive pitting odema.
1- Repeat eGFR in 3 months
On examination, her blood pressure is 156/76
2- Repeat eGFR in 6 months
mmHg, her BMI is 38 kg/m2 and fundoscopy
3- Arrange for 24 hour urine creatinine reveals changes of background diabetic
clearance measurement retinopathy in both eyes. Her current medication

includes Metformin 1 g twice daily, Enalapril 5 mg [ Q: 62 ] Question ID #233

once daily and simvastatin 20 mg once daily.
Investigations reveal a grossly elevated 24 hour A 71 year old lady has recently been diagnosed
urinary protein content of 4.6 g/24 hours (< 0.3). with type 2 diabetes, which is being managed by
She subsequently undergoes a renal biopsy as part lifestyle modification. She has a past medical
of her ongoing investigation, the result of which is history of hypertension but no other medical
reviewed at the weekly clinical pathology meeting. history of note. Her current therapy includes
ramipril 1.25mg, amlodipine 5 mg once daily,
Which of the following microscopic changes would simvastatin 20 mg once daily and aspirin 75 mg
confirm a diagnosis of diabetic nephropathy? once daily. On examination her blood pressure is
(Please select 1 option) 133/77 mmHg, her BMI is 33 kg / m2 and
fundoscpy reveals changes of background diabetic
1- Cellular eosinophillic nodules found at the
retinopathy in the left eye.
periphery of the glomerular tuft
2- Focal nodular mesangial tissue expansion Investigations reveal
3- Glomerular basement membrane thickening

HbA1c 7.1% (<6)
4- Glomerular basement membrane atrophy Total Cholesterol 4.3 mmol/l (<4)
5- Mesangial matrix thickening due to Plasma Triglyceride 1.9 mmol/l (0.9 - 2.2)
deposition of type V and Type VI collagen 48 ml/min/1.73m²
along with fibrinonectin eGFR
(90-110)
Urine Albumin to 6.9 mg/mmol creat
Answer & Comments Creatinine Ratio (ACR) (<3.5)
Answer: 2- Focal nodular mesangial tissue
expansion
therapeutic consideration for this lady?
Focal nodular mesangial tissue expansion is a
characteristic early feature of diabetic 1- Her Ramipril dose should be increased
nephropathy, with a close relationship existing aiming to produce blood pressure
between mesangial expansion and functional dependent reductions in her albuminuria
renal abnormalities. Immunostaining of the
expanded matrix material reveals it to be mainly 2- Her ACE-Inhibitor should be replaced by an
of type IV collagen with additional type V, laminin angiotensin receptor blocker (ARB) as this
and fibrinonectin. Basement membrane class of agents has a greater effect on
thickening is invariably present in people with preserving GFR in patients with type 2
diabetes, irrespective of whether or not they have diabetes
nephropathy and can be demonstrated within 2 –
3 years of diagnosis of type 1 diabetes. 3- An angiotensin receptor blocker (ARB)
should be added in to her current therapy as
The Kimmelsteil-Wilson nodule is a specific combination ACE and ARB therapy reduces
feature of diabetic nephropathy but only occurs in progression to end-stage renal disease
20 – 60% of patients with nephropathy. It
4- Her Ramipril should be replaced by a direct
comprises of acellular eosinophillic laminated
structure usually at the periphery of the rennin inhibitor as this may result in greater
glomerular tuft. reduction in albuminuria
5- The addition of a direct renin inhibitor to her
current therapy would be an option to

produce blood pressure independent Which of the following is the most appropriate
reductions in her albuminuria advice for this lady?
Answer & Comments 1- Her retinopathy may deteriorate if she
Answer: 1- Her Ramipril dose should be increased breast feeds.
aiming to produce blood pressure dependent 2- She does not require retinal screening during
reductions in her albuminuria her pregnancy.
3- She will require screening three times during
The results of studies such as BENEDICT (Bergamo
her pregnancy.
Nephrologic Diabetes Complications Trial) and
RENAAL (Reduction of Endpoints in NIDDM with 4- She will require an ACE-I to protect her from
the Angiotensin II Antagonist Losartan) suggest worsening retinopathy.
that blockade of the renin angiotensin system with
ACE-Inhibitors or Angiotensin receptor blockers 5- She will require aspirin to protect her from
produces reductions in microalbuminuria and worsening retinopathy.
delays development of microalbuminuria
independent of blood pressure reduction. Dual Answer & Comments
blockade of the rennin angiotensin system with
combination ACE-inhibitor and Angiotensin Answer: 3- She will require screening three times
receptor blocker therapy may reduce during her pregnancy.
microalbuminuria, however there is no evidence
that dual blockade reduces progression to end- Diabetic retinopathy may rapidly deteriorate
stage renal disease. during pregnancy due to the rapid improvement in
glycaemic control that is often achieved; she
The DETAIL study demonstrated that ACE inhibitor therefore needs dilated fundoscopy or
and ARB therapy exerted similar effects on GFR photography every trimester. ACE inhibitors are
(Barnett A.J Am Soc Nephrol. 2006 Apr;17(4 Suppl
contraindicated during pregnancy and aspirin
2):S132-5).
does not have any data to support its use in
pregnancy. Breast feeding will have no effect on
The addition of a direct rennin inhibitor to ongoing
retinopathy.
antihypertensive therapy including agents that
block the rennin angiotensin system has been
shown to result in blood pressure independent [ Q: 64 ] Question ID #237
reduction in microalbuminuria (N Engl J Med. 2008
Jun 5;358(23):2433-46 A 22 year old law student is reviewed in clinic
following her recent diagnosis with type 1
[ Q: 63 ] Question ID #236 diabetes six months previously. She has an HbA1c
of 8.9% (<6) and smokes 10 cigarettes a day. Her
main concern relates to the effect that diabetes
A 26 year old woman with pre-existing type 1
may have on her eyesight.
diabetes for 12 years attends your medical
antenatal clinic as she has just discovered that she
is pregnant. This is an unplanned pregnancy and Which of the following is the most appropriate
her HbA1c is 8.2% (<6). At her most recent retinal approach for this young lady?
screen she was noted to have background (Please select 1 option)
retinopathy affecting the right eye. She is
1- Achieving an HbA1c of 7% would reduce her
concerned as to the possible impact of her
risk of retinopathy developing by about 75%
pregnancy on her eyes.
2- Any future pregnancy will have no effect on
her eyes

3- She is unlikely to develop retinopathy if she 1- Delay giving her bolus until her blood
maintains an HbA1c <6.5% glucoses start to rise post-prandially
4- Stopping smoking will reduce her risk of 2- Do not give a mealtime bolus but measure
developing retinopathy the glucose 2 hours post-prandially and give
an appropriate correction bolus
5- She is unlikely to develop any problems with
her eyes for the next 10 years 3- Do not give a mealtime bolus but increase
the basal rate around the mealtimes to
Answer & Comments cover the rise in glucose.
Answer: 1- Achieving an HbA1c of 7% would 4- Give the bolus of insulin over a protracted
reduce her risk of retinopathy developing by time such as 60 to 120 minutes
about 75% 5- Put a longer acting insulin into the pump
instead of the usual short acting insulin
The Diabetes Control and Complications Trial
showed a 75% reduction in retinopathy Answer & Comments
developing and a 60% reduction in progression
from mild retinopathy associated with a reduction Answer: 4- Give the bolus of insulin over a
of HbA1c from 9% to 7%. Unfortunately even with protracted time such as 60 to 120 minutes
good control she will almost inevitably develop
retinopathy and the risk is greater in type 1
This can be a difficult issue to address to a
diabetes compared to type 2 diabetes as
satisfactory degree. Delaying giving a bolus until
demonstrated by the Wisconsin Epidemiologic
glucoses rise is likely to allow symptoms of
Diabetic Retinopathy Study. Interestingly that
hyperglycaemia to develop. If the basal rate is
study did not find an association between smoking increased this is restrictive in terms of timing of
and retinopathy. Features of retinopathy usually meals and both type and amount of food and
do not appear in patients with type 1 diabetes for allowing freedom of choice of food is a major
up to 5 years following diagnosis, while pregnancy
benefit of using continuous subcutaneous insulin
is associated with potential progression of infusion. Giving a bolus over a protracted period of
retinopathy. time (also known as a square wave bolus) can help
to overcome this problem.
A 37 year old woman has had type 1 diabetes for
34 years. For the last 2 years she has had a
A 60 year old female is seen as part of the retinal
problem of vomiting 2 hours after her meals
screening service. Her vision is fine at 6/9
intermittently. A barium meal study has suggested
bilaterally and she is noted to have a couple of
gastroparesis. She has tried various treatments for
microaenurysms only in both eyes.
this but all with limited success. She has difficulty
controlling her blood glucose levels post-
When should this patient next have retinal
prandially as these are either high if she doesn’t
screening?
give enough short acting insulin or low if she
vomits 2 hours after a meal. It is suggested that (Please select 1 option)
she tries a continuous subcutaneous insulin 1- one month
infusion to try to help with this problem.
2- three month
You are asked to advice on her mealtime boluses; 3- six months
you would suggest:
4- one year

5- two years This patient presens with weakness, has a

hyperkalaemia and hypernatraemia together with
mild chronic renal impairment. The biochemistry
Answer & Comments
is suggestive os a type IV renal tubular acidosis
Answer: 4- one year (hyporeninaemic hypoaldosteronism). This is not
uncommon in elderly patients, particularly with
diabetes and may be exacerbated by drugs such as
With background retinopathy the interval
NSAIDS and beta blockers. Treatment is usually
between screening is recommended as annual. A
successful with withdrawal of the offending
4 month interval is suggested for preproliferative
agents and a low potassium diet. Small doses of
retinopathy.
fludrocortisone can be used but care needs to be
exercised with hypertension.
A 74 year old male presents with a six month
history of deteriorating fatigue and weakness. He
was diagnosed with type 2 diabetes approximately
diabetes is referred to the clinic after moving to
15 years ago together with hypertension. He
the area for a new job. Amongst his notes you see
receives gliclazide 40mg bd, metformin 1g bd and
that previous retinal screening classifies him as
atenolol 50mg daily.
'Retinopathy R1'.
On examination, blood pressure is 154/88 mmHg
Which of these was therefore noted at his last
lying and standing, he has evidence of a peripheral
retinal screening?
neuropathy to mid tibia and has some dot
haemorrhages on fundal examination. (Please select 1 option)
1- Detached macula
Which of the following is the likely explanation for
his presentation and biochemistry? 2- Intraretinal microvascular abnormalities
(IRMAs)
Sodium 142 mmol/L (135-145) 3- Venous beading
Potassium 5.5 mmol/L (3.5-5)
4- Microaneurysms
5- New vessels
Creatinine 133 mmol/L (50-100)
Plasma glucose 10.1 mmol/L (3.5-6.0)
Answer & Comments
HbA1c 7.8% (<6)
Answer: 4- Microaneurysms
1- Drug induced The National Screening Committee has produced

2- Hypoadrenalism guidance grading the lesions present on retinal
screening. These are
3- Hyporeninaemic hypoaldosteronism
R1 - background retinopathy - in this case
4- Liddle's syndrome microaneurysms
5- Renal artery stenosis R2 - Preproliferative retinopathy
R3 - Proliferative retinopathy
Answer & Comments M - Maculopathy
Answer: 3- Hyporeninaemic hypoaldosteronism P - photocoagulation
U - ungradeable

[ Q: 69 ] Question ID #371 Bilirubin 0.6 mg/L (0.1-1 mg/L)

Proteins 69 g/L (60-80 g/L)
17.2 (11.5-22.7
diabetes undergoes digital retinal screening. The Free T4
pmol/L pmol/L)
report returns grading the retinal images as
'Retinopathy R2'. TSH 2.5 mU/L (0.35-5.5 mU/L)
2.0
Which of following lesions is present on retinal LDL
mmol/L
images to account for this grade? Total 4.0
(Please select 1 option) Cholesterol mmol/L
1- Microaneurysms 5.8
TGs
mmol/L
2- Maculopathy
HbA1C 6.6%
3- New vessels on the disc
4- Photocoagulation scars What is the next most appropriate step in his
management?
5- Venous beading
1- Increase atorvastatin to 80 mg
Answer & Comments
2- Start Ezetimibe
Answer: 5- Venous beading
3- Start Niacin
The National Screening Committee has produced 4- Start omega fatty acid
guidance grading the lesions present on retinal
screening. These are 5- No changes required
R1 - background retinopathy Answer & Comments

R2 - Preproliferative retinopathy Answer: 3- Start Niacin
R3 - Proliferative retinopathy
M - Maculopathy According to the NICE guidelines on Type 2
P - photocoagulation Diabetes, a Type 2 DM patient with high serum
triglyceride levels should be initially assessed for a
U - ungradeable possible secondary cause of hypertriglyceridaemia
(including poorly controlled diabetes,
The grading of retinopathy R2 suggests pre- hypothyroidism, Cushing`s syndrome, chronic
proliferative changes. renal failure, drugs such as steroids, estrogens,
isotretinoin) and treated if such a cause is
[ Q: 70 ] Question ID #490 identified. If the TG levels remain elevated then
Fibrates can be offered in the specialist setting.
However, in the most recent guidance no
A 55 year old diabetic male attends for annual
addiitonal therapy should be offered in terms of
review. He is currently on atorvastatin 40 mg and
primary prevention. Regarding IMPROVE-IT this
Fenofibrate 200 mg per day and has the following
was with ezetimibe in acute coronary syndromes.
profile:
Hypertriglyceridaemia
Albumin 38 g/L (30-50 g/L)
NICE on lipid lowering therapies
ALP 66 U/L (50-125 U/L)
ALT 41 mU/L (05-58 U/L)

What should be the weight of monofilament used Which of the following eye complications is likely
to check for peripheral neuropathy in Diabetics? to be associated with pioglitazone usage?
(Please select 1 option) (Please select 1 option)
1- 1g 1- Cataracts
2- 5g 2- Glaucoma
3- 10g 3- Macular oedema
4- 20g 4- Pre-proliferative retinopathy
5- 100g 5- Retinal degeneration
Answer & Comments Answer & Comments

Answer: 3- 10g Answer: 3- Macular oedema
According to the NICE guidelines regarding Pioglitazone and rosiglitazone are

management of diabetic foot ulcer (NICE clinical thiazolidinedione (TZD) compounds which act as
guideline 10), examination of patient`s feet should PPAR-ɣ agonists and help reduce peripheral insulin
include; resistance. These are contra-indicated in hepatic
impairment. According to MHRA advice issued in
 Testing of foot sensation using a 10 g December 2007, TZDs should be avoided in
monofilament or vibration patients with heart failure or history of heart
 Palpation of foot pulses failure. Rosiglitazone should not be used in acute
 Inspection of any foot deformity and coronary syndrome, ischaemic heart disease or
footwear peripheral vascular disease. According to recent
case reports usage of TZDs has been associated
The foot risks are classified as: with macular oedema (1,2,3) probably as a result
of associated fluid retention.
 At low risk (need annual review)
 At increased risk: In presence of Reference:
peripheral neuropathy or vascular Ryan et al., Diabetic macula oedema associated
insufficiency (arrange regular review at 3- with glitazone use. Retina 2006; 26: 562-70
6 monthly interval, by foot protection Coluciello, Vision loss due to macular edema
team) induced by rosiglitazone treatment of
 At high risk: In presence of peripheral diabetes mellitus. Arch Ophthalmol 2005;
neuropathy or vascular insufficiency along 123: 1273-5
with deformity or previous ulcer or skin
Liazos et al., Spontaneous resolution of macular
change (arrange frequent review ; 1-3
oedema after discontinuation of
monthly)
thiazolidinediones. Diabet Med 2008; 25:
 Foot care emergencies including new
860-2
ulceration, swelling or discolouration
(review by multidisciplinary foot care
team within 24 hours) [ Q: 73 ] Question ID #678
A 55 year old lady with background history of Type

2 DM presents to clinic with warm and swollen left
foot. Peripheral pulses are palpable but there is

bilateral sensory loss in distal extremities. There is otherwise essentially normal. His biochemistry
no superficial skin ulcer and range of movements shows:
is restricted as the foot looks swollen and
deformed. Albumin 42 g/L (30-50 g/L)
ALP 202 U/L (50-125 U/L)
What is the next best step in her management?
ALT 116 mU/L (5-58)
Bilirubin 35 micromol/L (0-18)
1- Complete contact cast
Proteins 72 g/L (60-80)
2- IV antibiotics
HbA1c 8.1% (<6)
3- NSAIDs
4- Oral antibiotics In view of the deranged LFTs an ultrasound
abdomen is arranged which reveals fatty
5- Urgent vascular assessment infiltration of the liver.
Answer & Comments Which of the following should be started in his

case?
Answer: 1- Complete contact cast
1- Exenetide
Charcot`s arthropathy is a rare, progressive
degeneration of weight bearing joints. It is seen 2- Insulin
associated with Diabetes Mellitus, alcoholic
neuropathy, cerebral palsy and spinal cord lesions. 3- Metformin
The underlying mechanism leading to Charcot`s 4- Pioglitazone
arthropathy is unclear although recurrent micro-
trauma to a joint (predisposed by absent 5- Sulfonylureas
peripheral sensation and proprio-reception) or
dysregulated autonomic nervous system (leading Answer & Comments
to increased perfusion) seem to play a part in its
pathogenesis. Answer: 3- Metformin
The commonest joints afflicted with Charcot`s This gentleman has non-alcoholic steatohepatitis
arthropathy in diabetes mellitus include tarso- (NASH) as evidenced by deranged liver function
metatarsal joint and metatatrso-phalangeal joint. tests and fatty infiltration on Ultrasound scan.
Patients present with swelling of the joint and NASH is commonly seen in Type 2 diabetic and
clinical examination reveals mildly raised associated with increased body mass index. It
temperature of the affected joint during the acute usually resembles alcoholic liver disease but the
phase. A MRI scan can aid in diagnosis and history of alcohol intake in such people is either
treatment includes complete contact cast to avoid absent or only modest. The diagnosis of this
development of deformities like rocker bottom condition is based on exclusion of common liver
foot and tarso-metatarsal dislocation. disorders like viral hepatitis, alcoholic liver
disease, drug induced and autoimmune liver
[ Q: 74 ] Question ID #681 disease (e.g. primary biliary cirrhosis). The
confirmatory test for diagnosis is liver biopsy. No
specific therapy for NASH exists and the patients
A newly diagnosed Type 2 Diabetic male is
should be encouraged to bring life style
referred to the clinic. His BMI is 28 kg/m2 and he
modification changes including regular exercise
drinks 4 units of alcohol every week. His blood
and weight loss.
pressure is 134/82 mmHg and examination is

[ Q: 75 ] Question ID #686 oral carbohydrates and her need for intravenous

fluids and insulin should be closely monitored.
A 35 week pregnant woman with a 10 year history
of type 1 Diabetes presents to A and E with The criteria for DKA is:
features of nausea, vomiting and generally being
unwell for last 48 hours. She has recently received  Plasma glucose: (>)11 mmol/L in DKA
a course of steroids for foetal lung maturation. Her  Arterial pH: 7.25-7.3 in mild DKA; 7.00-7.24
biochemistry results are as shown below: in moderate DKA ; less than 7.00 in severe
DKA
 Serum bicarbonate: 15 to 18 mmol/L in mild
Blood sugar 14 mmol/L (3.5-5.5)
DKA; 10 to 15 mmol/L in moderate DKA; less
Urine sugar ++, ketones 3+ than 10mmol/L in severe
(7.35-  Urine and serum ketones: + in DKA
pH 7.1
7.45)  Effective serum osmolality: variable in DKA
Bicarbonate 10 mmol/L (22-26)  Anion gap: more than 10 mmol/L in mild
DKA; more than 12 mmol/L in moderate and
Chloride 95 mmol/L (98-108) severe DKA
PCO2 24 mmHg (35-45)  Mental status: alert in mild DKA;
PO2 104 mmHg (80-100) alert/drowsy in moderate DKA;
stupor/coma in severe DKA.
Potassium 4.5 mmol/L (3.5-5.5) According to NICE guidelines on Diabetes in
Lactic acid 3.5 mmol/L (0.5-2.2) pregnancy (NICE clinical guidelines 63), patients
with suspected DKA during pregnancy should be
Amylase 44 U/L
admitted immediately for level 2 critical care and
provided with both medical and obstetric care.
Which is the likely underlying diagnosis?
(Please select 1 option) Her anion gap is 39 mEq/L [Anion gap Na - (Cl +
1- Acute adrenal insufficiency HCO3)]. Normal values for anion gap are 8-12
mEq/L. Causes of high anion gap acidosis include:
2- Acute pancreatitis
 Methanol
3- Diabetic ketoacidosis (DKA)
 Uraemia
4- Lactic acidosis  Diabetic ketoacidosis
 Paraldehyde
5- Methanol ingestion
 Infection
 Lactic acidosis
Answer & Comments  Ethylene glycol
 Salicylate
Answer: 3- Diabetic ketoacidosis (DKA)
[ Q: 76 ] Diabetic emergencies - Question ID

This lady has recently received a course of steroid
for foetal lung maturation, adversely affecting her #16
glycaemic control. She has metabolic acidosis with
a pH of 7.1 and serum bicarbonate levels of 10 A 20 year old lady is admitted to A+E with
mmol/L. Her blood sugars are mildly elevated and abdominal pain, nausea and vomiting. She has a 5
urinary ketone bodies are present. Essentially the year history of type 1 diabetes with poor
diagnosis is diabetic ketoacidosis and relatively adherence to her therapy. Her current insulin
mild increase in her blood sugar values is regimen comprises Insulin glargine and novorapid
secondary to reduced carbohydrate intake due to via a basal bolus regimen. On examination she is
nausea and vomiting. She should be treated with dehydrated and breathing deeply, her blood

pressure is 98 / 66 mm/hg and her pulse is 105 causes direct stimulation of carnitine acyl coA
bpm. transferase 1 and high glucagon levels inhibit the
formation of malonyl CoA, further stimulating
Investigations- transferase activity. Consequently there is a switch
NEFA resterification to oxidation.
Plasma Glucose 21.2 mmol/l (<7.8) Betahydroxybutyrate is produced in excess and is
subsequently metabolised to acetoacetate which
pH 6.9 (7.35 - 7.45) is detected in urine ketone analysis by dip stick
pCO2 3.2 kPa (4.7 - 6) testing. Glucagon levels also increase levels of
pO2 12.1 kPa (9.5 - 13) carnitine further enhancing fatty acid oxidation.
Cortisol and catecholamines directly stimulate
Serum bicarbonate 5.2 mmol/l (22 - 27) lipolysis. Glucagon is of particular importance as
haemoglobin 15.9 g / dl (12 - 16) ketone body levels rise early, with a continuous
wCC 21.1 X 109 (4 - 11) increase over 10 – 12 hours. Acidaemia, combined
with hyperglycaemia and hyperglucagonaemia
Which of the following is a feature of the promote intracellular loss of potassium. The final
serum potassium concentration largely depends
pathophysiology of diabetic ketoacidosis?
on the rate of urinary potassium loss. Platelet
(Please select 1 option) secretory activity is often increased in DKA, but
1- Acetoaceate is metabolized to beta aggregation decreased. Neutrophil count is also
hydroxybutyrate commonly raised and correlates with ketone body
levels, so does not necessarily imply underlying
2- Acidaemia is the primary cause of infection.
intracellular potassium loss
3- Hepatic glucose production reaches a [ Q: 77 ] Question ID #27
plateau within 4 hours of insulin withdrawal
A 21 year old lady with 10 year history of type 1
4- Hepatic glucose production rises gradually
diabetes has a most recent Hba1c of 7.8% ( < 6) is
over the first 6 - 8 hours following insulin
admitted to A+E following an overdose of her
withdrawal basal insulin. On examination she is conscious but
5- Insulin deficiency combined with cortisol and pale and sweaty, her blood pressure is 96 / 66
catecholamine excess is the main cause of mmHg, her pulse is 135 beats per minute and her
ketone body formation plasma glucose is 1.8 mmol/l.
At what plasma glucose level would you expect

Answer & Comments significant autonomic counter regulatory
Answer: 3- Hepatic glucose production reaches a responses to develop in patients with type 1
plateau within 4 hours of insulin withdrawal diabetes?
Diabetic ketacidosis is an extension of the normal 1- 1 mmol/l

fasting state. Hepatic glucose production rises
rapidly over the first 2 – 4 hours following insulin 2- 1.5 mmol/l
withdrawal reaching a plateau after around 4 3- 2 mmol/l
hours. These changes correlate with the initial
acute rise in glucagon concentrations, with other 4- 2.5 mmol/l
counter-regulatory hormones being little affected 5- 3.5 mmol/l
initially. Basal hepatic glucose production in DKA is
approximately twice that in stable diabetic
patients, with a much smaller decrease in
peripheral glucose utilisation. Lack of insulin

Answer & Comments 4- Total body potassium is reduced by up to 500

mmol
Answer: 5- 3.5 mmol/l
5- When blood glucose falls below 8 mmol/L,
Autonomic counter-regulatory responses 5% Dextrose should be substituted in place
including beta adrenergic stimulation and of normal saline
catecholamine secretion commence at a threshold
plasma glucose level ≤ 2.5 mmol/l in non-diabetic Answer & Comments
individuals and often occur at a higher level in
patients with diabetes. Counter-regulatory Answer: 4- Total body potassium is reduced by up
responses such as increased glucagon secretion to 500 mmol
and mobilisation of glucose stores in muscle and
liver usually commence at threshold plasma Fluid replacement is the cornerstone of therapy in
glucose levels of 3.5 – 3.8 mmol/l. the management of DKA. The total body deficit of
fluid is around 5 - 8 litres and rehydration by
Hypoglycaemia and counter-regulation reopening renal perfusion may on its own reduce
blood glucose by up to 2%. Infusion of large
[ Q: 78 ] Question ID #28 quantities of hyptonic fluid may result in
circulatory collapse and possible cerebral odema.
Consequently most authorities recommend initial
An 18 year old young lady is admitted to the acute
hydration with 0.1554 mol /l saline, switching to
medical unit with nausea, vomiting and abdominal
hypotonic saline or dextrose if plasma sodium
pain. She gives a history of approximately 5kg
rises beyond 155 mmol/l. Current practice
weight loss over the past month two months and
advocates fluid replacement at a rate of 2 litres
also complains of persisting thirst and polyuria
over 4 hours, 2 litres over 8 hours and
over the last 2 weeks. On examination her blood
subsequently 1 litre every 8 hours. This rate of
pressure is 105 / 65 mmHg, her pulse is 92 beats
rehydration results in slower increases in sodium
per minute and her and her body weight is 64.8 kg.
and chloride concentrations. Once the glucose has
fallen to around 14 mmol/l, infusion of 10%
glucose should be substituted for saline. This will
allow continued infusion of insulin to correct
Plasma glucose 21.7 mmol/l (3.5 - 5.5) metabolic acidosis and ketosis, saline may be
pH 7.03 (7.35 - 7.45) given simultaneously if the patient is still
pCO2 2.9 Kpa (4.6 - 6) dehydrated. Administration of bicarbonate is not
without risk, local irirritation, hypokalemia,
pO2 15.6 Kpa (11.1 - 14.4) rebound alkalosis and cerebral odema are all
Bicarbonate 4.6 mmol/l (22 - 27) potential consequences. Thus bicarbonate is
Haemoglobin 14.9 g/ dl generallyonly given in profound acidosis when the
PH is < 6.9. Neutrophilia is a recognised acute
WCC 17.9 X 109 (4 - 11) response to ketacidosis and antibiotics should only
be administered if an infective aetiology or focus
Which of the following is a feature of the clinical can be identified. As a result of both acidosis and
management of diabetic ketoacidosis? insulin deficiency there is a total body potassium
(Please select 1 option) deficit of up to 1000 mmol, hence with
rehydration, insulin replacement and correction of
1- Administer bicarbonate if the PH is below 7.1 acidosis resulting in further potassium loss with
2- Aim to give 8 litres of hypotionic fluid during restoration of urine flow, hypokalemia is a major
the first 10 hours cause of death in ketoacidosis.
3- IV antibiotics should be administered if

neutrophilia is present

[ Q: 79 ] Question ID #29 being to replace this deficit over 24 – 48 hours. The

pathophysiology of HONK involves a relative
An 80 year old male is admitted after being found insulin deficiency combined with grossly elevated
collapsed at home by his daughter. glucagon concentrations, resulting in a marked
increase in hepatic glucose output. Due to the
relative insulin deficiency peripheral glucose
He has a previous history of diet controlled type 2
utilisation is reduced and lipolysis relatively
diabetes and cerbrovascular disease. On
unrestrained leading to increased NEFA
examination, he is drowsy and dehydrated, his
concentrations and lipid oxidation rates which
blood pressure is 106/56 mm/Hg and a pulse rate
further stimulates hepatic gluconeogenesis.
of 123 beats per minute.
Unlike DKA, significant ketosis is absent in HONK,
despite similar levels of circulating insulin. Various
mechanisms have been suggested, with the most
convincing suggestion being that hyperosmolality
Plasma Glucose 56.5 mmol/l (<7.8) and dehydration per se inhibit ketogenesis.
Sodium 165 mmol/l (135 - 146) Correction of hyperglycaemia with infused insulin
Potassium 6.3 mmol/l (3.4 - 5.1) should be gradual, with the aim of reducing blood
glucose by no more than 8 – 10 mmol/l/hour.
Urea 18.1 mmol/l (3 - 7) More rapid correction of hyperglycaemia may
Creatinine 165 umol/l (68 - 118) result in cerebral oedema.
Haemoglobin 13.9 g/ dl (12 - 16)
WCC 19.6 X 109 (4 - 11) [ Q: 80 ] Question ID #30
pH 7.24 (7.35 - 7.45)
A 26 year old lady is reviewed in the clinic. She has
pCO2 4.3 Kpa (4.6 - 6) a 10 year history of type 1 diabetes and admits to
p02 12.1 Kpa (11.1 - 14.4) frequently missing insulin doses. Her current
Bicarbonate 14.9 mmol/l (22 - 27) medication includes insulin glargine 42 units at
night and novorapid 12 units prior to each meal.
Which of the following best reflects the mortality On examination her BMI is 21 kg / m2 her blood
pressure is 105 / 65 mmHg.
associated with the above condition?
(Please select 1 option) Investigations reveal:
1- 0-10%
Hba1c 10.8% (<6)
2- 10-20%
3- 20-30%
Plasma triglyceride 1.9 mmol/l (0.9 - 2.2)
4- 30-40% TSH 0.65 mu / l (0.32 - 5.5)
5- ~50% Urine Ketones +++
Urine Glucose +++
Answer & Comments
Which of the following is a feature of urine ketone
Answer: 5- ~50%
testing?
The mortality in patients with Hyperosmolar Non
ketototic (HONK) coma is very high approaching 1- Heavy ketonuria implies the need for insulin
up to 50% in some series, with infection being the initiation when identified in patients with
commonest precipitating factor; accounting for up type 2 diabetes
to 80% of cases. Fluid depletion in HONK is up to
10 litres with the aim of fluid replacement therapy

2- Ketonuria correlates closely with degree of 2- Advise that the pump be re-sited at least
acidosis in diabetic ketoacidois 10cm from the current insertion site
3- Ketonuria resolves with correction of 3- Remove her pump and repeat the process of
acidosis in diabetic ketoacidosis drawing up the insulin and priming the
pump and using a new giving set and
4- Urine ketone stix measure acetoacetate in
cannula in case of an error
the urine
4- Remove the pump and revert to insulin via a
5- Urine ketone stix measure
pen until a new pump is able to be delivered
betahydroxybutyrate levels in the urine
urgently
Answer & Comments 5- Reduce all basal rates to 50% and halve the
insulin to carbohydrate ratio
Answer: 4- Urine ketone stix measure
acetoacetate in the urine
Answer & Comments
Urine ketone testing measures acetoacetate in Answer: 1- Advise her to come into hospital
urine which is produced by metabolism of immediately for assessment for urgent
betahydroxybutyrate. Ketoneuria persists despite delivery of her baby.
correction of acidaemia in patients with
ketoacidosis and does not correlate with the Placental insufficiency can present in diabetes as
degree of acidosis. Ketonuria is not a marker of severe recurrent unwarranted hypoglycaemia.
absolute insulin deficiency and may occur as a This should always be regarded as an emergency
normal response to exercise or fasting. in the third trimester as this may herald placental
insufficiency and prompt action and delivery may
[ Q: 81 ] Question ID #244 prevent intrauterine death. Only after placental
insufficiency has been excluded should other
A 33 year old woman is currently 34 weeks causes of hypoglycaemia be explored.
pregnant. She was commenced on continuous
subcutaneous insulin infusion at the end of the [ Q: 82 ] Question ID #3451
first trimester after developing severe recurrent
hypoglycaemic episodes. Her HbA1c has been You are called via the arrest bleep to a 43 year old
5.8% and she has had an occasional woman who is on the surgical ward. She had a
hypoglycaemic episode but generally these have laparoscopic cholecystectomy performed two
been mild and she has been able to manage these days ago and has since had nausea and vomiting
herself. She telephones your department as and has been receiving IV dextrose. It transpires
during the last 24 hours she has developed that she had a fit for which the nursing staff
recurrent severe hypoglycaemic episodes such requested the arrest team. She is now drowsy. Her
that she is continually taking lucozade to prevent past medical history is unremarkable.
this despite dramatically reducing her insulin
rates.
On examination, she is drowsy with a GCS of 13.
Her pulse is 88 bpm and blood pressure 132/88
How would you advise her? mmHg with oxygen sats of 100% on air. There is no
(Please select 1 option) focal neurology and her plantar responses are
1- Advise her to come into hospital equivocal.
immediately for assessment for urgent
Of note, her blood results reveal:
delivery of her baby.

Potassium 3.5 mmol/l (3.5-5) What is the target sodium to which you would
treat this patient over the next 1hr?
Urea 3.8 mmol/l (3-8)
Glucose 4.1 mmol/l (3.5-6) 1- 116 mmol/l
2- 120 mmol/l
initial treatment for this patient? 3- 125 mmol/l
(Please select 1 option) 4- 130 mmol/l

1- 15mg oral Tolvaptan 5- 135 mmol/l
2- 100mg IV Hydrocortisone stat
Answer & Comments
3- 150mls of 3% hypertonic saline over 20 mins
Answer: 2- 120 mmol/l
4- 1litre Normal saline infused over 4 hrs
5- Fluid restriction to 500mls per day A decision has been taken to treat this patient with
hypertonic saline as she has acute symptomatic
Answer & Comments hyponatraemia which reflects underlying cerebral
oedema. In this context, treatment with 150mls
Answer: 3- 150mls of 3% hypertonic saline over 20 3% hypertonic saline given over three hours can be
mins lifesaving. The target sodium by which one should
elevate the sodium is 5 mmol/l over the first hour.
This patient is likely to have hyponatraemic The increase in sodium should be then limited to
encephalopathy which is life threatening and has 10mmol/l over the next 24hrs based on a clinical
presented with a fit. Post-operative improvement.
hyponatraemia is not uncommon and is likely to
be due to a combination of SIADH which develops Guidelines
inappropriate IVIs. The European Endocrine European Journal of Endocrinology (2014)
Society Guidelines on severe hyponatraemic Clinical practice guideline on diagnosis and
encephalopathy recommend a rapid correction of treatment of hyponatraemia
sodium by approximately 5 mmol/l. This can
ameliorate the cerebral oedema that underlies [ Q: 84 ] Question ID #3592
this disorder.
You are called to see a 42 year old male patient on
For more information on how to correct and what
the neurosurgical ward. He was admitted with a
head injury 3 days ago which required only
observation. However, he has become more
European Journal of Endocrinology (2014) confused in the last 12 hours and his most recent
Clinical Practice Guideline on the diagnosis U+Es performed this morning reveal:
and management of hyponatraemia,
Potassium 4.5 mmol/l (3.5-5.5)
A 62 year old woman with acute symptomatic
hyponatraemia likely due to SIADH and associated Urine Osmolality 620 mosmol/l
with drowsiness is considered to be appropriate Urine Sodium 125 mmol/l
for immediate treatment with hypertonic saline.
Her serum sodium is 115 mmol/l.

Checking through his records, the previous days the last few days. She is lethargic, has had
his U+Es were normal. He had been allowed to eat occasional episodes of abdominal pain, and is
and drink normally and had stopped IV fluids 2 clinically dehydrated. She has a recent history of
days ago. He was on dexamethasone the dose of metastatic breast cancer with bony involvement,
which had been reduced to 4mg daily from 8 mg for which she is receiving palliative treatment. Her
daily over the last day but he was on no other results reveal:
treatment.
On examination, he had Glasgow Coma Scale of
15, though seemed confused with him being
disorientated. Oxygen saturations were 97% on air Calcium 4.1 mmol/l (2.2-2.6)
and his blood pressure was 110/80 with a pulse of
88 bpm. Which of the following would you expect to find on
the ECG?
Which of the following is the most likely diagnosis? (Please select 1 option)
1- Prolonged PR Interval
1- Acute hypoadrenalism
2- QT shortening
2- Cerebral Salt Wasting
3- ST elevation
3- Pituitary apoplexy
4- Tall tented T waves
4- Syndrome of inappropriate ADH secretion
5- Widened QRS complexes
5- Type IV renal Tubular acidosis
Answer & Comments
Answer & Comments
Answer: 2- QT shortening
Answer: 2- Cerebral Salt Wasting
The predominant abnormality here will relate to
The most likely diagnosis in this patient with head the markedly elevated calcium, not the mild
injury who then develops acute symptomatic hypercalcaemia. The QT interval is typically
hyponatraemia and grossly elevated urine sodium shortened in hypercalcaemia. Other features in
is cerebral salt wasting. The grossly elevated urine severe hypercalcaemia include J waves and bizarre
sodium (>100) is highly suggestive as the sodium is QRS appearance.
usually less with SIADH. Similarly with SIADH,
there is a dilutional element so urea and Some examples of ECG abnormalities in
potassium typically reflect this dilution being hypercalcaemia
themselves low normal in contrast to CSW where
there is hypovolaemia and hence higher
concentrations. Hypoadrenalism is an incorrect
answer as the patient is already on a high dose of
steroids – dexamethasone 4mg/d. A 53 year old man is admitted with a 3 day history
of left leg pain and fever. He has an 8 year history
Reference: of type 2 diabetes for which he takes metformin
Cerebral Salt Wasting Medscape and gliclazide together with ramipril and
simvastatin.
[ Q: 85 ] Question ID #3593 On examination his BMI is 32.3 kg/m2, his

temperature is 38.5C, pulse 90 bpm and his blood
A 62 year old woman is admitted to MAU through pressure 120/80 mmHg. His left leg is swollen to
her GP as she has become increasingly unwell over mid-calf, the skin is red and inflamed with a clear

demarcation just below the knee. He has some [ Q: 87 ] Question ID #3595

onycholysis of the left toe nails with some
maceration between the toes. His peripheral A 62 year old woman is referred to the medical
pulses are all palpable. intake with tingling and paraesthesia. The patient
has been aware of deteriorating symptoms for one
Results show: week. The GP asks whether this is a stroke. She has
a background history of type 2 diabetes,
Sodium 136 mmol/l (134-144) hypertension and GORD for which she takes
Potassium 4.2 mmol/l (3.5-5.5) omeprazole, metformin, sitagliptin, simvastatin,
Ramipril and amlodipine. On examination there is
little of note.
Haemoglobin 13.3 g/l (120-160) Investigations reveal:
White cell Count 12.8x109/l (3-10)
Calcium 2.06 mmol/l (2.2-2.6)
Platelets 158x109/l (140-450)
Magnesium 0.3 mmol/l (0.7-1)
C-Reactive Protein 135 mg/dl (<5)
LFTs Normal
Glucose 12.3 mmol/l
HbA1c 7.8% (<6) You see on the computer that a 25OHD level
checked 1 month before by the GP reveals a level
Which of the following would be the most of 18 nmol/l (>50)
appropriate treatment for this patient?
(Please select 1 option) Which of the following is the likely cause of this
patient’s presentation?
1- IV flucloxacillin
2- Oral amoxicillin
1- Diabetic autonomic neuropathy
3- Oral ciprofloxacin
2- Metformin
4- Oral flucloxacillin
3- Omeprazole
5- IV Vancomycin
4- Sitagliptin
Answer & Comments 5- Vitamin D deficiency
Answer: 1- IV flucloxacillin
Answer & Comments
This patient has a clinical class II to class III cellulitis Answer: 3- Omeprazole
with systemic upset associated with a
comorbidity. The vast majority of cases of cellulitis This patient has a hypocalcaemia associated with
are due to beta haemolytic strep or S Aureus. a severe hypomagnesaemia. This is likely due to
Therefore, Flucloxacillin is the treatment of choice the omeprazole, which results in increased GI
in this setting and recommended in guidelines as magnesium losses. The hypomagnesaemia impairs
IV treatment in Class II-III patients. In subjects the calcium sensing on the parathyroid cells;
allergic to beta lactams, hence, this results in an induced
clarithromycin/clindamycin can be used. hypoparathyroidism with hypocalcaemia. It is a
good diagnosis to make but is often not
Guidance on management of cellulitis in adults appreciated.

This is not due to vitamin D deficiency as with 3- Initial priming bolus dose of IV insulin
osteomalacia the 25OHD would be lower, ALP followed by sliding scale insulin
raised and the patient would likely have a proximal
myopathy. 4- Sliding scale IV insulin infusion
5- developed diabetic ketoacidosis as
PPI induced hypoparathyroidism evidenced by the low bicarbonate and pH.
Guidelines recommend the use of an IV fixed
[ Q: 88 ] Question ID #3767 rate insulin infusion regime consisting of
0.1iu/kg/hr and to continue the patient’s
A 30 year old female is admitted with a 2 day usual long acting insulin.
history of abdominal pains and general
deterioration. She has a background history of Answer & Comments
type 1 diabetes for which she takes basal bolus
insulin regime consisting of a long acting insulin Answer: 1- Fixed rate IV insulin infusion of
(20 iu) in the evening and thrice daily short acting 0.1iu/kg/hr
insulin (10-12 iu) with each meal. She has
continued to take her insulin but has become iller,
Reference:
being nauseous with vomiting associated with a
Joint British Scoieties Diabetes Care Group DKA
diffuse abdominal pain.
Guidelines
On examination, she appears dehydrated, has a
pulse of 98 bpm reg and a blood pressure of [ Q: 89 ] Question ID #3768
108/76 mmHg. Her Glasgow coma scale is 15 and
she has oxygen saturations of 98% on air. A 30 year old female is admitted with a 2 day
Abdominal examination reveals nothing overt history of abdominal pains and general
with just diffuse tenderness. deterioration. She has a background history of
type 1 diabetes for which she takes basal bolus
Her results reveal the following: insulin regime consisting of a long acting insulin
(20 iu) in the evening and thrice daily short acting
Glucose 23.7 mmol/l (3.5-5.5) insulin (10-12 iu) with each meal. She has
continued to take her insulin but has become iller,
being nauseous with vomiting associated with a
Potassium 3.0 mmol/l (3.5-5.5) diffuse abdominal pain.
Creatinine Creatinine On examination, she appears dehydrated, has a
pulse of 98 bpm reg and a blood pressure of
pH 7.28 108/76 mmHg. Her Glasgow coma scale is 15 and
pO2 14.4kPa she has oxygen saturations of 98% on air.
PCO2 3.5 kPa Abdominal examination reveals nothing overt
with just diffuse tenderness.
Bicarbonate 15 mmol/l
Her results reveal the following:
initial management for this patient’s Glucose 23.7 mmol/l (3.5-5.5)
hyperglycaemia?
1- Fixed rate IV insulin infusion of 0.1iu/kg/hr
2- Give 15 units of SC short acting insulin Creatinine 105 micromol/l (50-100)
together with 10 units of long acting insulin

pH 7.28 90/66 mmHg and pulse 100 bpm reg. Her Glasgow
Coma Scale is 15 and there are no significant
pO2 14.4 kPa
findings on general examination.
PCO2 3.5 kPa
Bicarbonate 15 mmol/l Investigations reveal the following:
Which of the following is the most appropriate Glucose 9.9 mmol/l (3.5-5.5)
initial management for this patient? Sodium 129 mmol/l ((134-144)
(Please select 1 option) Potassium 5.5 mmol/l (3.5-5.5)
1- 100mls 8.4% sodium bicarbonate over 30 Urea 8.2 mmol/l (3-8)
mins, together with 1l Normal saline with 20 Ketones on meter 0.7 mmol/l (<1.5)
mmol potassium chloride over 1hr
2- 1l 5% dextrose given over 1 hr Which of the following would be the most
appropriate treatment for this patient?
3- 1l Hartmann’s solution given over 2 hrs
4- 1l Normal saline given over 2 hr
1- 100mcg Oral fludrocortisone
5- 1l Normal saline with 20mmol potassium
2- 1l N Saline over 1hr
chloride given over 1 hr
3- 100 mg IV Hydrocortisone as a blous
Answer & Comments 4- Fixed rate insulin infusion 0.1 iu/kg/hr
Answer: 5- 1l Normal saline with 20mmol 5- IV Insulin sliding scale
potassium chloride given over 1 hr
Answer & Comments
In this patient who has diabetic ketoacidosis, the
most appropriate treatment for immediate IV Answer: 3- 100 mg IV Hydrocortisone as a blous
resuscitation is 1l of Normal saline given over the
first hour and, in view of the low potassium, This patient appears to have a hypoadrenal crisis
potassium chloride should also be given as this will probably precipitated by the inability to retain the
fall quite abruptly when the insulin regime is oral hydrocortisone. In this case the glucose less
started. than 10 and the absence of ketones on the ketone
meter makes a diagnosis of DKA unlikely. The most
Reference: appropriate approach is to treat this patient with
Joint British Scoieties Diabetes Care Group DKA 100 mg IV hydrocortisone.
Guidelines
Reference:
[ Q: 90 ] Question ID #3769 Guidelines from the endocrine society
A 41 year old woman is admitted with a 24 hour [ Q: 91 ] Question ID #3777

history of nausea and vomiting. She has a history
of Addison’s disease and type 1 diabetes for which A 55 year old man is admitted through MAU with
she takes hydrocortisone 10 mg bd and twice daily 1 week history of deteriorating weakness and
mixed insulin 24 IU on the morning and 18 iu in the more recent nausea. His background includes a 10
late afternoon. yr history of diabetes and hypertension. He is
taking gliclazide 80mg bd, bendrofluazide
On examination she appears dehydrated and 2.5mg/d, atorvastatin 10mg/d and ramipril 10
unwell. Her temperature is 37C, blood pressure mg/d.

On Examination he appears ill and weak. His be stopped and in conjunction with the acute
temperature is 37 C and oxygen saturation is 97% kidney injury may be the precipitant.
on air. His blood pressure is 154/100 mmHg, heart
rate 92 bpm reg and respiratory rate is 22/min. Reference:
Renal Society Guidelines on treating
Results: hyperkalaemia
Potassium 7.6 mmol/l (3.5-5.5) [ Q: 92 ] Question ID #3779
Urea 19 mmol/l (3-8)
This is the ECG obtained on a 77 year old man with
type 2 diabetes who was admitted with lethargy
pH 7.36 and tiredness.
Bicarbonate 20 mmol/l
His ECG reveals some QRS widening and tenting of

T waves.

initial treatment for this man?
1- 10mg nebulised salbutamol

2- 10mls 10% IV calcium gluconate as a stat
dose
3- 100mls of 8.4% sodium bicarbonate given
over 30 mins
What does the ECG suggest?
4- 50mls IV 50% dextrose plus 10 iu insulin
given over 10 mins (Please select 1 option)
5- Oral Calcium resonium 1- Hypercalcaemia

2- Hyperkalaemia
Answer & Comments 3- Hypocalcaemia
Answer: 2- 10mls 10% IV calcium gluconate as a 4- Hypokalaemia
stat dose
5- Hypothermia
This patient has severe and life threatening

hyperkalaemia as determined by the potassium Answer & Comments
above 6.5 and the widened QRS complexes and Answer: 2- Hyperkalaemia
tented T waves on the ECG. The most important
initial step is protection of the heart – hence the
patient should receive 10 mls calcium gluconate This ECG shows tented T waves and p waves with
and the ECG should be repeated to look for a tachycardia suggestive of hyperkalaemia.
improvement. At the same time, the insulin and
dextrose infusion should be started, although this [ Q: 93 ] Question ID #3781
may take 1 hour to take effect by reducing the
potassium. In this case, the ACE inhibitor needs to
A 62 year old man is admitted acutely with a week
history of feeling increasingly unwell and tired. He

has a history of type 2 diabetes for which he takes [ Q: 94 ] Question ID #3783

metformin 1g bd and gliclazide 80mg bd. His last
HbA1c was 10.1%. An 81 year old man is admitted acutely with a
week history of feeling increasingly unwell and
On examination he appears dehydrated and weak. He has a history of type 2 diabetes for which
unwell. His temperature is 37C, blood pressure he takes metformin 1g bd and gliclazide 80mg bd.
116/70 mmHg and a pulse of 102 bpm. Oxygen His last HbA1c was 10.1%. He also takes Ramipril
saturation is 98% on air and he has a respiratory and simvastatin.
rate of 22/min.
On examination he appears dehydrated and
Blood results reveal: unwell. His temperature is 37C , blood pressure
116/70 mmHg and a pulse of 102 bpm. Oxygen
Sodium 150 mmol/l (134-144) saturation is 98% on air and he has a respiratory
Potassium 5.5 mmol/l (3.5-5.5) rate of 22/min.
Blood results reveal:
Glucose 24.5 mmol/l (3.5-5.5)
pH 7.28 (7.35-7.45)
Bicarbonate 10 mmol/l (22-28)
Which of the following is the likely diagnosis? Glucose 37.2 mmol/l (3.5-5.5)
(Please select 1 option) pH 7.35 (7.35-7.45)
1- Acute kidney injury associated with ACE Bicarbonate 18 mmol/l (22-28)
inhibitor Ketones 1.8 mmol/l (<1.5)
2- Diabetic Ketoacidosis
Which of the following is the likely diagnosis?
3- Hyperosmolar Hyperglycaemic state
4- Type A lactic acidosis 1- Acute kidney injury associated with ACE
5- Type B lactic acidosis associated with inhibitor
metformin 2- Diabetic Ketoacidosis
3- Hyperosmolar Hyperglycaemic state
Answer & Comments
4- Severe dehydration with acute kidney injury
Answer: 2- Diabetic Ketoacidosis
5- Type B lactic acidosis associated with
The most likely diagnosis is diabetic ketoacidosis metformin
(patient is acidotic) in a poorly controlled type 2
patient that may well have Latent Autoimmune Answer & Comments
Diabetes of Adulthood (LADA). Lactic acidosis with
metformin is very rare and the patient’s usually Answer: 3- Hyperosmolar Hyperglycaemic state
have severe renal impairment. There is likely to be
ketones present on POCT testing. This is not HHS The most likely diagnosis is HHS as plasma
as plasma osmolality is usually above 320 and osmolality 376 mosmol/l with glucose above 33,
glucose above 33 with a pH >7.3. bicarbonate above 15 and a pH >7.3. A trace of
ketones may be noted (<3).
Reference:
Hyperosmolar hyperglycaemic state

[ Q: 95 ] Question ID #3904 arm and lasting approximately 2 hours. He has a

past medical history of diabetes for which he takes
A 62 year old woman attends A&E feeling unwell. metformin 1g bd, together with simvastatin 40mg
She is lethargic, has had occasional episodes of daily and ramipril 10mg daily.
abdominal pain and is clinically dehydrated. She
has a recent history of metastatic breast cancer On presentation, his weakness has now entirely
with bony involvement, for which she is receiving resolved. He has a pulse of 80 bpm regular and a
palliative treatment. Her results reveal: blood pressure of 148/92 mmHg.
Which of the following denotes this man’s ABCD2

score?
1- 1
2- 3
Calcium 4.1 mmol/l (2.2-2.6)
3- 5
4- 6
initial treatment for this patient?
(Please select 1 option) 5- 7
1- IM Calcitonin
Answer & Comments
2- IM Denosumab
Answer: 5- 7
3- IV Hydrocortisone
4- IV N Saline – 1l over 2hrs initially The ABCD2 score is a risk assessment tool
designed to stratify TIAs according to future risk of
5- IV Pamidronate
stroke.
Answer & Comments A refers to age >60 =1

Answer: 4- IV N Saline – 1l over 2hrs initially
B refers to blood pressure with either systolic or
diastolic >140/90 = 1
The most appropriate initial treatment for this
patient is IV rehydration with N Saline (4-6l over C – Clinical Features: Unilateral weakness with or
24hrs). Once rehydration is considered adequate, without speech impairment =2. Speech
the patient can then be treated with IV impairment =1
bisphosphonates such as pamidronate, but
caution needs to be exercised with the acute D – Duration: 10-59mins =1. >60 mins = 2
kidney injury. In this case the likely cause is
metastatic bone disease, so regular 2 – Type 2 diabetes = 1
bisphosphonate infusions may be required.
In our example, the age =1, blood pressure =1,
Endocrine Society Guidelines on Acute Clinical features =2, duration =2 and he has
Hypercalcaemia diabetes =1
[ Q: 96 ] Question ID #4141 The score is therefore 7 which is the maximal score

indicating a high risk of a completed stroke 2, 7, 30
and 90 days after a TIA. With an ABCD2 score of 6-
A 70 year old man presents after a transient
7 there is an approximate 10% risk of stroke at 7
ischaemic attack involving weakness of the left

days and the recommendation in this case is one [ Q: 98 ] Question ID #87

of admission with observation.
A 25 year old male presents with reduced libido
ABCD2 Score and erectile dysfunction. There is nil of note on
examination and his visual fields are normal to
[ Q: 97 ] Gonads - Question ID #73 confrontation. His investigations reveal:
A 23 year old female is referred with irregularity of LH 1.1 mu/l (2 - 100)

her periods. She takes the combined oral FSH 2.0 mu/l (2 - 10)
contraceptive, microgynon and informs you that
Testosterone 6.2 nmol/l (8 - 30)
her periods are apt to being rather irregular
despite compliance with treatment. Menarche Prolactin 38,000 mu/l (<450)
was at 12 years of age and her periods were
occasionally irregular up until she commenced MRI reveals a 3 cm pituitary macroadenoma that
microgynon two years ago. She went to her GP displaces the optic chiasm.
about the irregular periods, he took some blood
tests and found the following which concerns him: Which of the following is the most appropriate
management of this patient?
Estradiol <80 pmol/l (130-800) (Please select 1 option)
LH 1 mu/l (2-10)
1- Commence cabergoline
FSH 1 mu/l (2-10)
2- Refer for pituitary radiotherapy
Prolactin 388 mu/l (50-450)
3- Refer for pituitary surgery
TFTs Normal
4- Treat with testosterone only and repeat MRI
Which of the following is the most likely in 3 months
explanation for her results?
5- Treat with somatostatin analogue
1- Drug induced Answer & Comments

2- Kallmann syndrome Answer: 1- Commence cabergoline
3- Pituitary macroadenoma
4- Polycystic ovarian syndrome This patient has a macroprolactinoma and
presented with features of hypogonadism. His
5- Turner's mosaic MRI reveals that the tumour is pressing on the
optic chiasm, yet the visual fields are normal. Even
Answer & Comments if this patient had a visual field defect, surgery is
rarely required for prolactinomas and he should
Answer: 1- Drug induced be treated initially with dopamine agonist therapy.
This would be expected to cause a rapid reduction
in the tumour volume with relief of chiasmal
This patient takes the OCP – microgynon. This
compression. Repeating the MRI in approximately
contains ethinyl-oestradiol which is a synthetic
3 months would be expected to reveal the abrupt
oestrogen that is not detected on conventional
reduction in volume and suppression of prolactin
17beta-oestradiol assays. The OCP is designed to
concentrations.
suppress LH/FSH, production of endogenous
oestradiol and hence ovulation. One should not
check estradiol/LH/FSH when the patient is
receiving the OCP.

[ Q: 99 ] Question ID #90 Estradiol 80 pmol/l (<130)

LH 18.2 mu/l (2 - 10)
A 33 year old female presents with deteriorating
FSH 38 mu/l (2 - 10)
hirsutism and amenorrhoea. Menarche had been
at the age of 12 and periods had generally been Testosterone 15.5 nmol/l (<3)
irregular. She has two children aged 8 and 6 but
has noted a deterioration of facial hirsutism over Which of the following is the most appropriate
the last 2-3 years. Investigations reveal: investigation for this patient?
Estradiol 450 pmol/l (130 - 800)
1- 1mg overnight dexamethasone test
LH 8.8 mu/l (2 - 10)
2- 17-hydroxyprogesterone concentration
FSH 2.8 mu/l (2 - 10)
Testosterone 3.3 mu/l (<3) 3- 24hr urine free cortisol
Prolactin 380 mu/l (<450) 4- CT abdomen/pelvis

Androstenedione 16.6 pmol/l (2 - 10) 5- Transvaginal ovarian ultrasound
What is the most likely diagnosis? Answer & Comments

Answer: 4- CT abdomen/pelvis
1- Adrenal tumour
2- Cushing's disease One needs to suspect a tumour (either ovary or
adrenal) in this patient from the rapidity of the
3- Non-classical congenital adrenal hyperplasia
development of postmenopausal hirsutism to the
4- Ovarian tumour very high testosterone concentration. Generally, a
testosterone concentration >5 nmol/l merits
5- Polycystic ovarian syndrome
further evaulation for a potential testosterone
secreting tumour. Thus CT of the abdomen would
Answer & Comments be the most appropriate investigation.
Answer: 5- Polycystic ovarian syndrome
The most likely diagnosis in this patient with a long
history of menstrual irregularity, hirsutism and A 26 year old male with a history of treated
mild hyperandrogenism is PCOS. An adrenal or childhood craniopharyngioma and associated
ovarian tumour is most unlikely and one should hypopituitarism wishes to discuss fertility. He has
investigate for a possible tumour with a confirmed pan-hypopituitarism and receives
testosterone above 5. The high androstenedione hydrocortisone, thyroxine, growth hormone and
is again compatible and suggestive of PCOS. testosterone for hypopituitarism but now wishes
to commence a family. On examination of the
genitalia, his testicular volumes are approximately
[ Q: 100 ] Question ID #92 10 mls bilaterally and he has normal secondary
sexual characteristics. A semen analysis after
A 55 year old female presents with deteriorating stopping testosterone reveals azoospermia and
hirsutism of 10 months duration together with a his plasma testosterone is also low.
six month history of amenorrhoea. Examination
reveals quite marked facial hisrutism around the Which of the following would be the most
jaw line and moustache region as well as hair on appropriate treatment for this man?
the arms and extending from the pubis to the (Please select 1 option)
umbilicus. Her investigations reveal:

1- Advise sperm donation Which of the following would be the most

appropriate approach to treating this patient?
2- Continue testosterone in current dose
3- Stop testosterone and commence HCG
injections 1- Bromocriptine
4- Stop testosterone, GH and commence HCG 2- Clomiphene

injections 3- Continue with no treatment
5- Refer for intracytoplasmic sperm injection 4- Metformin
(ICSI)
5- Requires IVF
Answer & Comments

Answer & Comments
Answer: 3- Stop testosterone and commence HCG
Answer: 2- Clomiphene
injections
This woman has subfertility, as infertility is

The patient has hypogonadotrophic
considered as 2 years or more unprotected
hypogonadism and needs assisted fertility. The
intercourse without conception. In this case, the
most appropriate approach would be treatment
most appropriate initial treatment would be
with HCG injections aiming to firstly restore
clomiphene as suggested by a study in the NEJM
testosterone concentrations and hopefully
2007. Conception rates were 22.5% with
generate semen production although one might
clomiphene vs 7% with metformin. If this fails then
need to add FSH if testosterone is restored yet
the addition of metformin to the clomiphene may
azoospermia persists. If HCG is unsuccessful then
improve chances still further.
the patient may need referral for ICSI or
alternatively may wish to consider sperm
donation. [ Q: 103 ] Question ID #95
[ Q: 102 ] Question ID #94 A 32 year old female who has been treated with
cabergoline for a microprolactinoma attends clinic
and informs you that she is 8 weeks pregnant. She
A 24 year old female with a diagnosis of polycystic
has been continuing to take the cabergoline 0.25
ovarian syndrome is keen to start a family. She was
mg twice weekly and the pregnancy was
diagnosed with PCOs at the endocrine clinic
unexpected but she would like to continue with
following presentation with oligomenorrhoea and
the pregnancy.
mild hirsutes. She is overweight with a BMI of 27
kg/m2 and she has a menstrual cycle of
Which of the following would you advise?
approximately 6-8 weeks. She has been trying for
the last year to conceive but has been (Please select 1 option)
unsuccessful. Her partner has had semen analysis 1- Advise termination due to the teratogenic
performed by the GP which is normal.
risk with cabergoline
2- Continue cabergoline at current dose
Estradiol 450 pmol/l (130 - 800) 3- Increase dose of cabergoline
LH 8.3 mu/l (2 - 10)
4- Stop cabergoline
FSH 2.2 mu/l (2 - 10)
5- Switch cabergoline to bromocriptine
Testosterone 2.2 pmol/l (<3)
Prolactin 380 mu/l (<450)

Answer & Comments and testosterone gel for the last 6 years and had
grown to an appropriate adult height and had
Answer: 4- Stop cabergoline normal secondary sexual characteristics.
Pregnancy on patients taking dopamine agonist
therapy for prolactin secreting tumours is not IGF-1 42.3 nmol/l (28 - 50)
uncommon and there is no evidence that taking
these agents is harmful to the fetus. However,
there is no need to take these agents during LH 1.2 mu/l (2 - 10)
pregnancy as the risks of tumour expansion are FSH 2.2 mu/l (2 - 10)
small (<1%). Thus, the patient should be advised to
Free T4 14.5 pmol/l (9 - 22)
stop cabergoline only.
TSH 2.2 mu/l (0.5 - 5)
[ Q: 104 ] Question ID #96 Prolactin 360 mu/l (50 - 450)
A 26 year old female with a microprolactinoma He is keen to continue GH therapy but is aware
falls pregnant after taking cabergoline. She is that if this is no longer necessary he is prepared to
advised to stop the cabergoline. stop it.
How would you continue to serially monitor the Which of the following is the most appropriate
patient during her pregnancy? action for this patient concerning his GH therapy?
1- Clinical observation 1- Continue GH at its current dose
2- Formal visual field assessment 2- Increase dose of GH
3- MRI pituitary every trimester 3- Re-assess GH secretion
4- Prolactin concentrations 4- Reduce dose of GH
5- Short synacthen tests 5- Stop GH therapy
Answer: 1- Clinical observation Answer: 3- Re-assess GH secretion
The prolactin concentration rises in normal Approximately 30% of subjects shown to be GH

pregnancy and is typically in the thousands. There deficient in childhood subsequently have normal
is no need to measure prolactin concentrations GH secretion in adulthood. Thus, it is
during pregnancy. There is a small risk of tumour recommended that all subjects should be re-
expansion during pregnancy (less than 1%) and so tested for GH deficiency in adulthood. If intact, the
the patient should be monitored clinically with GH can be discontinued. If however GH deficiency
clinical field assessment and if there is a suspicion persists then GH should continue, particularly if
of tumour expansion then MRI can be undertaken. the patient subjectively feels improvement
(assessed through AGHDA questionnaire) and also
as it contributes to the attainment of peak bone
[ Q: 105 ] Question ID #102 mass.
A 19 year old male with childhood onset idiopathic

hypopituitarism was referred to the adult
endocrine clinic. He had received growth hormone

[ Q: 106 ] Question ID #106 Testosterone 7.1 nmol/l (9 - 30)

LH 2.2 mu/l (2 - 10)
A 55 year old male with an 8 year history of type 2 FSH 3.6 mu/l (2 - 10)
diabetes is being treated for impotence with
sildenafil. He has tried sildenafil in escalating He informs you that he has two children who are
doses over the last three months but still has grown up, he drinks approximately 10 units of
problems with erectile dysfunction. His alcohol weekly and he has noticed that the
investigations show: development of erectile dysfunction has occurred
over a few years.
On examination he has a BMI of 37.5 kg/m2, a
LH 3.6 mu/l (2 - 10) blood pressure of 136/88 mmHg and a pulse of 68
FSH 4.5 mu/l (2 - 10) bpm. No abnormalities are found in
cardiovascular, chest or abdominal examination.
Which of the following would be the most Further results are obtained which reveal:
appropriate treatment for this man?
(Please select 1 option) U+Es Normal
Fasting Plasma Glucose 6.1 mmol/l
1- Intracavernosal injection of alprostidil
Free T4 12.1 pmol/l (9- 22)
2- Surgical insertion of an intracevernosal
TSH 3.2 mu/l (0.5 - 5)
pump
Prolactin 230 mu/l (50 - 450)
3- Tadalafil
4- Testosterone gel A CT headscan is performed which reveals no
abnormality of the pituitary.
5- Vacuum pump device
Which of the following is the most likely cause for
Answer & Comments his hypogonadism?
Answer: 1- Intracavernosal injection of alprostidil (Please select 1 option)
1- Haemochromatosis
Approximately 20% of patients fail PDE-5
2- Kallmann syndrome
inhibitors such as sildenafil/Tadalafil. It is
important to ensure that testosterone 3- Obesity
concentrations are normal if one is to secure the
4- Pituitary microadenoma
adequacy of PDE-5 inhibitor therapy. In this case,
the testosterone concentration is adequate. 5- Testicular fibrosis
Under these circumstances, the most appropriate
treatment would be intracavernosal injections
Answer & Comments
with alprostidil – caverject. The patient should be
shown how to draw up, dose and inject the Answer: 3- Obesity
alprostidil and to seek medical advice should
priapism develop.
This patient's results reveal a low testosterone
with 'inappropriately' normal LH and
[ Q: 107 ] Question ID #107 FSH indicating a hypogonadotrophic
hypogonadism. His other pituitary function is
A 48 year old male presents with a history of normal and his CT of the pituitary is also reported
reduced libido and erectile dysfunction. His GP as normal. However, he is obese and has features
encloses the following results: of the metabolic syndrome with an elevated
fasting plasma glucose. With these results, the

most probable cause of his hypogonadism is unprotected sex for at least three years without
obesity. conception. Investigations reveal:
This is a well described, emerging phenomena and Estradiol 420 pmol/l (130 - 800)
the exact cause is ill-understood although is
LH 8.8 iu/l (3 - 10)
believed to directly relate to visceral fat mass with
increasing aromatisation of testosterone to FSH 2.2 iu/l (3 - 10)
oestradiol and then feedback on the Pituitary. Prolactin 580 mu/l (50 - 500)
TFTs Normal
A 22 year old female presents with a long history appropriate agent for this patient?
of oligomenorrhoea, weight gain and hirsutism. (Please select 1 option)
Elevation of which of the following would be most 1- Bromocriptine

suggestive of a diagnosis of polycystic ovarian 2- Cabergoline
syndrome?
3- Metformin
4- Spironolactone
1- Androstenedione
5- Yasmin
2- DHEAS
3- Insulin Answer & Comments
4- LH Answer: 3- Metformin
5- Prolactin
This patient has the features of PCOs and the
Answer & Comments modest elevation of prolactin is quite typical of
this condition occurring in approximately 10%. In
Answer: 1- Androstenedione this case, the hyperprolactinaemia appears not to
be pathological as the estradiol is normal.
Androstenedione, a weak androgen produced in Metformin would be the most appropriate
the ovaries is typically elevated in PCOS. Although, treatment here as it is associated with increased
prolactin is elevated in approx 10% of patients rates of conception particularly when used with
with PCOs with concentrations typically less than clomiphene. Sprironolactone should not be used
1000 mu/l, higher concentrations may prompt in patients wishing to conceive as it is teratogenic.
investigation for prolactinoma. Although insulin
resistance is a feature of PCOs, its concentration, [ Q: 110 ] Question ID #137
per se, is rather meaningless in PCOs.
A 25 year old female presents with problematical
[ Q: 109 ] Question ID #112 facial hirsutism. All investigations support a
diagnosis of polycystic ovarian syndrome. You
A 32 year old female with a diagnosis of polycystic decide to prescribe Eflornithine cream.
ovarian syndrome is referred to the endocrine
clinic. She has a history of weight gain and modest Which of the following describes its mechanism of
facial hirsutes. Her periods are reasonably action?
irregular occurring once every two-three months. (Please select 1 option)
She is keen to commence a family and has had
1- 5-alpha reductase inhibitor

2- Dehydrotestosterone receptor antagonist 4- Non-functional pituitary tumour

3- Insulin sensitiser 5- Obesity
4- Lipase inhibitor
Answer & Comments
5- Ornithine decarboxylase inhibitor
Answer: 5- Obesity
Answer & Comments
The most likely cause of this man’s
Answer: 5- Ornithine decarboxylase inhibitor hypogonadotrophic hypogonadism is obesity.
Increasingly, obesity is being recognized as a cause
Eflornithine is an ornithine decarboxylase inhibitor of hypogonadism although the mechanism is
and interferes with the urea cycle important in somewhat obscure. The other options which
hair growth. It is used in the treatment of cause hypogonadotrophic hypogonadism are
hirsutism and is associated with significant listed but these are less likely although one would
improvement in cosmetic appearance. undertake pituitary imaging.
A 55 year old male presents with problems with A 15 year old female with long standing obesity
erectile function. He has a poor libido and denies was referred with abdominal swelling and mild
any early morning erections. He has fathered two ankle oedema. On examination the blood pressure
children and his current problems date over the was 142/88 mmHg. Investigations reveal:
last two years. On examination, he appears a
phenotypically normal male, has a BMI of 38 kg/m2 Haemoglobin 10.5 g/dL (11.5-16.5)
and has normal male distribution of body hair.
Serum biochemistry Normal
Testicular examination reveals testes of 12-15 mls
bilaterally. Serum albumin 34 g/L (37-49)
Urine dipstick Proteinuria +
E+Us Normal investigation for this patient?
Fasting Plasma Glucose 6.1 mmol/l (3.5-5.5) (Please select 1 option)
Testosterone 6.6 nmol/l (9-30) 1- 24 hour urinary protein estimation
LH 2.8 iu/l (3-10) 2- Abdominal ultrasound
FSH 3.4 iu/l (3-10)
3- Protein electrophoresis
4- Urinary albumin: creatinine ratio
Free T4 12.8 pmol/l (9-23)
TSH 3.2 mu/l (0.5-5) 5- Urinary B-human chorionic gonadotrophin
test (B-HCG)
Which of the following is likely to explain this
man’s results? Answer & Comments
Answer: 5- Urinary B-human chorionic
1- Craniopharyngioma gonadotrophin test (B-HCG)
2- Haemochromatosis
This young girl has been 'gained weight'with
3- Kallmann syndrome abdominal swelling and ankle oedema. She is

hypertensive, has proteinuria and is anaemic. This rise by no more than 0.5 ng/ml following
should raise a suggestion of a concealed testosterone treatment
pregnancy with pre-eclampsia. The most relevant
investigation would be a pregnancy test - urinary There is no evidence that testosterone causes
B-HCG. prostate cancer but, hypogonadism is associated
with prostate shrinkage. Hence, there is evidence
[ Q: 113 ] Question ID #423 suggesting that testosterone replacement may
actually unveil a prostate malignancy and one
should be vigilant with regard to a potential rise in
A 55 year old male is diagnosed with weight- PSA concentrations. 15% of men qith prostate
related hypogonadotrophic hypogonadism and is cancer have a PSA below 4.
treated with topical titratable testosterone 60mg
daily. Previous examination revealed a normal PR
examination. Original investigations revealed PSA [ Q: 114 ] Question ID #424
concentration 2.2 ng/ml, testosterone 7 nmol/l
and haematocrit 38%. A 72 year old male is referred by his GP who was
concerned about an elevated prolactin
On attendance at the clinic three months he feels concentration. He had been well up until 3 years
better in himself, with more energy and improved ago when he was diagnosed with prostate cancer
libido. Results reveal: and was treated with GnRH analogues. Since he
has been tired but his prostate cancer is well
Testosterone 13.8 nmol/l (8-30) controlled, being on 6 monthly appointments with
urology. His GP had checked a few results and
PSA 3.8 ng/ml (2.6-4)
found that his Prolactin was 980 mu/l (50-450),
Haematocrit 43% (40-50) precipitating referral. He currently receives
amlodipine, ramipril, simvastatin and
Which of the following is the most appropriate domperidone
approach to the management of this man's
testosterone He appears hypogonadal in appearance and his
blood pressure is 134/74 mmHg with a BMI of
32kg/m2.
1- Continue current dose of testosterone
2- Increase dose of testosterone Investigations reveal:
3- Reduce dose of testosterone Testosterone 1.2 nmol/l (8-30)

4- Stop testosterone and refer to urology Prolactin 800 mu/l (50-450)
5- Stop testosterone and refer to haematology LH 1.2 mu/l (1-10)
FSH 1.1 mu/l (1-10)
Answer & Comments Free T4 9.1 nmol/l (9-23)
Answer: 4- Stop testosterone and refer to urology TSH 4mu/l (0.5-5)
IGF-1 18 nmol/l (15-30)
This patient has made a good response to
testosterone replacement with a now reasonable Which of the following is the likely cause for the
testosterone concentration of 13.8. However, his hyperprolactinaemia?
PSA concentration has increased by 1.4 ng/ml and (Please select 1 option)
this should alert the physician to a potential
underlying neoplasm. Current guidance suggests 1- Drug induced
referral to a urologist if the PSA rises above 1.5 2- Metastatic prostatic disease
ng/ml from baseline value. Typically PSA would

3- Microprolactinoma Answer & Comments

4- Non-functioning pituitary tumour Answer: 3- Semen analysis
5- Primary hypothyroidism
Infertility is defined as failure to conceive despite
2 years of unprotected sexual intercourse.
Answer & Comments
Investigations are warranted if the couples fail to
Answer: 1- Drug induced conceive despite 1 year of unprotected
intercourse. One third of causes of infertility are
related to male factor. The commonest of male
This patient is receiving a dopamine antagonist -
factor infertility causes include primary Gonadal
domperidone. This is the most likely cause for his
failure, secondary Gonadal failure, genital tract
hyperprolactinaemia. The thryoid function tests
abnormalities, erectile dysfunction, systemic
are entirely normal and a microprolactinoma
illness or iatrogenic due to drugs such as Steroids,
would be very unusual in a man of this age. The
Antiandrogens, Spironlactone etc. Primary
suppression of LH, FSH and testosterone indicates
gonadal failure is commonly due to genetic
adequate treatment with GnRH analogues.
syndromes like Klinefelter syndrome or orchitis,
testicular torsion, mumps or congenital
[ Q: 115 ] Question ID #607 cryptorchidism. While secondary Gonadal failure
is most commonly due to pituitary or
A 25 year old man has been referred to the fertility hypothalamic disease.
clinic for routine assessment. He has been in a
steady relationship for last 2 years but his partner The investigations for male factor infertility
has been unable to conceive despite unprotected include semen analysis, which if normal practically
sexual intercourse between the couple for more rules out any male factor contributing to infertility.
than 1 year. Other investigations include measurement of FSH,
LH and Testosterone levels to categorise patients
His partner has been thoroughly investigated with into primary or secondary gonadal failure.
no obvious physical or hormonal abnormality
noticed in her as a cause for infertility. [ Q: 116 ] Question ID #608
He is otherwise asymptomatic, with no significant

A 24 year old gentleman, presents to the
past medical history and denies usage of any illicit
Endocrine clinic for further assessment regarding
substance. Physical examination performed in
azoospermia, noted on investigation of infertility.
clinic is normal, with normal secondary sexual
He is 182 cm tall with a body weight of 70 Kg and
characteristics and testicular volume of 20 ml.
Body Mass Index (BMI) of 21. On examination, he
has bilateral gynaecomastia and testicular volume
What's the first investigation you would offer to of 6 ml with testes being firm in consistency. His
him for further analysis of any male factor involved investigations are shown below:
in infertility?
(Please select 1 option) FH 28 U/L (1.4-18.1)
1- FSH/LH LH 42 U/L (3.0-8.0)
2- Karyotyping Prolactin 110 mU/L (45-375)
Testosterone 4.2 nmol/L (8.4-28.7)
3- Semen analysis
Free T4 18 pmol/L (11.5-22.7)
4- Testosterone levels
TSH 1.6 mU/L (0.35-5.5)
5- TFT
What is the most appropriate next step for the
management of his infertility?

(Please select 1 option) 4- Pregnancy test

1- Cabergoline 5- 17 Hydroxy progesterone levels (17 OHP)
2- GnRH analogue therapy
Answer & Comments
3- Refer to fertility clinic for evaluation
4- Sildanefil Answer: 2- Karyotyping
5- Testosterone replacement
This 16 year old has complete androgen
insensitivity syndrome as suggested by presence
Answer & Comments of primary amenorrhoea, scanty hair growth and
history of previous inguinal hernial repair pointing
Answer: 3- Refer to fertility clinic for evaluation
towards presence of ectopic testicular tissue
previously. It is an X linked recessive disorder due
This gentleman has primary gonadal failure based to mutation of androgen receptor gene located on
on his low testosterone levels and increased FSH/ Xq11-12, although a negative family history may
LH levels. His tall stature, bilateral gynaecomastia be present in more than one third cases.
and small testicular volume point towards
testosterone deficiency developing before he The diagnosis is usually suspected based on clinical
attained puberty, leading to eunuchoid physical profile including primary amenorrhoea, normal
appearance. It is likely that he suffers from a breast development, lack of axillary and pubic hair
genetic disorder like Klinefelter`s syndrome and and testis like masses in inguinal canal or labia. The
will need further karyotype analysis to establish testosterone levels are clearly higher than normal
the diagnosis. female range and oestrogen levels are low. LH
levels are elevated with normal FSH levels. The
These patients require lifelong replacement with management includes affirmation and
testosterone and are infertile. In contrast to reinforcement of female gender identity and
secondary hypogonadism which can be treated removal of testicular tissue (orchidectomy) after
with pulsatile GnRH treatment, the management attaining puberty as to avoid development of any
of infertility in primary hypogonadism usually malignancy in the ectopic gonadal tissue.
requires modalities like In vitro fertilisation (IVF)
or intra-cytoplasmic sperm injection (ICSI) and
better achieved under specialist fertility clinic.
A 16 year girl presents to the clinic with primary

[ Q: 117 ] Question ID #609 amenorrhoea. She has Tanner 4 stage breast
development but scanty axillary and pubic hair.
A 16 year girl presents to the clinic with primary The only past medical history of note is an inguinal
amenorrhoea. She has Tanner stage 4 breast hernial repair at the age of 16.
development but scanty axillary and pubic hair.
The only past medical history of note is an inguinal What is the likely diagnosis?
hernial repair at the age of 6. (Please select 1 option)
Which of the following is the next best 1- Androgen insensitivity syndrome

investigation to establish her diagnosis? 2- CAH
3- Gonadal dysgenesis
1- FSH/LH/Estradiol levels
4- PCOS
2- Karyotyping
5- Turner`s syndrome
3- Pelvic Ultrasound

Answer & Comments uterus. On Karyotyping, a XY mosaic chromosomal

pattern is seen.
Answer: 1- Androgen insensitivity syndrome
Which is the next crucial step in her long term
This 16 year old has complete androgen management?
insensitivity syndrome as suggested by the (Please select 1 option)
presence of primary amenorrhoea, scanty hair
growth and history of previous inguinal hernial 1- Cabergoline
repair pointing towards presence of ectopic 2- Calcihew D3
testicular tissue previously. It is an X linked
recessive disorder due to mutation of the 3- Gonadectomy
androgen receptor gene located on Xq11-12,
4- HRT
although a negative family history may be present
in more than one third cases. 5- Transdermal oestrogen replacement
The diagnosis is usually suspected based on clinical

Answer & Comments
profile including primary amenorrhoea, normal
breast development, lack of axillary and pubic hair Answer: 3- Gonadectomy
and testis like masses in inguinal canal or labia. The
testosterone levels are clearly higher than normal
This lady has primary gonadal failure secondary to
female range and oestrogen levels are low. LH
Gonadal dysgenesis with XY mosaic pattern on
levels are elevated with normal FSH levels. The
Karyotype analysis. The XY Gonadal dysgenesis
management includes affirmation and
can be complete or incomplete. Patients with
reinforcement of female gender identity and
complete form present with no phenotypic
removal of testicular tissue (orchidectomy) after
features of Turner`s syndrome, with normal or tall
attaining puberty as to avoid development of any
stature, female external genitalia, bilateral streak
malignancy in the ectopic gonadal tissue.
gonads and sexual infantilism. Incomplete form
presents with presents with variable degree of
[ Q: 119 ] Question ID #611 ambiguity in external female genitalia
development. There is increased risk of
A 22 year lady presents with primary malignancy associated with dysgenetic gonads as
amenorrhoea. Her hormonal profiles as checked in a result prophylactic gonadectomy should be
the Endocrinology clinic are shown below: considered in all cases.
(Follicular 0.5-5, Mid-cycle [ Q: 120 ] Question ID #633

FSH 0.4 U/L
8-33, Luteal 2-8 U/L)
(Follicular 3-12, Mid-cycle A 17 year old girl diagnosed to have Turners
LH 1.5 U/L
20-80, Luteal 3-16 U/L) syndrome has completed 2 years of growth
25 (Follicular 17-260, Luteal hormone therapy and attained her final height.
Oestradiol
pmol/L 180-1100 pmol/L)
160 What should be the next step as far as her GH
Prolactin (60-620) replacement therapy is concerned?
mU/L
17.2 (Please select 1 option)
Free T4 (11.5-22.7)
pmol/L 1- Continue GH therapy indefinitely
1.1 2- Half the dose of GH therapy
TSH (0.35-5.5)
mU/L
3- Need to continue GH therapy until she is 25
Her further investigations include an Ultrasound 4- Reassess her GH axis
of the pelvis which shows a small rudimentary

5- Stop GH therapy its presence in circulation in the free state.

Nevertheless, excess DOC secretion as seen in
congenital adrenal hyperplasia (CAH) is associated
Answer & Comments
with hypertension, hypokalaemia and suppression
Answer: 5- Stop GH therapy of plasma renin activity and serum aldosterone
levels.
Therapy in Turner`s syndrome is aimed towards
In CAH, excessive DOC production is seen with
induction of secondary sexual characteristics and
deficiency of either 11 β Hydroxylase deficiency or
attainment of maximum possible final height.
17 α hydroxylase deficiency. The later is associated
Growth hormone replacement forms the mainstay
with decreased production of androgens in
of treatment for the later purpose and given at
addition to defective synthesis of cortisol. As a
dose of 45-50 µg/ kg daily for a period of 3-7 years.
result affected males present with features of
It is contraindicated if there is presence of any
pseudo-hermaphroditism and affected females
active malignancy, post renal transplant for at
present with primary amenorrhoea and features
least one year or if there is evidence of epiphysial
of sexual infantilism.
fusion. GH treatment is discontinued on
attainment of final height or if the response is poor
(an increase in growth velocity of less than 50% [ Q: 122 ] Question ID #665
from baseline) in the first year of treatment.
A 21 year old girl with long standing history of
[ Q: 121 ] Question ID #653 menstrual irregularities presents to her GP with
breast tenderness and 2 months history of
amenorrhoea. She has BMI of 31 and features of
A 17 year old girl presents with delayed puberty
hirsutism on examination.
(Tanner stage 2, breast and hair development),
she is also hypertensive and has hypokalaemia.
What single test will you advice her GP to perform
What is the likely underlying enzymatic defect? before she is referred to Endocrinology clinic?
1- 3 β HSD 1- 17 OH Progesterone levels
2- 11 β HSD 2- DHEAS
3- 11 β Hydroxylase 3- Prolactin
4- 17 α hydroxylase 4- Testosterone
5- 21 α Hydroxylase 5- Urinary pregnancy test
Answer: 4- 17 α hydroxylase Answer: 5- Urinary pregnancy test
Aldosterone and Deoxycorticosterone (DOC) are It is imperative that pregnancy is ruled out in a
the two most important mineralocorticoid female (in reproductive age group), presenting
hormones, with aldosterone binds weakly with with secondary amenorrhoea to avoid
corticosteroid binding globulin (CBG) and mostly unnecessary investigations and wastage of
circulates bound to albumin. In contrast DOC is resources. Further investigations (for example -
highly bound to CBG and usually undetectable in FSH, LH, Prolactin, TFT) are only warranted if the
urine. Both of these have equal affinity for initial urinary pregnancy test is negative
mineralocorticoid receptor but the former is more
important as a mineralocorticoid hormone due to

[ Q: 123 ] Question ID #676  Systemic illness (heart failure, cirrhosis,

uraemia etc.)
 Neurological conditions such as
A 45 year old man with Type 2 DM for 8 years
presents to clinic with lack of libido and erectile autonomic neuropathy, cord compression
 Vascular conditions such a peripheral
dysfunction. His BMI is 32 kg/m2 and there is no
loss of secondary sexual characteristics. He denies vascular disease
 Endocrine disease (hypogonadism,
usage of any substance of abuse and his alcohol
intake is 14 units in a week. His biochemistry diabetes, thyroid dysfunction)
 Psychological
shows:
 Urogenital abnormalities like trauma,
priapism and Peyronie`s disease
FSH 2.2 U/L (1-10)  Alcohol, substance of abuse like heroin,
LH 3.5 U/L (3-10) marijuana
Testosterone 7.5 nmol/L (9-28.5)
This gentleman has features of secondary gonadal
Prolactin 350 mU/L (45-400) failure as evidenced by low testosterone and low
LFT Normal FSH/LH levels. His age group and normal
secondary sexual characteristics make it unlikely
He undergoes a MRI which shows no obvious for him to have any genetic abnormality like
abnormality. Kallmann syndrome. A normal MRI rules out any
structural pituitary or hypothalamic disease. He is
What is the likely explanation for his low libido? not on any medication and systemically well. A
normal LFT and transferrin saturation makes it
unlikely for him to have Haemochromatosis.
1- Anabolic steroid usage
Obese individuals have increased activity of
2- Haemochromatosis
aromatase which converts testosterone to
3- Kallmann syndrome estrogens which in turn suppress FSH/LH levels.
Total testosterone concentrations are influenced
4- Kleinfelter`s syndrome
by sex hormone-binding globulin (SHBG)
5- Obesity concentrations, which are decreased by obesity
and increased with ageing.
Answer & Comments
Answer: 5- Obesity
A 23 year old man, with muscular build, presents
Erectile dysfunction is defined as inability to to the clinic with reduced libido. He visits the gym
achieve or maintain an erection for sufficient time regularly and denies usage of any substance of
duration and firmness resulting in incomplete abuse. His BMI is 30kg/m2 and normal secondary
sexual activity in > 25% of the attempts. About sexual characteristic development with some acne
10% of men are affected by low libido and erectile on back. His blood results are as shown below:
dysfunction and the prevalence increases with
age. FSH 1.8 U/L (1-10)
The following is a list of main causes for erectile LH 3.2 U/L (3-10)
dysfunction: Testosterone 8.1 nmol/L (9-28.5)
Prolactin 220 mU/L (45-400)
 Medications such as diuretics, β blockers,
MAO inhibitors, opioids, glucocorticoids, LFT normal
tranquilizers, digoxin, antiandrogens, MRI Brain normal
gemfibrozil

What is the likely cause for his hypogonadism? [ Q: 125 ] Question ID #690
1- Anabolic steroid abuse A 22 year old lady, planning for a family in near
future, has been diagnosed to have a
2- Kallmann syndrome microprolactinoma based on raised prolactin
levels and MRI scan results.
3- Kleinfelter syndrome
4- Idiopathic hypogonadotrophic Which is the best management option in her case?
hypogonadism (Please select 1 option)
5- Weight related hypogonadotrophic 1- Bromocriptine
hypogonadism
2- Cabergoline
Answer & Comments 3- Observe
Answer: 1- Anabolic steroid abuse 4- Radiotherapy

5- Removal of tumour
This gentleman has secondary hypogonadism as
reflected by low testosterone, low FSH and LH Answer & Comments
levels. His normal secondary sexual characteristic
development makes the diagnosis of genetic Answer: 1- Bromocriptine
disorder unlikely. A normal MRI rules out any
structural lesion involving pituitary gland or Bromocriptine is a safe option for females in
hypothalamus. Anabolic steroid abuse is quite reproductive age group presenting with a
common in body builders and sportsmen. The microprolactinoma if they are seeking a family in
increase aromatase activity in such cases leads to near future. The therapy can be stopped once the
increased conversion of testosterone to patient conceives and pregnancy is confirmed. The
oestrogens as a result gonadotrophins secretion is dopamine agonists help reduce prolactin levels
suppressed. and induce ovulation. Therefore, if pregnancy is
desired women should be given advice regarding
The following is the list of major causes of contraception on initiation of therapy.
secondary hypogonadism: Cabergoline usage in pregnant women has also
not been associated with any increased risk of
 Genetic disorders such as Kallamann foetal malformation, but the available data on
syndrome, DAX-1 mutation
 Structural disorders of pituitary and/or
hypothalamus (pituitary adenoma, [ Q: 126 ] Parathyroid/calcium - Question ID
craniopharyngioma, germinoma) #60
 Post surgical (pituitary and/or
hypothalamic) or post cranial A meta-analysis on a thiazolidendione reports an
radiotherapy increased risk of fractures associated with the long
 Functional - secondary to excessive term use of the drug.
exercise (e.g. long distance runners),
systemic illness, obesity, anorexia, stress, Which of the following effects of thiazolidendione
anabolic steroids, recreational drugs (TZD) therapy is implicated in this increased
 Infiltrative disease like sarcoidosis, fracture risk?
haemochromatosis
 Congenital syndromes like Laurence-
Moon-Biedl or Prader-Willi syndrome 1- Increased osteoclast activity
2- Reduced osteoblast activity

3- Reduced calcitonin secretion 5- Tertiary hyperparathyroidism

4- Reduced PTH secretion
Answer & Comments
5- Reduced vitamin D synthesis
Answer: 4- Secondary hyperparathyroidism
Answer & Comments
This patient has a lowish calcium and elevated PTH
Answer: 2- Reduced osteoblast activity concentration. The most likely explanation in a 65
year old female is vitamin D deficiency and hence
TZDs as a class have been associated with an secondary hyperparathyroidism. Vitamin D
increased risk of fracture. PPAR-gamma receptor deficiency is common and some studies suggest
activation in bone has been shown to reduce that it is present to a variable extent in up to 30%
osteoblast activity, but have no effect on of the general population.
osteoclast activity resulting in an increase in fat
deposition within bone. Rosiglitazone is not Reference:
recommended for use in patients with ischaemic Emedicine Vitamin D deficiency
heart disease, while both rosiglitazone and
pioglitazone are contraindicated in patients at risk [ Q: 128 ] Question ID #66
of heart failure or with a previous history of heart
failure. TZDs as a class have been shown to reduce
bone specific alkaline phosphatase, but have no A 45 year old female has been commenced on
detrimental effects on left ventricular systolic strontium ranelate for the treatment of
function. Roisglitazone and pioglitazone osteoporosis.
predominantly undergo hepatic metabolism and
are not recommended for patients with significant Which of the following most appropriately
hepatic dysfunction, defined by transaminase describes the mechanism of action of strontium?
levels 2.5 X upper limit of normal. (Please select 1 option)
1- Increases bone formation

2- Increases calcium reabsorption from the gut
A 65 year old female is referred from primary care 3- Reduces bone reabsorption and increases
with various aches and pains. She has no past bone formation
history of note and takes no medication. The GP
encloses the following biochemistry: 4- Reduces bone reabsorption only
5- Reduces calcium excretion
U+Es Normal
Calcium 2.36 mmol/l (2.2 - 2.6) Answer & Comments
Phosphate 0.8 mmol/l (0.7 - 1.4) Answer: 3- Reduces bone reabsorption and
PTH 18.2 nmol/l (3 - 6) increases bone formation
Which of the following is the likely diagnosis? Strontium appears to have a dual mechanism of
(Please select 1 option) action reducing bone reabsorption (like
1- Familial hypercalciuric hypercalcaemia bisphosphonates) and increasing bone formation
(like PTH).
2- Primary hyperparathyroidism
3- Pseudohypoparathyroidism
4- Secondary hyperparathyroidism

[ Q: 129 ] Question ID #79 Calcium 2.36 mmol/l (2.2 - 2.6)

Alkaline Phosphatase 88 iu/l (50 - 110)
A 42 year old male presents with tiredness and
PTH 8.6 pmol/l (3 - 5.5)
general aches and pains. He has a past history of
bipolar disorder for which he takes Lithium and Vitamin D 12.7 nmol/l (>20)
Aripiprazole. He is also a type 2 diabetic for which
he takes metformin. His investigations reveal the Which of the following would be the most
following: appropriate treatment for this patient?
Calcium 2.86 mmol/l (2.2 - 2.6)
1- Calcium and vitamin D supplements
Phosphate 0.78 mmol/l (0.8 - 1.4)
2- Continuous combined HRT
PTH 11.2 pmol/l (3 - 5.5)
3- Raloxifene
Which of the following is the likely diagnosis? 4- Strontium
5- Weekly Alendronate
1- Drug induced hyperparathyroidism
2- Familial hypocalciuric hypercalcaemia Answer & Comments
3- Pseudo-hypoparathyroidism Answer: 1- Calcium and vitamin D supplements
4- Secondary hyperparathyroidism
This patient has secondary hyperparathyroidism
5- Tertiary hyperparathyroidism
and vitamin D deficiency and
osteoporosis/osteopaenia. The most appropriate
Answer & Comments treatment in this scenario would be vitamin D
replacement which would be expected to improve
Answer: 1- Drug induced hyperparathyroidism bone mineral density. This can be reviewed with
serial scanning.
Lithium is a recognised cause of
hyperparathyroidism although the mechanism is [ Q: 131 ] Question ID #127
ill understood. Stopping therapy, if possible, may
result in a resolution of the hyperparathyroidism
although the condition may persist and may A 45 year old woman is referred by her GP for
require surgery. If it is not possible to stop investigation of her hypercalcaemia. He noted the
treatment, the hyperparathyroidism, often due to following investigations:
an adenoma, can be treated surgically and
medication continued. U+Es Normal
Calcium 2.8 mmol/l (2.2 - 2.6)
[ Q: 130 ] Question ID #101 Phosphate 1.0 mmol/l (0.8 - 1.4)
A 56 year old female is referred as she has been The patient originally attended the GP with vague
concerned about osteoporosis. She went through aches and pains which have been present for two
the menopause uneventfully at the age of 50 and months or so and she also admits to feeling rather
has no particular problems of note. She has a depressed. She is only taking Fluoxetine 20 mg
strong family history of osteoporosis. A DEXA scan daily at present. There is nil of note on
that she had obtained privately reveals a T score examination. Further investigations reveal:
of -2.5 at the hip and -2.0 at the lumbar spine. Her
investigations reveal: PTH 4.4 pmol/l (3 - 5)

Vitamin D 10.2 micromol/l (8 - 50) FreeT4 18.2 nmol/l (9-23)

Urine calcium 7 mmol/d (0 - 7.5) TSH 0.07 mu/l (0.5-5)
Which of the following is the likely diagnosis? Which of the following is the most appropriate
(Please select 1 option) management of his DEXA result?
1- Drug-induced
1- Growth hormone therapy
2- Familial hypocalciuric hypercalcaemia
2- Increase dose of testogel
3- Milk-Alkali syndrome
3- No specific treatment required
4- Primary hyperparathyroidism
4- Reduce dose of thyroxine
5- Tertiary hyperparathyroidism
5- Weekly alendronate
Answer & Comments
Answer & Comments
Answer: 4- Primary hyperparathyroidism
Answer: 5- Weekly alendronate
This patient has mild hypercalcaemia, an
inappropriately normal PTH concentration and has The most appropriate approach to treating this
a normal/highish urine calcium excretion. The man’s osteoporosis, as demonstrated with a T
latter would argue against a diagnosis of FHH score of less than -2.5, is a bisphosphonate such as
where urine calcium excretion is low (less than 5 weekly alendronate. The causes of low BMD in
mmol/d) and so the likely diagnosis is primary association with hypopituitarism are multi-
hyperparathyroidism. factorial and GH deficiency may contribute.
Although this man is highly likely to have GH
[ Q: 132 ] Question ID #136 deficiency as demonstrated by his low IGF-1, he
does not appear to have specific symptoms of GH
deficiency that might merit treatment and NICE do
52 year old male is referred as his GP had not advocate the use of GH as a treatment of
organised a DEXA scan for him as he had been reduced BMD in adults hypopituitary patients.
concerned about his bone thickness. This concern Unlike bisphosphonates, where there is evidence
had arisen as he had read about reduced bone of reduced fracture risk, GH therapy has no data of
mineral density in relation to hypopituitarism. Ten reduced fracture risk.
years ago he had surgical removal of a non-
functional pituitary macroadenoma and had
developed hypopituitarism for which he receives [ Q: 133 ] Question ID #138
hydrocortisone 10mg bd, thyroxine 150
micrograms daily and testogel 50mg daily. His A 55 year old female presents with a one week
DEXA scan reveals T scores of -2.6 in some areas of history of sickness, lethargy and fatigue. She has a
the lumbar spine and -2.4 in the hip. two year history of metastatic breast carcinoma.
On examination, she appears dehydrated and
He is generally fit and quite well but, after reading unwell.
an article on bone strength in hypopituitarism is
concerned about osteoporosis. Her investigations reveal:
His other investigations reveal: Sodium 148 mmol/l (134-144)

Potassium 4.8 mmol/l (3.5-5)
IGF-1 10.8 nmol/l (28-42)
Testosterone 14.5 nmol/l (9-30)

Creatinine 180 micromol/l (50-100) Answer & Comments

Calcium 3.8 mmol/l (2.2 - 2.6) Answer: 4- Initially arrange DEXA scan

In a patient less than 65 years of age, any
initial treatment for this patient? therapeutic intervention for osteoprotection in
(Please select 1 option) association with steroid therapy should be guided
initially by DEXA scanning. A T score above 0 does
1- IV Calcitonin
not require any intervention nor further repeat
2- IV Dextrose DEXA unless high dose steroids are to be used. A T
score of 0 to -1.5 would promote lifestyle
3- IV Normal saline
interventions with values less than -1.5 requiring
4- IV Pamidronate therapies with alendronate as the first line agent.
5- IV Prednisolone
Answer & Comments
A 17 year old caucasian female is seen due to
Answer: 3- IV Normal saline various aches and pains. She takes no medication
other than the combined oral contraceptive. She
This patient has marked hypercalcaemia as has been generally well but has had general
reflected by the calcium above 3 mmol/l. The most muscle aches for a couple of years. There is
appropriate initial management of this patient nothing to note on physical examination and she
with dehydration and hypercalcaemia which is has normal height and normal secondary sexual
likely to be malignancy related is IV rehydration characteristics. Her results reveal:
with normal saline. One would not contemplate IV
bisphosphonate until rehydration is completed as Full blood count Normal
this would compound the nephrotoxicity. U+Es Normal
Calcium 1.96 mmol/l 2.2-2.6
Phosphate 1.68 mmol/l 0.7-1.2
PTH 68 nmol/l 3-5.5
A 35 year old female is receiving 10mg of
prednisolone daily as a treatment of ophthalmic Free T4 9.8 pmol/l 9-23
Graves’ disease with the intention of her TSH 2.2 mu/l 0.5-5
remaining on this dose for the next six months.
Which is the most appropriate approach regarding
potential osteoprotection for this patient?
1- Factitious results
1- Commence calcium and vitamin D 2- Primary hypoparathyroidism

supplements 3- Pseudohypoparathyroidism
2- Commence strontium ranelate 4- Pseudo-pseudohypoparathyroidism
3- Commence weekly alendronate 5- Secondary hyperparathyroidism
4- Initially arrange DEXA scan
Answer & Comments
5- No treatment/further investigation required
Answer: 3- Pseudohypoparathyroidism

This young girl has a long history of muscle aches of a 'young' control. The Z score is the number of
and pains and has a low calcium concentration but standard deviations between the BMD of the
elevated phosphate. The latter is suggestive of a subject and that expected for an aged and sex
hypoparathyroidism rather than vitamin D matched control.
deficiency (where a phosphate would be expected
to be low). However, the patient has an elevated T scores greater than -1 are normal. T scores
PTH concentration and so this would suggest an between -1 to -2.5 reflect osteopenia and T scores
unresponsiveness to PTH and hence a diagnosis of less than -2.5 reflect osteoporosis. This DEXA
pseudo-hypoparathyroidism. The fact that she has report of the hip reveals T scores between +0.38
no skeletal abnormalities (short 4th Metacarpal and -2.0 which indicate osteopaenia at Ward's
for instance) would suggest a type 1b or type 2 triangle and the intertrochanteric region.
pseudohypoparathyroidism.
A 67 year old lady with newly diagnosed
The following results were obtained on a DEXA osteoporosis re-presents to clinic with intolerance
scan of the hip of a 55 year old female who was to Alendronate 70 mg weekly after 4 weeks of
concerned regarding her risk of osteoporosis since persistence. There is history of previous fracture
there was a strong family history of fragility at the left wrist when she fell off the fourth step of
fractures. a ladder 4 years ago. She is also taking calcium and
vitamin D supplementation. She underwent
BMD T score Z score menopause at age 40 and did not take hormone
replacement therapy. There is a family history of
Neck 0.74 -1.5 -0.29
osteoporosis and hip fracture in her late mother.
Trochanteric 0.73 +0.38 +1.1 Other secondary causes of osteoporosis have
Intertrochanteric 0.91 -1.29 -0.68 been excluded.
Total 0.83 -0.95 -0.11
Her DEXA scan T scores are:
Ward's triangle 0.50 -2.0 -0.21
AP Spine -3.9
Which of the following is the correct interpretation
of this DEXA scan? Total Hip -3.3

Which treatment is appropriate as per NICE
1- Normal bone mineral density guidelines?
2- Osteomalacia (Please select 1 option)
3- Osteopenia 1- Intravenous zolendronic acid
4- Osteopetrosis 2- Oral calcium and vitamin D supplementation

without bisphosphonate
5- Osteoporosis
3- Oral etidronate
Answer & Comments 4- Oral risedronate
Answer: 3- Osteopenia 5- Oral strontium ranelate
A DEXA scan measures bone mineral density Answer & Comments

(BMD) at various sites, typically the lumbar spine
Answer: 5- Oral strontium ranelate
and hip are reported. The T score is the number of
standard deviations of the patient's BMD and that

This question refers to the NICE guidelines (TA161) 3- Osteopenia on BMD

for the secondary prevention of osteoporotic
4- Worsening liver function
fractures which relates only to treatments for the
secondary prevention of fragility fractures in 5- Decrease in creatinine clearance by >30%
postmenopausal women who have osteoporosis
and have sustained a clinically apparent
Answer & Comments
osteoporotic fragility fracture. Osteoporosis is
defined by a T-score1 of -2.5 standard deviations Answer: 5- Decrease in creatinine clearance by
(SD) or below on dual-energy X-ray >30%
absorptiometry (DXA) scanning.
Alendronate is recommended as a first line According to the NIH consensus statement, the
treatment option for the secondary prevention of following parameters can be used as indications
osteoporotic fragility fractures in postmenopausal for parathyroidectomy in asymptomatic patients
women who are confirmed to have osteoporosis. with primary hyperthyroidism:
Risedronate and etidronate are recommended as
alternative treatment to alendronate, if it is  Age < 50 years
contraindicated. In this case, the patient was  T score of < -2.5 on bone mineral
intolerant of alendronate, is likely to be intolerant densitometry (BMD)
of other oral bisphophonates and so the next most  Plasma calcium > 2.85 mmol/L
appropriate treatment would be strontium. IV  Urinary calcium excretion of 10 mmol/d
Zolendronate is another possibility but arguably (or > 400 mg/day)
there is a lot less hassle providing the patient with  Decrease in creatinine clearance by >30%
an oral preparation, so making it the preferable as compared to age matched normal
choice. subjects
Number of independent clinical risk factors for Other indications for parathyroidectomy in
fracture primary hyperparathyroidism include
 Symptomatic patient (definitive signs and

Age 0 1 2
symptoms of hypercalcaemia- such as
65-69 N/R -3.5 -3.0 proximal weakness, gait disturbance,
70-74 -3.5 -3.0 -2.5 hyper-reflexia)
 Evidence of end organ damage (renal
75+ -3.0 -3.0 -2.5
failure, renal stones, osteitis fibrosa
cystica and pancreatitis)
N/R = Not recommended
Reference: [ Q: 139 ] Question ID #482

NICE clinical guidelines 161: Osteoporosis
secondary prevention A GP has referred a 42 year old gentleman with
hypercalcaemia to the endocrine clinic with a
probable diagnosis of primary
hyperparathyroidism based on the following
blood results:
According to the NIH consensus criteria, which of
the following is an indication to operate in patients
Corrected 2.75
with primary hyperparathyroidism? (2.2-2.6)
Calcium mmol/L
0.7
Phosphate (1-1.4)
1- Age > 50 years mmol/L
2- Corrected Calcium >2.75 mmol/L

25-OH Vitamin (desirable above score at the lumbar spine has fallen from -2.8 to -
32 nmol/L 3.5 and at the neck of femur it is stable at -3.6.
D 30)
7.2
PTH (1.0-6.0) Which of the following management options
pmol/L
would you select for the management of this
Which of the following results/ observations will patient?
go against the suggested diagnosis? (Please select 1 option)
(Please select 1 option) 1- Continue strontium ranelate and repeat

1- A family history of hypercalcaemia DEXA in 12 months
2- Calcium excretion of < 50 mg/ day 2- Continue strontium ranelate unless fractures
again
3- History of renal stones
3- Start ibandronate monthly treatment and
4- Normal renal function repeat DEXA in 12 months
5- Patient on Thiazide diuretics 4- Start teriparatide treatment for 12 months
5- Start teriparatide treatment for 18 months
Answer & Comments
Answer: 2- Calcium excretion of < 50 mg/ day Answer & Comments
Answer: 5- Start teriparatide treatment for 18
Familial hypocalciuric hypercalcaemia (FHH) is an
months
autosomal dominant condition secondary to a
mutation of the calcium-sensing receptor leading
to a decreased excretion of calcium from the body, NICE guidelines recommend the use of
with an end result of mild hypercalcaemia. It is a teriparatide for secondary osteoporosis in women
benign disorder and an important differential who are unable to take bisphosphonates or have a
diagnosis for primary hyperparathyroidism (PHT). contraindication to or are intolerant of
The key distinguishing features include: alendronate and either risedronate or etidronate;
or who have had an unsatisfactory respond to
 A family history of mild hypercalcaemia treatment with bisphosphonates and who are 65
 No evidence of end organ damage years or older and have a T-score of - 4.0 SD or
(normal renal function, absence of below, or a T-score of - 3.5 SD or below plus more
nephrolithiasis, no evidence of bone than two fractures, or who are aged 55-64 years
disease) and have a T-score of -4 SD or below plus more
 Decreased 24 hour urinary calcium than two fractures.
excretion (<50 mg/day or < 2.5 mmol/day)
or fasting calcium/creatinine excretion Reference:
ratio of < 0.01 http://www.nice.org.uk/nicemedia/live/11748/
42508/42508.pdf
A 67 year old woman comes to see you in
osteoporosis clinic. She has had 2 vertebral A 65 year old gentleman presents with deformity
fractures in the past. Her GP has given her and some discomfort in his tibia. His bloods show
alendronate and residronate but she developed raised alkaline phosphate with normal calcium and
oesophagitis with both. She was taking strontium phosphate levels. His skull and spinal X rays
ranelate which was withdrawn and now continues confirm the diagnosis of Paget`s disease.
on raloxifene together with calcium and vitamin D.
Her DEXA scan was repeated and shows her T-

Which one of the following is the most appropriate Answer & Comments
treatment for his underlying condition?
Answer: 5- X-ray of tibia
1- IV Pamidronate As about 90% of patients with Paget`s disease are

2- IV Zolendronate usually asymptomatic, the diagnosis is often
incidental based on radiological findings. In the
3- Oral calcium carbonate early stages, the lesions seen are mostly osteolytic
and in tubular long bones begin in the metaphysic
4- Oral Risedronate
and migrate down the shaft in a V shaped `cutting
5- Strontium cone`. As the disease progresses, mixed lytic and
sclerotic lesions are seen including trabecular
thickening and increased density. In later stages,
Answer & Comments
most of the lesions are sclerotic. Although isotope
Answer: 2- IV Zolendronate bone scan is a useful investigation to assess the
extent of disease and bone biopsy is used
occasionally to confirm the diagnosis, X-ray of
The prevalence of Paget`s disease is about 2% over
afflicted bone is often the most useful initial
the age of 55 years in UK. Only 1 out of 10 patients
diagnostic test.
are symptomatic. The indications for treating
Paget`s disease include presence of symptoms
(pain), deformity, complications (such as deafness, [ Q: 143 ] Question ID #620
spinal cord compression) and hypercalcaemia.
Bisphosphonates form the mainstay for the A 62 year old lady with previous history of fracture
treatment. The bisphosphonates licensed for of the forearm and spine presents with a
treatment in Paget`s disease include Pamidronate, mechanical fall leading to fracture of ulnar bone.
Risedronate, Etidronate, Tiludronic acid and She is already on alendronate 70mg weekly. Her
Zolendranate. Out of these Zolendranate has the BMD profile shows severe osteroporosis (Z value <
longest action and often only a single dose is -3.5- -4.5).
required for treatment purposes.
What is the next best therauptic option for her
[ Q: 142 ] Question ID #619 treatment?
A 72 year old gentleman presents with a painful
1- Ibradronate IV
leg. His investigations and clinical profile is
suggestive of Paget`s disease. 2- Raloxifene
3- Strontium
What is the next most appropriate investigation to
establish the underlying diagnosis? 4- Teriparatide
(Please select 1 option) 5- Zolendronate IV
1- Bone biopsy
2- Bone densitometry Answer & Comments
3- Bone scan Answer: 4- Teriparatide
4- MRI tibia
Teriparatide is recommended for treatment of
5- X-ray of tibia severe osteoporosis (osteoporosis in presence of
1 or more fragility fractures) in patients in whom
treatment with bisphosphonates has been
unsatisfactory. The high cost associated with this

agent restricts their use to only a selective group OPG in contrast binds to RANKL and inhibits its
of patients. Teriparatide is contraindicated in interaction with RANK receptor. Therefore
presence of renal impairment (eGFR < 30 inhibition of RANKL factor leads to down
mL/minute/ 1.73 m2), severe hepatic impairment, regulation of osteoclast production.
hypercalcaemia, metabolic bone disease (Paget`s
disease, primary hyperparathyroidism) and
unexplained rise in alkaline phosphatase levels.
Reference: A 70 year old man with Rheumatoid arthritis is on

Guideline for the diagnosis and management of a long term steroid therapy (Prednisolone-7.5 mg
osteoporosis in postmenopausal women and per day).
men from the age of 50 years in the UK,
Produced by JA Kanis, J Compston, A Cooper, At what range of T scores on Bone mineral
C Cooper, R Francis, D Marsh, EV McCloskey, densitometry (BMD), you will consider to start him
D Reid, P Selby and M Wilkins, on behalf of on bisphosphonates?
the National Osteoporosis Guideline Group (Please select 1 option)
(NOGG).
1- T score < -1
[ Q: 144 ] Question ID #628 2- T score < -2

3- T score < -2.5
A new experimental drug is being introduced for
4- T score < -3
treatment of osteoporosis. It has been shown to
act by inhibiting production of RANKL factor. 5- T score< 1
Which of the following cells are specifically

Answer & Comments
targeted by this class of agent?
(Please select 1 option) Answer: 1- T score < -1
1- Lining cells
This gentleman has two clinical risk factors (CRFs)
2- Marrow cells for development of osteoporosis- rheumatoid
3- Osteoblasts arthritis and usage of steroids. Both of these are
moderate risk factors for the development of
4- Osteoclasts osteoporosis in contrast with smoking and alcohol
intake which are considered weak CRFs. Parental
5- Osteocytes
history of hip fracture and previous fragility are
generally classified as strong risk factors for
Answer & Comments osteoporosis development. According to the
national guidelines for diagnosis and management
Answer: 3- Osteoblasts
of osteoporosis1, treatment with bisphosphonates
should be considered if the T score on BMD
The communication between Osteoblasts and assessment is < -1 in presence of 2 or more CRFs
Osteoclasts seems to occur as a result of locally and strongly recommended if T score is < -2.5.
produced signals which include osteoclast
differentiation factor called RANK ligand (RANKL) Reference:
and osteoprotegerin (OPG). RANKL is a protein Guideline for the diagnosis and management of
derived from OSTEOBLASTS, which binds to the osteoporosis in postmenopausal women and men
RANK receptor and activates NF-?B on the surface from the age of 50 years in the UK, Produced by JA
of OSTEOCLAST precursors leading to increased Kanis, J Compston, A Cooper, C Cooper, R
osteoclast production. Francis,D Marsh, EV McCloskey, D Reid, P Selby
and M Wilkins, on behalf of the National
Osteoporosis Guideline Group (NOGG).

[ Q: 146 ] Question ID #640 Investigations reveal:
A 22 year old boy is reviewed in clinic to Hba1c 7.5% (<6)

investigate cause for his low calcium levels. He is total
noticed to have short stature and shortened 6.3 mmol/l (<5)
cholesterol
fourth and fifth metacarpals. The following are the
LDL-C 4.1 mmol/l (<2)
blood results as checked in Endocrinology clinic:
triglyceride 2.1 mmol/l (0.9 - 2.2)
Calcium 2.05 mmol/L (2.2-2.6 mmol/L) eGFR > 96 /min / 1.73 m2 (90 - 110)
Phosphate 1.8 mmol/L (0.8-1.5) TSH 8.6 mu / l (0.32 - 5.5)
ALP 110 U/L (50-125) Free T4 10.9 pmol/l (9.3 - 23.4)
PTH 18 pmol/L (1.0-6.1)
What is the likely diagnosis? treatment option to optimise this lady’s lipid
profile?
1- McCune Albright syndrome
1- Add Fenofibrate
2- Osteomalcia
2- Commence Atorvastatin
3- Paget's disease
3- Increase Simvastatin
4- Pseudohypoparathyroidism
4- Increase Metformin
5- Pseudo Pseudohypoparathyroidism
5- Increase thyroxine
Answer & Comments

Answer & Comments
Answer: 4- Pseudohypoparathyroidism
Answer: 5- Increase thyroxine
Pseudohypoparathyroidism (PHP) is a
heterogeneous group of disorders characterized This lady appears to have sub-optimal thyroid
by low calcium, elevated phosphate levels and hormone replacement which is likely to contribute
resistance to PTH activity. These individuals have to her dyslipidaemia. Hypothyroidism is a
short statue, round face and shortened fourth recognised risk factor for lipid lowering therapy
metacarpals. associated myoptoxicity, therefore prior to
escalating her specific lipid lowering medications
it is important to correct her thyroid profile.
[ Q: 147 ] Thyroid - Question ID #35
diabetes is reviewed in clinic; she has a previous
history of hypothyroidism but has no other A 42 year old South Asian gentleman is referred to
medical history of note. Her current medication the diabetic clinic by his GP. He has a 5 year history
includes metformin 500mg three times a day, of type 2 diabetes. He complains of feeling tired
simvatatin 20 mg at night, ramipirl 2.5 mg once a and has a previous history of ischemic heart
day and thyroxine 100 mcg once a day. disease.
On examination her BMI is 32 kg /m2 blood On examination BMI 34 kg m2, pulse 52 bpm,
pressure 135/85 mmHg and her pulse is 62 beats blood pressure 148/78 mm/Hg. Current
per minute. medication consists of 'Novomix 30/70' mixed
insulin - 42 IU twice daily, metformin 500 mg twice

daily, simvastatin 20 mg od, aspirin 75 mg od, Free T4 10.1 pmol/l (9-22)

enalapril 20 mg od, atenalol 50 mg od.
TSH 10.2 mu/l (0.5-5)
Investigations –
Recently she has been treated for menopausal
symptoms with female HRT and has also begun
Hbalc 7.9% (<6)
taking aspirin and simvastatin.
LDL-Cholesterol 4.5 mol/l (< 3) What is the likely cause for the change in her
Triglyceride 2.9 mmol/l (0.9 - 2.2) thyroid function?
U + Es Normal
TSH 32.8 mu / l (0.3 - 5.5) 1- Aspirin
Free T4 6.9 pmol / l (9.8 - 23.6) 2- Atrophic thyroiditis
3- HRT
approach to optimise this patient’s lipid profile? 4- Non-compliance
(Please select 1 option) 5- Statin therapy
Answer & Comments
2- Commence thyroxine
3- Commence fenofibrate Answer: 3- HRT
4- Commence Omega 3 fish oil

The likely cause for the change in TFTs is the
5- Increase Simvastatin dose addition of HRT which causes a rise in thyroid
binding proteins and so would effectively reduce
the free thyroid hormone concentrations
Answer & Comments
requiring an increase in thyroxine dose.
Answer: 2- Commence thyroxine
TFTs with HRT
This patient is hypothyroid and correction of his
thyroid status will also improve both his glucose [ Q: 150 ] Question ID #71
control and lipid profile. Increasing the statin dose
or commencing a fibrate is not appropriate as A 21 year old male presents with a sudden onset
hypothyroidism is a risk factor for dyslipidaemia weakness and is unable to move for approximately
per se and is also associated with increased risk of 1 hour. He gives little other history except for
myotoxicity with lipid-lowering therapies. Omega- losing two to three pounds in weight over the last
3 fish oils are not routinely recommended for use two months. On admission to hospital, he has a
in this setting. pulse of 100 bpm, a blood pressure of 105/80
mmHg but he has made a full recovery and muscle
[ Q: 149 ] Question ID #67 strength is normal with normal reflexes and flexor
plantar responses. His investigations reveal:
A 51 year old female with a ten year history of
hypothyroidism takes thyroxine 100 micrograms FBC Normal
daily. Previous thyroid function tests performed U+Es Normal
on an annual basis were normal however a most LFTs Normal
recent thyroid function test reveals:
Calcium 2.25 mmol/l (2.2 - 2.6)
Glucose 5.5 mmol/l (3.5 - 5.5)

Which of the following would be an appropriate 4- Non-compliance

investigation for this patient?
5- Oral contraceptive
1- 24hr Urine free cortisol Answer & Comments

2- EMG Answer: 3- Iron tablets
3- Oral glucose tolerance test
The patient’s TFTs have deteriorated since her last
4- Thyroid function tests
annual TFT and she now appears hypothyroid
5- Vitamin D concentration despite assurance as to her compliance. The most
likely explanation is the addition of iron tablets
which reduce absorption of thyroxine. The patient
Answer & Comments
should be explained that the thyroxine and iron
Answer: 4- Thyroid function tests should be taken separately. Non-compliance is
unlikely and the use of the OCP co-exists with
previous normal thyroid function. Coeliac disease
This young male presents with a sudden onset of
is a less likely explanation for the iron deficiency
complete weakness with speedy recovery. The
anaemia and is not associated with reduced
diagnosis suggests hypokalaemic period paralysis
thyroxine absorption.
and one finds that the potassium is low only during
the episodes of weakness. However, a form fruste
of this is thyrotoxic periodic paralysis and the [ Q: 152 ] Question ID #76
patient should have TFTs assessed.
In a study of 950 subjects with thyroid nodules, a
[ Q: 151 ] Question ID #74 new serological marker for thyroid carcinoma was
assessed against formal histology. The following
results were obtained:
A 24 year old female presents for annual thyroid
function testing but complains of tiredness. She
has been diagnosed with hypothyroidism 3 years Test positive Test Negative
ago and has been on thyroxine 100 micrograms Histology Positive 40 10
daily. She also takes the OCP, microgynon for the
last three years and over the last six months takes Histology Negative 60 840
iron tablets due to iron deficiency anaemia. She
claims to be compliant with therapy. Her TFTs Which of the following describes the sensitivity of
have been quite stable over the last few years on the new test?
the dose of thyroxine but her most recent TFT (Please select 1 option)
reveals:
1- 40%
Free T4 8.8 pmol/l (9-22) 2- 55%
TSH 12.1 mu/l (0.5-5) 3- 66%
Which of the following is the likely explanation for 4- 80%

her change in thyroid function? 5- 95%
1- Atrophic thyroiditis Answer & Comments
2- Diverticulitis Answer: 4- 80%

3- Iron tablets

Sensitivity is a measure of how likely a test is to both TPO and TSH Receptor antibodies are
pick up the presence of a disease in a person who negative. The most appropriate way of
has it. Sensitivity is calculated by dividing the determining if there is a functional adenoma is
number of test positives, by the test positives plus through a RAI uptake scan. An ultrasound of the
the test negatives. Therefore, in this case thyroid really provides no useful information in
sensitivity = 40 ÷ (40 + 10) = 0.8, therefore the this scenario.
answer is 80%.
Reference:
http://courses.ncssm.edu/math/Stat_Inst/Stats
2007/Stat%20and%20Calc/Sensitivity%20an A 28 year old female presents with anxiety and
d%20Specificity.pdf tremor. On examination she has a pulse of 88 bpm,
a fine tremor of the outstretched hands and a
modest goitre with a faint bruit. There are no eye
[ Q: 153 ] Question ID #97 signs. Her investigations reveal:
A 33 year old female presents with a 3 month Free T4 38.9 pmol/l (9 - 22)
history of agitation. On examination, she has a fine
TSH 2.1 mu/l (0.5 - 5)
tremor of the out-stretched hands and lid lag.
There is no palpable goitre. Her investigations TSH receptor Antibody 1.1 mu/l (<2)
reveal:
An MRI of the pituitary reveals a 0.9 cm adenoma
Free T4 15.5 pmol/l (9 - 23) of the pituitary.
TSH <0.02mu/l (0.5 - 5)
Free T3 9.9 pmol/l (3 - 6) appropriate initial treatment for this patient?
TSh Receptor Antibody 1.1 u/l (<2) (Please select 1 option)
TPO antibodies 105 u/l (<140)
1- Ablative radioactive iodine
Which of the following would be the most 2- Carbimazole

appropriate investigation for this patient? 3- Pituitary surgery
4- Radiotherapy
1- Alpha-subunit concentration
5- Somatostatin analogue
2- Assessment for mutations in TR-beta gene
3- Radio-iodine uptake scan Answer & Comments
4- TRH stimulation test Answer: 2- Carbimazole
5- Ultrasound thyroid
This patient appears to have secondary
thyrotoxicosis rather than thyroid hormone
Answer & Comments
resistance as she is thyrotoxic with an abnormally
Answer: 3- Radio-iodine uptake scan 'normal' TSH. The patient would therefore require
pituitary surgery but should first be rendered
euthyroid as surgical/anaesthetic risk is higher in
This patient has overt thyrotoxicosis with
hyperthyroid cases. The most appropriate
suppressed TSH but isolated elevation of T3. This
treatment prior to pituitary surgery would be
is not thyroid hormone resistance. Whilst there is
restoration of euthyroidism and this can be
no palpable abnormality of the thyroid, the
achieved with carbimazole. Radio-iodine would
likelihood is that there is a functional adenoma, as

not be appropriate, as it is feasible that after [ Q: 156 ] Question ID #100

surgery the patient would become euthyroid.
A 32 year old female is referred by her GP as she
[ Q: 155 ] Question ID #99 had complained of a pain in the anterior aspect of
her neck for a couple of months. The GP had
A 22 year old female presents with tiredness and arranged an ultrasound of the neck which
weight gain. She has a past history of childhood revealed a 1.3 cm nodule of the left lobe of the
deafness and has been diagnosed with thyroid and he had referred the patient to the
sensorineural deafness under the care of the ENT thyroid clinic. There were no definite symptoms
surgeons. On examination, she has a pulse of 64 other than a vague complaint of discomfort in the
bpm and a modest goitre is palpable. Her GP throat which were probably anxiety related. Her
encloses the following blood results: weight had been steady and she was unaware of
any lumps but had now been told that she had a
lump in the thyroid by her GP and understandably
Free T4 7.8 pmol/l (9 - 23)
was now more anxious and aware of a sticking
TSH 30 mu/l (0.5 - 5) feeling on swallowing. There are no abnormalities
TPO antibodies 180 u/l (<140) to note on examination of the neck and the patient
appears clinically euthyroid. Investigations reveal:
What is the most appropriate investigation for this
patient? Free T4 14.5 pmol/l (9 - 22)
(Please select 1 option) TSH 2.4 mu/l (0.5 - 5)
1- Alpha subunit measurement Thyriod Antibodies negative
2- MRI pituitary What is the most appropriate course of action for

3- PDS gene mutational analysis this patient?
4- Perchlorate test
1- Arrange FNA under ultrasound guidance
5- TR-beta gene mutation analysis
2- Arrange radio-iodine uptake scan
Answer & Comments 3- Reassure and discharge
Answer: 3- PDS gene mutational analysis 4- Refer for surgery
5- Repeat ultrasound in 6 months
The suggested diagnosis here is Pendred
syndrome with a typical history of presentation in
teens to early adulthood of primary Answer & Comments
hypothyroidism and early onset sensorineural Answer: 1- Arrange FNA under ultrasound
deafness. The condition is autosomal recessive guidance
and associated with mutations of the PDS gene
(SLC26A4) found on chromosome 7. SLC26A4 is a
Iodide/Chloride cotransporter and defects in this This patient has a clinically inapparent thyroid
lead to reduced organification of iodine and hence nodule detected via ultrasound. The symptoms do
reduced uptake. The perchlorate test is seldom not really tally with this lesion which would be
used in clinical practice being replaced by clinically silent. However, one needs to establish if
mutational analysis. this lesion is benign or malignant and the first step
should be a FNA of the lesion under ultrasound
guidance as one cannot clinically feel the lesion.

Reference: excess – there is no need to measure free T3 and

Management guidelines for patients with the dose of thyroxine should be left unchanged.
thyroid nodules and differentiated thyroid
cancer [ Q: 158 ] Question ID #104
[ Q: 157 ] Question ID #103 A 22 year old male is referred by his GP with

tiredness. Since the age of 5 with a he was treated
A 22 year old male is referred to the endocrine for hypothyroidism and has had poor growth. He
clinic by the GP. He has a history of is currently receiving 100 micrograms of thryoxine
craniopharyngioma for which he takes full daily. He is of short stature but has normal
hormone replacement therapy including pubertal development. His investigations reveal:
thyroxine 150 micrograms daily, hydrocortisone
10 mg bd and testosterone gel 60 mg daily. He is Free T4 14.6 pmol/l (9 - 22)
well, but his GP refers him to you as he is
TSH 0.5 mu/l (0.5 - 5)
concerned by the attached thyroid function tests:
Free T4 15.5 pmol/l (9 - 22) LH 2.8 mu/l (2 - 10)
TSH <0.02 (0.5 - 4.5) FSH 3.2 mu/l (2 - 10)
IGF-1 5.2 nmol/l (28 - 50)
There are no abnormalities to find on clinical
examination of this patient.
Cortisol post-synacthen 850 nmol/l (>550)
action for this patient? CT of the head reports no abnormality of the
pituitary.
1- Leave dose of thyroxine unchanged What is the most appropriate investigation for this
2- Reduce dose of thyroxine to 100 patient?
micrograms/d (Please select 1 option)
3- Reduce dose of thyroxine to 125 1- Request KAL-1 mutational analysis

micrograms/d 2- Request MENIN mutational analysis
4- Request free T3 concentration 3- Request MRI of the pituitary and olfactory
5- Request TSH receptor antibodies bulbs
4- Request Pit-1 mutational analysis
Answer & Comments
5- Request SOX-1 mutational analysis
Answer: 1- Leave dose of thyroxine unchanged
Answer & Comments
This is a frequent GP request. The important thing
Answer: 4- Request Pit-1 mutational analysis
to recognise is that the patient is hypopituitary
and so one cannot rely on TSH measurement.
Therefore, the dose of thyroxine should be It is rather unusual for a young child to have
sufficient to aim for a thyroid hormone developed primary hypothyroidism and what is
concentration in the mid to upper half of the more this adult is now short with a low IGF-1
normal range. This patient is stated to be well suggesting GH deficiency and a low prolactin
without any reported features of thyroid hormone suggesting hypoprolactinaemia. This would
suggest a combined partial hypopituitarism – TSH,

PRL and GH typical of a mutation of the The most appropriate first line treatment for this
transcriptional activator - pit-1. Prop-1 mutations patient who has recurrent thyrotoxicosis following
(Prophet of Pit-1) are the most common defects in anti-thyroid treatment would be radioactive
combined childhood pituitary hormone defiencies iodine. She should ensure that she does not
and are characterised by LH/FSH deficiency become pregnant for six months after treatment
together with GH, TSH and Prolactin. Later, ACTH but she is already taking the OCP. There is no
deficiency may ensue. Imaging may reveal a small report of eye disease associated with the Graves’
or indeed normal appearance of the pituitary and so concomitant steroids is probably unnecessary.
does tell us nothing of the functionality. Following radioiodine treatment, approximately
80% of patients become hypothyroid.
A 24 year old female has received a six month
course of carbimazole for Graves disease. She is a A 28 year old female who is one month post-
non-smoker, with no family history of thyroid partum develops tiredness. Thyroid function tests
dysfunction. She recently stopped treatment and reveal:
attends two months later for subsequent review
and complains of recurrence of her previous Free T4 25.6 pmol/l (9 - 22)
symptoms. On examination, she has a modest
TSH <0.02 mu/l (0.5 - 5)
goitre with pulse of 80 bpm and has a fine tremor
of the outstretched hands. There are no eye signs TPO antibodies 550 iu/l (<140)
associated with Graves disease. The results of her
thyroid function tests reveal: When she is seen 2 months later she is still tired
and emotionally labile. The results of TFTs reveal:
Free T4 32.3 pmol/l (9 - 22)
TSH <0.02 mu/l (0.5 - 5) Free T4 8.5 pmol/l (9 - 22)
TSH 12 mu/l (0.5 - 5)
She informs you that she is keen on getting
pregnant after about 6 months time (as she is due She is treated with thyroxine 50 micrograms daily
to get married in the summer). She is currently and her thyroid function tests improve. She is
taking the oral contraceptive, microgynon. reviewed regularly and you see her one year later
where she is well and has with the following
Which of the following would be the most thyroid function tests:
appropriate action for this patient?
(Please select 1 option) Free T4 21.5 pmol/l (9 - 22)
1- Continue with further six months TSH 0.3 mu/l (0.5 - 5)
propylthiouracil
2- Continue with long term propylthiouracil action for this patient?
3- Continue to treat with long term carbimazole (Please select 1 option)
4- Radioactive iodine 1- Continue thyroxine in current dose

5- Refer for thyroid surgery 2- Increase dose of thyroxine by 25 micrograms
3- Reduce dose of thyroxine in 25 microgram
Answer & Comments increments
Answer: 4- Radioactive iodine 4- Stop thyroxine and arrange radio-iodine
uptake scan

5- Stop thyroxine and reassess thyroid function This patient appears to have developed episodic
and profound muscle weakness. The potassium is
normal on admission but the patient has
Answer & Comments
recovered fully. The history is compatible with
Answer: 5- Stop thyroxine and reassess thyroid hypokalaemic periodic paralysis yet the
function tachycardia and recent weight loss is quite
compatible with thyrotoxicosis. Therefore, a
diagnosis of thyrotoxic periodic paralysis should
This patient is likely to have post-partum
be considered. During attacks, hypokalaemia
thyroiditis as suggested by the initial
typically occurs and the condition is best treated
hyperthyroidism with subsequent hypothyroidism
with restoration of euthyroidism.
occurring post-partum. Approximately 30% have
persistent hypothyroidism but the majority
recover. There is a strong chance of further thyroid [ Q: 162 ] Question ID #126
dysfunction in subsequent pregnancies. The most
appropriate approach therefore, is to stop A 35 year old female presented with a three
thyroxine and reassess thyroid function in month history of 3kg weight loss and anxiety. On
approximately one month. examination, she had mild tremors of the
outstretched hands, proptosis and lid lag.
[ Q: 161 ] Question ID #113 Examination of the neck reveals an asymmetrically
enlarged goitre with a 3.5cm irregular nodule
palpable in the left lobe. Investigations reveal:
A 21 year old male is admitted with a one hour
history of profound muscle weakness such that he
was immobile and unable to move his arms or legs. Free T4 24 pmol/l (9-23)
He was otherwise well, had noted some weight TSH <0.22 mu/l (0.5-5)
loss of late but denied use of illicit substances. He TPO antibodies >1500 mu/l (<150)
had one similar episode two months ago from
which he recovered fully. TSH-R antibodies 3.3 iu/l (<1)
Calcium 2.65 mmol/l (2.2 -2.6)
2
On admission, his BMI was 21 kg/m , his pulse was U+Es Normal
102bpm, blood pressure was 112/80 mmHg and
he had full muscle strength. Investigations reveal:
The patient was initiated on carbimazole therapy.
U+Es Normal Which of the following is the most appropriate

next investigation for this patient?
appropriate next investigation for this patient?
(Please select 1 option) 1- Thyroid ultrasound
1- Muscle biopsy 2- Fine needle aspiration
2- Oral glucose tolerance test 3- PTH concentration
3- Thyroid function tests 4- RET proto-onogene
4- Urine catecholamines 5- Radio-iodine uptake scan
5- Urine free cortisol measurement

Answer & Comments
Answer & Comments Answer: 2- Fine needle aspiration
Answer: 3- Thyroid function tests

This woman has Graves’ disease and also has a left This patient has mild hypercalcaemia, an
sided discrete nodule. In any nodule one should inappropriately normal PTH concentration and has
consider the possibility of a carcinoma and the a normal/highish urine calcium excretion. The
most appropriate initial investigation would be a latter would argue against a diagnosis of FHH
FNA which would be diagnostic. This is not likely to where urine calcium excretion is low (less than 5
be a toxic adenoma as the patient has positive TSH mmol/d) and so the likely diagnosis is primary
receptor antibodies indicating Graves’ disease. hyperparathyroidism.
Therefore, radioiodine uptake scan would merely
reveal increased uptake and the nodule may be
cold or hot – this procedure would not be
diagnostic. Ultrasound would add little diagnostic
information. The slight elevation of calcium is not A 32 year old female presents with a six month
unusual in thyrotoxicosis. history of weight loss and anxiety. She does not
report any visual symptoms and her visual acuity
is normal. She is diagnosed with Graves’ disease
[ Q: 163 ] Question ID #127 based on confirmatory thyroid function tests and
a positive TSH receptor antibody. She is treated
A 45 year old woman is referred by her GP for with carbimazole and thyroxine in a block and
investigation of her hypercalcaemia. He noted the replacement regime for approximately six
following investigations: months. Treatment is then stopped. She re-
attends clinic three months after stopping
U+Es Normal treatment and complains of once again feeling
rather anxious and having poor sleep. She is a non-
Calcium 2.8 mmol/l (2.2 - 2.6)
smoker and drinks little alcohol.
Phosphate 1.0 mmol/l (0.8 - 1.4)
On examination, she has a fine tremor of the
The patient originally attended the GP with vague outstretched hands, lid lag and a goitre. Her
aches and pains which have been present for two thyroid function tests reveal:
months or so and she also admits to feeling rather
depressed. She is only taking Fluoxetine 20 mg Free T4 38.2 pmol/l (9 - 23)
daily at present. There is nil of note on
TSH <0.05 mu/l (0.5 - 5)
examination. Further investigations reveal:
She elects to have radio-iodine treatment.

PTH 4.4 pmol/l (3 - 5)
Vitamin D 10.2 micromol/l (8 - 50) Which of the following concerning treatment with
Urine calcium 7 mmol/d (0 - 7.5) steroids would you elect?
1- Commence treatment with prednisolone
20mg daily on day of radio-iodine
1- Drug-induced
2- Commence treatment with prednisolone
2- Familial hypocalciuric hypercalcaemia 40mg daily on day of radio-iodine
3- Milk-Alkali syndrome 3- Commence treatment with prednisolone
4- Primary hyperparathyroidism 40mg daily, 1 week following radioiodine
5- Tertiary hyperparathyroidism 4- Commence treatment with prednisolone

40mg daily, 1 week before radio-iodine
Answer & Comments 5- No requirement to pre-treat with steroids
Answer: 4- Primary hyperparathyroidism


Answer: 5- No requirement to pre-treat with
steroids A 35 year old female with Graves’ disease is
treated carbimazole and relapses after treatment
is withdrawn. Consequently, she elects to receive
In this patient, there does not appear to be any radio-iodine but after this treatment develops
reported evidence of Graves’ Ophthalmopathy, in some grittiness and irritation of the eyes.
which case there is no need to pre-treat with
steroids. If this patient had evidence of GO, then Which of the following in this case may have
there is a 15% risk of deterioration of GO following contributed to the development of Graves’
RAI. This risk may be minimised by pre-treatment
Ophthalmopathy?
with prednisolone (0.5 mg/kg/d) continuing for 1
month then tapering down over the following (Please select 1 option)
month. 1- Consumption of approximately 22 units of
alcohol weekly
2- Myopia
A 42 year old female is seen due to anxiety and 3- Previous treatment with thionamides
weight loss. She is found to have Graves disease 4- Smoker of 10 cigarettes per day
with positive TSH receptor antibodies. The
physician elects to treat her with a block and 5- Use of the oral contraceptive
replacement regime consisting of carbimazole and
thyroxine for six months. He explains at that stage Answer & Comments
treatment will be withdrawn and thyroid function
tests monitored for relapse. The patient enquires Answer: 4- Smoker of 10 cigarettes per day
as to what are the chances of relapse after this
treatment. Factors recognised to contribute to the
development/deterioration of Graves’
Which of the following most accurately reflects the Ophthalmopathy include smoking, rise in TSH and
relapse rate after treatment with antithyroid undertreatment of hypothyroidism together with
drugs? high TSH receptor antibodies.
1- 10% [ Q: 167 ] Question ID #158
2- 20%
A 45 year old female is referred by her GP with
3- 30% deranged thyroid function tests. She has been
complaining of occasional palpitations hence her
4- 50% GP checked investigations and found the
5- 70% following:
Answer & Comments Free T4 16.5 pmol/l

TSH <0.05 mu/l (0.5-5)
Answer: 4- 50%
TPO Antibodies 100 iu/l (<300)
This is a relatively standard approach to the TSH Receptor Antibody 0.2 iu/l (<1.5)
treatment of Graves' disease - give a block and
replace regime for between 6-12 months. Studies There is nothing of note on examination with no
suggest that this approach is associated with an palpable thyroid goitre.
approximate 50% long term remission rate.

Which of the following would be the most Which of the following is the likely diagnosis?
appropriate investigation for this patient? (Please select 1 option)
1- Hashimoto's encephalopathy
1- Request alternative TFT assay at another
2- Lymphocyctic hypophysitis
centre
3- Limbic encephalomyeltis
2- Thyroid FNA
4- MELAS
3- Thyroid microsomal antibodies
5- POEMS
4- Thyroid ultrasound
5- Thyroid uptake scan Answer & Comments
Answer: 1- Hashimoto's encephalopathy
Answer & Comments
Answer: 5- Thyroid uptake scan This patient has a short history of confusion yet
the neurological investigations are normal. The
This patient has subclinical hyperthyroidism and likely diagnosis is therefore Hashimoto's
this is most likely due to a toxic impalpable encephalopathy - considered to be part of an
adenoma. The most appropriate investigation autoimmune encephalitis. The condition was
would be a thyroid uptake scan which may be described in the 1960s by a Prof Brain! The
expected to reveal the toxic adenoma. Then, condition can be progressive or relapsing
treatment with radio-iodine would be remitting and the treatment is steroids. Often, the
appropriate. condition presents prior to the development of
hypothyroidism and patients can be entirely
euthyroid yet with quite profound neurological
[ Q: 168 ] Question ID #301 dysfunction.
A 55 year old female presents with a three week

history of confusion. She has otherwise been well.
Three years ago she was diagnosed with
hypothyroidism for which she takes thyroxine 100 A 70 year old male presents with a two month
micrograms per day. On examination, she appears history of tiredness and lethargy. Six months ago
euthyroid but is confused, with inappropriate he was treated for paroxysmal atrial fibrillation
answers to questions and strange affect. CVS, with amiodarone 200 mg daily.
respiratory and abdominal examination are all
normal with a blood pressure of 126/78 mmHg. On examination, he appeared to be euthyroid with
no goitre palpable.
Investigations including CSF examination, Head CT
and MRI together with U+Es, Calcium and LFTs are Investigations revealed:
all normal.
Serum free T4 26.2 pmol/L (9-23)
Free T4 15.6 nmol/l (9-22) Serum total T3 0.8 nmol/L (3-5.5)
TSH 5.6 mu/l (0.5-5) Serum TSH 9 mU/L (0.5-5)
TPO antibodies >1500 mu/l (<150)
Random cortisol 330 nmol/ (200-800) Which of the following is the likely diagnosis?
LH 33 mu/l (>10)
FSH 55 iu/l (>10) 1- Amiodarone-induced hypothyroidism
2- Amiodarone induced thyrotoxicosis

3- Hashimoto's hypothyroidism In which of the following would this result be

expected?
4- Sick euthyroid syndrome
5- TSH secreting pituitary adenoma
1- DeQuervain
Answer & Comments 2- Graves
Answer: 1- Amiodarone-induced hypothyroidism 3- Multi-nodular toxic goitre

4- Thyroid nodule with papillary thyroid cancer
The results show increased T4, low T3 but elevated
5- Type 1 amiodarone induced thyrotoxicosis
TSH, indicating hypothyroidism. This suggests
type 1
amiodarone induced hypothyroidism which
inhibits the peripheral conversion of T4 to T3.
Answer & Comments
Thyroid and Amiodarone
Answer: 1- DeQuervain

DeQuervain's thyroiditis is typically associated
with a generalised low or absent 123I tracer
A 32 year old male is diagnosed with Pendred's uptake. The others will have high or normal
syndrome. uptake. In particular type 1 amiodarone induced
thyrotoxicosis may be distinguished from the
Which of the following is typically found in thyroiditis of type 2 by the normal or high uptake
Pendred's syndrome scan.
1- Cataract [ Q: 172 ] Question ID #359

2- Mental retardation
A 56-year-old woman presents with
3- Optic atrophy thyrotoxicosis. Examination reveals an enlarged
thyroid with multiple nodules, confirmed on
4- Sensorineural deafness
ultrasound scanning. Treatment with radioactive
5- Thyroid agenesis iodine is planned.
Which of the following is the recommended dose

Answer & Comments
of radioiodine suggested for this patient?
Answer: 4- Sensorineural deafness (Please select 1 option)
1- 50-100 MBq
Pendred syndrome is an autosomal recessively
inherited condition characterised by deafness, 2- 200-400 MBq
goitre, hypothyroidism and is due to defective
3- 500-800 MBq
iodine binding.
4- 900-1100 MBq
[ Q: 171 ] Question ID #348 5- 1200-1500 MBq
A 32 year old female undergoes a radio-iodine Answer & Comments

uptake scan and this is reported to show
'generalised reduced uptake of 123I tracer Answer: 3- 500-800 MBq
throughout the thyroid'.

The recommended dose of RAI is typically Into which of the following classifications does this
between 500 - 800 MBq with the frequent dose fit?
being 555 MBq. (Please select 1 option)
1- Thy 1
2- Thy 2
A 68 year old female presents with recurrent 3- Thy 3
Graves' disease after having received one course
of block and replacement therapy with 4- Thy 4
carbimazole and thyroxine. After discussion, she 5- Thy 5
elects to receive radioiodine treatment. Prior to
receiving treatment she is rendered euthyorid
again with carbimazole. Answer & Comments
Answer: 1- Thy 1
At least how many days prior to her radioactive
iodine should she stop her carbimazole?
The classification of thyroid biopsy samples is
based upon five criteria:
1- 7 days
Insufficient sample or unable to report
2- 14 days Thy 1:
due to heavy blood staining.
3- 21 days Non-neoplastic; normal thryoid,
Thy 2:
4- 28 days thryoiditis, colloid
5- No requirement to stop carbimazole Neoplasm possible; samples

Thy 3:
suggesting follicular neoplasm
Thy4: Suspicious of malignancy
Answer & Comments
Malignancy - confidence in diagnosing
Answer: 1- 7 days Thy5: a malignancy with malignant cells
seen
Carbimazole needs to be stopped at least 7 days
prior to radioiodine to ensure appropriate uptake. [ Q: 175 ] Question ID #363
The treatment is often used in patients who need
to be rendered euthyroid prior to RAI due to the
risk of early deterioration of thryotoxicosis. A 28 year old female undergoes an FNA of an
isolated 2 cm thyroid nodule, this is reported as:
'Non-neoplastic suggestive of thyroiditis)'.
Which of the following is the correct classification
A 35 year old female is referred with a left lower of this report?
thyroid nodule that she inadvertently noticed (Please select 1 option)
whilst putting on a necklace. Examination reveals
a 2 cm firm, mobile, non-tender nodule without 1- Thy 1
any lymphadenopathy.
2- Thy 2
A FNA was performed in clinic and was reported 3- Thy 3
as:
4- Thy 4
 'Insufficient sample. Non diagnostic or 5- Thy 5
inadequate'.

Answer & Comments Non-neoplastic; normal thryoid,

Thy 2:
thryoiditis, colloid.
Answer: 2- Thy 2
Neoplasm possible; samples
Thy 3:
suggesting follicular neoplasm.
based upon five criteria: Thy4: Suspicious of malignancy.
Insufficient sample or unable to report Thy5: a malignancy with malignant cells
Thy 1: seen.
Non-neoplastic; normal thryoid,
Thy 2: In this case, the cytology reports a follicular
thryoiditis, colloid
neoplasm - suspicious THY3.
Thy 3:
A 28 year old female undergoes an FNA of an
Thy5: a malignancy with malignant cells
isolated 2cm thyroid nodule, This is reported as:
seen
'Abnormal cells, suspicious of malignancy'.
In this case, the cytology reports a thyroiditis - Which of the following is the correct classification
benign THY2.
of this report?
1- Thy 1
A 28 year old female undergoes an FNA of an 2- Thy 2
isolated 2cm thyroid nodule This is reported as:
3- Thy 3
'...a follicular neoplasm'.
4- Thy 4
Which of the following is the correct classification
5- Thy 5
of this report?
Answer & Comments
1- Thy 1
Answer: 4- Thy 4
2- Thy 2
3- Thy 3 The classification of thyroid biopsy samples is
4- Thy 4 based upon five criteria
5- Thy 5 Thy 1: insufficient sample or unable to report due

to heavy blood staining.
Answer & Comments
Thy 2: Non-neoplastic; normal thryoid, thryoiditis,
Answer: 3- Thy 3 colloid
The classification of thyroid biopsy samples is Thy 3: Neoplasm possible; samples suggesting
based upon five criteria: follicular neoplasm

Thy 1:

Thy5: Malignancy - confidence in diagnosing a [ Q: 179 ] Question ID #367

malignancy with malignant cells seen
In this case the suspicion of malignancy on the isolated 2cm thyroid nodule, this is reported as
report indicates THY4 THY5.
[ Q: 178 ] Question ID #366 Which of the following is the correct classification

of this report?
A 28 year old female undergoes an FNA of an (Please select 1 option)
isolated 2cm thyroid nodule, This is reported as:
1- Abnormal, suspicious (but not diagnostic of)
'...diagnostic of malignancy'.
malignancy
Which of the following is the correct classification 2- Diagnostic of malignancy
of this report?
3- Follicular lesions
4- Non diagnostic or inadequate
1- Thy 1
5- Non-neoplastic (consistent with nodular
2- Thy 2
goitre or thyroiditis)
3- Thy 3
4- Thy 4 Answer & Comments
5- Thy 5 Answer: 2- diagnostic of malignancy
Answer & Comments The classification of thyroid biopsy samples is

based upon five criteria
Answer: 5- Thy 5
Thy 1:
The classification of thyroid biopsy samples is due to heavy blood staining.
based upon five criteria: Non-neoplastic; normal thryoid,
Thy 2:
thryoiditis, colloid.
Thy 1: Neoplasm possible; samples
due to heavy blood staining. Thy 3:
Thy 2: Thy4: Suspicious of malignancy.
thryoiditis, colloid
Thy 3: Thy5: a malignancy with malignant cells
seen.
seen
isolated 2cm thyroid nodule, this is reported as
In this case the sample is diagnostic of malignancy
THY4.
indicating THY5
of THY4?

1- Abnormal, suspicious (but not diagnostic of) 4- Non diagnostic or inadequate

malignancy
2- Diagnostic of malignancy goitre or thyroiditis)
Answer & Comments
4- Non diagnostic or inadequate
Answer: 3- follicular lesions
goitre or thyroiditis)
based upon five criteria
Answer & Comments
Answer: 1- abnormal, suspicious (but not Insufficient sample or unable to report
Thy 1:
diagnostic of) malignancy due to heavy blood staining.
Thy 2:
The classification of thyroid biopsy samples is thryoiditis, colloid.
based upon five criteria Neoplasm possible; samples
Thy 3:
Insufficient sample or unable to report Thy4: Suspicious of malignancy.
Thy 1:
Non-neoplastic; normal thryoid, Thy5: a malignancy with malignant cells
Thy 2:
thryoiditis, colloid. seen.
Thy 3:
suggesting follicular neoplasm. In this case follicular neoplasm indicates THY3
Thy4: Suspicious of malignancy.
Malignancy - confidence in diagnosing [ Q: 182 ] Question ID #469
seen. A 76 year old lady presents with an enlarged
thyroid gland with retrosternal extension. She is
In this case the suspicion of malignancy on the otherwise well in herself and clinically and
report indicates THY4 biochemically euthyroid.
What is the next best investigation for further

management of this lady?
isolated 2cm thyroid nodule This is reported as 1- Endoscopy (upper GI)
THY3.
2- Flow volume loop
Which of the following is the correct interpretation 3- FNAC
of this report?
4- Radioiodine uptake
5- US neck
1- Abnormal, suspicious (but not diagnostic of)
malignancy
Answer & Comments
2- Diagnostic of malignancy
Answer: 2- Flow volume loop

The thyroid gland is normally located beneath the What is the most appropriate step in her
cricoid cartilage midway between the apex of management?
thyroid cartilage and the supra-sternal notch. It (Please select 1 option)
normally weighs about 10-20 g. The growth of
thyroid gland usually occurs in a downward and 1- FNAC
posterior direction as the anterior/upward growth
2- Observation
of the gland is limited by attachment of sterno-
thyroid muscle to the thyroid cartilage. As a result 3- Radioiodine ablation
an enlarging thyroid gland can expand and grow in
4- Thyroidectomy
retrosternal space compressing the surrounding
structures like trachea and oesophagus. 5- Thyroxine (low dose)
An inspiratory stridor is an indicator of

Answer & Comments
compression of trachea and should be
investigated by flow loop volume as it provides Answer: 4- Thyroidectomy
physiological evidence of obstruction. An
ultrasound of thyroid gland is a useful modality for
Thyroid gland is normally located beneath the
detection of thyroid nodules and can help
cricoid cartilage midway between the apex of
differentiate cystic from solid nodules but it is not
thyroid cartilage and the supra-sternal notch. It
a sensitive investigation to detect retrosternal
normally weighs about 10-20 g. The growth of
gland extension and not employed routinely for
thyroid gland usually occurs in a downward and
evaluation of patients with goitre. CT imaging is
posterior direction as the anterior/upward growth
also helpful to evaluate the retrosternal growth of
of the gland is limited by attachment of sterno-
thyroid gland and usually employed pre-
thyroid muscle to the thyroid cartilage.
operatively. The following are some of the keys
points regarding surgical management of goitre:
As a result an enlarging thyroid gland can expand
and grow in retrosternal space compressing the
 Patients with physiological evidence of
surrounding structures like trachea and
airway obstruction (on flow volume loop)
oesophagus. An inspiratory stridor is an indicator
should have thyroidectomy (if they are fit
of compression of trachea and should be
for operation).
investigated by flow loop volume as it provides
 Any hint of malignancy is an indication for
physiological evidence of obstruction. An
surgical resection of the gland
ultrasound of thyroid gland is a useful modality for
 Elderly patient with a stable retrosternal
detection of thyroid nodules and can help
goitre (with no significant symptoms and
differentiate cystic from solid nodules but it is not
signs of tracheal/oesophageal
a sensitive investigation to detect retrosternal
compression), should be managed
gland extension and not employed routinely for
conservatively. Follow up for such patient s
evaluation of patients with goitre. CT imaging is
should include serial flow volume loops to
also helpful to evaluate the retrosternal growth of
assess for any airway compromise or serial
thyroid gland and usually employed pre-
CT thyroid/thorax to assess for any change
operatively. The following are some of the keys
in size of the gland.
points regarding surgical management of goitre:
[ Q: 183 ] Question ID #470  Patients with physiological evidence of

airway obstruction (on flow volume loop)
A 76 year old lady presents with enlarged thyroid should have thyroidectomy (if they are fit
gland with retrosternal extension. It is leading to for operation).
inspiratory stridor. She is otherwise well in herself  Any hint of malignancy is an indication for
and is clinically/biochemically euthyroid. surgical resection of the gland
 Elderly patient with a stable retrosternal
goitre (with no significant symptoms and

signs of tracheal/oesophageal metanephrines and measurement of serum

compression), should be managed calcium respectively.
conservatively. Follow up for such patient s  Patients with MTC should undergo total
should include serial flow volume loops to thyroidectomy and level 6 lymph node
assess for any airway compromise or serial dissection
CT thyroid/thorax to assess for any change  Prophylactic surgery should be offered in
in size of the gland. disease free carriers of germ line RET
mutation. Surgery should be performed
before age of 5 years for MEN 2A patients
and by the age of 1 year in MEN 2B patients.
 Patients should be monitored lifelong with
A 17 year old with background history of monitoring of Calcitonin levels.
medullary thyroid carcinoma (MTC) which was
previously treated with surgical resection,
presents with a solitary cervical lymph node which [ Q: 185 ] Question ID #472
on FNAC shows features of metastasis from MTC.
A 44 year old with previous history of papillary
What is the most appropriate step in her thyroid cancer (3 cm nodule), treated with total
management? thyroidectomy and central lymph node dissection,
presents for a regular annual review. Post
operatively she had received radioiodine ablation
1- External beam radiotherapy and has been asymptomatic leading up to the
clinic visit. The blood tests done during the review
2- Octreotide
reveal elevated Thyroglobulin (Tg) levels which
3- Radical neck dissection were previously normal and suppressed TSH <
0.01 (on thyroxine). Her Thyroglobulin antibodies
4- Radioiodine ablation
are negative and an ultrasound of the neck plus
5- Suppressive dose of thyroxine whole body scan are negative.
What is most appropriate next step in her

Answer & Comments
management?
Answer: 3- Radical neck dissection (Please select 1 option)
1- Decrease thyroxine dose

The following points sum up the guidelines from
British Thyroid Association regarding 2- PET scan
management of Medullary Thyroid Cancer (MTC):
3- Radio-iodine ablation
 The initial evaluation of suspected MTC 4- Repeat Thyroglobulin levels in 3 months
patients should include FNAC and plasma
5- Surgical exploration
Calcitonin measurement.
 All patients (and affected families) should
be offered clinical genetics service and RET Answer & Comments
gene testing.
Answer: 2- PET scan
 RET mutation testing should include
screening of exons 10, 11, 13, 14, 15 and 16.
 Patients with MTC should be screened for Thyroglobulin (Tg) is a useful tumour marker,
MEN 2A and 2B secreted by normal as well as cancerous thyroid
 Screen for phaeochromocytomas and cells. After complete thyroidectomy and post
primary hyperparathyroidism by measuring operative radio-ablative therapy of a
24 hour urinary catecholamine/ differentiated thyroid cancer (papillary or
follicular), the Tg levels are usually undetectable.

A detectable Tg level in such a scenario is What is the most appropriate modality which can
indicative of the presence of thyroid remnants or be used for his definitive management?
recurrence of the tumour. (Please select 1 option)
Presence of endogenous Tg antibodies may also 1- Carbimazole

interfere with the assay so should be excluded by 2- Observe
its simultaneous measurement. In patients with
rising or detectable Tg levels the following points 3- Propylthiouracil
should be kept in mind:
 Check Tg heterophile antibody levels to rule 5- Total thyroidectomy
out interference in assay
 Check if the TSH is completely suppressed Answer & Comments
 Did the patient undergo complete surgical
resection Answer: 4- Radioiodine ablation
 Rule out any possible iodine contamination
(e.g. amiodarone therapy or recent contrast
The patient has underlying toxic multinodular
injection) in cases where Tg is detectable
goitre which should be initially rendered euthyroid
and uptake scan negative
by using thionamides therapy (Carbimazole or
 Arrange a neck ultrasound to look for any
Propylthiouracil). These are usually effective in
thyroid remnant or lymph node
controlling the hyperthyroid state but not
enlargement
curative. The treatment of choice in such patients
 If neck ultrasound negative arrange for CT
remains radio-iodine ablative therapy. Surgical
thorax
removal of the gland can be offered but would be
 If both the above mentioned investigations
regarded as second line to radio-iodine in this
are negative arrange for a 99mTc MIBI to rule
scenario.
out bony deposits
 If all above mentioned investigations are
negative consider a PET scan, if that too is [ Q: 187 ] Question ID #477
negative consider therapeutic 131I ablation
A 64 year old lady with known Hashmoto's
http://www.british-thyroid- thyroiditis presents with features of tiredness,
association.org/news/Docs/Thyroid_cancer_ cold intolerance and constipation. Apart from
guidelines_2007.pdf being on thyroxine 250 µg/ day, she is on Ferrous
Fumarate tablets and takes alendronate 70 mg/
[ Q: 186 ] Question ID #474 week.
On examination she has a pulse of 56/minute, cold

A 75 year old presents with history of weight loss,
extremities and delayed knee reflexes. Her
palpitations and heat intolerance of 8 weeks
biochemistry results are as shown below:
duration. Examination reveals a resting tremor
and atrial fibrillation with a ventricular rate of
110/minute. He is haemodynamically stable and Sodium 136 mmol/L (135-145)
has a goitre on palpation of the neck. An Potassium 4.1 mmol/L (3.5-5.5)
ultrasound neck confirms the presence of multiple Urea 6.2 mmol/L (3-8)
nodules in the thyroid gland with the largest of the
nodules measuring 0.6 cm in size. His TFTs show Creatinine 84 µmol/L (60-115)
suppressed TSH of < 0.01 and free T4 which is (11.5-
FreeT4 8.4 pmol/L
mildly elevated. 22.7)
TSH 18.1 mU/L (0.35-5.5)
Anti TPO antibody Positive

Haemoglobin 12.8 g/dL (12-16) although have been irregular for 6 months. On
examination she has BMI of 21 and general
Ferritin 302 pmol/L (30-330)
physical as well as systemic examination is
unremarkable. Her blood show:
What is the most appropriate course of action in
her management for her overall improvement?
Haemoglobin 9.4 g/dL (12-16)
139 (135-145
1- Increase the thyroxine dose to 275 µg/ day Sodium
mmol/L mmol/L)
2- Repeat the TFTs in 6 weeks 4.4 (3.5-5.5

Potassium
mmol/L mmol/L)
3- Start her on Vitamin C tablets
5.3
4- Stop the alendronate tablets Urea (3-8 mg/dL)
mmol/L
5- Stop the iron tablets Creatinine 66 µmol/L (60-115 µmol/L)
7.8 (11.5-22.7
FT4
Answer & Comments pmol/L pmol/L)
TSH 14.4 mU/L (0.35-5.5 mU/L)
Answer: 5- Stop the iron tablets
Anti TPO
Positive
antibody
The following is a list of the major causes leading
to persistently elevated TSH levels despite Corrected 2.04 (2.2-2.6
adequate thyroxine therapy: Calcium mmol/L mmol/L)
 Compliance What is the most appropriate next step in her

 Drugs such as omeprazole, ferrous management?
sulphate, calcium carbonate (Please select 1 option)
 Malabsorption syndromes like coeliac
disease 1- Anti TTG antibodies
 Nephrotic syndrome 2- Assess urinary protein loss
Compliance with the medications is the 3- Check compliance

commonest cause for persistently elevated TSH 4- Upper GI endoscopy
levels despite adequate thyroxine replacement. In
this lady normal Ferritin and Hb levels indicate a 5- 21 alpha hydroxylase
trial without Ferrous Fumarate tablets which may
help prevent any interference with thyroxine Answer & Comments
absorption. Alternatively, thyroxine and iron
tablets should be taken separately. Answer: 1- Anti TTG antibodies
[ Q: 188 ] Question ID #478 The following is a list of the major causes leading
to persistently elevated TSH levels despite
adequate thyroxine therapy:
A 24 year old with Type I DM and autoimmune
thyroiditis, presents to the endocrine clinic with
 Compliance
history of 6 Kg of weight loss over last 4-6 months.
 Drugs such as omeprazole, ferrous
She denies going on any diet or indulging in
excessive exercise. She denies any issues sulphate, calcium carbonate
 Malabsorption syndromes like coeliac
regarding compliance with insulin injections and/
or thyroxine tablets. Her appetite is normal and disease
 Nephrotic syndrome
denies any nausea and vomiting. Her bowel habits

In her case history of weight loss, alteration in  Hashimoto's thyroiditis (increased risk of
bowel habit, low Hb and low corrected calcium lymphoma)
should raise the suspicion of associated coeliac  Family or personal history of thyroid
disease. adenoma
 Cowden`s syndrome
 Familial adenomatous polyposis
 Familial thyroid cancer
Which of the following is suggestive of the
A thyroid nodule is more likely to be malignant if:
suspicious nature of the histology/radiology of a
thyroid nodule?  The affected individual is a child or an
(Please select 1 option) elderly male
 It is a firm, solitary, non toxic nodule
1- Epithelial cells
 Associated hoarseness of voice and/or
2- Haemorrhage palpable cervical lymph node
 In presence of micro-calcification on FNAC
3- Lymphocytes
4- Macrophages [ Q: 190 ] Question ID #481
5- Micro-calcification
A 32 year old lady with known papillary carcinoma
Answer & Comments of thyroid (which was treated with total
thyroidectomy and post operative radio-iodine
Answer: 5- Micro-calcification ablation 3 years ago), presents to the GP for a
routine check up. Presently she is on Thyroxine 75
Ultra-sound features suggestive of thyroid µg/day and otherwise well in herself. Her
malignancy: examination is normal with evidence of a healed
thyroid scar and no palpable cervical lymph nodes.
Her biochemical results are as shown below:
>1cm sized nodule which is taller than it is wide
Microcalcification Sodium 136 mmol/L (135-145)

Local invasion and lymph node metastases Potassium 4.1 mmol/L (3.5-5.5)
Urea 8 mmol/L (3-8)
Ill-defined and irregular margin and contour
Creatinine 92 µmol/L (60-115)
Intrinsic hypervascularity
(11.5-
FT4 14.8 pmol/L
Solid and hypoechoic 22.7)
TSH 2.2 mU/L (0.35-5.5)
Absence of a completely uniform halo around
the nodule Anti TPO antibody Negative
2.26
Corrected Calcium (2.2-2.6)
US features suggestive of thyroid malignancy mmol/L
According to the guidelines issued by British What is the most appropriate next step in her
thyroid Association on management of thyroid management?
cancer, the following are considered to be risk (Please select 1 option)
factors for thyroid cancer:
1- Arrange Ultrasound of the neck
 History of neck irradiation in childhood 2- Check Calcitonin levels
 Endemic goitre
3- Decrease thyroxine dose

4- Increase thyroxine dose Managed

Same day Urgent Non Urgent
by GP
5- Repeat TFTs in 4-6 weeks
Stridor Patient with
Palpable No
associated hyper or
cervical change in
Answer & Comments with hypothyroidism
lymph size over
thyroid refer to
nodes years
Answer: 4- Increase thyroxine dose lump endocrinologist
Rapidly No
enlarging Lump enlarging known
In view of her non suppressed TSH levels, the (days- over months risk
thyroxine dose should be increased in the first weeks) factors
instance. The aim should be to titrate the Presence
Sudden pain and <1cm,
thyroxine dose to keep TSH levels <0.01 mU/L. By of risk
enlarged mass incidental
factors for
increasing the T4 dose the serum FT4 is usually (bleeding in a thyroid
thyroid
elevated and my not fall within the ‘reference cyst) nodule
cancer
range’; however clinical features of over
Hoarsness
treatment should be noted. The dose of thyroxine of voice
should be adjusted by 25µg (about every 6 weeks)
Nodule in
until the serum TSH is adequately suppressed. a child
Most patients will require 175 or 200 µg daily.

What is the likely physiological mechanism
A 32 year old lady is noticed to have a <1 cm involved in critically unwell patients leading to a
thyroid nodule noticed by GP on routine sick euthyroid state?
examination. She has no history of radiation
exposure as a child and no family history of (Please select 1 option)
polyposis coli. She is otherwise well and the size of 1- Decrease in 31 deiodinase Type 1 levels
the nodule has not changed over last 3-4 years.
Her biochemistry reveals, TFTs being within the 2- Increase in 51 deiodinase Type 1 levels
normal range. 3- Increase in 51 deiodinase Type 3 levels
What is the most appropriate next step in her 4- Increase in 31 deiodinase Type 1 levels
management? 5- Increase in TBG levels
1- Check Tg levels Answer & Comments
2- Early referral Answer: 3- Increase in 51 deiodinase Type 3 levels

3- Manage in primary care
The conversion of T4 to T3 is mediated by the
4- Routine referral activity of 51 deiodinase upenzymes. Deiodination
5- Urgent referral of the outer ring of T4 results in formation of T3 (3-
8 times more potent then T4), while deiodination
of the inner ring leads to formation of reverse T3
Answer & Comments (metabolically inert). Three different types of 51
Answer: 3- Manage in primary care deiodinase are known to exist.
The following table shows a summary of different

The following table shows the summary of the 51 deiodinase enzymes and their respective role:
British Thyroid Association (BTA) guidelines to the
GP regarding referral of a thyroid nodule: Type Location Role Significance

Most [ Q: 194 ] Question ID #613

abundant
Increases in
of all, Acts on both
hyperthyroid What's the likely mode of action of Carbimazole?
51 Present outer as well
state and vice
deiodinase in liver, as inner ring (Please select 1 option)
versa PTU
Type 1 muscle of thyroxine
inhibits it
and (T4)
(not CBZ) 1- Inhibition of the sodium -Iodide symport
kidney
etc 2- Inhibition of TPO activity
Acts on outer
51 3- Inhibition of conversion of T4 to T3
ring to step Provide T3 to
deiodinase Neurons
up T3 brain 4- Inhibition of TBG
Type 2
production
Acts on inner 5- Inhibition of TSH receptors
Protect
51 Placenta ring to
placent from
deiodinase Foetal produce
excess T4 and Answer & Comments
Type 3 liver metabolically
T3
inert RT3
Answer: 2- Inhibition of TPO activity

Carbimazole (CBZ) and Propylthiouracil (PTU) act
by inhibiting the action of thyroid peroxidase
What is the likely mechanism involved in thyroid (TPO) enzyme. PTU in addition inhibits the
hormone resistance? peripheral conversion of T4 to T3 (by inhibition of
(Please select 1 option) 51 deiodinase Type 1 activity). Perchlorate and
thiocyanates inhibit iodide transport.
1- β chain mutation
2- Mutation in glycoprotein receptor [ Q: 195 ] Question ID #614
3- Nuclear receptor defect
4- Thyroxine hormone synthesis defect A 38 year old gentleman presents with a 3 month
history of weight loss, palpitations and tremors.
5- Thyroxine hormone ultra-filtration defect On examination he has a small goitre and fine
tremors in both hands. His blood results are as
Answer & Comments shown below:
Answer: 1- β chain mutation 28.2 (11.5-22.7

Free T4
pmol/L pmol/L)
Resistance to thyroid hormone can either be 8.1 (3.5-6.5
generalised, selective pituitary or selective Free T3
pmol/L pmol/L)
peripheral resistance to hormone action. Most of
TSH 5.2 mU/L (0.35-5.5 mU/L)
the resistance syndromes are familial in origin.
Patients are generally clinically euthyroid (except AntiTPO negative
in cases of pituitary resistance to thyroid Anti TSH
hormone) and the presence of goitre is negative
antibody
sometimes, the only positive sign. The mutation is
usually at thyroid hormone receptor level. The β What's the next investigation to establish the
chain gene for the receptor is defective resulting diagnosis?
in defective binding of thyroid hormones to the
receptor. Most of the patients do not require any
treatment. The biochemistry shows an elevated 1- α-subunit ratio
TSH level with normal or rarely high Free T4 and
Free T3 levels. An important differential diagnosis 2- MRI brain
in such a scenario is a TSHoma.

3- TBG levels 3- US neck

4- TRH stimulation test 4- Urinary iodide excretion
5- TSH receptor antibodies 5- Uptake scan

Answer: 1- α-subunit ratio Answer: 4- Urinary iodide excretion
The presence of inappropriately normal or Enlargement of the thyroid gland (goitre) can be
elevated TSH levels in the presence of elevated T3 secondary to physiological states of increased
and T4 levels is indicative of either a TSH secreting iodide demand such as puberty and pregnancy,
pituitary adenoma or Thyroid hormone resistance. congenital defects of thyroid hormone synthesis,
Rarely such a biochemical profile is a result of the iodide deficiency, autoimmune thyroiditis
presence of heterophile antibodies leading to (Hashimoto`s thyroiditis), drug induced
spurious results. TSH secreting tumours usually (amiodarone, lithium, interferon), post partum
present with features of mild thyrotoxicosis and thyroiditis etc.
goitre. The TSH a-subunit secretion is increased in
such tumours and is used to distinguish from In the developed world iodine deficiency goitre is
Thyroid hormone resistance. A molar ratio of a- uncommon as the optimum Iodide requirement of
subunit to TSH of > 5.7 is considered diagnostic in 150 µg per day (according to WHO
such cases. A TRH stimulation test can occasionally recommendations) is easily met through diet. This
be used to distinguish between the two conditions patient has been on a world tour and visited Iodide
but is hardly performed these days. depleted areas such as Himalayas making her
susceptible to Iodide deficiency goitre. As more
In contrast thyroid hormone resistance can either than 95% of dietary Iodide is excreted in urine, a
be generalised, selective pituitary or selective 24 hour urinary excretion of iodide is an excellent
peripheral (resistance to hormone action). Most of index of dietary iodine intake and can unmask a
the resistance syndromes are familial in origin. iodide deficiency state.
Patients are generally clinically euthyroid except in
cases of pituitary resistance to thyroid hormone.
The mutation is usually at thyroid hormone
receptor level.
A 75 year old gentleman presents to the Endocrine
clinic with an 8 week history of weight loss,
[ Q: 196 ] Question ID #615 palpitations and tremors. He has past medical
history of ischaemic heart disease and AF. He is
A 32 year old has decided to go on a strict vegan currently taking Aspirin, Ramipril, Metoprolol and
diet for a year. She has recently returned from a Rosuvastatin. He was on Amiodarone which was
world tour and visited sub-Saharan countries and stopped recently by the cardiologist (1 week ago).
went on an expedition in the Himalayas. She His blood results are as shown below:
presents with a diffuse smooth goitre. Her bloods
show a euthyroid status and negative anti TPO TSH < 0.01mU/L (0.35-5.5 mU/L)
antibodies.
Free T4 28 pmol/L (11.5-22.7 pmol/L)
What is the next investigation to establish the Free T3 7.9 nmol/L (3.5-6.5 pmol/L)
likely diagnosis? Anti TPO negative
(Please select 1 option) Uptake < 1%
1- CT neck scan uptake
2- FNAC

What is the most appropriate next therauptic for the last 1 year as far as symptoms of
option for his management? palpitations are concerned. His recent routine
blood tests show:
1- Carbimazole TSH 15.5 mU/L (0.35-5.5 mU/L)

2- Prednisolone Free T4 4.6 pmol/L (11.5-22.7 pmol/L)
3- Propylthiouracil Anti TPO negative
4- Propanolol
What is the next therapeutic intervention you will
5- Radioiodine ablation consider?
Answer & Comments 1- Liothyronine 20 µg twice a day
Answer: 2- Prednisolone 2- Radioiodine ablation
3- Start thyroxine 25 µg per day
Amiodarone has a close structural resemblance
with thyroxine and contains 2 atoms of iodine per 4- Start thyroxine 50 µg per day
molecule which represent approximately 37.5% of
5- Stop amiodarone
its molecular weight. It has a wide tissue
distribution and a half life of 52.6 days.
Abnormalities of thyroid gland are extremely Answer & Comments
common in patients on amiodarone and include
Answer: 3- Start thyroxine 25 µg per day
both hypothyroidism (AIH) as well as
thyrotoxicosis (AIT).
This patient has Amiodarone induced
AIT in turn can be secondary to iodide excess (AIT hypothyroidism which is the commonest side
-Type 1) usually on background of an abnormal effect associated with amiodarone treatment in
thyroid gland or due to an inflammatory reaction iodine replete areas (in contrast to amiodarone
evoked by amiodarone (AIT - Type 2). The clinical induced thyrotoxicosis more commonly seen in
distinction between these two types is often iodine depleted areas). Discontinuation of
extremely difficult. AIT-Type 2 is generally amiodarone should be considered if possible. In
associated with no signs of clinical thyroid disease, this case because of previous history of life
negative thyroid autoantibody status and threatening arrthymias the safer option will be to
decreased uptake on radioiodine scan. start low dose of thyroxine.
Discontinuation of amiodarone therapy (if [ Q: 199 ] Question ID #688

possible) and steroids form the main stay for
treatment of AIT - Type 2. While in AIT -Type 1,
Thionamides (CBZ, PTU) are generally effective. A 31 year old woman who is 11 weeks pregnant
Due to practical difficulties to distinguish between presents with tachycardia, tremors and
the 2 types, often a combination of steroids and palpitations. She has strong family history of
thionamides is used for treatment of AIT. autoimmune thyroid disease and goitre. Her
thyroid function test results are as shown below:

Free T4 32.8 pmol/L (9-23)
Free T3 11.2 pmol/L (3.5-6.5)
A 74 year old with past medical history of life
threatening arrthymias, is on long term TSH < 0.01 mU/L (0.35-5.5)
amiodarone therapy and fitted with a defibrillator
2 years ago. He has been clinically asymptomatic What is the best therapeutic option in her case?

(Please select 1 option) What should be the most appropriate step in her
1- Carbimazole management?
2- Lugols iodine
1- Lobectomy
3- Propanolol
4- Propylthiouracil
5- Radioiodine
4- Refer for total thyroidectomy
Answer & Comments 5- Repeat FNAC in 3-6 months
Answer: 4- Propylthiouracil
Answer & Comments
The patient is likely to have Graves` thyrotoxicosis Answer: 5- Repeat FNAC in 3-6 months
as suggested by features of hyperthyroidism and
associated strong family history of autoimmune
The guidelines from the British Thyroid
thyroid disease. In view of her pregnant state,
Association (BTA) recommend repeating cytology
treatment with lowest dose of Propylthiouracil,
with repeat FNAC in those nodules where THY2
which renders her euthyroid, should be initiated.
results are obtained at 3-6 month interval.
The following are few of the salient points to be
remembered as far as pregnancy and thyroid
dysfunction is concerned: [ Q: 201 ] Question ID #692
 Thyroxine requirement increase in A 45 year old with a 1 cm nodule in thyroid,

hypothyroid women during first trimester undergoes a fine-needle aspiration cytology
of pregnancy. (FNAC). The results of FNAC show Thy 3.
 TSH levels increase during 2nd and 3rd
trimester of pregnancy. What is the next step in management?
 Hyperthyroidism in pregnancy is
commonly due to Graves` disease (d/d
hyperemesis gravidarum, H mole), so 1- Lobectomy
check TSH receptor antibodies (TRAb) in
all such patients. 2- Reassure and discharge
 Graves` disease can relapse during first 3- Radioiodine ablation
trimester and post partum period (more
likely to remit during 2nd and 3rd trimester) 4- Repeat FNAC
 Check TRAb in third trimester, as it can be 5- Total thyroidectomy
transmitted through placenta to baby,
leading to neonatal hyperthyroidism
 Treat maternal hyperthyroidism with Answer & Comments
lowest possible dose of PTU (more protein Answer: 1- Lobectomy
bound, less transfer across placenta)
 1 out of 4 Type 1 Diabetics, have evidence
of thyroid dysfunction during pregnancy Fine-needle aspiration (FNA) gives tissue for
cytology. It is performed either under US guidance
(for maximum accuracy) or without if the nodule
[ Q: 200 ] Question ID #691 is palpable. It is safe, inexpensive and provides
direct information. FNA is best for uninodular
A 35 year old lady presents with 1.5 cm nodule in lesions. Sensitivity is near 80% with specificity
her thyroid. FNAC results show Thy 2 lesion. approaching 100%. False-negative and false-
positive results occur in less than 6%. FNA is the

first and, in the vast majority of cases after US, the 4- Oral carbimazole
only test required for the evaluation of a solitary
5- Oral propylthiouracil
thyroid nodule.
Thy 3 is a follicular lesion/suspected follicular Answer & Comments

neoplasm. While some of these will be tumours,
Answer: 3- IV propranolol
many will be shown to be hyperplastic nodules on
surgical excision. Most of these patients should be
treated by surgical removal of the lobe containing This patient appears to be developing thyroid
the nodule. These cases should be discussed in the storm as revealed by a temperature, agitation,
MDT meeting if a therapeutic procedure is being confusion, atrial fibrillation and goitre. We are not
considered. Completion thyroidectomy may be provided with the TFTs as these will often take
necessary if the histology proves malignant. some time to process even if asked for acutely. In
this case the IV beta-blockers would be the most
Investigating the thyroid nodule appropriate approach as treatment for the atrial
Investigating the thyroid nodule fibrillation and these also prevent the peripheral
conversion of T4 to T3. Either oral propylthiouracil
or carbimazole should be given but both will take
[ Q: 202 ] Question ID #3787 2 hours to have an effect on the production of
thyroid hormone and of course neither will
A 60 year old woman is admitted with a history of prevent the release of stored hormone.
being acutely unwell, diarrhoea and more recent Thioamides must be given at least one hour prior
confusion. She gives no other history of note and to the use of iodides which do block the release of
is particularly agitated on admission. Her husband stored hormone. Also, the patient should receive
informs you that she has little of note in her IV steroids.
history but has become increasingly agitated and
has lost weight over the last one month. Reference:
Forth Valley Guidelines on thyroid storm
Examination reveals that she is confused with a
GCS of 15. She has a BMI of 18 kg/m2, a pulse of [ Q: 203 ] Hypothalamus and Pituitary -
120 bpm irregular, blood pressure of 110/65
Question ID #62
mmHg and a temperature of 38.9C. She has an
obvious goitre with an audible bruit.
A 47 year old female is referred by her GP as she
Results reveal: has a 3 month history of headaches and tiredness.
She has a 5 year history of bipolar disorder for
which she takes lithium and olanzapine. She has
FBC Normal
regular menses and no galactorrhoea. On
U+Es Normal examination, there is nil to find. The GP includes
CRP 15 (<5) the following biochemistry:
ECG Atrial fibrillation
LH 2.2 mu/l (2-10)
Which of the following is the most appropriate FSH 3.1 mu/l (2-10)
initial treatment for this patient? Estradiol 280 pmol/l (150-800)
(Please select 1 option) Prolactin 1450 mu/l (<500)
1- IV amoxicillin and metronidazole
What is the likely cause of her
2- IV potassium Iodide
hyperprolactinaemia?
3- IV propranolol (Please select 1 option)

1- Drug-induced This patient has active acromegaly which is

refractory to somatostatin analogue therapy. In
2- Microprolactinoma
this case the most appropriate treatment could be
3- Macroprolactinoma pegvisamont, a GH receptor blocker which
therefore reduces the production of IGF-1. the
4- Polycystic ovarian syndrome hormone through which most of the actions of GH
5- Stress are mediated.
Answer: 1- Drug-induced
A 23 year old female presents with a two year
history of failure to conceive and
This patient is taking a dopamine antagonist – oligomenorrhoea. She is investigated, found to
olanzapine which will cause hyperprolactinaemia. have a prolactin of 1015 mu/l (50-500) and is
The fact that the menstrual function is normal and diagnosed with a microprolactinoma. She explains
estradiol is normal would argue against the that she is keen to conceive.
hyperprolactinaemia being pathological due for
instance to a microprolactinoma. Which of the following is the most appropriate
treatment for this patient?
Reference:
Drug-induced hyperprolactinaemia
1- Bromocriptine
[ Q: 204 ] Question ID #68 2- Pituitary surgery
3- Pergolide
A 72 year old female is diagnosed with acromegaly
due to a macroadenoma of the pituitary and 4- Radiotherapy
underwent surgery. Surgical resection was 5- Somatostatin analogues
unsuccessful, no further surgery was
recommended and she had received radiotherapy
2 years ago. However, her growth hormone Answer & Comments
concentrations on day profile and IGF-1
Answer: 1- Bromocriptine
concentrations remain elevated despite the use of
octreotide LAR 30 mg every 4 weeks.
Bromocriptine is the treatment for
Which of the following is the most appropriate hyperprolactinaemia that is licensed for use in
management for this patient’s ongoing patients wishing to conceive. Quinagolide is also
acromegaly? licensed. Surgery is rarely required for the
treatment of prolactinomas.
1- Dopamine agonist therapy [ Q: 206 ] Question ID #70

2- Further radiotherapy
A 45 year old female is being treated for a
3- Increase dose of octreotide
prolactinoma and has been receiving cabergoline
4- Pegvisamont at a dose of 2 mg twice weekly. However, the
prolactin concentration remains elevated at
5- Switch to lanreotide
15,000 mu/l (although there was an initial decline
of prolactin levels from 70,000 mu/l at initial
Answer & Comments presentation) these have not fallen since dose was
increased to 2 mg twice weekly. She remains
Answer: 4- Pegvisamont

amenorrhoeic. Her most recent MRI scan reveals Answer & Comments
that the tumour has shrunk since the original scan
of 3 months ago but she still has a 2 cm pituitary Answer: 1- GH receptor antagonist
tumour which is just touching the chiasm. Her
visual fields are full to confrontation. Pegvisamont is a GH receptor blocker and results
in a decline in IGF-1 concentrations in active
Which of the following is the most appropriate acromegaly. It is generally reserved for the
treatment for this patient? treatment of active acromegaly that is resistant to
somatostatin analogues.
1- Add bromocriptine to cabergoline

2- Advise pituitary surgery
3- Advise pituitary radiotherapy A 40 year old female undergoes a MRI by the ENT
surgeons as an investigation of episodic balance
4- Increase dose of cabergoline further problems. No abnormality is noted of the
5- Switch cabergoline to bromocriptine posterior fossa or auditory apparatus but
incidental note is made of a 5mm microadenoma
of the pituitary. The patient has no symptoms nor
Answer & Comments are there any signs of endocrine disorder.
Answer: 2- Advise pituitary surgery
This patient appears to have dopamine agonist

550 pmol/l (130 -
resistant prolactinoma and no further benefit can Estradiol
800)
be gained from further dose increase, as the
prolactin concentration hasn’t fallen despite LH 2.2 mu/l (2 - 10)
gradual dose titration. The most appropriate FSH 3.3 mu/l (2 - 100)
treatment would be surgery and possibly
radiotherapy thereafter depending on the success
of surgery. 24hr urine Free Cortisol 188 nmol/d (<280)
TSH 2.2 mu/l (0.5 - 4.5)
[ Q: 207 ] Question ID #80 IGF-1 28.9 nmol/l (22 - 40)
A 72 year old female is receiving treatment with Which of the following is the most appropriate
pegvisamont for acromegaly which is management strategy for this patient?
unresponsive to somatostatin analogues. (Please select 1 option)
What is the mechanism of action of pegvisamont? 1- Arrange insulin tolerance test
(Please select 1 option) 2- Arrange oral glucose tolerance test

1- GH receptor antagonist 3- Arrange repeat MRI in 1 year
2- GHRH receptor antagonist 4- Reassure and discharge
3- Highly selective dopamine agonist 5- Refer for pituitary surgery
4- IGF-1 receptor antagonist
Answer & Comments
5- Somatostatin receptor agonist
Answer: 3- Arrange repeat MRI in 1 year

This patient has an incidentally noted pituitary 3- Repeat MRI in 6 months

microadenoma and the investigations suggest that
4- Treat with bromocriptine
this is non-functional. Hypopituitarism is most
unlikely based on the size and absence of 5- Treat with cabergoline
symptoms and IST is not warranted. The normal
IGF-1 concentration is an excellent test for
Answer & Comments
acromegaly and its normality would exclude this
diagnosis in an otherwise healthy person. Answer: 2- refer for pituitary surgery
Studies suggest that microadenomas rarely

This patient has a co-incidentally noted pituitary
enlarge (<10%) and so with this in mind, a further
adenoma which does impinge on the optic chiasm.
MRI should be arranged for 1 year and if there is
Despite the normal visual fields the most
no evidence of growth no further imaging is
appropriate treatment would be surgical removal,
warrranted, as suggested by others.
as, in view of his youth, it is likely to grow and pose
a threat to his vision. The slightly elevated
[ Q: 209 ] Question ID #86 prolactin does not mean that the patient has a
prolactinoma – this is likely to reflect stalk
A 55 year old male is reviewed after referral from compression and dopamine agonist therapy
the general physicians. He was investigated for a would ineffective.
vague headache and had a CT scan which quite co-
incidentally revealed a pituitary macroadenoma. [ Q: 210 ] Question ID #87
An MRI subsequently reports a 2cm
macroadenoma which encroaches upon the optic
A 25 year old male presents with reduced libido
chiasm. There are no obvious abnormalities to
and erectile dysfunction. There is nil of note on
suggest endocrine dysfunction on examination
examination and his visual fields are normal to
and his visual field assessment is entirely normal.
confrontation. His investigations reveal:
His investigations reveal:
LH 1.1 mu/l (2 - 100)

Cortisol response to short 840 nmol/l
synacthen test (>550) FSH 2.0 mu/l (2 - 10)
Thyriod function test Normal Testosterone 6.2 nmol/l (8 - 30)
780 mu/l Prolactin 38,000 mu/l (<450)
Prolactin
(<450)
3.3 mu/l (2 - MRI reveals a 3 cm pituitary macroadenoma that
LH displaces the optic chiasm.
10)
2.8 mu/l (2 -
FSH Which of the following is the most appropriate
10)
management of this patient?
7.8 nmol/l (8 -
Testosterone (Please select 1 option)
30)
12.9 nmol/l 1- Commence cabergoline
IGF-1
(18 - 33) 2- Refer for pituitary radiotherapy
What is the most appropriate management for 3- Refer for pituitary surgery
this patient? 4- Treat with testosterone only and repeat MRI
(Please select 1 option) in 3 months
1- Refer for pituitary radiotherapy 5- Treat with somatostatin analogue
2- Refer for pituitary surgery

Answer & Comments 3- Non-functioning pituitary tumour

Answer: 1- Commence cabergoline 4- Prolactinoma
5- Silent pituitary infarction
This patient has a macroprolactinoma and
presented with features of hypogonadism. His
Answer & Comments
MRI reveals that the tumour is pressing on the
optic chiasm, yet the visual fields are normal. Even Answer: 2- Lymphocytic hypophysitis
if this patient had a visual field defect, surgery is
rarely required for prolactinomas and he should
This pregnant woman presents in the third
be treated initially with dopamine agonist therapy.
trimester with a hyponatraemia, secondary
This would be expected to cause a rapid reduction
hypothyroidism, an appropriate prolactin and
in the tumour volume with relief of chiasmal
oestradiol concentrations for this stage of
compression. Repeating the MRI in approximately
pregnancy and an inadequate cortisol response to
3 months would be expected to reveal the abrupt
synacthen. This suggests partial hypopituitarism
reduction in volume and suppression of prolactin
during the latter stages of pregnancy which is
concentrations.
likely due to lymphocytic hypophysitis. Even
without the MRI, pituitary tumour is unlikely as
[ Q: 211 ] Question ID #89 the patient became pregnant - unlikely if there
was pre-existent hypopituitarism associated with
A 28 year old female who is 30 weeks pregnant a pituitary tumour either functional or non-
presents with profound tiredness and lethargy. functional.
She is noted to have a sodium of 130 mmol/l on
routine testing and this sparks further [ Q: 212 ] Question ID #93
investigation.
A 26 year old male with a history of treated
Her investigations reveal:
childhood craniopharyngioma and associated
hypopituitarism wishes to discuss fertility. He has
Cortisol post short confirmed pan-hypopituitarism and receives
252 nmol/l (>550)
synacthen test hydrocortisone, thyroxine, growth hormone and
Free thyroxine 5.5 pmol/l (9-22) testosterone for hypopituitarism but now wishes
TSH 2.2 mu/l (0.5 - 5) to commence a family. On examination of the
genitalia, his testicular volumes are approximately
Prolactin 3300 m/l (<450) 10 mls bilaterally and he has normal secondary
1300 pmol/l (130 - sexual characteristics. A semen analysis after
estradiol
800) stopping testosterone reveals azoospermia and
his plasma testosterone is also low.
LH 1.1 mu/l (2 - 10)
FSH 1.0 mu/l (2 - 10) Which of the following would be the most
appropriate treatment for this man?
An MRI of the pituitary is performed which reveals
enlargement of the pituitary bulging slightly
beyond the sellar but with no obvious tumour. 1- Advise sperm donation
2- Continue testosterone in current dose
(Please select 1 option) 3- Stop testosterone and commence HCG
injections
1- Dysgerminoma
4- Stop testosterone, GH and commence HCG
2- Lymphocytic hypophysitis injections

5- Refer for intracytoplasmic sperm injection these agents is harmful to the fetus. However,
(ICSI) there is no need to take these agents during
pregnancy as the risks of tumour expansion are
small (<1%). Thus, the patient should be advised to
Answer & Comments
stop cabergoline only.
injections [ Q: 214 ] Question ID #96
The patient has hypogonadotrophic A 26 year old female with a microprolactinoma

hypogonadism and needs assisted fertility. The falls pregnant after taking cabergoline. She is
most appropriate approach would be treatment advised to stop the cabergoline.
with HCG injections aiming to firstly restore
testosterone concentrations and hopefully How would you continue to serially monitor the
generate semen production although one might patient during her pregnancy?
need to add FSH if testosterone is restored yet
azoospermia persists. If HCG is unsuccessful then
the patient may need referral for ICSI or 1- Clinical observation
alternatively may wish to consider sperm
2- Formal visual field assessment
donation.
3- MRI pituitary every trimester
[ Q: 213 ] Question ID #95 4- Prolactin concentrations
5- Short synacthen tests
A 32 year old female who has been treated with
cabergoline for a microprolactinoma attends clinic
and informs you that she is 8 weeks pregnant. She Answer & Comments
has been continuing to take the cabergoline 0.25
Answer: 1- Clinical observation
mg twice weekly and the pregnancy was
unexpected but she would like to continue with
the pregnancy. The prolactin concentration rises in normal
pregnancy and is typically in the thousands. There
Which of the following would you advise? is no need to measure prolactin concentrations
during pregnancy. There is a small risk of tumour
expansion during pregnancy (less than 1%) and so
1- Advise termination due to the teratogenic the patient should be monitored clinically with
risk with cabergoline clinical field assessment and if there is a suspicion
of tumour expansion then MRI can be undertaken.
2- Continue cabergoline at current dose
3- Increase dose of cabergoline [ Q: 215 ] Question ID #102
4- Stop cabergoline
A 19 year old male with childhood onset idiopathic
5- Switch cabergoline to bromocriptine
hypopituitarism was referred to the adult
endocrine clinic. He had received growth hormone
Answer & Comments and testosterone gel for the last 6 years and had
grown to an appropriate adult height and had
Answer: 4- Stop cabergoline
normal secondary sexual characteristics.
Pregnancy on patients taking dopamine agonist
therapy for prolactin secreting tumours is not IGF-1 42.3 nmol/l (28 - 50)
uncommon and there is no evidence that taking

LH 1.2 mu/l (2 - 10) Free T4 15.5 pmol/l (9 - 22)

FSH 2.2 mu/l (2 - 10) TSH <0.02 (0.5 - 4.5)
Free T4 14.5 pmol/l (9 - 22)
There are no abnormalities to find on clinical
TSH 2.2 mu/l (0.5 - 5)
examination of this patient.
He is keen to continue GH therapy but is aware action for this patient?
that if this is no longer necessary he is prepared to
stop it.
1- Leave dose of thyroxine unchanged
Which of the following is the most appropriate 2- Reduce dose of thyroxine to 100
action for this patient concerning his GH therapy?
micrograms/d
3- Reduce dose of thyroxine to 125
1- Continue GH at its current dose micrograms/d
2- Increase dose of GH 4- Request free T3 concentration
3- Re-assess GH secretion 5- Request TSH receptor antibodies
4- Reduce dose of GH
5- Stop GH therapy Answer & Comments
Answer: 1- Leave dose of thyroxine unchanged
Answer & Comments
Answer: 3- Re-assess GH secretion This is a frequent GP request. The important thing
to recognise is that the patient is hypopituitary
and so one cannot rely on TSH measurement.
Approximately 30% of subjects shown to be GH Therefore, the dose of thyroxine should be
deficient in childhood subsequently have normal sufficient to aim for a thyroid hormone
GH secretion in adulthood. Thus, it is concentration in the mid to upper half of the
recommended that all subjects should be re- normal range. This patient is stated to be well
tested for GH deficiency in adulthood. If intact, the without any reported features of thyroid hormone
GH can be discontinued. If however GH deficiency excess – there is no need to measure free T3 and
persists then GH should continue, particularly if the dose of thyroxine should be left unchanged.
the patient subjectively feels improvement
(assessed through AGHDA questionnaire) and also
as it contributes to the attainment of peak bone [ Q: 217 ] Question ID #104
mass.
A 22 year old male is referred by his GP with
tiredness. Since the age of 5 with a he was treated
for hypothyroidism and has had poor growth. He
is currently receiving 100 micrograms of thryoxine
A 22 year old male is referred to the endocrine daily. He is of short stature but has normal
clinic by the GP. He has a history of pubertal development. His investigations reveal:
craniopharyngioma for which he takes full
hormone replacement therapy including
Free T4 14.6 pmol/l (9 - 22)
thyroxine 150 micrograms daily, hydrocortisone
10 mg bd and testosterone gel 60 mg daily. He is TSH 0.5 mu/l (0.5 - 5)
well, but his GP refers him to you as he is Testosterone 12.9 nmol/l (9 - 30)
concerned by the attached thyroid function tests:
LH 2.8 mu/l (2 - 10)

FSH 3.2 mu/l (2 - 10) LH 2.2 mu/l (2 - 10)

IGF-1 5.2 nmol/l (28 - 50) FSH 3.6 mu/l (2 - 10)
He informs you that he has two children who are
Cortisol post-synacthen 850 nmol/l (>550)
grown up, he drinks approximately 10 units of
alcohol weekly and he has noticed that the
CT of the head reports no abnormality of the development of erectile dysfunction has occurred
pituitary. over a few years.
What is the most appropriate investigation for this On examination he has a BMI of 37.5 kg/m2, a
patient? blood pressure of 136/88 mmHg and a pulse of 68
(Please select 1 option) bpm. No abnormalities are found in
cardiovascular, chest or abdominal examination.
1- Request KAL-1 mutational analysis
Further results are obtained which reveal:
2- Request MENIN mutational analysis
3- Request MRI of the pituitary and olfactory U+Es Normal
bulbs Fasting Plasma Glucose 6.1 mmol/l
4- Request Pit-1 mutational analysis Free T4 12.1 pmol/l (9- 22)

TSH 3.2 mu/l (0.5 - 5)
5- Request SOX-1 mutational analysis
Answer & Comments

A CT headscan is performed which reveals no
Answer: 4- Request Pit-1 mutational analysis abnormality of the pituitary.
Which of the following is the most likely cause for

It is rather unusual for a young child to have
developed primary hypothyroidism and what is his hypogonadism?
more this adult is now short with a low IGF-1 (Please select 1 option)
suggesting GH deficiency and a low prolactin 1- Haemochromatosis
suggesting hypoprolactinaemia. This would
suggest a combined partial hypopituitarism – TSH, 2- Kallmann syndrome
PRL and GH typical of a mutation of the
3- Obesity
transcriptional activator - pit-1. Prop-1 mutations
(Prophet of Pit-1) are the most common defects in 4- Pituitary microadenoma
combined childhood pituitary hormone defiencies
and are characterised by LH/FSH deficiency 5- Testicular fibrosis
together with GH, TSH and Prolactin. Later, ACTH
deficiency may ensue. Imaging may reveal a small Answer & Comments
or indeed normal appearance of the pituitary and
does tell us nothing of the functionality. Answer: 3- Obesity
[ Q: 218 ] Question ID #107 This patient's results reveal a low testosterone

with 'inappropriately' normal LH and
FSH indicating a hypogonadotrophic
A 48 year old male presents with a history of hypogonadism. His other pituitary function is
reduced libido and erectile dysfunction. His GP normal and his CT of the pituitary is also reported
encloses the following results: as normal. However, he is obese and has features
of the metabolic syndrome with an elevated
Testosterone 7.1 nmol/l (9 - 30) fasting plasma glucose. With these results, the

most probable cause of his hypogonadism is She now presents to clinic and explains that she is
obesity. 8 weeks pregnant.
This is a well described, emerging phenomena and What do you advise regarding her management?
the exact cause is ill-understood although is (Please select 1 option)
believed to directly relate to visceral fat mass with
increasing aromatisation of testosterone to 1- Advise surgery
oestradiol and then feedback on the Pituitary. 2- Continue somatostatin analogue therapy at
current dose
3- Increase dose of somatostatin analogue
therapy
A 44 year old male is diagnosed with a pituitary
macroadenoma. He undergoes trans-sphenoidal 4- Stop depot somatostatin analogue therapy
resection of this lesion and the histology is
5- Switch to tds short acting analogue
reported as a chromophobe adenoma.
somatostatin therapy.
Which of the following would be the likely cause of
this histological description? Answer & Comments
(Please select 1 option) Answer: 4- Stop depot somatostatin analogue
1- ACTH secreting adenoma therapy
2- GH secreting tumour
SMS analogue therapy is not licensed for
3- Non-functional adenoma pregnancy and should be stopped. In this scenario,
with the patient being effectively cured with SMS
4- Prolactinoma
therapy in the presence of a microadenoma, it
5- TSH secreting adenoma would seem most appropriate to stop analogue
therapy. However, many experts, particularly in
the context of a macroadenoma may take the
Answer & Comments
approach of continuing treatment as no ill effects
Answer: 3- Non-functional adenoma have been reported. This is quite an unusual
scenario as surgery would have been considered
first line treatment for acromegaly, yet many
A chromophobe adenoma does not take up any
young women who may wish to begin a family,
dye – chromo-phobe. Hence this is typical of a
may elect SMS analogues in the first instance as
non-functional pituitary tumour. Eosinophilic
the risks of hypopituitarism after surgery are quite
adenomas are typically GH or Prolactin producing
high.
whereas basophilic describe ACTH tumours.

A 33 year old female presents one month after

A 33 year old female with a diagnosis of
giving birth to a baby boy. She has been diagnosed
acromegaly due to a microadenoma and has been
with a microprolactinoma and has been treated
treated with monthly depot somatostatin
with cabergoline 0.25mg bd. Shortly after
analogues. Her GH day profile concentrations and
commencing cabergoline she fell pregnant and the
IGF-1 are as follows:
cabergoline was stopped. She had no problems
during pregnancy and now is breast feeding. She
GH day profile all results <2 mu/l now enquires as to the most appropriate
IGF-1 22.8 nmol/l (15-40) management strategy relating to the ongoing
treatment of her microprolactinoma. Her visual

fields are normal to confrontation. Her results His other investigations reveal:
reveal:
IGF-1 10.8 nmol/l (28-42)
Prolactin 1040 mu/l (50-450) Testosterone 14.5 nmol/l (9-30)
TFTs Normal FreeT4 18.2 nmol/l (9-23)
Which do you advise? TSH 0.07 mu/l (0.5-5)

1- Arrange pituitary MRI management of his DEXA result?
2- Commence quinagolide (Please select 1 option)
3- Commence bromocriptine 1- Growth hormone therapy
4- Recommence cabergoline 2- Increase dose of testogel
5- No intervention required 3- No specific treatment required

Answer & Comments 5- Weekly alendronate
Answer: 5- No intervention required
Answer & Comments
This patient has been successfully treated with Answer: 5- Weekly alendronate
cabergoline and has conceived following
treatment. The patient is well and continues to
breast feed. The high prolactin is typical of the The most appropriate approach to treating this
post-partum period and in view of the patient’s man’s osteoporosis, as demonstrated with a T
desire to continue breast feeding and in the score of less than -2.5, is a bisphosphonate such as
absence of any particular problems suggestive of weekly alendronate. The causes of low BMD in
expansion of the prolactinoma, there is no need association with hypopituitarism are multi-
for any intervention. factorial and GH deficiency may contribute.
Although this man is highly likely to have GH
deficiency as demonstrated by his low IGF-1, he
[ Q: 222 ] Question ID #136 does not appear to have specific symptoms of GH
deficiency that might merit treatment and NICE do
52 year old male is referred as his GP had not advocate the use of GH as a treatment of
organised a DEXA scan for him as he had been reduced BMD in adults hypopituitary patients.
concerned about his bone thickness. This concern Unlike bisphosphonates, where there is evidence
had arisen as he had read about reduced bone of reduced fracture risk, GH therapy has no data of
mineral density in relation to hypopituitarism. Ten reduced fracture risk.
years ago he had surgical removal of a non-
functional pituitary macroadenoma and had
developed hypopituitarism for which he receives
hydrocortisone 10mg bd, thyroxine 150
micrograms daily and testogel 50mg daily. His A patient is suspected of having acromegaly and
DEXA scan reveals T scores of -2.6 in some areas of undergoes an oral glucose tolerance test. The
the lumbar spine and -2.4 in the hip. results of this are shown:
He is generally fit and quite well but, after reading 120

Time 0
an article on bone strength in hypopituitarism is minutes
concerned about osteoporosis. Glucose (mmol/l) 5.6 8.8

Growth Hormone (mu/l) 4.4 5.5 Answer & Comments

Answer: 2- GHRH/Arginine test
of this test?
The most appropriate test is the GHRH/Arginine
test. The patient is being treated with valproate
1- Acromegaly and diabetes mellitus for seizures and so, the insulin tolerance test, a
gold standard for the diagnosis of GH deficiency, is
2- Acromegaly and impaired glucose tolerance contra-indicated. Whilst IGF-1 concentration may
3- Acromegaly and normal glucose tolerance support a diagnosis of GHD in panhypopituitary
patients, this man doesn't appear to be
4- Normal GH response and impaired glucose panhypopituitary as he is not taking testosterone
tolerance supplementation. Therefore in this case one
5- Normal results would undertake dynamic testing.
Answer: 2- Acromegaly and impaired glucose A 44 year old female presents with amenorrhoea,
tolerance weight gain and ease of bruising. She is diagnosed
with Cushing’s syndrome based on elevated 24hr
This patient has a paradoxical rise in GH urine free cortisol concentrations of 880 nmol/d
concentrations during the OGTT and this indicates (<250) and a cortisol of 88 nmol/l after low dose
acromegaly as the GH concentrations should dexamethasone test. An ACTH is 108 ng/l (20-60).
suppress below 2 mu/l. With regard to the glucose An MRI is performed of the pituitary and is
concentrations, the glucose at 120 mins is 8.8 reported as normal.
mmol/l indicating impaired glucose tolerance.
next step for this patient?
A 43 year old man underwent a resection of a non- 1- Domeperidone test

functional pituitary tumour. Post-operatively he
2- CT scan of adrenals
had developed seizures which had been treated
with sodium valproate. He is also receiving 3- Inferior petrosal sinus sampling
hydrocortisone and thyroxine. Despite treatment
he has felt tired and frequently lethargic following 4- Octreotide scan
the procedure. 5- Pituitary exploration

Answer & Comments
appropriate test to confirm a suspected diagnosis
of growth hormone deficiency? Answer: 3- Inferior petrosal sinus sampling
1- Clonidine test These results point to an ACTH dependent

Cushing’s syndrome. It is possible that this could
2- GHRH/Arginine test be ectopic although it seems unlikely. Often the
MRI does reveal no abnormality but one would
3- Glucose tolerance test
want to ensure that one is dealing with pituitary
4- IGF-1 concentration dependent Cushing’s syndrome and IPSS would do
this. A gradient of above 3:1 central to peripheral
5- Insulin tolerance test

ACTH would clinch the diagnosis and sensitivity is treatment is prednisolone and beta blockade and
improved following CRF. if possible withdrawal of amiodarone. This
contrasts with AIT type 1 where the patient
High dose dexamethasone was once considered to typically has pre-existent thyroid disease or
differentiate between Cushing’s disease and positive thyroid auto-antibodies. Thyroid uptake
ectopic but this has proven not to be the case and scan may be useful in differentiating between the
generally the test adds little to results of Low dose two as in AIT type 1 uptake may be increased and
testing and so is used infrequently. CT of adrenals low in type 2, but this is not often the case as
would not provide diagnostic information as it is uptake is typically very low due to competition of
ACTH dependent disease. radio-iodine with the iodine in amiodarone.
A 66 year old male with a past history of ischaemic A 28 year old male with hypopituitarism due to a
heart disease and episodes of ventricular non-functioning pituitary tumour now wishes to
tachycardia has been treated with amiodarone start a family. He underwent surgery at the age of
200 mg for two years. His VT is well controlled on 20 and since has been treated with Testostrerone
this treatment but latterly he presents with gel 50mg daily, hydrocortisone 10mg bd,
fatigue, anxiety and weight loss. thyroxine 100 micrograms daily and growth
hormone 1.5 mg daily. He has normal erectile
On examination, he has a fine tremor of the function but a most recent semen analysis
outstretched hands, a pulse rate of 88 bpm but is demonstrates azoospermia.
receiving beta blockers, has lid lag but no goitre is
palpable. His Thyroid function tests reveal: Which of the following is the most appropriate
approach to fertility on this man?
Free T4 55 pmol/l (10-23) (Please select 1 option)
TSH <0.02 (0.5-5) 1- Continue testosterone and commence HCG
Thyroid Antibodies Negative injections
2- Refer for ICSI
(Please select 1 option) 3- Refer for sperm donation
1- Amiodarone induced thyrotoxicosis type 1 4- Stop testosterone and commence

clomiphene
2- Amiodarone induced thyrotoxicosis type 2
5- Stop testosterone and commence HCG
3- De Quervain's thyroiditis
injections
4- Graves' disease
5- Hashitoxicosis Answer & Comments
Answer & Comments injections
Answer: 2- Amiodarone induced thyrotoxicosis
type 2 This patient desires fertility but has
hypogonadotrophic hypogonadism. The patient
should stop testosterone, as this is associated with
The most likely diagnosis is amiodarone induced impaired spermatogenesis and commence HCG
thyrotoxicosis type 2 – this is a thyroiditis type injections. This approach should initially stimulate
picture with thyroid follicle inflammation and testosterone production and then sperm
release of stored thyroxine. The most appropriate production. Often co-prescription of FSH is

required. If one fails to stimulate testosterone IGF-1 12.5 nmol/l (28-42)

then it is unlikely that sperm can be generated and
referral for ICSI or alternative fertility treatments Which of the following is the most appropriate
may be necessary. treatment for this patient?
1- Commence Fludrocortisone
NICE guidance recommends the use of insulin 2- Commence Growth hormone
tolerance test in the investigation of potential
3- Increase dose of testosterone
growth hormone deficiency (Level 1a).
4- Increase hydrocortisone to 30mg daily
Based upon which of the following does level 1a
evidence pertain?
Answer & Comments
1- Case-control study
Answer: 2- Commence Growth hormone
2- Non-consecutive studies
3- Systematic review of case control studies GH deficiency is the most likely diagnosis here and
is responsible for the tiredness. All other
4- Systematic review of randomized control
hormones appear to be appropriately replaced –
trials
the suppressed TSH is not due to over-
5- Systematic reviews of cohort studies replacement of thyroxine but is a consequence of
the hypopituitarism. The dose of hydorocortisone
is likely typically adequate at 10mg bd.
Answer & Comments
Answer: 4- Systematic review of randomized GH therapy is associated with improvements in
control trials energy as well as well being and should be
monitored through IGF-1 maintaining this in the
upper half of the age related normal range.
The levels of evidence include 1abc, 2 abc, 3ab, 4
and 5 and are used to grade recommendations.
Level 1a is superior and based on systematic [ Q: 230 ] Question ID #152
reviews of RCTs. 1b is based on one quality RCT.
A 42 year old hypopituitary male is being treated
[ Q: 229 ] Question ID #151 with thyroxine 100 micrograms daily,
hydrocortisone 10mg bd, testosterone gel and has
just commenced growth hormone therapy.
A 55 year old male has been treated for
hypopituitarism following surgical resection of a Which of the following is the most appropriate for
non-functional pituitary tumour 2 years ago. He
monitoring his response to GH therapy?
feels generally tired despite receiving treatment
with thyroxine 100 micrograms daily, (Please select 1 option)
hydrocortisone 10 mg bd and testosterone gel 1- AGHDA quality of life score
50mg daily. His investigations reveal:
2- Bioelectrical impedance analysis
Free T4 18.6 pmol/l (9-23) 3- DEXA scanning
TSH <0.05 (0.5-5) 4- PGWBS questionnaire
5- SF-36 form
Testosterone 12.8 nmol/ (9-30)

Answer & Comments therapy and the prior history of fits is a contra-
indication to IST. Therefore, the most appropriate
Answer: 1- AGHDA quality of life score test would be GHRH/Arginine.
NICE recommend the monitoring of the Although IGF-1 concentrations may be low in GHD,
effectiveness of GH therapy with the AGHDA they may still reside within the normal range and
score. Patients should begin with an AGHDA score are not used diagnostically.
above 11 which reflects a poor quality of life –
(normal scores are 4 or less). [ Q: 232 ] Question ID #156
[ Q: 231 ] Question ID #153 A 45 year old male is being treated for a

prolactinoma with cabergoline 1mg twice weekly.
A 43 year old male with hypopituitarism due to Original MRI of the pituitary one year ago revealed
previous treatment of a non-functional adenoma a 1.3cm macroprolactinoma which approached
5 years ago presents to the clinic complaining of but did not compress the optic chiasm. He was
persistent tiredness and lethargy. He also has a commenced on cabergoline and the dose has been
history of recently treated hypertension and had a gradually increased and he tolerates medication
fit post-operatively but continues to be fit free well. On examination, he appears well and his
over the last three years whilst taking visual fields are entirely full to confrontation. You
anticonvulsants. He is receiving hydrocortisone note that his prolactin has fallen from an original
10mg bd, thyroxine 100 micrograms daily, concentration of 30,000 mu/l to its current level of
testosterone gel 50mg daily, atorvastatin 10 mg 150 mu/l (50-500).
daily, amlodipine 5mg daily and also sodium
valproate 800mg daily. He is felt likely to have Which of the following investigations should be
adult Growth Hormone (GH) deficiency and would undertaken?
be a candidate for GH therapy.
Which of the following would be the most 1- 24hr ECG

appropriate investigation for the confirmation of 2- CT pituitary
GH deficiency in this patient?
3- Echocardiography
4- MRI pituitary
1- Clonidine test
5- Thrombophilia screen
2- GHRH/Arginine test
3- Glucagon test
Answer & Comments
4- IGF-1 concentration
Answer: 3- Echocardiography
Recent recommendations from the MHRA suggest
Answer & Comments that all patients being treated with dopamine
agonists such as bromocriptine, pergolide and
Answer: 2- GHRH/Arginine test cabergoline should have echo to assess for
potential cardiac fibrosis. Although this is disputed
NICE criteria indicate that GH deficiency need be by authorities in endocrinology, the
confirmed in a patient with suspected GHD. A recommendations now state that all patients
stimulation test such as Insulin tolerance test or should have echo 3-6 months after commencing
GHRH/Arginine would be appropriate with a GH these ergot derived dopamine agonists and then
response less than 9 mu/l being confirmatory. In at least annually to assess for any evidence of
this case, the patient is receiving anticonvulsant valvular fibrosis and dysfunction. This patient has

been successfully treated with cabergoline and Answer & Comments

shrinkage of the tumour would be expected
commensurate with the fall and normalisation of Answer: 2- Lymphocytic hypophysitis
prolactin. There is no need for a MRI.
The patient appears to have a pan-hypopituitarism
Reference: and the likely diagnosis is a lymphocytic
http://www.mddus.com/mddus/news-and- hypophysitis, as there is no evidence of Sheehan
media/news/october-08/mhra-warning-on- syndrome (pituitary infarction following obstetric
ergot-derived-dopamine-agonists.aspx haemorrhage). The patient is unlikely to have a
non-functional pituitary tumour as, we are told,
[ Q: 233 ] Question ID #159 she had no problems with conception or
pregnancy. Previously, many of the patients who
had been considered to have Sheehan syndrome
A 32 year old female is 2 weeks post partum and probably had Lymphocytic Hypophysitis.
presents with considerable fatigue and failure to
lactate. She is para 2, gravida 2 and her second
pregnancy and delivery were relatively uneventful [ Q: 234 ] Question ID #162
giving birth to a healthy baby boy. During the last
trimester she did feel particularly tired and this did In a study of 1000 patients, a new serological test
differ from her previous pregnancy. She had a for pituitary adenomas was assessed against
normal standard vaginal delivery and did not imaging. The following results were obtained:
require any blood post delivery although was told
that she was slightly anaemic during her Test Positive Test Negative
pregnancy. On examination, her blood pressure is
MRI Positive 80 20
94/66 mmHg and her pulse is 70bpm with a BMI
of 25 kg/m2. Her investigations reveal: MRI Negative 100 800
Free T4 8.1 pmol/l (9.8 – 23) To what does the sensitivity of the new test
approximate?
TSH 1.5 mu/l (0.35-5)
Prolactin <50 (50-450)
Estradiol <100 (130 – 850) 1- 50%
LH 1.1 mu/l (1-10) 2- 60%

FSH 1.4 mu/l (1-10) 3- 70%
Cortisol (pre-synacthen) 88 nmol/l (220 – 800) 4- 80%
Cortisol (post- 180 nmol/l (220 –
5- 90%
synacthen) 800)
Which of the following is most likely the diagnosis? Answer & Comments
(Please select 1 option) Answer: 4- 80%
1- Factitious results
Assuming that the MRI is the gold standard here,
2- Lymphocytic hypophysitis
sensitivity of the test is the number of true
3- Non-functional pituitary tumour positives (80)/ number of true positives (80) +
false negatives (20). In this case, sensitivity is 80%.
4- Post-partum thyroiditis
In the case of specificity, this relates to the number
5- Sheehan syndrome of true negatives (800)/ the number of true
negatives (800) + false positives (100). This is
approximately 90% (88.9%).

[ Q: 235 ] Question ID #327 sinus trigemminal nerve. The importance of

recognising this headache is that it responds well
A 35 year old female presents with a six month to treatment with indomethacin. In functional
history of headaches, oligomenorrhoea and adenomas such as prolactinomas, reports suggest
galactorrhoea. She describes episodic, 'bad' that it may respond or indeed develop/deteriorate
headaches which affect the left eye and left frontal following dopamine agonist therapy.
region, are associated with lacrimation of the left
eye and also some injection of that eye. These [ Q: 236 ] Question ID #339
episodes typically last 10-15 mins with little relief
from analgesia such as paracetamol. The A 62 year old woman is referred with persistent
headaches often occur with a frequency of 2-5 hypertension and obesity. She also complains of
episodes daily. excessive pigmentation and headaches. 30 years
ago she was diagnosed with Cushing's disease and
Her GP has undertaken some blood tests which underwent a bilateral adrenalectomy. She is
reveal an elevated prolactin of 3500 mu/l and a ct treated with hydrocortisone 10mg bd and
scan revealed a pituitary intrasellar adenoma of fludrocortisone 100 micrograms daily and also
approximately 0.9cm. On examamination there is receives amlodipine and atenolol as long standing
little note other than she has a bmi of <30kg/m2, treatment of the hypertension
and some galactorrhoea to expression but
otherwise visual fields, acuity and fundal On examination, she is noted to be generally
examination are normal pigmented, has abdominal striae and blood
pressure is 168/100mmHg. Visual fields are full to
Which of the following is the likely explanation of confrontation.
the headaches associated with her pituitary
tumour? Which of the following is the most appropriate
(Please select 1 option) investigation for this patient?
1- Benign intracranial hypertension (Please select 1 option)
2- Cluster headaches 1- 24-hour urinary free cortisol meassurement
3- Migraine 2- ACTH concentration
4- Paroxysmal hemicrania 3- Aldosterone:plasma renin ratio
5- Trigeminal neuralgia 4- Renal ultrasound with dopplers of renal

arteries
Answer & Comments 5- Short synacthen test
Answer: 4- Paroxysmal hemicrania

Answer & Comments
This is a classical description of paroxysmal Answer: 2- ACTH concentration

hemicrania, a distinct type of headache described
in conjunction with pituitary tumours. A further Nelson's syndrome occurs in roughly 30% of
revision of this headache is termed Short-lasting patients who have undergone adrenalectomy for
Unilateral Neuralgiform headache attacks with pituitary-dependent Cushing's disease. It is a
Conjunctival injection and Tearing (SUNCT). consequence of the clinical progression of any pre-
existent pituitary adenoma possibly after the
The aetiology of such headaches is unknown but feedback of hypercortisolism has been removed
may relate to neurohormonal effects or in some by adrenalectomy. Plasma ACTH levels are
circumstances where the tumour is larger, markedly elevated and pituitary imaging is likely to
pressure effects of the tumour on the cavernous reveal an adenoma. Pituitary irradiation is

frequently performed early after adrenalectomy Answer & Comments

in Cushing's disease in order to avert Nelson's
disease. Answer: 4- Syndrome of inappropriate ADH
(SIADH)

This patient has a deteriorating hyponatraemia
with an inappropriately elevated urine osmolality
A 52 year old female is admitted with an and urine sodium excretion (should be less than 20
intracranial bleed. She undergoes clipping of an mmol/l). The most likely diagnosis is therefore
cerebral arterial aneurysm and was well the SIADH. There is no evidence of hypoadrenalism.
following morning. The following biochemistry are Diabetes insipidus would produce excessive fluid
noted post-operatively: (Normal ranges Sodium loss with hypernatraemia. Fluid overload is a
135-145, potassium 3.5 -5, Urea 3-8, Creatinine potential diagnosis yet we are informed that the
50-100) patient underwent fluid restriction.
Plasma
Day Sodium Potassium Urea 4.5 Creatinine [ Q: 238 ] Question ID #344
1 131 3.6 mmol/l mmol/l 95 µmol/L
mmol/l
A 38 year old female presents with tiredness,
Plasma
Day Sodium Potassium Urea 4.2 Creatinine
lethargy and weight gain. Five years previously she
2 126 3.4 mmol/L mmol/L 88 µmol/L had undergone trans-sphenoidal hypophysectomy
mmol/L for a non-functional pituitary tumour. She had a
Plasma complicated post-operative course having
Day Sodium Potassium Urea 5 Creatinine developed a CSF leak which required re-
3 123 3.5 mmol/L mmol/L 88 µmol/L exploration and then seizures for which she
mmol/L
remains on sodium valproate. She was
Plasma demostrated to be hypopituitary for which she
Day sodium Potassium Urea 5 Creatinine
receives hydrocortisone 10mg bd, thyroxine 100
4 120 3.5 mmol/L mmol/L 88 µmol/L
mmol/L micrograms/d and combined HRT. You suspect
that a growth hormone deficiency is likely to be
responsible for her current symptoms.
On day 4 she was commenced on a fluid restriction
of 1 litre per day. The following were noted at that
stage: Plasma osmollity 258 mosmol/l (275-305) Which of the following investigations would be the
urine osmolality 688 mosmol/l with urine sodium most appropriate test to confirm growth hormone
84 mmol/l. deficiency in this patient?
Which of the following is the most likely diagnosis
1- Clonidine test
to explain the hyponatraemia?
(Please select 1 option) 2- Combined GHRH/Arginine test
1- Cranial diabetes insipidus 3- IGF-1 concentration
2- Hypoadrenalism 4- Insulin tolerance test
3- Fluid overload 5- Oral glucose tolerance test
4- Syndrome of inappropriate ADH (SIADH)

Answer & Comments
5- Sick cell syndrome
Answer: 2- Combined GHRH/Arginine test
This patient is more than likely to be GH deficient

which would explain the lethargy but this requires

confirmation before initiating treatment. Answer & Comments

Although an insulin tolerance test is the gold
standard for the diagnosis of GHD, it is contra- Answer: 1- Drug induced
indicated due to the epilepsy. Therefore
GHRH/arginine is regarded as a suitable This patient is receiving a dopamine antagonist -
alternative. domperidone. This is the most likely cause for his
hyperprolactinaemia. The thryoid function tests
[ Q: 239 ] Question ID #424 are entirely normal and a microprolactinoma
would be very unusual in a man of this age. The
suppression of LH, FSH and testosterone indicates
A 72 year old male is referred by his GP who was adequate treatment with GnRH analogues.
concerned about an elevated prolactin
concentration. He had been well up until 3 years
ago when he was diagnosed with prostate cancer [ Q: 240 ] Question ID #635
and was treated with GnRH analogues. Since he
has been tired but his prostate cancer is well A 16 year old is reviewed in Endocrinology
controlled, being on 6 monthly appointments with transition clinic. He was diagnosed to have a
urology. His GP had checked a few results and craniopharyngioma at the age of 14 and operated
found that his Prolactin was 980 mu/l (50-450), upon. Post operatively, he is lagging behind his
precipitating referral. He currently receives peers as far as his height is concerned (2 standard
amlodipine, ramipril, simvastatin and deviation below normal). Both of his parents are
domperidone of average height and none of the siblings has
short stature. His biochemical profile is as shown
He appears hypogonadal in appearance and his below:
blood pressure is 134/74 mmHg with a BMI of
32kg/m2. 320
9 am cortisol
nmol/L
30 minutes Post 580
ACTH nmol/L
Testosterone 1.2 nmol/l (8-30)
(1.4-18.1
Prolactin 800 mu/l (50-450) FSH 10.4 U/L
U/L)
LH 1.2 mu/l (1-10) LH 5.5 U/L (3.0-8.0 U/L)
FSH 1.1 mu/l (1-10) 12 (16-118
IGF-1
Free T4 9.1 nmol/l (9-23) nmol/L nmol/L)
TSH 4mu/l (0.5-5) (45-375
Prolactin 92 mU/L
IGF-1 18 nmol/l (15-30) mU/L)
11.2
Testosterone
Which of the following is the likely cause for the nmol/L
hyperprolactinaemia? (0.35-5.5
TSH 2.2 mU/L
(Please select 1 option) mU/L)
1- Drug induced
Subsequently an insulin stress test is arranged for
2- Metastatic prostatic disease him in the Endocrine day unit which shows a peak
growth hormone value of 9 mU/L (3µg/L).
3- Microprolactinoma
4- Non-functioning pituitary tumour What is the most useful advice as far as growth
hormone replacement is concerned?
5- Primary hypothyroidism

1- GH replacement is contraindicated Which of the following tests should be employed

considering his history of tumour for this patient?
2- No need to replace him with GH therapy (Please select 1 option)
based on these results 1- Clonidine test

3- Start him on adult dose of GH replacement 2- Glucagon stimulation test
and monitor IGF-1 levels
3- Glucose tolerance test
4- Start him on GH replacement if he scores >
4- IGFBP3 levels
12 on AGHDA
5- Start him on paediatric dose of GH
replacement
Answer & Comments
Answer & Comments Answer: 2- Glucagon stimulation test

Answer: 3- Start him on adult dose of GH
replacement and monitor IGF-1 levels The gold standard for diagnosis of growth
hormone secretion is insulin tolerance test (ITT).
GH levels of <3 µg/L (<10 mU/L) are usually
This 16 year old clearly has GH deficiency as a post indicative of severe GH deficiency on ITT. The
operative complication of craniopharyngioma contraindications for ITT include history of
resection. He will require 0.15-0.3 mg daily epilepsy, ischaemic heart disease and basal
subcutaneous growth hormone injections and the cortisol levels < 100 nmol/L. ITT is contraindicated
dose titration is based on IGF-1 levels (to a in this patient as he is an epileptic evidenced by
maximum of 1 mg/day). The main side effects Levariactem therapy he is receiving. GHRH-
associated with growth hormone injections Arginine test is also highly sensitive as well as
include fluid retention, myalgia, arthralgia and specific to detect GH deficiency and would have
benign intracranial hypertension. It is been an ideal choice as an alternative to ITT in this
contraindicated in presence of any active patient, if this choice was provided as an answer.
malignancy in the body. Glucagon stimulation test can also be used for GH
deficiency assessment if ITT is contraindicated.
NICE clinical guidelines 64: Growth hormone
deficiency in adults summary
A 27 year old lady, who delivered a healthy baby
girl 3 months back, by a normal vaginal delivery,
A 29 year old currently who had undergone presents with 2 weeks history of headache and
resection of a 2.5 cm non functioning pituitary visual blurring. Her biochemistry results are shown
tumour 2 years ago presents to the clinic with low below:
mood and non-specific symptoms. He has a
background history of epilepsy for which he is
Sodium 126 mmol/L (135-145 mmol/L)
currently taking Levatiracetam.
Potassium 3.8 mmol/L (3.5-5.5 mmol/L)
His initial screening reveals normal Urea 8.5 mg/dL (7-20 mg/dL)
FSH/LH/TFT/Prolactin/Testosterone levels. A
Creatinine 105 µmol/L (60-115 µmol/L)
short synacthen test shows 30 minute cortisol
value of 620 nmol/L. His IGF-1 level is 20.5 Calcium 2.4 mmol/L (2.2-2.6 mmol/L)
nvolved/l (25-45). TSH 2.4 mU/L (0.35-5.5 mU/L)
Free T4 8.5 pmol/L (11.5-22.7 pmol/L)

Prolactin 550 mU/L (50-500) 5- Urea and electrolytes

Glucose 6.3 mmol/L (3.5-5.5)
Answer & Comments
MRI images show enlarged pituitary gland. Answer: 2- Basal and 1 hour post steroid dose
ACTH levels
What is the likely underlying diagnosis?
Bilateral adrenalectomy is still occasionally
1- Lymphocytic hypophysitis employed in patients with inoperable pituitary
adenoma. These patients have about 50% risk of
2- Macroprolactinoma
development of Nelson`s syndrome after 10 years
3- Non functioning pituitary adenoma of operation as a result of increased ACTH levels
(due to loss of feedback inhibition). The incidence
4- Sheehans syndrome can be reduced if pituitary gland is subjected to
5- SIADH preoperative radiotherapy. After bilateral
adrenalectomy annual monitoring is usually
recommended by measurement of basal and 1
Answer & Comments hour post steroid dose ACTH levels and yearly MRI
Answer: 1- Lymphocytic hypophysitis scans.
Lymphocytic hypophysitis is a rare infiltrative [ Q: 244 ] Question ID #662

disorder leading to anterior pituitary destruction
during late pregnancy or post partum period. It A 54 year old male with acromegaly and treated
usually presents with symptoms of mass effect unsuccessfully with a trans-sphenoidal resection
including headache, nausea and vomiting. of tumour, is currently receiving pegvisomant in
Deficiency of ACTH and TSH hormones is more view of his residual disease. His blood results are
commonly observed as compared to GH/ as shown:
Gonadotrophin deficiency. MRI shows an enlarged
mass with thickening of pituitary stalk. Treatment IGF-1 12 nmol/L (10-35 nmol/L)
includes replacement of the deficient anterior
pituitary hormone. Role of steroid replacement in GH 44 mU/L (0-20 mU/L)
Lymphocytic hypophysitis remains unproven. Prolactin 250 mU/L (45-375 mU/L)
[ Q: 243 ] Question ID #647 What is the likely advice you will give?
A 65 year old male with an inoperable ACTH- 1- Continue the same dose of pegvisomant
secreting pituitary adenoma, undergoes bilateral
adrenalectomy. 2- Decrease the dose
3- Repeat radiotherapy
The follow up for this gentleman should include the
following investigations? 4- Start him on octreotide
(Please select 1 option) 5- Stop pegvisomant

1- 17 OH progesterone measurement
Answer & Comments
2- Basal and 1 hour post steroid dose ACTH
levels Answer: 1- Continue the same dose of
pegvisomant
3- Calcitonin
4- Cortisol levels

Pegvisomant is a genetically modified analogue of consistent with pregnant state and needs further
growth hormone which acts as a highly selective confirmation with urinary pregnancy test /
growth hormone receptor antagonist. It is licensed Ultrasonography.
for treatment of patients with acromegaly who
have undergone incomplete/ inadequate surgical [ Q: 246 ] Question ID #677
resection and are unresponsive to somatostatin
analogue therapy. It leads to normalisation of IGF-
1 levels in more than 90% patients although the A 23 year old man, with muscular build, presents
GH levels need to be monitored as it may show an to the clinic with reduced libido. He visits the gym
increase. regularly and denies usage of any substance of
abuse. His BMI is 30kg/m2 and normal secondary
Usage of pegvisomant is limited due to the high sexual characteristic development with some acne
cost of therapy. The above mentioned patient is on back. His blood results are as shown below:
showing good response to Pegvisomant therapy as
reflected by normalisation of IGF-1 levels so the FSH 1.8 U/L (1-10)
therapy should be continued at the same dose LH 3.2 U/L (3-10)
with regular monitoring of liver function tests.
Testosterone 8.1 nmol/L (9-28.5)
LFT normal
A 26 year old is referred to Endocrinology clinic MRI Brain normal
with a 3 months history of amenorrhoea (but no
galactorrhoea) due to a suspected What is the likely cause for his hypogonadism?
microprolactinoma. Her investigations show; (Please select 1 option)
1- Anabolic steroid abuse

Prolactin levels 1804 mU/L (60-620)
Oestradiol 1025 pmol/L (130-1000) 2- Kallmann syndrome
FSH 0.1 mu/l (1-10) 3- Kleinfelter syndrome
LH 0.2 mu/l (1-10) 4- Idiopathic hypogonadotrophic
hypogonadism
What is the most likely underlying diagnosis?
5- Weight related hypogonadotrophic
hypogonadism
1- CAH
2- Hypothyroidism Answer & Comments
3- Microprolactinoma Answer: 1- Anabolic steroid abuse
4- Oestradiol secreting ovarian tumour
This gentleman has secondary hypogonadism as
5- Pregnancy reflected by low testosterone, low FSH and LH
levels. His normal secondary sexual characteristic
Answer & Comments development makes the diagnosis of genetic
disorder unlikely. A normal MRI rules out any
Answer: 5- Pregnancy structural lesion involving pituitary gland or
hypothalamus. Anabolic steroid abuse is quite
Presence of 3 month history of secondary common in body builders and sportsmen. The
amenorrhoea, elevated oestrogen levels, and increase aromatase activity in such cases leads to
suppressed FSH/LH levels with elevated prolactin increased conversion of testosterone to
levels in a female in reproductive age group is

oestrogens as a result gonadotrophins secretion is The risk of significant growth in size of a

suppressed. macroprolactinoma is about 25% (as compared to
1-2% in patients with a microprolactinoma).
The following is the list of major causes of Therefore, patients with macroprolactinoma
secondary hypogonadism: should be closely monitored during pregnancy
with clinical examination and formal visual field
 Genetic disorders such as Kallamann assessment. An increase in size of the lesion
syndrome, DAX-1 mutation warrants initiation of Bromocriptine therapy.
 Structural disorders of pituitary and/or Alternatively patients with macroprolactinoma
hypothalamus (pituitary adenoma, can either undergo surgical debulking of tumour
craniopharyngioma, germinoma) before conception or Bromocriptine can be
 Post surgical (pituitary and/or continued throughout the pregnancy.
hypothalamic) or post cranial
radiotherapy [ Q: 248 ] Question ID #713
 Functional - secondary to excessive
exercise (e.g. long distance runners),
systemic illness, obesity, anorexia, stress, A 26 year old male is referred by the GP who
anabolic steroids, recreational drugs queries a diagnosis of acromegaly. His symptoms
 Infiltrative disease like sarcoidosis, include headaches, sweats and he has noticed
haemochromatosis enlargement of the hands and feet. He informs
 Congenital syndromes like Laurence- you that he has a cousin who has been diagnosed
Moon-Biedl or Prader-Willi syndrome with a pituitary tumour and his father died of
acromegaly many years ago. He is a non-smoker
and has otherwise been well.
On examination he has a slight acromegalic
A 28 year old female who is 35 weeks pregnant appearance and his investigations reveal:
presents with worsening headache and visual loss.
She has a history of macroprolactinoma for which IGF -1 112 nmol/l (30-55)
she originally took Quinagolide but has not taken
GH response to OGTT 5.5 mcg/l (<1)
any medications since she discovered she was
pregnant. Urgent MRI reveals increase in size of
Macroprolactinoma with compression of the optic Regarding any potential genetic screening, which
chiasm. of the following would be most appropriate?
Which is the most appropriate next step in her
1- AIP mutations
management?
2- MEN type 1 mutations
1- Octreotide infusion 3- No genetic screening required
2- Radiotherapy 4- SDHD type B or D mutations
3- Refer to neurosurgery for removal of tumour 5- vHL gene deletion
4- Re-commence dopamine agonist therapy

Answer & Comments
5- Urgent caesarean section
Answer: 1- AIP mutations
Answer & Comments

This patient presents with a convincing history of
Answer: 4- Re-commence dopamine agonist hereditary pituitary tumours. In particular, familial
therapy acromegaly has been associated with mutation of

the aryl- hydrocarbon Receptor Interactive Protein HLA DR3 / DR4 on chromosome 6 are common
(AIP) within the 11q13 region. The mechanism genetic markers for type 1 diabetes. Diabetes
underlying this propensity to pituitary tumour associated with polyglandular endocrinopathy
formation is unknown but recognition of the (Schmidt syndrome) preferentially occurs in
diagnosis s important in identification of at risk middle age women and is strongly associated with
kindreds. HLA-DR-3. Type 1 diabetes has a higher prevelance
in northern European and Scandanavian countries
and relatively low prevalence in Asia. The
[ Q: 249 ] Other - Question ID #10
histological features of islets from patients with
late onset type 1 diabetes are similar to those from
A 22 year old law student is referred to clinic with patients with classical type1 diabetes, although
a 2 month history of progressive polydypsia and there may be differences in major
polyuria and also complains of unplanned weight histocomapatability complex expression, with
loss in the region of 5 kg over the last 3 months. fewer islets being effected in late onset compared
She has a 25 year old sister diagnosed with type 1 with classical type 1 diabetes.
diabetes 5 years previously. On examination her
BMI is 20 kg / m2 her body weight is 64 kg, her
blood pressure is 112 / 66 mm/hg and visual acuity [ Q: 250 ] Question ID #11
6/ 9 in both eyes.
A 33 year primary school teacher is referred to
Investigations reveal: clinic by her GP. She has recently moved in to the
area having been diagnosed with diabetes 5 years
Fasting plasma glucose 14.9 mmol/l (3.5 - 5.6) previously and commenced immediately on
insulin. She however denies any history of weight
Hba1c 13.1% (<6) loss or osmotic symptoms prior to initiation on
13.9 pmol/l (9.3 - insulin. She has a younger brother recently
T4
23.4) diagnosed with diabetes. Her glycaemic control
TSH 0.51 mu/l (0.32 - 5) has always been good and she describes
hypoglycaemic symptoms once to twice weekly.
Which of the following is a recognized feature of On examination her BMI is 25 kg / m2 her body
weight is 64 kg, her waist circumference is 69 cm,
type 1 diabetes?
her blood pressure is 120 / 65 mmHg and her
(Please select 1 option) visual acuity is 6 / 6 in both eyes. Her current
1- Association with a single susceptibility locus medication includes insulin glargine 8 units at
night combined with novorapid 4 units prior to
2- HLA genes on chromosome 6 are closely lunch and dinner.
linked to immune modulation
3- High prevalence in Asia Investigations reveal:
4- More Islet cell destruction in late onset type Hba1c 6.3% (<6)
1 diabetes compared with classical type1
Islet cell
diabetes. Negative
antibodies
5- Malnutrition in utero may be linked with GAD antibodies Negative
increased risk of developing Type 1 diabetes
TSH 0.36 mu/l (0.32 - 5)
>99 ml/min 1.73m2 (90 -
Answer & Comments eGFR
110)
Answer: 2- HLA genes on chromosome 6 are
closely linked to immune modulation What is the genetic basis of this lady’s diabetes?

1- Autosomal co dominant [ Q: 251 ] Question ID #31

2- Autosomal dominant
A 27 year old man is referred to the lipid clinic
3- Autosomal recessive following a routine lipid blood test at his surgery
4- Polygenic which revealed turbid looking plasma with a total
cholesterol measuring 6.9 mmol/l (< 4) and plasma
5- X-linked recessive triglyceride measuring 10.9 mmol/l (<1.7).
Answer & Comments Which of the following would indicate a diagnosis

of type III hyperlipoproteinaemia for this patient?
Answer: 2- Autosomal dominant
This patient has Maturity onset diabetes of the 1- Apo E2 / E2 genotype with increased LDL and
young (MODY) based on the clinical presentation. chylomicron concentrations.
The diagnosis of MODY is supported the following 2- Apo E2 / E 4 genotype with increased LDL and
clinical characteristics chylomicron concentrations.
 Mild to moderate hyperglycemia (typically 3- Apo E4 / E4 genotype with increased LDL and
130-250 mg/dl, or 7-14 mM) discovered chylomicron concentrations.
before 30 years of age.
4- Apo E2 / E2 genotype synthesis with
increased IDL and chylomicron
 A first degree relative with a similar
degree of diabetes. concentrations.
5- Apo E 4/ E4 genotype with increased VLDL
 Absence of positive antibodies or other and chylomicron synthesis.
autoimmune conditions (e.g thyroiditis) in
patient and family.
Answer & Comments
 Persistence of a low insulin requirement Answer: 4- Apo E2 / E2 genotype synthesis with
(e.g., less than 0.5 u/kg/day) past the increased IDL and chylomicron
usual quot;honeymoon" period.
concentrations.
 Absence of obesity (though obese people
can get MODY), or other problems Type III hyperlipoproteinaemia occurs as a
associated with type 2 diabetes or consequence of elevated chylomicron and IDL
(intermediate density lipoprotein) concentrations.
 Cystic kidney disease in patient or close Also known as broad beta disease or
relatives. dysbetalipoproteinemia, the most common cause
for this form is the presence of Apo E2/E2
 Non-transient neonatal, or apparent type genotype. It is due to cholesterol-rich VLDL (β-
1diabetes with onset before 6 months of VLDL). Prevalence is 0.02% of the population.
age. Apolipoprotein E (APOE) is an apoprotein found in
chylomicron and IDL particles that binds to a
Inheritance is autosomal dominant with specific receptor on liver cells and peripheral cells.
penetrance of 40 – 90%, thus most patients will It is essential for the normal catabolism of
have other family members with diabetes. triglyceride-rich lipoprotein constituents. APOE
was initially recognized for its importance in
lipoprotein metabolism and cardiovascular
disease. More recently, it has been studied for its
role in several biological processes not directly
related to lipoprotein transport, including

Alzheimer's disease, immunoregulation, and 3- Fenofibrate

cognition. Defects in APOE result in familial
4- Nicotinic acid
dysbetalipoproteinemia, or type III
hyperlipoproteinemia (HLP III), in which increased 5- Omega - 3 fish oil
plasma cholesterol and triglycerides are the
consequence of impaired clearance of
Answer & Comments
chylomicron, VLDL and LDL remnants.
Answer: 3- Fenofibrate
APOE is 299 amino acids long and transports
lipoproteins, fat-soluble vitamins, and cholesterol
This lady has type III familial
into the lymph system and then into the blood. It
hyperlipoproteinaemia based on the detection of
is synthesized principally in the liver, but has also
an APO E2 genotype. Type III
been found in other tissues such as the brain,
hyperlipoproteinaemia occurs as a consequence
kidneys, and spleen. In the nervous system, non-
of high chylomicrons and IDL (intermediate
neuronal cell types, most notably astroglia and
density lipoprotein). Also known as broad beta
microglia, are the primary producers of APOE,
disease or dysbetalipoproteinemia, the most
while neurons preferentially express the receptors
common cause for this form is the presence of Apo
for APOE. There are seven currently identified
E2/E2 genotype. It is due to cholesterol-rich VLDL
mammalian receptors for APOE which belong to
(β-VLDL). Prevalence is 0.02% of the population, a
the evolutionarily conserved low density
fibrate is the agent of choice for the management
lipoprotein receptor gene family.
of this form of dyslipidaemia

A 26 year old lady is referred to the lipid clinic for
A 31 year old man is referred to the lipid clinic for
assessment. She is well and is currently taking no
assessment following a lipid profile carried out by
medication. She was referred by her GP following
his GP as part of a routine employment medical.
having her lipid profile measured prior to
On examination his blood pressure is 125 / 75
commencing the oral contraceptive pill. She has a
mm/hg, his BMI is 28 kg / m2 and no obvious
strong family history of cardiovascular disease
tendon xanthomata can be identified. On
with her mother suffering a myocardial infarction
questioning he is currently taking no medication,
at the age of 54. On examination her blood
has no family history of note and drinks alcohol
pressure is 134 / 75 mmHg, her BMI is 27 kg / m2
infrequently.
and no definitive tendon xanthomata can be seen.
Fasting plasma
Turbid Plasma 6.8 mmol/l (3.5- 5.6)
glucose
Total cholesterol 8.1 mmol/l ( < 5)
Plasma Triglyceride 8.9 mmol/l (0.9 - 2.2)
Plasma
Apo E2 / E2 Genotype Positive 9.5 mmol/l (0.9 - 2.2)
Triglyceride
TSH 2.1 mu / l (0.32 - 5.5) TSH 2.1 mu / l ( 0.32 - 5.5)
AST 89 iu / l (5 - 45)
What would be the drug of choice to treat this
patient’s dyslipidaemia? ALP 112 iu / l (30 - 115)
(Please select 1 option) Gamma GT 96 iu / l (8 - 70)
1- Atorvastatin Hb 13.9 g /dl (12-16)

MCV 84 fl (80 - 98)
2- Ezetemibe

Uric acid 8.8 mg/ dl (3.5 - 8.5) 1- ApoE dysfunction

Increased VLDL and 2- Lysosomal esterase deficiency
Plasma
chylomicron
electrophoresis 3- LCAT deficiency
concentrations
4- Reduced lipoprotein lipase activity
Which of the following is the correct diagnosis for
5- Reduced hepatic lipase
this patient?
Answer & Comments
1- Primary hyperlipoproteinaemia
Answer: 4- Reduced lipoprotein lipase activity
2- Type III familial hyperlipoproteinaemia
3- Type V hyperlipoproteinaemia This very rare form (also known as Buerger-Gruetz
syndrome, primary hyperlipoproteinaemia, or
4- Type IIb combined hyperlipidaemia
familial hyperchylomicronemia) is due to a
5- Type IV hyperlipoproteinaemia deficiency of lipoprotein lipase (LPL) or altered
apolipoprotein C2, resulting in elevated
chylomicrons, the particles that transfer fatty
Answer & Comments
acids from the digestive tract to the liver.
Answer: 3- Type V hyperlipoproteinaemia Lipoprotein lipase is also responsible for the initial
breakdown of endogenously made
triacylglycerides in the form of very low density
Type V hyperlipoproteinaemia or endogenous
lipoprotein (VLDL). As such, one would expect a
hypertriglyceridaemia is characterized by an
defect in LPL to also result in elevated VLDL. Its
excess of VLDL and chylomicron particles and
prevalence is 0.1% of the population.
reduced LPL activity along with elevated hepatic
transaminases. The serum has a creamy top layer
Apolipoprotein C2 is an apolipoprotein
and turbid bottom. Treatment is either with a
responsible for the activation of lipoprotein lipase
fibrate or nicotinic acid. Type V
hyperlipoproteinaemia is also associated with (LPL) in capillaries and thus begins the catabolism
of the chylomicrons and VLDL. It is also found in
glucose intolerance and hyperuricaemia.
HDL. Deficits of this apoprotein C2 present with
grave hypertriglyceridemia and
[ Q: 254 ] Question ID #37 hyperchylomicronemia during fasting
A 32 year old man is referred to the lipid clinic [ Q: 255 ] Question ID #38
following a routine fasting lipid profile carried out
by his GP which reveals a total cholesterol level of
A 48 year old lady is referred to the lipid clinic
8.3 mmol/l (<4) and a plasma triglyceride level of
following a fasting lipid profile checked by her GP.
18.6 mmol/l ( <1.7). He has no family history of
She has no family history or past medical history
note, denies any alcohol excess and other
of note. She is a non-smoker, is receiving no
investigations include a fasting plasma glucose of
regular medication and drinks alcohol
5.3 mmol/l (<5.6), normal thyroid function tests,
infrequently. On examination her blood pressure
liver function tests and renal function. On
is 160 / 85 mmHg, her BMI is 33 kg / m2 her waist
examination his blood pressure is 135 / 75 mm/hg,
his BMI is 27 kg / m2 and no tendon xanthomata circumference is 92 cm and she has no evidence of
tendon xanthomata.
can be found.
Which of the following is a feature of this
dyslipidaemia?
Fasting Plasma Glucose 6.8 mmol/l (3.5 - 5.6)

Total Cholesterol 6.9 mmol/l (<5) Investigations reveal:

Which of the following is a feature of type IIb Total Cholesterol 6.1 mmol/l (<5)
combined hyperlipidaemia? Plasma triglyceride 9.9 mmol/l (0.9 - 2.2)
Which of the following is a feature of type IV
1- Characterized by elevated IDL and VLDL
familial hyperlipaemia?
concentrations
2- Characterized by elevated VLDL and
chylomicron concentrations 1- Characterized by increased chylomicron
concentrations
3- Characterized by increased LDL and VLDL
concentrations 2- Characterized by increased VLDL
concentrations
4- Prevalence in the population is around 30%
3- Has a population prevalence of around 30%
5- Results from reduced LPL activity and APO
A1 concentrations 4- Results from defective lipoprotein lipase
activity
Answer & Comments 5- Statins are the mainstay of treatment
Answer: 3- Characterized by increased LDL and

Answer & Comments
VLDL concentrations
Answer: 2- Characterized by increased VLDL
Type II b hyperlipidaemia is characterized by concentrations
elevated concentrations of Apo B containing
particles in particular LDL and VLDL. The high VLDL Type IV hyperlipoproteinaemia also known as
levels are due to overproduction of substrates, hypertriglyceridaemia has a population
including triglycerides, acetyl CoA, and an increase prevalence according to NCEP APT III classification
in B-100 synthesis. They may also be caused by the of hypertriglyceridaemia of around 16%. It is
decreased clearance of LDL. Prevalence in the characterized by increased levels of VLDL as a
population is 10%. Type II b hyperlipidaemia may result of increased synthesis and reduced
arise in the context of either familial combined clearance. One of the major clinical consequences
hyperlipoproteinaemia (FCH) or secondary of hypertriglyceridaemia is an increased risk of
combined hyperlipoproteinaemia resulting from pancreatitis and fibrates are the mainstay of
the metabolic syndrome (for which it forms part of therapy.
the diagnostic criteria) or type 2 diabetes.

A 35 year old lady is referred to the lipid clinic
A 41 year old man is referred to the lipid clinic following the measurement of her fasting lipid
following a routine fasting lipid sample collected profile by her GP. She is a non smoker and drinks
by his GP. He has no past medical history of note, alcohol very infrequently and exercises regularly.
is a non-smoker and denies any excess alcohol She has a strong family history of cardiovascular
consumption. On examination his blood pressure disease with her older brother requiring coronary
is 145 / 75 mmHg, his BMI is 29 kg / m2 his waist by-pass surgery at the age of 41 and her mother
circumference is 88 cm and no tendon xanthoma suffering an MI at the age of 47. On examination
can be identified. her blood pressure is 133 / 61 mmHg and her BMI
is 24 kg / m2

Investigations reveal: caused by loss-of-function mutations in LDLRAP1,

which encodes a protein required for clathrin-
Total Cholesterol 7.6 mmol/l (<5) mediated internalization of the LDL receptor by
liver cells, has also been documented. LDLR
LDL-Cholesterol 5.9 mmol/l (<2)
mutations are more common in certain
Plasma Triglyceride 1.1 mmol/l (0.9 - 2.2) populations, presumably because of a genetic
HDL-Cholesterol 1.2 mmol/l (>1.2) phenomenon known as the founder effect—they
were founded by a small group of individuals, one
Which of the following is a feature of familial or several of whom was a carrier of the mutation.
hypercholesterolaemia (FH)? The Afrikaner, French Canadians, Lebanese
Christians, and Finns have high rates of specific
(Please select 1 option) mutations that make FH particularly common in
1- Arises from mutations of the LDL-receptor these groups. APOB mutations are more common
on the short arm of chromosome 16 in Central Europe.
2- Diagnosis is based on LDL and total The most recent addition to the database of genes
cholesterol levels above the 75th centile in which defects cause FH is one encoding a
combined with appropriate family history, member of the proprotein convertase family,
tendon xanthomata and xanthelasma PCSK9. Rare dominant gain-of-function mutations
in PCSK9 cosegregate with hypercholesterolemia,
3- Heterozygous FH has a population and one mutation is associated with a particularly
prevalence of 1:5000 in most countries severe FH phenotype. Expression of PCSK9
4- LDL receptor mutations account for 90% of normally down-regulates the LDL-receptor
cases of FH. pathway by indirectly causing degradation of LDL-
receptor protein, and loss-of-function mutations
5- Thickening of the Achilles tendon is a in PCSK9 result in low plasma LDL levels.
characteristic physical sign associated with
FH The diagnosis of FH is primarily based on clinical
grounds and may be confirmed by genetic testing.
Typical clinical features include cholesterol
Answer & Comments
deposition in the tendons result in the formation
Answer: 5- Thickening of the Achilles tendon is a of tendon xanthomata, with thickening of the
characteristic physical sign associated with FH Achilles tendon being an early classical
coetaneous manifestation of FH. Such soft tissue
manifestations combined with LDL-cholesterol
Familial hypercholesterolemia (FH) is levels above the 95th centile and a family history
characterized by raised serum LDL cholesterol of premature cardiovascular disease which
levels, which result in excess deposition of classically demonstrates intra-familial
cholesterol in tissues, leading to accelerated concordance of onset suggests a diagnosis of FH.
atherosclerosis and increased risk of premature Subsequent genetic testing for LDL-receptor and
coronary heart disease. In most populations Apo B mutations reveal mutations in between 50
studied, heterozygous FH occurs in about 1:500 and 80% of cases; those without a mutation often
people, but not all develop symptoms. have higher triglyceride levels and may in fact
Homozygous FH occurs in about 1:1,000,000. FH have other causes for their high cholesterol, such
results from defects in the hepatic uptake and as combined hyperlipidemia due to metabolic
degradation of LDL via the LDL-receptor pathway, syndrome.
commonly caused by a loss-of-function mutation
in the LDL-receptor gene (LDLR) on the short arm FH is usually treated with statins. Statins act by
of chromosome 19 or by a mutation in the gene inhibiting the enzyme hydroxymethylglutaryl CoA
encoding apolipoprotein B (APOB). FH is primarily reductase (HMG-CoA-reductase) in the liver. In
an autosomal dominant disorder with a gene- response, the liver produces more LDL receptors,
dosage effect. An autosomal recessive form of FH

which remove circulating LDL. Statins effectively is connected to the vena cava thus by-passing liver
lower cholesterol and LDL levels, although metabolism. Inhibition of the microsomal
sometimes add-on therapy with other drugs is triglyceride transfer protein, for example with the
required, such as bile acid sequestrants investigational drug AEGR-733, and infusion of
(cholestyramine or colestipol), nicotinic acid recombinant human apolipoprotein A1 are being
preparations or fibrates. Control of other risk explored as medical treatment options, with gene
factors for cardiovascular disease is required, as therapy also as a possible future alternative.
risk remains somewhat elevated even when
cholesterol levels are controlled. Professional Given that FH is present from birth and
guidelines recommend that the decision to treat atherosclerotic changes may begin early in life, it
an FH patient with statins should not be based on is sometimes necessary to treat adolescents or
the usual risk prediction tools (such as those even teenagers with agents that were originally
derived from the Framingham Heart Study), as developed for adults. Due to safety concerns,
they are likely to underestimate the risk of many doctors prefer to use bile acid sequestrants
cardiovascular disease; unlike the rest of the and fenofibrate as these are licensed in children.
population, FH have had high levels of cholesterol Nevertheless, statins seem safe and effective, and
since birth, probably increasing their relative risk. in older children may be used as in adults.
The addition of Ezetimibe may also be a
therapeutic option. Although controversy persists A multidisciplinary expert panel in 2006 advised
around the role of ezetemibe due to the absence on early combination therapy with LDL apheresis,
of a significant effect of combination ezetmibe / statins and cholesterol absorption inhibitors in
statin compared with statin monotherapy on children with homozygous FH at the highest risk.
carotid intima media thickness in patients with FH.
There are no interventional studies that directly
show mortality benefit of cholesterol lowering in
FH patients. Rather, evidence of benefit is derived A 45 year old Asian man is reviewed by his GP as
from a number of trials conducted in people who part of a cardiovascular risk factor screening
have polygenic hypercholesterolemia (in which programme. He is a non-smoker with the only
heredity plays a smaller role). Still, an family history of note being his father who has
observational study of a large British registry been diagnosed with type 2 diabetes at the age of
showed that mortality in FH patients had started 68 following admission to hospital with an episode
to improve in the early 1990s, when statins were troponin negative chest pain. On examination his
introduced. blood pressure is 165 / 75 mmHg, his BMI is 28 kg
/ m2 and his waist circumference is 89 cm
Homozygous FH is harder to treat. The LDL
receptors are minimally functional, if at all. Only Investigations reveal:
high doses of statins, often in combination with
other medications, are modestly effective in 5.5 mmol/l (3.5 -
Fasting Plasma Glucose
improving lipid levels. If medical therapy is not 5.6)
successful at reducing cholesterol levels, LDL Fasting Total Cholesterol 5.6 mmol/l (<5)
apheresis may be used; this filters LDL from the
plasma in a process reminiscent of dialysis. Very Fasting Plasma 1.7 mmol/l (0.9 -
severe cases may be considered for a liver Triglyceride 2.2)
transplant leading to rapid improvement in 0.8 mmol/l (0.9 -
HDL-Cholesterol
cholesterol levels, but at the risk of complications 1.8)
from any solid organ transplant. Other surgical LDL-Cholesterol 3.8 mol/l (< 3)
techniques include partial ileal bypass surgery, in
which part of the small bowel is bypassed to 2.1 mu/l (0.32 -
TSH
decrease the absorption of cholesterol, and 5.5)
portacaval shunt surgery, in which the portal vein

How would you manage this gentleman’s lipid 4- Fasting Total and LDL-Cholesterol levels
profile?
5- Fasting LDL and HDL-cholesterol levels
1- Atorvastatin 20 mg OD Answer & Comments

2- Diet / lifestyle modification Answer: 2- Fasting Total cholesterol and HDL-C
3- Rosuvastatin 10 mg OD levels
4- Omega fatty acids

NICE guidelines now state that a person’s 10 year
5- Ezetimibe 10mg OD CVD risk should be assessed using a QRISK2
assessment calculator. Other factors used in this
Answer & Comments calculation include, age, gender, smoking status,
blood pressure and presence or otherwise of LVH.
Answer: 2- Diet / lifestyle modification The role of including diabetes status in this
calculation remains debatable as the source data
for this calculator (Framingham risk equation)
Estimate the level of risk using the QRISK2
underestimates CVD risk associated with diabetes,
assessment tool. The 10 year Cardiovascular risk in
with diabetes increasing the risk of CVD by 2- 3
this gentleman is less than 10% according to
times that of the non-diabetic population. Family
QRISK2 Score. So, the first step is to advice diet
history and ethnicity are also important factors
and lifestyle modification.
with premature family history requiring a
multiplication factor of 2 and Asian ethnicity a
[ Q: 259 ] Question ID #42 factor of 1.4 to applied to the initial CVD risk
calculation.
A 46 year old man undergoes cardiovascular risk
factor screening by his GP as part of a routine life [ Q: 260 ] Question ID #44
insurance medical. On examination his BMI is 31
kg / m2 and his blood pressure is 155 / 85 mmHg.
A 45 year old female is receiving Orlistat 120 mg
tds for assistance with weight loss. Prior to
commencing Orlistat, the patient's weight was
108kg and her BMI was 36.8 kg/m2. The patient re-
5.5 mmol/l (3.5 -
Fasting Plasma Glucose attends clinic, three months after commencing
5.6)
Orlistat and her weight is now 102.2kg. She is keen
Fasting Cholesterol 5.3 mmol/l (<5)
to continue Orlistat as she feels it has helped her
0.9 mmol/l (0.8 - and has only been aware of occasional diarrhoea.
HDL-Cholesterol
1.9)
LDL-Cholesterol 2.9 mmol/l (< 3) Which of the following is the most appropriate
Fasting Plasma 1.6 mmol/l (0.9 -
approach to her management?
triglyceride 2.2)
When initially assessing a patient’s risk of 1- Add Sibutramine 10mg daily
cardiovascular disease which of the following lipid
profiles is most important? 2- Continue Orlistat at current dose
(Please select 1 option) 3- Increase dose of Orlistat to 150mg tds

1- Random total cholesterol level 4- Reduce dose of Orlistat to 60mg tds
2- Fasting Total cholesterol and HDL-C levels 5- Stop Orlistat
3- Fasting Total cholesterol and plasma
Triglyceride levels

Answer & Comments On examination, his weight is 142 kg and his BMI
is 51 kg/m2. His blood pressure is 136/84 mmHg
Answer: 2- Continue Orlistat at current dose and his pulse is 72 bpm.
This patient has lost 5.8 kg of weight over three Investigations reveal:
months equating to roughly a 5% weight loss
which is the figure recommended by NICE U+Es Normal
supporting continued treatment. The maximal
Fasting Glucose 8.2 mmol/l
Orlistat dose is 120mg tds and there is no value in
increasing this. NICE do not recommend the
combination of sibutramine and Orlistat as there Which of the following would be the most
is no evidence to support the combined appropriate approach to his weight management?
treatment. (Please select 1 option)
1- Recommend admission for supervised very

[ Q: 261 ] Question ID #45 low calorie diet (600 kcal/d)
2- Recommend for bariatric surgery
A 42 year old female is commenced on Orlistat as
treatment of her obesity. Through which of the 3- Recommend Metformin
following mechanisms does Orlistat function in
4- Recommend Orlistat 60 mg tds
helping to reduce weight?
5- Recommend Orlistat 120 mg tds
1- Combined Noradrenergic/Serotinergic
Answer & Comments
uptake inhibitor
2- Endocannabinoid receptor antagonist Answer: 2- Recommend for bariatric surgery
3- GLP-1 receptor agonist

The most appropriate treatment for this patient's
4- Intestinal lipase inhibitor weight problems is bariatric surgery. NICE
recommend bariatric surgery as the primary
5- PYY 3-36 agonist treatment modality in individuals with a BMI
above 50. In this patient, the fasting plasma
Answer & Comments glucose also suggests a diagnosis of diabetes, yet
the question focuses on weight management and
Answer: 4- Intestinal lipase inhibitor so metformin is really not associated with any real
weight loss. Again, the very low calorie diets have
Orlistat is an effective agent to assist with weight little to support their use for sustained weight loss.
loss acting as a lipase inhibitor reducing the
absorption of fat from the GI tract by the order of [ Q: 263 ] Question ID #47
approximately 30%. Thus, side effects of Orlistat
include flatulence, watery diarrhoea and GI upset.
A 28 year old female has been struggling with her
weight for a number of years and now attends
[ Q: 262 ] Question ID #46 clinic. She has tried a number of dietary schemes
without much success and is currently trying to
A 50 year old male seeks advice regarding employ a hypocaloric diet. She has a history of
treatment of his obesity. He has had a struggle polycystic ovarian syndrome and has been advised
with weight problems for many years and has had from the gynaecological clinic that she needs to
difficulty losing weight with diet and exercise lose weight. Lately she has also been a little tearful
regimes. He has not tried any medical therapies. concerning her weight and is occasionally tearful
during the consultation. Currently she is not taking

any treatment. Her weight is 86kg and she has a Answer & Comments
BMI of 27.8 kg/m2. Her pulse is 72 bpm and her
blood pressure is 126/78 mmHg. She is keen to Answer: 2- Autosomal recessive
receive some kind of intervention to help with her
weight loss. Laurence-Moon-Biedl syndrome is an autosomal
recessive disorder that is typified by severe
Which of the following would you recommend? obesity, hypogonadism, hyperphagia and optic
(Please select 1 option) atrophy.
1- Bariatric surgery
2- Continue with education, diet and exercise
3- Fluoxetine A 51 year old gentleman is referred by his GP for
review of his glucose control and insulin dosage.
4- Orlistat He has a 7 year history of type 2 diabetes. He has
5- Sibutramine a previous history of ischemic heart disease having
been commenced on insulin following his
myocardial infarction 3 years previously.
Answer & Comments
Answer: 2- Continue with education, diet and On examination, body weight is 144 kg, BMI 51 Kg
exercise / m2 pulse 67 bpm, blood pressure 160/88 mmHg.
He has already tried an exercise regime and other
weight loss measures recommended by his doctor
This young female has a BMI indicating that she is with little effect. His current mediation includes
overweight. The NICE criteria recommends metformin 1 gram twice daily, simvastatin 40 mg
pharmacological intervention in patients with a daily, Novomix 30/70 mixed insulin 114 units in
BMI above 27 who have other co-morbidities the morning, 120 units evening time, ramipril 10
including diabetes, hypertension etc. The mg daily, bisoprolol 5 mg daily and Aspirin 75 mg
presence of PCOs does not fulfill this criteria and daily having been previously intolerant of orlistat.
the patient should be counselled and advised on
adhering to a hypocaloric diet which should be Investigations reveal
complemented by an appropriate exercise regime.
Hba1c 9.8% (<6)
A 16 year old male with severe obesity is
diagnosed with Laurence-Moon-Biedl syndrome. TSH 2.9 mu l (0.32 - 5.5)
58 ml / min / 1.73 m2 (90
Which of the following is the mode of inheritance eGFR
- 110)
of this condition? albumin creatinine
5.5 mg / mmol (<2.5)
(Please select 1 option) Ratio
1- Autosomal dominant
2- Autosomal recessive therapy option for this patient?
3- Mitochondrial (Please select 1 option)
4- X-linked dominant 1- Conversion to insulin detemir
5- X-linked recessive 2- Conversion from insulin to exenetide

3- Addition of Exenatide

4- Addition of Orlistat This patient has failed to lose appropriate weight

using medical therapies. The Orlistat should be
5- Referral for Bariatric surgery.
stopped and the patient does fulfil the criteria for
bariatric surgery and this should be considered.
Answer & Comments Laparoscopic banding is the recommended
treatment for patients with a BMI above 35 with
Answer: 5- Referral for Bariatric surgery. an associated co-morbidity (such as diabetes) and
for those patients with a BMI above 40. In patients
This patient fulfils referral criteria for bariatric with a BMI above 50, bariatric surgery is regarded
surgery in that he is morbidly obese (BMI above as the primary therapeutic modality.
40) with associated co-morbidities including
poorly controlled diabetes, hypertension and [ Q: 267 ] Question ID #105
ischaemic heart disease. Conversion to another
insulin regimen is unlikely to have additional
benefit while sibutramine is contraindicated due A 62 year old male is being treated for ischaemic
to his hypertension. Long-term weight loss heart disease with simvastatin. However, he
response to gastroplasty or banding is between 16 develops myalgia whilst taking this treatment and
and 25% at 10 years. Bariatric surgery has been is switched to ezetimibe.
shown to result in a 39% relative risk reduction in
all cause mortality at 10 years post surgery, while Which of the following best describe the
diabetes remission rate at 10 years is around 40%. mechanism of action of ezetimibe?
[ Q: 266 ] Question ID #84 1- A 3-HMG-CoaA inhibitor
2- PPAR-alpha agonist
A 44 year old female attends the weight
management service. She has a three year history 3- PPAR-gamma agonist
of diet controlled type 2 diabetes with a HbA1c of
4- Reduces cholesterol reabsorption through
6.7%. She has been unsuccessful in losing weight
over the last 1 year. Most recently she is taking inhibition of cholesterol transport protein
Orlistat 200mg tds for the last three months and 5- Reduces cholesterol reabsorption through
her weight has fallen by 1 kg. Her BMI is 38.8 binding intestinal bile salts
kg/m2. She remains frustrated at not being able to
lose weight and is keen to receive treatment.
Answer & Comments
Which of the following would you recommend? Answer: 4- Reduces cholesterol reabsorption
(Please select 1 option) through inhibition of cholesterol transport
1- Add metformin to current dose of Orlistat protein
2- Continue with Orlistat for further 3 months

Ezetimibe is a new class of cholesterol lowering
3- Increase dose of Orlistat agent which acts through the inhibition of a
cholesterol transport protein reducing the
4- Stop Orlistat and refer for bariatric surgery
reabsorption of cholesterol from the GI tract. It
5- Stop Orlistat and refer for further dietary may therefore contribute to an approximate 20%
advice reduction in total cholesterol concentrations and
is useful agent in those unable to take statins –
3HMG-CoA inhibitors.
Answer & Comments
Answer: 4- Stop Orlistat and refer for bariatric
surgery

From which of the following is Glucagon-like An 18 year old female who presents with
Peptide 1 (GLP-1) produced? oligomenorrhoea is found to have non-classical
(Please select 1 option) congenital adrenal hyperplasia. She enquires as to
the risk of any of her future children suffering the
1- Body of stomach disorder.
2- Ileum
Which of the following is correct concerning this
3- Liver risk?
4- Pancreas (Please select 1 option)
5- Pylorus 1- Virtually 0%
2- 1%
Answer & Comments
3- 5%
Answer: 2- Ileum
4- 25%
GLP-1 is a hormone produced by the L-cells of the 5- 50%

ileum and has effects on insulin and glucagon
secretion by the pancreatic islets, as well as having Answer & Comments
central effects regulating caloric intake.
Answer: 2- 1%

The patient has non-classical CAH which is most
likely due to 21 hydroxylase deficiency. It is an
Which of the following effects are mediated by
autosomal recessive condition and the gene
GLP-1?
frequency is approximately 1 in 40 in the general
(Please select 1 option) population. Thus, the chances of this girl meeting
1- Delayed gastric emptying time a partner heterozygous for CAH is 1 in 40 yet she
is homozygous for the condition. Therefore, the
2- Increased jejunal transit time chances of her having a child with CAH is 1 in 2
3- Increased gastric acid secretion with this person (50% chance that any children will
be HMZ and 50% chance that they will be
4- Increased pancreatic exocrine enzyme unaffected HTZ). Thus the overall chance of having
secretion a child with CAH would be 1 in 40 x 1 in 2 = 1 in 80
or roughly 1%.
5- Increased bile acid secretion

Answer & Comments
Answer: 1- Delayed gastric emptying time A 45 year old male attends the weight
management service. He receives advice from the
GLP-1 produces satiety through a number of nurse regarding diet and exercise as his BMI is 33
mechanisms including reduced gastric emptying kg/m2. He is informed about a hypocaloric diet
and is also felt to act through central effects particularly in relation to his total daily energy
reducing hunger. expenditure and hence the likely weight loss one
would see from this calorie restriction. He
enquires as to what is his total daily energy
expenditure.

Which of the following is the total daily energy ESR 10 mm/hr (0 - 15)
expenditure for an average male?
(Please select 1 option) Which of the following is the most likely diagnosis?
1- 1000 kcal (Please select 1 option)
2- 1500 kcal 1- Becker's muscular dystrophy
3- 2000 kcal 2- McArdle's disease
4- 2500 kcal 3- Non-alcoholic steatohepatosis
5- 3000 kcal 4- Thyrotoxic periodic paralysis

5- Vitimin D Deficiency
Answer & Comments
Answer & Comments
Answer: 4- 2500 kcal
Answer: 2- McArdle's disease
The typical total energy expenditure for a male is
2500 kcal/d and 2000 kcal per day for a female. Of The most likely diagnosis in this scenario is
course, with increasing weight, the patient will McArdle's disease, a type V glycogen storage
have increased total energy expenditure but these disorder associated with myophosphorylase
averages are important as restricting calorie deficiency resulting in a reduction in the
intake to recommended levels of 1500-1600 glycogenolysis within muscle. This is not likely to
kcals/d will result in a calorie deficit which be thyrotoxic periodic paralysis as typically the
translates into approximately 0.5kg weight loss CPK is normal. Nor is this likely to be Becker’s
per week. Muscular dystrophy as weakness is reported
without any obvious muscle loss or fasciculation.
[ Q: 272 ] Question ID #133 The so-called ‘liver enzymes’ are also found in
muscle and signify damage. Often the CPK may be
elevated after doing some exercise.
A 21 year old male presents with a long history of
weakness, muscle cramps and ease of fatigue. He
denied use of any illicit substances and was [ Q: 273 ] Question ID #134
otherwise fine. His mother had type 2 diabetes
and he had two other brothers who were well. A 44 year old male with a long history of epilepsy
There was little of note on examination, his BMI and associated learning difficulties was admitted
was 29 kg/m2 and the following results were as his carers felt that he was more subdued and
obtained: unwell. There was little history to obtain directly
although his carers stated that he was normally
U+Es Normal much brighter and communicative. He was taking
AST 94 iu/l (5 - 40) Omeprazole for GORD, Thyroxine, Olanzapine, Co-
codamol on a PRN basis, Topirmate and had
ALT 90 iu/l (5 - 40) recently been prescribed Co-trimoxazole by his GP
Alkaline phosphatase 88 ui/l (50 - 110) for assumed UTI.
Bilirubin 12 micromol/l (0 - 18)
On examination, he appeared subdued and
CPK 1020 iu/l (30 - 220) uncommunicative with a GCS of 15. His
LDH 300 iu/l (90 - 250) temperature was 37.2C, blood pressure 118/72
Calcium 2.4 mmol/l (2.2 - 2.6) mmHg, pulse of 110 bpm, oxygen saturations of
98% on air and a respiratory rate of 30/min. No
Antibody screen Negative specific signs were noted on examination of the
FBC Normal

chest, praecordium or abdomen. No focal fistulas, hyperparathyroidism are all capable of

neurology was noted. producing a normal anion gap acidosis.
Investigations revealed: [ Q: 274 ] Question ID #145
FBC Normal
A 44 year old male presents with a three month
Sodium 144 mmol/l (134 - 144) history of profuse watery diarrhoea. No specific
Potassium 3.9 mmol/l (3.5 - 5) abnormalities are noted on examination and
colonoscopy and stool culture are negative.
urea 10.2 mmol/l (3 - 8)
Investigations reveal the following results:
140 micromol/l (50 -
Creatinine
100) Polypeptide P 210 pmol/l (<300)
Chloride 122 mmol/l (95 - 105) VIP 350 pmol/l (<30)
Fasting Plasma Gastrin 33 pmol/l (<40)
7.8 mmol/l (3.5 - 5.6)
Glucose
Glucagon 25 pmol/l (<50)
pH 7.12 (7.35 - 7.45)
Standard bicarbonate 11 mmol/l (22 - 28) Which of the following is the most appropriate
pCO2 4.2 kPa (4.5 - 6) investigation?
pO2 14.5 kPa (10 - 13) (Please select 1 option)
Lactate 1.2 mmol/l (0.5 - 1.5) 1- Endoscopic ultrasound

2- MRI abdomen
(Please select 1 option) 3- No further investigation required
1- Co-trimoxazole induced acidosis 4- Selective pancreatic sampling
2- Diabetic ketoacidosis 5- Somatostatin scintigraphy
3- Methanol consumption
Answer & Comments
4- Olanzapine induced acidosis
Answer: 2- MRI abdomen
5- Topiramate induced acidosis
This patient appears to have a VIPoma – Werner-
Answer & Comments Morrison syndrome. This is due to a pancreatic
neuroendocrine tumour in over 90% of cases and
Answer: 5- Topiramate induced acidosis
is associated with profuse watery diarrhoea and
fasting VIP concentrations typically 10 times
The patient has a hyperchloraemic acidosis with a elevated. Imaging the pancreas would be the most
normal anion gap {sodium – appropriate step here with and would be expected
(bicarboinate+chloride) = 11 – NR 8-16}. In this to localize the tumour effectively as they are
case the normal anion gap would exclude all the typically larger than 2cm. Surgical resection is the
typical causes as found with high anion gap – lactic treatment of choice but somatostatin analogues
acidosis, DKA, methanol etc (A useful mnemonic would be used to control symptoms prior to
for high anion gap metabolic acidosis is surgery.
MUDPILES). Loss of bicarbonate ions is often a
cause of normal anion gap acidosis – renal tubular
acidosis. In our case, Topiramate causes a type 2
RTA and loss of bicarbonate ions. Acetazolamide,

[ Q: 275 ] Question ID #149 This is quite a common referral from general

practice. Do not measure estradiol concentrations
A 21 year old female is referred to clinic by her in patients on the OCP.
general practitioner who is concerned regarding
menstrual irregularity and abnormal [ Q: 276 ] Question ID #154
investigations. She describes rather irregular
periods with cycles of between 28-40 days. Her A 44 year old male presents with a rash in the
last period was 40 days ago. Her menarche was at groin, weight loss and diarrhea. He is diagnosed
the age of 13 and her periods were generally with a glucagonoma.
regular. She commenced the oral contraceptive
Microgynon one year ago for contraception and Which of the following is the correct diagnosis of
claims to regularly take this. She denies any use of
this rash?
illicit substances.
She is otherwise well, has a BMI of 30.2 kg/m2 and 1- Acrodermatitis enteropathica
has a no abnormalities on examination.
2- Epidermolysis bullosa
The investigations included by the GP reveal: 3- Necrolytic migratory erythema
4- Pellagra
Thyroid function tests Normal
Prolactin 350 mu/l (<450) 5- Pyoderma gangrenosum
Estradiol <80 pmol/l (130-800)
Answer & Comments
LH 1.2 mu/l (2-10)
FSH 1.4 mu/l (2-10) Answer: 3- Necrolytic migratory erythema
Which of the following is the likely explanation? The typical rash associated with glucagonoma is a
(Please select 1 option) necrolytic migratory erythema which is often
located in the perineal region. The underlying
1- Craniopharyngioma histology is inflammation and separation of the
2- Drug induced superficial layers of the epidermis.
3- Non-functioning pituitary tumour Necrolytic Migratory Erythema

4- Primary ovarian failure
5- Silent pituitary infarction [ Q: 277 ] Question ID #155
A 55 year old female is diagnosed with carcinoid

Answer & Comments
syndrome after presentation with diarrhoea. She
Answer: 2- Drug induced is treated with octreotide 50 micrograms tds and
is noted to have a marked improvement in her
diarrhoea. With dose increase she begins to notice
This patient has low LH/FSH and undetectable
that the stools now become rather bulky, pale and
estradiol – a consequence of the use of the
oily.
combined oral contraceptive – microgynon. The
synthetic estrogen, ethinyl estradiol, is used in the
Which of the following is the most likely
OCP and is not detected by 17beta oestradiol
assays. Thus, the high concentration of ethinyl explanation for this?
oestradiol effectively suppresses LH/FSH and (Please select 1 option)
prevents ovulation – this is how it works as an
1- Diverticular disease
OCP.

2- Extensive terminal ileal disease Answer & Comments

3- Gallstones Answer: 5- Syndrome of inappropriate ADH
4- Pancreatic exocrine deficiency secretion
5- Pancreatic tumour infiltration

The diagnosis is SIADH, based on the biochemistry
results.
Answer & Comments
Answer: 4- Pancreatic exocrine deficiency [ Q: 279 ] Question ID #164
The most likely explanation is pancreatic exocrine A 55 year old male attends for an insurance
insufficiency, a side effect of the octreotide medical. He is generally fit and has no medical
therapy and caused by inhibition of pancreatic history of note. He is a non smoker and drinks
enzyme secretion. This is well described and may approximately 10 units of alcohol each week. His
be treated with pancreatic enzyme family history includes his father having died at the
supplementation such as Creon. age of 54 of a heart attack.
His blood pressure is 132/80 mmHg and his BMI is

[ Q: 278 ] Question ID #157 31.6 kg/m2. Blood investigations reveal:
You are asked to review a patient on the Cholesterol 5.8 mmol/l (<5)
neurosurgical ward. He has had an aneurysm
clipped following subarachnoid haemorrhage but Triglyceride 1.5 mmol/l (0.8- 2.0)
the neurosurgeons are concerned that his sodium HDL 1.0 mmol/l (0.9 - 1.9)
concentration has fallen. Currently his sodium Plasma Glucose 5.4 mmol/l (3.5 - 5.6)
concentration is 118 mmol/l. Further
investigations reveal: He is advised a low cholesterol diet only. By how
much would this be expected to lower his
Urea 4 mmol/l (3-8) cholesterol concentration?
Potassium 4.4 mmol/l (3.5-5) (Please select 1 option)
Plasma Osmolality 254 mosmol/l (275-295) 1- 10%
Urine Sodium 50 mmol/l
2- 20%
Urine Osmolality 440 mosmol/l
3- 30%
Which of the following is the most likely 4- 40%
explanation of this patient’s hyponatraemia?
5- 50%
1- Acute hypoadrenalism Answer & Comments

2- Hypovolaemic hyponatraemia
Answer: 1- 10%
3- Pituitary apoplexy
4- Pseudohyponatraemia This patient has a strong family history of
premature cardiovascular disease with his father
5- Syndrome of inappropriate ADH secretion having died of a MI at the age of 54. In this man's
case, risk equations would suggest a 15% risk of a
cardiovascular event in the next 10 years which
would be regarded as moderate. Yet, when one
considers the significant family history, this risk

needs to be multiplied by a factor of 1.5, placing

him at a high risk in excess of 20%. In this scenario,
a healthy diet, low in saturated fats should be
suggested. His modest alcohol is protective
against cardiovascular disease. Similarly lifestyle
interventions such as increased exercise should be
encouraged. However, one would wish to target
his cholesterol concentration with an aim to
reduce his cholesterol to below 5 mmol/l. Diet
would be expected to reduce cholesterol by only
10% which would not succeed in achieving target
cholesterol. Hence, the most appropriate
approach to reducing this patient's cardiovascular
risk would be the introduction of a statin which
reduces cholesterol by the order of 30-50%.
Reference:
British Heart Society - Cardiovascular Risk
Prediction Chart
A 41 year old gentleman attends his GP for a

routine life insurance medical. He has no past
medical history of note and feels generally well.
On examination his blood pressure is 155 / 85
mmHG, his BMI is 32 kg / m2, his waist
circumference is 102 cm and his body weight is
98.4 kg.
Fasting Plasma Glucose 5.3 mmol/l (3.5 - 6)

Total Cholesterol 5.4 mmol/l (<5.5)
Plasma Triglyceride 2.1 mmol/l ().9 - 2.2)
HDL Cholesterol 0.9 mmol/l (0.9-1.9)
LDL Cholesterol 3.3 mmol/l (<2)

Based upon the IDF criteria, which of the following Reference:

would support a diagnosis of the metabolic http://www.idf.org/webdata/docs/MetSyndro
syndrome in this man? me_FINAL.pdf
1- His BMI, triglyceride concentration and
fasting glucose
A 49 year old man attends the medical outpatient
2- His BMI, blood pressure and triglyceride clinic for review of his blood pressure control. His
concentration current medication includes perindopril 8 mg
daily, amlodipine 5 mg daily and doxazosin 4 mg
3- His Waist circumference, blood pressure and
daily. On examination, his blood pressure is 156 /
fasting glucose 88 mm Hg, his BMI is 34 kg / m2 and his waist
4- His Waist circumference, blood pressure and circumference is 96 cm.
HDL concentration
Fasting Plasma Glucose 5.4 mmol/l (3.5 - 6)
5- His Waist circumference, HDL-cholesterol
and total cholesterol Total Cholesterol 4.6 mmol/l (<5.5)
Plasma Triglycerides 1.8 mmol/l (0.9 - 2.2)
Answer & Comments HDL Cholestgerol 0.8 mmol/l (0.9 - 1.9)
Answer: 4- His Waist circumference, blood LDL Cholesterol 3.2 mmol/l (< 3)
pressure and HDL concentration
Which of the following criteria would suggest a
diagnosis of metabolic syndrome in this gentleman
This gentleman meets the criteria for the according to the International Diabetes
metabolic syndrome, as defined by the
Federation?
International Diabetes Federation, since he has
central obesity (waist circumference ≥94 cm), a (Please select 1 option)
plasma triglyceride ≥1.7 mmol/l, blood pressure 1- BMI, LDL-C concentration and blood
≥130 / 85 mm Hg and a HDL-cholesterol < 1.04 pressure
mmol/l.
2- BMI, fasting plasma glucose and plasma
The IDF definition of the metabolic syndrome is triglyceride concentration
based on the presence of central obesity (waist
3- Waist circumference, HDL-cholesterol
circumference in Europeans is ≥94 cm in men and
concentration and blood pressure
≥80 cm in women) combined with any two of the
following: 4- Waist circumference, triglyceride
concentration and LDL-cholesterol
Plasma concentration
≥1.7 mmol/l
Triglyceride
5- Waist circumference, HDL-cholesterol and
HDL LDL-cholesterol concentration
< 1.04 ( Men)
Cholesterol
HDL
< 1.29 (Women) Answer & Comments
Cholesterol
Fasting Answer: 3- Waist circumference, HDL-cholesterol
Plasma ≥ 5.5 mmol/l concentration and blood pressure
Glucose
Blood ≥ 130/85 mm Hg or recieving This gentleman meets the criteria for the
Pressure Anti-Hypertensive Treatment metabolic syndrome, as defined by the
International Diabetes Federation, since he has

central obesity (waist circumference ≥94 cm), a Which of the following treatments is associated
plasma triglyceride ≥1.7 mmol/l, blood pressure with the greatest reduction in future
≥130 / 85 mm Hg and a HDL-cholesterol < 1.04 morbidity/mortality for this man?
mmol/l.
The IDF definition of the metabolic syndrome is 1- Bariatric surgery

based on the presence of central obesity (waist
2- Gliclazide 80mg twice daily
≥80 cm in women) combined with any two of the 3- Exenetide 5 micrograms twice daily
following:
4- Sitagliptin 100 mg once daily
Plasma 5- Pioglitazone 30 mg daily

≥1.7 mmol/l
Triglyceride
HDL Answer & Comments
< 1.04 ( Men)
Cholesterol
Answer: 1- Bariatric surgery
HDL
< 1.29 (Women)
Cholesterol
Data from the Swedish obesity study coupled with
Fasting long term follow up data post-bariatrc surgery
Plasma ≥ 5.6 mmol/l have demonstrated diabetes remission in up to
Glucose 70% of patients at 5 years following bariatric
Blood ≥ 130/85 mm Hg or recieving surgery, with up to 40 % of patients demonstrating
Pressure Anti-Hypertensive Treatment remission of diabetes at 10 years post surgery.
These observations are coupled with a 29%
Reference: reduction in all cause mortality associated with 16
http://www.idf.org/webdata/docs/MetSyndro – 25% excess weight loss at 10 years post bariatric
me_FINAL.pdf surgery, along with a 92% reduction in diabetes
related mortality.
A 39 year old gentleman is referred to clinic for
review. He has a 2 year history of type 2 diabetes A 71 year old gentleman is admitted to hospital
and his current medication includes Metformin 1 following admission to hospital with a mechanical
gram twice daily, perindopril 8 mg daily and fall. On admission, his random plasma glucose is
simvastatin 40 mg daily. He was also taking 12.4 mmol/l (<7.8) and a subsequent fasting
rosiglitazone 4 mg daily, but discontinued this 4 plasma glucose measures 7.9 mmol/l (<6). He is
months ago due to progressive weight gain; he has generally well, taking no regular medications and
also been intolerant of orlistat due to abdominal on examination his blood pressure is 146/86
discomfort and diarrhoea. On examination, his mmHg and his BMI is 31 kg / m2.
BMI is 43 kg/m2 and his blood pressure is 166/88
mmHg. Further investigations reveal:
Investigations reveal: Hba1c 7.1% (<6)

Hba1c 8.9% (<6)
Plasma Triglyceride 3.1 mmol/l (0.9 - 2.2) LDL Cholesterol 3.7 mmol/l (<2)
TFTs Normal HDL Cholesterol 0.9 mmol/l (0.9 - 1.9)

According to the Strong Heart Study, which of the 1- Metabolic alkalosis

following is the most important determinant of the
2- Respiratory alkalosis
future risk of cardiovascular events in this
gentleman? 3- Laboratory error
(Please select 1 option) 4- Metabolic alkalosis with respiratory acidosis
1- Total cholesterol level 5- Mixed metabolic and respiratory alkalosis
2- LDL-cholesterol level
Answer & Comments
3- HDL-cholesterol level
4- Plasma Triglyceride Level Answer: 5- Mixed metabolic and respiratory
alkalosis
5- Non-HDL-cholesterol level
To begin the interpretation, the patient has an
Answer & Comments alkalosis as reflected by the high pH. The
bicarbonate is high indicating a metabolic alkalosis
Answer: 5- Non-HDL-cholesterol level
but she is also hypoxic with a lowish pCO2. This
suggests a combined metabolic and respiratory
The results of the Strong Heart Study indicate that alkalosis. This picture could be found in
non-HDL-C may be a superior predictor of association with lung disease and prolonged
cardiovascular events than LDL-C; HDL-C or plasma vomiting.
TG levels alone in both men and women with type
2 diabetes. The utility of non-HDL-C in predicting
cardiovascular events in non-diabetic subjects is
supported by data from the SHEP (Systolic
Hypertension in the Elderly Program) and Lipid A 15 year old male is investigated for fatigue. His
Research Clinics (LRC) studies, in which non-HDL-C academic performance is also very poor being in
was found to be a better predictor than LDL-C of the remedial class. Examination is normal with a
cardiovascular events in patients followed over pulse of 68bpm and blood pressure of 106/70
4.5 years and 19 years respectively. mmHg. Investigations reveal:
Non-HDL cholesterol includes VLDL, IDL, LPa apart Analysis of a 24hour urine collection reveals:
from LDL Cholesterol.
[ Q: 284 ] Question ID #340 Potassium 2.9 mmol/L (3.5-5)
A 63 year old female is admitted with a two day Bicarbonate 36 mmol/L (20-28)
history of being unwell and deteriorating
confusion. Arterial blood gas analysis reveals: Random Glucose 4.5 mmol/L (3.0-6.0)
Potassium 266 mmol/24h (25-100)
pH 7.65 (7.36-7.44) Sodium 92 mmol/24h (100-250)
pO2 8 kPa (11.3-12.6) Serum Magnesium 0.8 mmol/L (0.7-1.2)
pCO2 4.5 kPa (4.7-6.0)
Standard Bicarbonate 35 mmol/L (20-28)
Which of the following is the correct interpretation 1- Bartter syndrome
of these blood gas results?
2- Conn's syndrome

3- Gitelmann syndrome 30 minute 780 (post 250 µg

4- Liddle's syndrome cortisol nmol/L ACTH injection)
Serum 254
5- Renal artery fibromuscular dysplasia
osmolality mOsm/Kg
Urine 480
Answer & Comments osmolality mOsm/Kg
Answer: 1- Bartter syndrome Urine spot Na 6 mmol/L
The patient has a hypokalaemic metabolic What is the most appropriate next step in his
alkalosis with urinary potassium wasting, a normal management?
blood pressure and in the context of poor (Please select 1 option)
academic performance is likely to have Bartter
1- Fluid restriction of 1.5 l/day
syndrome. The normal blood pressure makes
Conn's, fibromuscular dysplasia and Liddle's 2- Hypertonic normal saline 1 litre over 6 hours
unlikely. Bartter's syndrome usually presents in and repeat electrolytes
childhood with polyuria, nocturnal enuresis and
growth retardation. Bartter's syndrome is 3- Normal saline 1 litre over 6 hours and repeat
associated with hyperplasia of the juxtaglomerular electrolytes
apparatus. 4- Start demeclocycline
5- Start Tolveptan
A 24 year old who was involved in a car crash 3 Answer & Comments
days ago, is presently being nursed in intensive Answer: 3- Normal saline 1 litre over 6 hours and
care unit. His general physical and systemic repeat electrolytes
examination is unremarkable. The recent
biochemistry results are as shown below:
This 24 year old appears slightly hypovolaemic
(with raised urea and creatinine but has normal
119
Sodium (135-145) physical examination) and has hyponatraemia in
mmol/L
presence of normal thyroid and adrenal function
3.8 (TFT/short synacthen test normal). The serum
Potassium (3.5-5.5)
mmol/L osmolality is low with low levels of sodium
18.3 excretion from the urine (in contrast to SIADH
Urea (3-8) which is associated with low serum osmolality
mmol/L
along with excessive urinary sodium loss- >20
115
Creatinine (60-115) mmol/L). As a result patient may benefit from fluid
µmol/L
replacement and rechecking of his electrolyte
2.65 levels.
Calcium (2.2-2.6 mmol/L)
mmol/L
TSH 2.24 mU/L (0.35-5.5 mU/L) [ Q: 287 ] Question ID #487
16.9 (11.5-22.7
Free T4
pmol/L pmol/L) According to NICE guidelines, which of the
Prolactin 480 mU/L following oral hypoglycaemic agent is safe to use
6.3 in women with gestational diabetes in pregnancy?
Glucose
mmol/L (Please select 1 option)
0 hour 404 1- Acarbose

cortisol nmol/L

2- Gliclazide which is the most common X- chromosomal

abnormality seen in females, with an incidence of
3- Glibenclamide
1:2500 live female births. It is associated with
4- Pioglitazone premature ovarian failure in 90% of affected
patients.
5- Sitagliptine
The characteristic phenotypic features include -
Answer & Comments short stature, webbed neck, high arched palate,
cubitus valgus, epicanthal folds and widely spaced
Answer: 3- Glibenclamide nipples. The associated abnormalities include co-
arctation of aorta, hypothyroidism,
According to NICE guidelines on diabetes and lymphoedema, celiac disease, chronic liver disease
pregnancy (NICE Clinical guidelines 63), and rheumatoid arthritis. The management
Glibenclamide is a safe agent to be used in women includes growth hormone replacement till the
with gestational diabetes. The other agents which final height is reached and life-long oestrogen
can be used safely in pregnancy include: replacement therapy.
 Metformin [ Q: 289 ] Question ID #613

 Rapid acting insulin analogues such as
aspart and lispro
What's the likely mode of action of Carbimazole?
 Isophane insulin (NPH)
[ Q: 288 ] Question ID #612 1- Inhibition of the sodium -Iodide symport

2- Inhibition of TPO activity
A 17 year girl with history of sensory-neural
hearing loss and primary hypothyroidism presents 3- Inhibition of conversion of T4 to T3
to the clinic with primary amenorrhoea. She is 148 4- Inhibition of TBG
cm tall with body weight of 60 Kg. She has widely
spaced nipples and cubitus valgus on examination. 5- Inhibition of TSH receptors
Her uterus is small on ultrasound with left kidney
not visualised. Answer & Comments
What is the likely underlying diagnosis? Answer: 2- Inhibition of TPO activity

Carbimazole (CBZ) and Propylthiouracil (PTU) act
1- Alport syndrome by inhibiting the action of thyroid peroxidase
2- Congenital adrenal hyperplasia (TPO) enzyme. PTU in addition inhibits the
peripheral conversion of T4 to T3 (by inhibition of
3- Mixed Gonadal dysgenesis (XY mosaic) 51 deiodinase Type 1 activity). Perchlorate and
4- Polycystic ovarian syndrome thiocyanates inhibit iodide transport.
5- Turner syndrome
Answer & Comments

A 42 year old lady, with past medical history of
Answer: 5- Turner syndrome breast cancer, presents with a lump in neck. She is
clinically euthyroid and on examination has
irregular nodules on tongue. A 1.2 cm, firm thyroid
Presence of primary amenorrhoea, short stature,
nodule is palpable on the left side. There is no
thyroid and renal abnormalities noted in this girl, enlargement of cervical lymph nodes.
points towards the diagnosis of Turner syndrome,

What is the likely underlying syndrome? Answer & Comments

(Please select 1 option) Answer: 5- Reassure and discharge
1- Carney complex
2- Cowden syndrome In a child with idiopathic growth hormone
deficiency diagnosed in childhood, the growth
3- MEN 2b syndrome hormone axis should be reassessed on transition
4- Neurofibromatosis to adulthood as the spontaneous remission can be
seen in a number of such children. The gold
5- vHL syndrome standard for assessment of GH secretion remains
insulin tolerance test (ITT) in absence of
Answer & Comments contraindications for the test. GH levels of <3 µg/L
(<10 mU/L) are usually indicative of severe GH
Answer: 2- Cowden syndrome deficiency. This 16 year old is showing adequate
growth hormone secretion on ITT, as a result his
Cowden syndrome is an Autosomal dominant therapy can be safely discontinued.
condition a consequence of an inactivating
mutation of PTEN tumour suppressor gene. It is [ Q: 292 ] Question ID #641
characterised by multiple hamartomas involving
all the germ cell layers, susceptibility to develop MEN-2 syndrome is associated with
breast, thyroid and endometrial cancers and
involvement of thyroid gland in majority of the
patients. The thyroid pathologies associated with 1- Activating mutation of RET proto-oncogene
Cowden syndrome include differentiated thyroid
2- Inactivating mutation of RET proto-oncogene
carcinomas, adenomas and multinodular goitre.
3- MENIN mutation
[ Q: 291 ] Question ID #634 4- NF-1 mutation
5- VHL mutation
A 16 year old with past medical history of
idiopathic growth hormone deficiency is reviewed
in the transition clinic. He has been on growth Answer & Comments
hormone replacement therapy for last 7 years. His
Answer: 1- Activating mutation of RET proto-
Insulin tolerance test (ITT) done after
oncogene
discontinuation of GH injections for 4 weeks, show
GH response of > 25 mU/L.
MEN- 2 syndrome is an autosomal dominant
What is the most appropriate step in his further condition due to mutation in RET proto-oncogene
management? located on chromosome 10. RET is a single
transmembrane domain comprising of an
extracellular domain (which is cysteine rich) and
1- Check IGF-1 levels an intracellular tyrosine kinase domain. MEN 2A is
associated with activating mutation of
2- Check IGFBP 3 levels
extracellular cadherin like domain in contrast to
3- Continue growth hormone injections MEN 2B which is associated with mutation in the
intracellular domain.
4- Reassess the growth hormone secretion in 6
months
A 44 year old undergoes bariatric surgery which
leads to loss of 3 stone weight loss. 6 months post

operatively, while driving down a tunnel, he Sulfonylurea screen negative

develops inability to see clearly and narrowly
misses having an accident. What is the next best step to establish the likely
underlying diagnosis?
Which is the likely mineral/vitamin deficiency
contributing to his visual impairment?
(Please select 1 option) 1- Check her IGF-1 to IGF-2 ratio
1- Copper 2- CT abdomen
2- Vitamin A 3- CT angiography
3- Vitamin B6 4- Enquire about likely use of exogenous

injections
4- Vitamin B12
5- Gut hormone profile
5- Zinc
Answer & Comments

Answer & Comments
Answer: 4- Enquire about likely use of exogenous
Answer: 2- Vitamin A injections
Vitamin A and D are fat soluble vitamins which Hypoglycaemia in non-diabetics is traditionally
may be deficient in patients who undergo bariatric classified as post-absorbative (fasting)
surgery and develop malabsorption during post hypoglycaemia or post-prandial (reactive)
operative phase. The shortening of length of
hypoglycaemia. However, whether a patient
bowel and dumping syndrome contribute to appears to be ill or well, is now regarded as a
process of malabsorption. better factor in assessing the cause of
hypoglycaemia. In a well appearing individual,
Vitamin A deficiency is associated with night causes of hypoglycaemia include:
blindness, xerophthalmia and occasionally
complete blindness (Vitamin A deficiency being  Drugs - insulin or insulin secretagogue;
one of the leading preventable causes of blindness alcohol; other drugs
in developing countries!). Night blindness usually  Accidental, surreptitious, or malicious
manifests as inability in adjustment to dimmed hypoglycaemia
light and is an early feature of Vitamin A  Endogenous hyperinsulinism - insulinoma;
deficiency. The production of eye pigment - functional beta cell disorders
Rhodopsin (found in retina), which is responsible nesidioblastosis); noninsulinoma
for sensing low light situations is impaired in pancreatogenous hypoglycaemia;
Vitamin A deficiency. postgastric bypass hypoglycaemia; insulin
autoimmune hypoglycaemia; anti-insulin
[ Q: 294 ] Question ID #660 antibody; anti-insulin receptor antibody
 Idiopathic postprandial hypoglycaemia
A 44 year old woman is admitted for further
investigations of her hypoglycaemic episodes. Her In this non-diabetic patient with hypoglycaemia,
72 hour fasting blood results are shown below: her fasting blood results reveal a raised insulin
level with a normal c-peptide level, which is
suggestive of an exogenous insulin source.
(3.5-
Blood sugar 2.2 mmol/L
5.5)
The biochemical pattern for different causes of
Insulin 155 µU/L (<10) hypoglycaemia in non-diabetics are as follows:
C Peptide 10.2 pmol/L (<500)

 Exogenous insulin - raised insulin, normal Erectile dysfunction is defined as inability to

c-peptide, normal proinsulin, negative achieve or maintain an erection for sufficient time
sulphonylurea, negative insulin antibody duration and firmness resulting in incomplete
 Insulinoma - raised insulin, raised c- sexual activity in > 25% of the attempts. About
peptide, raised proinsulin, negative 10% of men are affected by low libido and erectile
sulphonylurea, negative insulin antibodies dysfunction and the prevalence increases with
 Sulphonylurea - raised insulin, raised c- age.
peptide, raised proinsulin, positive
sulphonylurea, negative insulin antibody The following is a list of main causes for erectile
dysfunction:
Reference:
Hypoglycaemia in non-diabetic patients  Medications such as diuretics, β blockers,
MAO inhibitors, opioids, glucocorticoids,
[ Q: 295 ] Question ID #676 tranquilizers, digoxin, antiandrogens,
gemfibrozil
 Systemic illness (heart failure, cirrhosis,
A 45 year old man with Type 2 DM for 8 years uraemia etc.)
presents to clinic with lack of libido and erectile  Neurological conditions such as
dysfunction. His BMI is 32 kg/m2 and there is no autonomic neuropathy, cord compression
loss of secondary sexual characteristics. He denies  Vascular conditions such a peripheral
usage of any substance of abuse and his alcohol vascular disease
intake is 14 units in a week. His biochemistry  Endocrine disease (hypogonadism,
shows: diabetes, thyroid dysfunction)
 Psychological
FSH 2.2 U/L (1-10)  Urogenital abnormalities like trauma,
LH 3.5 U/L (3-10) priapism and Peyronie`s disease
 Alcohol, substance of abuse like heroin,
Testosterone 7.5 nmol/L (9-28.5) marijuana
LFT Normal This gentleman has features of secondary gonadal
failure as evidenced by low testosterone and low
FSH/LH levels. His age group and normal
He undergoes a MRI which shows no obvious
secondary sexual characteristics make it unlikely
abnormality.
for him to have any genetic abnormality like
Kallmann syndrome. A normal MRI rules out any
What is the likely explanation for his low libido?
(Please select 1 option) not on any medication and systemically well. A
1- Anabolic steroid usage normal LFT and transferrin saturation makes it
unlikely for him to have Haemochromatosis.
2- Haemochromatosis
3- Kallmann syndrome Obese individuals have increased activity of
aromatase which converts testosterone to
4- Kleinfelter`s syndrome estrogens which in turn suppress FSH/LH levels.
Total testosterone concentrations are influenced
5- Obesity
by sex hormone-binding globulin (SHBG)
concentrations, which are decreased by obesity
Answer & Comments and increased with ageing.
Answer: 5- Obesity

[ Q: 296 ] Question ID #688  Check TRAb in third trimester, as it can be

transmitted through placenta to baby,
A 31 year old woman who is 11 weeks pregnant leading to neonatal hyperthyroidism
 Treat maternal hyperthyroidism with
presents with tachycardia, tremors and
palpitations. She has strong family history of lowest possible dose of PTU (more protein
autoimmune thyroid disease and goitre. Her bound, less transfer across placenta)
 1 out of 4 Type 1 Diabetics, have evidence
thyroid function test results are as shown below:
of thyroid dysfunction during pregnancy
Free T4 32.8 pmol/L (9-23)

Free T3 11.2 pmol/L (3.5-6.5)
TSH < 0.01 mU/L (0.35-5.5)
A 22 year old lady, planning for a family in near
future, has been diagnosed to have a
What is the best therapeutic option in her case? microprolactinoma based on raised prolactin
(Please select 1 option) levels and MRI scan results.
1- Carbimazole
Which is the best management option in her case?
2- Lugols iodine (Please select 1 option)
3- Propanolol 1- Bromocriptine
4- Propylthiouracil 2- Cabergoline
5- Radioiodine 3- Observe
4- Radiotherapy
Answer & Comments
5- Removal of tumour
Answer: 4- Propylthiouracil
Answer & Comments

The patient is likely to have Graves` thyrotoxicosis
as suggested by features of hyperthyroidism and Answer: 1- Bromocriptine
associated strong family history of autoimmune
thyroid disease. In view of her pregnant state, Bromocriptine is a safe option for females in
treatment with lowest dose of Propylthiouracil, reproductive age group presenting with a
which renders her euthyroid, should be initiated. microprolactinoma if they are seeking a family in
The following are few of the salient points to be near future. The therapy can be stopped once the
remembered as far as pregnancy and thyroid patient conceives and pregnancy is confirmed. The
dysfunction is concerned: dopamine agonists help reduce prolactin levels
and induce ovulation. Therefore, if pregnancy is
 Thyroxine requirement increase in desired women should be given advice regarding
hypothyroid women during first trimester contraception on initiation of therapy.
of pregnancy. Cabergoline usage in pregnant women has also
 TSH levels increase during 2nd and 3rd not been associated with any increased risk of
trimester of pregnancy. foetal malformation, but the available data on its
 Hyperthyroidism in pregnancy is safety profile is limited.
commonly due to Graves` disease (d/d
hyperemesis gravidarum, H mole), so
check TSH receptor antibodies (TRAb) in [ Q: 298 ] Question ID #3348
all such patients.
 Graves` disease can relapse during first A 54 year old man attends for clinical assessment.
trimester and post partum period (more He sustained an MI at the age of 40, but is now
likely to remit during 2nd and 3rd trimester)

clinically stable with no cardiovascular symptoms. Reference:

His lipid profile is well controlled on a combination NICE CG71 (2008) Identification and
of atorvastatin 80 mg once daily and ezetimibe 10 management of familial
mg once daily. He also takes ramipril 10 mg once hypercholesterolaemia for familial
daily and aspirin 75 mg once daily. He has seen a hypercholesterolaemia
specialist privately, who has advised him that he
has ‘possible familial hypercholesterolaemia (FH)’
[ Q: 299 ] Question ID #3350
based upon his history and lipid results. He
recommends that his children, now aged 20 and
24 have ‘appropriate testing’. The patient has read A 35 year old doctor seeks your advice as he has a
that genotyping is advised in individuals with FH, family history of heart disease and has been found
but is concerned as the specialist indicated that to have high cholesterol following tests carried out
this test was not available locally. for a clinical trial. He is very fit and undertakes
regular triathalons. He takes no medication, is a
What is the most appropriate advice with respect non-smoker and teetotal. He is fastidious about
to genetic testing? maintaining a healthy diet. You ascertain that his
father, who is also a non smoker and generally fit,
(Please select 1 option) sustained a non-fatal myocardial infarction (MI) at
1- DNA testing is not required for him but is the age of 44. A paternal uncle sustained a fatal MI
obligatory for his children at the age of 53. He has no stigmata of
hyperlipidaemia, his blood pressure is 118/76
2- DNA testing is obligatory for him, but is not mmHg and waist circumference 80cm, BMI 23
required for his children kg/m2.
3- Genetic testing is not required as the risk of
His lipid profile measurements are:-
his children inheriting the same condition as
him is very unlikely
Reference
Results
4- His children should be started on a statin interval
regardless of any further testing Total
9.8 mmol/L
5- In the absence of DNA testing, his children cholesterol
should be offered lipid testing HDL
1.3 mmol/L >1.0
cholesterol
Answer & Comments Triglycerides 5.7 mmol/L <2.0
Answer: 5- In the absence of DNA testing, his Unable to

Calculated LDL
calculate
children should be offered lipid testing
Fasting glucose 4.6 mmol/L 3.0-6.0
Genetic testing for FH is desirable to confirm the Thyroid profile normal
diagnosis and facilitate cascade testing in his HbA1c 35 mmol/mol <48
relatives. Testing is not universally available in the
Apolipoprotein
UK or elsewhere in the world, although its use is 1.9 g/L 0.4-1.2
B
recommended within NICE guidance. If he were
found to have an FH causing mutation, family
Which of the following is the most likely diagnosis?
members should be offered testing to ascertain if
the family mutation is present. Lipid testing and (Please select 1 option)
potentially treatment should be organised 1- Anabolic steroid misuse
thereafter. In the absence of genetic testing a
clinical diagnosis can be made and lipid testing 2- Familial Combined Hyperlipidaemia
offered to family members. 3- Familial Hypercholesterolaemia

4- Lipoprotein lipase deficiency identified. She has been advised that on this basis,
‘cascade testing’ of her family should be
5- Polygenic Hypercholesterolaemia
undertaken.
Answer & Comments She seeks your advice about cascade testing and
what should be done now:
Answer: 2- Familial Combined Hyperlipidaemia
Familial combined hyperlipidaemia (FCH) is a 1- Cascade testing using DNA is not appropriate
commonly encountered hyperlipidaemia and is as LDL receptor mutations are very rare and
associated with premature cardiovascular disease. full gene sequencing of the son is required
Unlike familial hypercholesterolaemia, the
genetics of the condition are not clear and the 2- Offer a cholesterol test to her son and her
presentation much more variable. Whilst obesity other family members to assess if
and insulin resistance are more commonly hypercholesterolaemia is present in them
associated with FCH, this is not invariably the case. before offering a DNA test
The commonest laboratory findings are raised
3- Offer a DNA test to adult family members
cholesterol and triglycerides (i.e. combined),
and a cholesterol test in family members
together with a raised concentration of
apolipoprotein B. This is the surface protein aged between 8 and 16 years old
present on both very low density lipoproteins 4- Offer a DNA test to adult family members
(VLDL) as well as low density lipoprotein (LDL) and only to assess if the identified mutation is
is a good marker of atherosclerotic risk. Both present in them before offering a
familial and polygenic hypercholesterolaemia are
cholesterol test
less commonly associated with
hypertriglyceridaemia in the absence of diabetes 5- Offer a DNA test to her son and her other
mellitus, obesity or alcohol excess. Anabolic family members to assess if the identified
steroid misuse usually causes low HDL cholesterol. mutation is present in them before offering
Lipoprotein lipase deficiency is very rare, is usually a cholesterol test
associated with a more severe dyslipidaemia and
is inherited in an autosomal recessive manner,
which is not consistent with his family history. Answer & Comments
Answer: 5- Offer a DNA test to her son and her
Reference:
other family members to assess if the
Heart UK Familial Combined Hyperlipidaemia
identified mutation is present in them before
(FCH)
offering a cholesterol test
Larry A. Weinrauch, LA (MD) MedlinePlus
Medical Encylcopedia (2014) Familial
combined hyperlipidemia Individuals who have a high clinical probability of
having FH should be offered genotyping. This can
confirm the diagnosis, but importantly can
[ Q: 300 ] Question ID #3351 facilitate cascade testing. Once the DNA mutation
has been identified in the presenting patient
A 15 year old boy attends clinic with his mother. (known as the ‘index’ patient), testing for the
The mother has just been diagnosed with familial presence or absence of this specific mutation can
hypercholesterolaemia (FH). She has a strong be undertaken in family members. This is carried
family history of premature cardiovascular disease out in a step wise fashion, such that first degree
and was found to have significant relatives i.e. parents, children and siblings are
hypercholesterolaemia. She recently had a genetic tested first and subsequent relatives thereafter.
test carried out and has been advised that a For example if the index patient’s brother does not
mutation in the LDL receptor causing FH has been have the mutation, testing in his children is not

required. If the index patient’s sister does have the The following clinical findings are relevant for the
mutation, her children will be offered testing. diagnosis of familial hypercholesterolaemia:
Offering DNA testing, rather than initial
cholesterol testing in family members is 1- Premature corneal arcus is pathognomonic
recommended, as it provides a definitive answer, of FH and confirms the diagnosis
particularly in younger people when the
2- Premature marked xanthelasma are
cholesterol results may be harder to interpret.
pathognomonic of FH and confirm the
Cholesterol testing should be carried out in family
members who have the family mutation, but in diagnosis
those who do not; this may not be required, 3- Tendon xanthomata are pathognomonic of
particularly for children. DNA testing should be FH and confirm the diagnosis
offered to children by the age of 10. LDL receptor
mutations are the commonest cause of FH. Less 4- The clinical findings are not relevant as the
commonly mutations are found in the apo B or LDL is >7.9 mmol/L, which confirms the
PCSK9 genes. diagnosis
5- The diagnosis may only be confirmed with a
Reference:
Heart UK Children and familial DNA test
hypercholesterolaemia
Answer & Comments
[ Q: 301 ] Question ID #3352 Answer: 3- Tendon xanthomata are
A 39 year old man previously fit and well is diagnosis
admitted to hospital with an acute myocardial
infarction (MI). He is successfully treated with
Tendon xanthomata are pathognomonic of FH and
percutaneous coronary intervention. The
confirm the diagnosis. These may manifest as
admitting doctor notes that his father sustained a
thickening and/or hardening of tendons, usually
fatal MI at the age of 52 and his paternal
associated with distinct nodularity. They are
grandfather sustained a fatal MI at the age of 48.
commonly found in the Achilles’ tendons and
On examination he is found to have xanthomata in
sometimes in other extensor tendons, such as
both Achilles’ tendons, bilateral corneal arcus and
those of the hands. The presence of xanthelasma
marked xanthelasma. His lipid profile is measured
and premature arcus are suggestive, but are not
on admission:
specific for FH. Xanthelasma may be found in the
absence of hypercholesterolaemia, but its finding
Reference should prompt measurement of a lipid profile.
Results
interval Corneal arcus becomes more common with
Total 11.2 advancing age, but it’s presence in a person under
cholesterol mmol/L the age of 40 is suggestive of a lipid disorder. The
HDL 1.3 probability of FH increases with higher LDL
>1.0 cholesterols, but there is no definitive diagnostic
cholesterol mmol/L
cut-off above which the diagnosis is confirmed. A
1.5 DNA test may confirm the diagnosis, but the
Triglycerides <2.0
mmol/L patient may be described as having definite FH in
9.2 the presence of the above profile with xanthoma.
Calculated LDL
mmol/L
5.2 Reference:
Fasting glucose 3.0-6.0 NICE guidelines CG71 (2008) Identification and
mmol/L
management of familial
Thyroid profile normal hypercholesterolaemia

FH Wales Clinical signs of familial Answer & Comments

Answer: 5- The results suggest familial
hypercholesterolaemia and a specialist
[ Q: 302 ] Question ID #3353 referral is appropriate
An 11 year old boy attends clinic with his mother.

Cholesterol is lower in children than in adults and
The boy’s father has just died of a myocardial
the results in the context of the history are
infarction at the age of 32 and the mother is
suggestive of familial hypercholesterolaemia (FH).
concerned. The boy has a paternal uncle who also
Assessment within a specialist paediatric setting is
developed premature ischaemic heart disease at a
appropriate. In FH, ideally the diagnosis should be
young age and is reported to have had a total
made by testing for the known family DNA
cholesterol of 11.5 mmol/L before treatment. Her
mutation, but if this is neither known nor
son has now had his lipid profile measured.
available, lipid testing is appropriate. Deferring the
diagnosis with such a concerning family history is
Reference undesirable. Statins may be used in children from
Results
interval the age of 10.
Total 6.5
cholesterol mmol/L Reference:
HDL 1.3 NICE guidelines CG71 (2008) Identification and
0.8-1.9 management of familial
cholesterol mmol/L
1.2
Triglycerides 0.5-2.2 HEART UK- the cholesterol charity Children and
mmol/L
familial hypercholesterolaemia (FH)
4.7
Calculated LDL FH Wales- website for the FH service in Wales,
mmol/L
which offers a comprehensive clinical and
4.8 family testing service
Fasting glucose 3.0-6.0
mmol/L
[ Q: 303 ] Question ID #3354
The following next step would be the most
appropriate:
A 32 year old man attends clinic asking for advice
as his older brother has recently had a myocardial
1- Advise that the diagnosis of familial infarction at the age of 40. He is concerned as his
hypercholesterolaemia can only be made symptoms, which he thinks are due to indigestion
with a DNA test are getting worse. His father died of an MI at the
age of 43. He is a very fit non-smoker, and has a
2- He and the mother should be reassured that healthy diet. He has gastro-oesophageal reflux, for
the lipids are unremarkable which he takes omeprazole. Physical examination
3- Offer annual testing of the lipid profile is normal with a blood pressure of 130/78 mmHg.
You organise investigations with the following
through puberty
results:
4- The lipid profile should be re-checked when
he is an adult Reference
Results
interval
5- The results suggest familial
hypercholesterolaemia and a specialist Total 9.7
referral is appropriate cholesterol mmol/L
HDL 1.5
>1.0
cholesterol mmol/L

0.6 FH Wales- information from a service which

Triglycerides <2.0 offers comprehensive clinical and family
mmol/L
testing
7.9
Calculated LDL AS04 : H·E·A·R·T UK Advice sheetDiagnosing FH-
mmol/L
Simon Broome Criteria
4.8
mmol/L
[ Q: 304 ] Question ID #3355
Liver profile normal
Which of the following is the most likely diagnosis? A 37 year old man attends for evaluation due to
his family history of premature vascular disease
and is advised that he should have his lipid profile
1- Familial hypercholesterolaemia checked. He asks if fasting will make a difference
to the results of the test.
2- Hypercholesterolaemia secondary to diet
3- Hyperlipidaemia secondary to myocardial What is the relevance of fasting status in the
ischaemia interpretation of a lipid profile?
4- Hypothyroidism (Please select 1 option)
5- Polygenic hypercholesterolaemia 1- All the parameters within a lipid profile are

significantly affected by fasting status
Answer & Comments 2- Fasting is only relevant for the assessment of

an apolipoprotein profile
Answer: 1- Familial hypercholesterolaemia
3- The equation used to calculate triglycerides
is not applicable if the patient is not fasting
Heterozygous familial hypercholesterolaemia (FH)
is estimated to affect 1 in 500 of the population 4- Total cholesterol and HDL cholesterol only
and causes significantly elevated LDL cholesterol are affected by fasting status
from birth. It is inherited in an autosomal
dominant fashion, meaning that for any individual 5- Triglycerides and calculated LDL cholesterol
with the condition 50% of relatives will be only may be affected by fasting
affected. If untreated it is estimated that 50% of
men will develop cardiovascular disease by the Answer & Comments
age of 60, but lipid lowering therapies are very
effective at reducing this risk. As he has symptoms Answer: 5- Triglycerides and calculated LDL
which may be due to myocardial ischaemia, this cholesterol only may be affected by fasting
requires further evaluation, despite his youth. The
family and personal history indicate that diet, Most laboratories measure total cholesterol, HDL
polygenic causes and thyroid dysfunction are less cholesterol and triglycerides and calculate LDL
likely. Total cholesterol is often lower following a cholesterol by using the following formula (all
myocardial infarction. parameters in mmol/L):
Reference: LDL cholesterol= total cholesterol- HDL

NICE CG71 (2008) Identification and cholesterol- (triglycerides/2.2) Triglycerides can
management of familial increase in the non-fasting state and therefore
hypercholesterolaemia also affect calculated LDL cholesterol. Current
Heart UK (2015) What is Familial NICE guidance recommends using non-fasting
Hypercholesterolaemia (FH)? parameters such as non-HDL cholesterol (i.e. total
cholesterol -HDL cholesterol) as these parameters
are less affected by fasting status. Using a

calculated LDL value can still be helpful for the 3- Hyperlipidaemia secondary to skeletal
assessment of familial hypercholesterolaemia. muscle damage
The above equation is not applicable when the 4- Hypothyroidism induced

triglycerides are >4.4 mmol/L hypercholesterolaemia
5- Polygenic hypercholesterolaemia
Reference:
Joint British Society (2014) guidelines on
prevention of cardiovascular disease 3 Answer & Comments
NICE guideline CG181 (2014) Lipid modification: Answer: 4- Hypothyroidism induced
cardiovascular risk assessment and the hypercholesterolaemia
modification of blood lipids for the primary
and secondary prevention of cardiovascular
Untreated hypothyroidism can cause a significant
disease
secondary hypercholesterolaemia, as thyroid
hormones are involved with hepatic lipid
[ Q: 305 ] Question ID #3356 metabolism. Secondary causes of dyslipidaemia
should always be considered and include
A 42 year old lady attends clinic complaining of medications, alcohol, obesity, obstructive liver
persistent lethargy. She works as a teacher and is disease and nephrotic syndrome. Inherited causes
generally well. She has no relevant medical history of dyslipidaemia are less likely in the absence of a
and takes no regular medication. Her mother relevant family history. A raised CK is a relatively
developed angina at the age of 75 and her father common finding in hypothyroidism, but is
has no medical problems at the age of 78. On unrelated to the hypercholesterolaemia.
examination her pulse is 56/min, blood pressure is Inappropriate diet alone rarely causes such a
122/72 mmHg, BMI of 26 kg/m2 with no other profound hypercholesterolaemia.
obvious findings. Investigations reveal:
Reference:
GP notebook (2015) links to examples of
Reference
Results secondary causes of hyperlipidaemia - UK
interval
Medical Reference
Total 11.0
cholesterol mmol/L
[ Q: 306 ] Question ID #3357
HDL 1.2
>1.2
cholesterol mmol/L
A 52 year old man with familial
1.1 hypercholesterolaemia (FH) and a previous
Triglycerides <2.0
mmol/L myocardial infarction 3 years ago attends for
9.3 review. He recalls pre-treatment total cholesterol
Calculated LDL
mmol/L of 8.0 mmol/L, but no other details are available.
4.8 He has had difficulty tolerating a statin due to
Fasting glucose 3.0-6.0 troublesome muscle pain. His symptoms settle
mmol/L
following discontinuation of therapy but return
Creatine kinase 1350 u/L 25-200 within a week of recommencement. His serum
creatine kinase has always been within the
Which of the following is the most likely diagnosis? reference range. You have tried to use the
(Please select 1 option) following drug therapies, using the minimum dose
indicated in the BNF: simvastatin, atorvastatin and
1- Familial hypercholesterolaemia
rosuvastatin. He has tolerated pravastatin 40 mg
2- Hypercholesterolaemia secondary to diet once daily. His current biochemistry:

Reference maximum recommended dose of pravastatin is 40

Results mg once daily.
interval
Total
5.9 mmol/L Reference:
cholesterol
NICE guidelines CG71 (2008) Identification and
HDL management of familial
1.0 mmol/L >1.0
cholesterol hypercholesterolaemia for familial
Triglycerides 1.6 mmol/L 0.1-2.0 hypercholesterolaemia
Calculated NICE guideline CG181 (2014) Lipid modification:
4.2 mmol/L cardiovascular risk assessment and the
LDL
modification of blood lipids for the primary
Creatinine 125 mmol/L 70-120
and secondary prevention of cardiovascular
54 mL/min/ disease
eGFR >90
1.73 m2
HEART UK What is LDL-apheresis?
What would be the most appropriate next step to
manage his lipid profile? [ Q: 307 ] Question ID #3358
A 54 year old man attends for clinical assessment.
1- Add ezetimibe 10 mg once daily He sustained an MI at the age of 40, but is now
2- Add fenofibrate 160 mg once daily clinically stable with no cardiovascular symptoms.
His lipid profile is well controlled on a combination
3- Increase pravastatin to 80 mg once daily of atorvastatin 80 mg once daily and ezetimibe 10
4- Prescribe CoEnzyme Q10 mg once daily. He also takes ramipril 10 mg once
daily and aspirin 75 mg once daily. He has seen a
5- Start lipoprotein apheresis immediately specialist privately, who has advised him that he
has ‘possible familial hypercholesterolaemia (FH)’
Answer & Comments based upon his history and lipid results. He
recommends that his children, now aged 20 and
Answer: 1- Add ezetimibe 10 mg once daily 24 have ‘appropriate testing’. The patient has read
that genotyping is advised in individuals with FH,
but is concerned as the specialist indicated that
This patient is at high risk of recurrent
this test was not available locally.
cardiovascular events. NICE guidelines for FH
recommend achieving a 50% reduction in
cholesterol from the baseline measurement, What is the most appropriate advice with respect
which would be a reasonable initial target for this to genetic testing?
patient. Ezetimibe can effectively reduce LDL (Please select 1 option)
cholesterol by blocking intestinal absorption of
1- DNA testing is not required for him but is
dietary and biliary cholesterol, particularly in
obligatory for his children
conjunction with a statin. Fenofibrate have a
limited effect in reducing LDL cholesterol and 2- DNA testing is obligatory for him, but is not
should be used with caution in renal dysfunction, required for his children
particularly in conjunction with a statin. Use of
CoEnzyme Q10 to prevent statin induced myalgia 3- Genetic testing is not required as the risk of
is currently not recommended. He may be a his children inheriting the same condition as
candidate for lipoprotein apheresis, which is a him is very unlikely
treatment akin to renal dialysis for
4- His children should be started on a statin
hypercholesterolaemia. All available drug
therapies should be explored first as access to regardless of any further testing
apheresis in the UK is limited and is costly. The

5- In the absence of DNA testing, his children Reference

Results
should be offered lipid testing interval
Total 7.3
Answer & Comments cholesterol mmol/L
Answer: 5- In the absence of DNA testing, his HDL 1.9

>1.0
children should be offered lipid testing cholesterol mmol/L
1.8
Triglycerides <2.0
mmol/L
Genetic testing for FH is desirable to confirm the
diagnosis and facilitate cascade testing in his 4.6
Calculated LDL
relatives. Testing is not universally available in the mmol/L
UK or elsewhere in the world, although its use is 5.2
recommended within NICE guidance. If he were Fasting glucose 3.0-6.0
mmol/L
found to have an FH causing mutation, family
Thyroid profile normal
members should be offered testing to ascertain if
the family mutation is present. Lipid testing and
potentially treatment should be organised Last month
thereafter. In the absence of genetic testing a
clinical diagnosis can be made and lipid testing Reference
Results
offered to family members. interval
7.7
Total cholesterol
Reference: mmol/L
NICE CG71 (2008) Identification and 1.8
HDL cholesterol >1.0
management of familial mmol/L
hypercholesterolaemia for familial 1.8
Triglycerides <2.0
hypercholesterolaemia mmol/L
5.1
Calculated LDL
mmol/L
[ Q: 308 ] Question ID #3359
5.4
mmol/L
A 66 year old lady attends for routine review of her Thyroid profile normal
hypertension. She is fit and well with no other eGFR >90 >90
medical history. She takes Perindopril 8 mg once Urine protein: <30 <30
daily for her hypertension, is a non- smoker and creatinine mg/mmol mg/mmol
drinks about 10 units of alcohol per week. Her
mother is alive at the age of 91, is in a nursing The most likely diagnosis explanation for her lipid
home with Alzheimer’s disease, but has no history profile is:
of vascular disease. Her father died at the age of
84 from carcinoma of the prostate. He also had (Please select 1 option)
treated hypertension, but had no history of 1- Drug-induced hyperlipidaemia
vascular disease. She does not know of any family
history of hyperlipidaemia or premature 2- Familial combined hyperlipidaemia
cardiovascular disease. Her blood pressure is well 3- Familial hypercholesterolaemia
controlled. She has superior corneal arcus but no
other physical signs and has a BMI of 22 kg/m2. As 4- Polygenic hypercholesterolaemia
part of cardiovascular risk assessment she had a 5- Secondary hyperlipidaemia due to
lipid profile requested 5 years ago and repeated
hypertension- induced nephropathy
last month.
5 years ago Answer & Comments

Answer: 4- Polygenic hypercholesterolaemia

Polygenic hypercholesterolaemia is a common Fasting glucose 4.6 mmol/L 3.0-6.0

finding, but unlike familial hypercholesterolaemia
Thyroid profile normal
(FH) the genetics of the condition are less distinct.
The hypercholesterolaemia often deteriorates HbA1c 35 mmol/mol <48
over time and maybe associated with Apolipoprotein
cardiovascular disease, particularly in the context 1.9 g/L 0.4-1.2
B
of other risk factors. The impact of polygenic
hypercholesterolaemia in terms of atherogenesis Which of the following is the most likely diagnosis?
is likely to be less significant than FH, bearing in
mind that an individual with FH will have been
exposed to high levels of atherogenic lipoproteins 1- Anabolic steroid misuse
from birth, rather than just later in life. The
absence of a family history makes FH and familial 2- Familial Combined Hyperlipidaemia
combined hyperlipidaemia less likely. ACE 3- Familial Hypercholesterolaemia
inhibitors do not cause a dyslipidaemia and there
is no evidence of nephropathy in this patient. 4- Lipoprotein lipase deficiency
5- Polygenic Hypercholesterolaemia
Reference:
General Practice Notebook Polygenic
hypercholesterolaemia Answer & Comments
Answer: 2- Familial Combined Hyperlipidaemia
[ Q: 309 ] Question ID #3360
Familial combined hyperlipidaemia (FCH) is a
A 35 year old doctor seeks your advice as he has a commonly encountered hyperlipidaemia and is
family history of heart disease and has been found associated with premature cardiovascular disease.
to have high cholesterol following tests carried out Unlike familial hypercholesterolaemia, the
for a clinical trial. He is very fit and undertakes genetics of the condition are not clear and the
regular triathalons. He takes no medication, is a presentation much more variable. Whilst obesity
non-smoker and teetotal. He is fastidious about and insulin resistance are more commonly
maintaining a healthy diet. You ascertain that his associated with FCH, this is not invariably the case.
father, who is also a non smoker and generally fit, The commonest laboratory findings are raised
sustained a non-fatal myocardial infarction (MI) at cholesterol and triglycerides (i.e. combined),
the age of 44. A paternal uncle sustained a fatal MI together with a raised concentration of
at the age of 53. He has no stigmata of apolipoprotein B. This is the surface protein
hyperlipidaemia, his blood pressure is 118/76 present on both very low density lipoproteins
mmHg and waist circumference 80cm, BMI 23 (VLDL) as well as low density lipoprotein (LDL) and
kg/m2. is a good marker of atherosclerotic risk. Both
familial and polygenic hypercholesterolaemia are
His lipid profile measurements are:- less commonly associated with
hypertriglyceridaemia in the absence of diabetes
Reference mellitus, obesity or alcohol excess. Anabolic
Results steroid misuse usually causes low HDL cholesterol.
interval
Lipoprotein lipase deficiency is very rare, is usually
Total associated with a more severe dyslipidaemia and
9.8 mmol/L
cholesterol is inherited in an autosomal recessive manner,
HDL which is not consistent with his family history.
1.3 mmol/L >1.0
cholesterol
Triglycerides 5.7 mmol/L <2.0 Reference:
Heart UK Familial Combined Hyperlipidaemia
Unable to (FCH)
Calculated LDL
calculate

Larry A. Weinrauch, LA (MD) MedlinePlus Individuals who have a high clinical probability of
Medical Encylcopedia (2014) Familial having FH should be offered genotyping. This can
combined hyperlipidemia confirm the diagnosis, but importantly can
facilitate cascade testing. Once the DNA mutation
[ Q: 310 ] Question ID #3361 has been identified in the presenting patient
(known as the ‘index’ patient), testing for the
presence or absence of this specific mutation can
A 15 year old boy attends clinic with his be undertaken in family members. This is carried
mother. The mother has just been diagnosed out in a step wise fashion, such that first degree
with familial hypercholesterolaemia (FH). She relatives i.e. parents, children and siblings are
has a strong family history of premature tested first and subsequent relatives thereafter.
cardiovascular disease and was found to have For example if the index patient’s brother does not
significant hypercholesterolaemia. She has have the mutation, testing in his children is not
recently had a genetic test carried out and has required. If the index patient’s sister does have the
been advised that a mutation in the LDL mutation, her children will be offered testing.
receptor causing FH has been identified. She
has been advised that on this basis, ‘cascade Offering DNA testing, rather than initial
testing’ of her family should be undertaken. cholesterol testing in family members is
recommended, as it provides a definitive answer,
She seeks your advice about cascade testing and particularly in younger people when the
what should be done now: cholesterol results may be harder to interpret.
Cholesterol testing should be carried out in family
members who have the family mutation, but in
1- Cascade testing using DNA is not appropriate those who do not; this may not be required,
as LDL receptor mutations are very rare and particularly for children. DNA testing should be
full gene sequencing of the son is required offered to children by the age of 10. LDL receptor
mutations are the commonest cause of FH. Less
2- Offer a cholesterol test to her son and her commonly mutations are found in the apo B or
other family members to assess if PCSK9 genes.
hypercholesterolaemia is present in them
before offering a DNA test Reference:
Heart UK Children and familial
and a cholesterol test in family members
aged between 8 and 16 years old
[ Q: 311 ] Question ID #3362
only to assess if the identified mutation is A 39 year old man previously fit and well is
present in them before offering a admitted to hospital with an acute myocardial
cholesterol test infarction (MI). He is successfully treated with
5- Offer a DNA test to her son and her other percutaneous coronary intervention. The
admitting doctor notes that his father sustained a
family members to assess if the identified
fatal MI at the age of 52 and his paternal
mutation is present in them before offering
grandfather sustained a fatal MI at the age of 48.
a cholesterol test On examination he is found to have xanthomata in
both Achilles’ tendons, bilateral corneal arcus and
Answer & Comments marked xanthelasma. His lipid profile is measured
on admission:
Answer: 5- Offer a DNA test to her son and her
other family members to assess if the
Reference
identified mutation is present in them before Results
interval
offering a cholesterol test

Total 11.2 Corneal arcus becomes more common with

cholesterol mmol/L advancing age, but it’s presence in a person under
the age of 40 is suggestive of a lipid disorder. The
HDL 1.3
>1.0 probability of FH increases with higher LDL
cholesterol mmol/L
cholesterols, but there is no definitive diagnostic
1.5 cut-off above which the diagnosis is confirmed. A
Triglycerides <2.0
mmol/L DNA test may confirm the diagnosis, but the
9.2 patient may be described as having definite FH in
Calculated LDL the presence of the above profile with xanthoma.
mmol/L
5.2
Fasting glucose 3.0-6.0 Reference:
mmol/L
Thyroid profile normal management of familial
The following clinical findings are relevant for the FH Wales Clinical signs of familial
diagnosis of familial hypercholesterolaemia: hypercholesterolaemia
1- Premature corneal arcus is pathognomonic [ Q: 312 ] Question ID #3363

of FH and confirms the diagnosis
2- Premature marked xanthelasma are An 11 year old boy attends clinic with his mother.
infarction at the age of 32 and the mother is
diagnosis
concerned. The boy has a paternal uncle who also
3- Tendon xanthomata are pathognomonic of developed premature ischaemic heart disease at a
FH and confirm the diagnosis young age and is reported to have had a total
4- The clinical findings are not relevant as the son has now had his lipid profile measured.
LDL is >7.9 mmol/L, which confirms the
diagnosis Reference
Results
5- The diagnosis may only be confirmed with a interval
DNA test Total 6.5
cholesterol mmol/L
Answer & Comments HDL 1.3
0.8-1.9
cholesterol mmol/L
Answer: 3- Tendon xanthomata are
1.2
pathognomonic of FH and confirm the Triglycerides 0.5-2.2
mmol/L
diagnosis
4.7
Calculated LDL
mmol/L
Tendon xanthomata are pathognomonic of FH and
confirm the diagnosis. These may manifest as 4.8
thickening and/or hardening of tendons, usually mmol/L
associated with distinct nodularity. They are
commonly found in the Achilles’ tendons and The following next step would be the most
sometimes in other extensor tendons, such as appropriate:
those of the hands. The presence of xanthelasma (Please select 1 option)
and premature arcus are suggestive, but are not
1- Advise that the diagnosis of familial
specific for FH. Xanthelasma may be found in the
absence of hypercholesterolaemia, but its finding hypercholesterolaemia can only be made
should prompt measurement of a lipid profile. with a DNA test

2- He and the mother should be reassured that which he takes omeprazole. Physical examination
the lipids are unremarkable is normal with a blood pressure of 130/78 mmHg.
You organise investigations with the following
3- Offer annual testing of the lipid profile results:
through puberty
4- The lipid profile should be re-checked when Reference
Results
he is an adult interval
5- The results suggest familial Total 9.7

cholesterol mmol/L
hypercholesterolaemia and a specialist
referral is appropriate HDL 1.5
>1.0
cholesterol mmol/L
Answer & Comments 0.6

Triglycerides <2.0
mmol/L
Answer: 5- The results suggest familial 7.9
hypercholesterolaemia and a specialist Calculated LDL
mmol/L
referral is appropriate
4.8
mmol/L
Cholesterol is lower in children than in adults and
Liver profile normal
the results in the context of the history are
suggestive of familial hypercholesterolaemia (FH).
appropriate. In FH, ideally the diagnosis should be (Please select 1 option)
made by testing for the known family DNA 1- Familial hypercholesterolaemia
available, lipid testing is appropriate. Deferring the 2- Hypercholesterolaemia secondary to diet
diagnosis with such a concerning family history is 3- Hyperlipidaemia secondary to myocardial
undesirable. Statins may be used in children from
ischaemia
the age of 10.
4- Hypothyroidism
Reference:
management of familial
hypercholesterolaemia Answer & Comments
HEART UK- the cholesterol charity Children and Answer: 1- Familial hypercholesterolaemia
familial hypercholesterolaemia (FH)
FH Wales- website for the FH service in Wales,
Heterozygous familial hypercholesterolaemia (FH)
which offers a comprehensive clinical and
is estimated to affect 1 in 500 of the population
family testing service
and causes significantly elevated LDL cholesterol
[ Q: 313 ] Question ID #3364 dominant fashion, meaning that for any individual
with the condition 50% of relatives will be
A 32 year old man attends clinic asking for advice affected. If untreated it is estimated that 50% of
as his older brother has recently had a myocardial men will develop cardiovascular disease by the
infarction at the age of 40. He is concerned as his age of 60, but lipid lowering therapies are very
symptoms, which he thinks are due to indigestion effective at reducing this risk. As he has symptoms
are getting worse. His father died of an MI at the which may be due to myocardial ischaemia, this
age of 43. He is a very fit non-smoker, and has a requires further evaluation, despite his youth. The
healthy diet. He has gastro-oesophageal reflux, for family and personal history indicate that diet,
polygenic causes and thyroid dysfunction are less

likely. Total cholesterol is often lower following a LDL cholesterol= total cholesterol- HDL
myocardial infarction. cholesterol- (triglycerides/2.2) Triglycerides can
increase in the non-fasting state and therefore
Reference: also affect calculated LDL cholesterol. Current
NICE CG71 (2008) Identification and NICE guidance recommends using non-fasting
management of familial parameters such as non-HDL cholesterol (i.e. total
hypercholesterolaemia cholesterol -HDL cholesterol) as these parameters
Heart UK (2015) What is Familial are less affected by fasting status. Using a
Hypercholesterolaemia (FH)? calculated LDL value can still be helpful for the
assessment of familial hypercholesterolaemia.
FH Wales- information from a service which
offers comprehensive clinical and family
The above equation is not applicable when the
testing triglycerides are >4.4 mmol/L
AS04 : H·E·A·R·T UK Advice sheetDiagnosing FH-
Simon Broome Criteria Reference:
Joint British Society (2014) guidelines on
[ Q: 314 ] Question ID #3365 prevention of cardiovascular disease 3
NICE guideline CG181 (2014) Lipid modification:
A 37 year old man attends for evaluation due to cardiovascular risk assessment and the
his family history of premature vascular disease modification of blood lipids for the primary
and is advised that he should have his lipid profile and secondary prevention of cardiovascular
checked. He asks if fasting will make a difference disease
to the results of the test.
[ Q: 315 ] Question ID #3366
What is the relevance of fasting status in the
interpretation of a lipid profile? A 42 year old lady attends clinic complaining of
(Please select 1 option) persistent lethargy. She works as a teacher and is
generally well. She has no relevant medical history
1- All the parameters within a lipid profile are
and takes no regular medication. Her mother
significantly affected by fasting status
developed angina at the age of 75 and her father
2- Fasting is only relevant for the assessment of has no medical problems at the age of 78. On
an apolipoprotein profile examination her pulse is 56/min, blood pressure is
122/72 mmHg, BMI of 26 kg/m2 with no other
3- The equation used to calculate triglycerides obvious findings. Investigations reveal:
is not applicable if the patient is not fasting
4- Total cholesterol and HDL cholesterol only Reference
Results
are affected by fasting status interval
Total 11.0
5- Triglycerides and calculated LDL cholesterol
cholesterol mmol/L
only may be affected by fasting
HDL 1.2
>1.2
cholesterol mmol/L
Answer & Comments
1.1
Triglycerides <2.0
Answer: 5- Triglycerides and calculated LDL mmol/L
cholesterol only may be affected by fasting 9.3
Calculated LDL
mmol/L
Most laboratories measure total cholesterol, HDL 4.8
cholesterol and triglycerides and calculate LDL Fasting glucose 3.0-6.0
mmol/L
cholesterol by using the following formula (all
Creatine kinase 1350 u/L 25-200
parameters in mmol/L):

Which of the following is the most likely diagnosis? pressure is 110/68 mmHg. At 7 weeks gestation
(Please select 1 option) her weight was 54 kg, BMI 22 kg/m2.
Reference
Results
2- Hypercholesterolaemia secondary to diet interval
3- Hyperlipidaemia secondary to skeletal Total 7.1

cholesterol mmol/L
muscle damage
HDL 1.7
4- Hypothyroidism induced >1.0
cholesterol mmol/L
1.1
Triglycerides 0.1-2.0
5- Polygenic hypercholesterolaemia mmol/L
4.9
Calculated LDL
Answer & Comments mmol/L
Answer: 4- Hypothyroidism induced 5.0

mmol/L
Which of the following diagnoses is the most

Untreated hypothyroidism can cause a significant likely?
hormones are involved with hepatic lipid
metabolism. Secondary causes of dyslipidaemia 1- Analytical error due to pregnancy affecting
should always be considered and include binding protein metabolism
medications, alcohol, obesity, obstructive liver
disease and nephrotic syndrome. Inherited causes 2- Familial hypercholesterolaemia
of dyslipidaemia are less likely in the absence of a 3- Hypothyroidism
relevant family history. A raised CK is a relatively
common finding in hypothyroidism, but is 4- Nephrotic syndrome
unrelated to the hypercholesterolaemia. Dietary 5- Pregnancy induced hyperlipidaemia
indiscretion alone rarely causes such a profound
hypercholesterolaemia.
Answer & Comments
Reference:
Answer: 5- Pregnancy induced hyperlipidaemia
GP notebook (2015) links to examples of
secondary causes of hyperlipidaemia - UK
Medical Reference Pregnancy can cause an oestrogen-mediated
significant increase in cholesterol and
measurement is best avoided during pregnancy.
[ Q: 316 ] Question ID #3367 Relatives developing heart disease at an older age
is less suggestive of an inherited
A 38 year old woman is 20 weeks pregnant and has dyslipidaemia.This patient can be reassured that
her lipid profile tested at a private antenatal clinic her risk of developing cardiovascular disease in
because she has worried about heart disease in pregnancy is very low and that no further
pregnancy since reading about this in a woman’s assessment is required.
magazine. She has no history or symptoms
suggestive of cardiovascular disease. She informs Reference:
you that her anxiety has been heightened as her Metabolic changes during pregnancy
father had a stroke at the age of 72 and her
mother developed angina at the age of 70. The
pregnancy is progressing well and her blood

[ Q: 317 ] Question ID #3368 Lipid lowering with a statin is recommended for all
patients who have established cardiovascular
A 64 year old man is reviewed 3 months following disease (secondary prevention). In an individual
admission with a myocardial infarction. He who has never experienced side-effects, he should
required coronary artery bypass surgery but has be reassured that statins are safe and effective at
made a good recovery and is asymptomatic. He is reducing the risk of recurrent cardiovascular
a life long non-smoker, has had treated events. Risk factor calculators are not appropriate
hypertension for 10 years and plans to return back for use in secondary prevention. Dietary advice is
an important adjunct to drug therapy in this
to work on a part-time basis. His lipid profile prior
to his MI reveals: situation, but not as the only intervention. Drug
therapies, other than statins should not be offered
at this stage as monotherapy.
Reference
Results
interval
Reference:
Total 5.7
Hypercholesterolaemia- secondary prevention
cholesterol mmol/L
HDL 1.0 NICE CG 181
>1.0
cholesterol mmol/L
0.8 [ Q: 318 ] Question ID #3369
mmol/L
4.3
Calculated LDL A 52 year old man attends for a cardiovascular risk
mmol/L
assessment. He is not concerned about his health,
4.8
Fasting glucose 3.5-5.5 but his wife has mentioned that he has gradually
mmol/L
put on weight over the last few years and should
have a check up. He is generally well with no family
He has never taken a statin because of concerns history of premature vascular disease. He carries
about side-effects and has not started the out little physical activity and is a non-smoker. The
atorvastatin recommended by his cardiac following are results from your assessment.
surgeon.
Results Reference interval
Which of the following actions is appropriate?
Blood pressure 160/95
Weight 105 kg
1- Advise that dietary measures alone are
appropriate and refer to a dietitian 33
BMI
kg/m2
2- Advise that statin therapy is safe in nearly all
Total
people and is recommended for all patients 7.4
cholesterol
following CABG
HDL cholesterol 0.8 >1.0
3- Recommend a bile acid sequestrant Triglycerides 2.4 0.1-2.0
4- Recommend starting a fibrate Calculated LDL 5.5
5- Recommend starting ezetimibe Fasting glucose 5.4 3.5-5.5
HbA1c 36 20-42
Answer & Comments
His calculated 10 year cardiovascular risk (QRISK 2)
Answer: 2- Advise that statin therapy is safe in
is 34%. He is started on atorvastatin 20mg once
nearly all people and is recommended for all daily, which is gradually up titrated to 80 mg once
patients following CABG daily, and ramipril 5 mg once daily. Twelve months
later his parameters are as follows:

Results Reference interval [ Q: 319 ] Question ID #3370

Blood pressure 145/95
A 10 year old boy attends clinic with his mother.
Weight 106 kg
33 infarction at the age of 36 and the mother is
BMI
kg/m2 concerned. The boy has a paternal uncle who also
Total developed premature ischaemic heart disease at a
3.7 young age and is reported to have had a total
cholesterol
HDL cholesterol 0.8 >1.0
son has now had his lipid profile measured.
Triglycerides 2.3 0.1-2.0
Calculated LDL 1.9 Reference
Results
Fasting glucose 5.2 3.5-5.5 interval
HbA1c 35 20-42 Total 6.5
cholesterol mmol/L
The following is the next most appropriate HDL 1.3
>1.0
management step cholesterol mmol/L
(Please select 1 option) 1.2
mmol/L
1- Add a fibrate
4.7
2- Consider HDL raising therapy Calculated LDL
mmol/L
3- Increase dose of statin 4.8
mmol/L
4- No change, monitor annually
5- Reinforce diet and lifestyle advice The following next step would be the most
appropriate:
Answer & Comments (Please select 1 option)
Answer: 5- Reinforce diet and lifestyle advice 1- Advise that the diagnosis of familial
hypercholesterolaemia can only be made
This gentleman is offered treatment in the context with a DNA test
of primary prevention. Pharmacological 2- He and the mother should be reassured that
intervention is appropriate, but there are no the lipids are unremarkable
specific ‘lipid targets’. The current guidance for
lipid modification from NICE recommends offering 3- Offer annual testing of the lipid profile
intervention if CV risk is greater than 10% over 10 through puberty
years. His hypertriglyceridaemia and low HDL
4- The lipid profile should be re-checked when
cholesterol are related to obesity and lifestyle
he is an adult
intervention will provide the greatest opportunity
for health improvement. Clinical trials are 5- The results suggest familial
underway with specific HDL raising drugs to hypercholesterolaemia and a specialist
ascertain their safety and potential utility. referral is appropriate
Reference:
Joint British Society guidelines on prevention of Answer & Comments
cardiovascular disease 3 (2014) Answer: 5- The results suggest familial
NICE CG 181 hypercholesterolaemia and a specialist
referral is appropriate

Cholesterol is lower in children than in adults and Which of the following actions would be the most
the results in the context of the history are appropriate?
suggestive of familial hypercholesterolaemia (FH). (Please select 1 option)
appropriate. In FH, ideally the diagnosis should be 1- Introduce no new medication
made by testing for the known family DNA
2- Prescribe a fibrate
available, lipid testing is appropriate. Deferring the 3- Prescribe a statin
diagnosis with such a concerning family history is
4- Prescribe ezetimibe 10 mg once daily
undesirable. Statins may be used in children from
the age of 10. 5- Prescribe omega 3 fatty acids g once daily
Reference:
Answer & Comments
NICE guidelines for familial
hypercholesterolaemia Answer: 2- Prescribe a fibrate
HEART UK- the cholesterol charity- FH and
children Hypertriglyceridaemia can cause pancreatitis, and
FH Wales- website for the FH service in Wales, in this situation, drug therapy to reduce
which offers a comprehensive clinical and triglycerides is appropriate. The most effective
family testing service group of agents for this are the fibrates. Statins
and ezetimibe have a minimal effect on
hypertriglyceridaemia. High dose (4g/day) of
[ Q: 320 ] Question ID #3371
omega 3 fatty acids can be helpful, often in
conjunction with a fibrate; however at a low dose
A 33 year old woman is discharged from the the impact on triglyceride metabolism is minimal.
surgical ward following acute admission with She is likely to have an underlying defect in
abdominal pain and a diagnosis of acute triglyceride metabolism which will require further
pancreatitis, this settled with conservative assessment.
management. She drinks no alcohol, has no
relevant medical history and takes no medication. Reference:
Her hepatic ultrasound shows no evidence of Management of hypertriglyceridaemia
gallstones. On admission the surgical team had
checked a fasting lipid profile and ask you to follow
up on the results below: [ Q: 321 ] Question ID #3372
Reference A 41 year old man attends for a general medical

Results review. He is under the care of the mental health
interval
team with schizophrenia which has been
successfully treated with olanzapine for 2 years.
Total He has smoked since adolescence and does not
12.1 mmol/L
cholesterol drink alcohol for religious reasons. His other
HDL medications include bendroflumethiazide and
0.6 mmol/L >1.0 omeprazole. He was recently started on
cholesterol
varenicline to help him stop smoking. There is no
Triglycerides 45 mmol/L 0.1-2.0 family history of premature vascular disease. He
unable to calculate last attended your practice 3 years ago, when the
Calculated
due to high following were measured.
LDL
triglycerides
Fasting Assessment and investigations 3 years ago:
4.8 mmol/L 3.5-5.5
glucose

Reference 5- Varenicline induced dyslipidaemia

Results
interval
Blood 135/85 Answer & Comments
pressure mmHg
Answer: 4- Olanzapine induced dyslipidaemia
Weight 85 kg
BMI 26 kg/m2 Olanzapine and other atypical anti-psychotic drugs
Total can cause weight gain through increased appetite,
5.8 mmol/L
cholesterol as well as hyperglycaemia and hyperlipidaemia.
HDL Substitution of a more metabolically favourable
0.9 mmol/L >1.0 drug is an option, but rarely happens in clinical
cholesterol
practice, where dealing with the adverse
Triglycerides 1.8mmol/L 0.1-2.0 metabolic consequences is the more usual course
Calculated LDL 4.1 mmol/L of action. The fasting glucose and HbA1c are
Fasting consistent with impaired fasting glycaemia. The
5.4 mmol/L 3.5-5.5 absence of a relevant family history make both
glucose
familial combined hyperlipidaemia and the very
rare condition lipoprotein lipase deficiency
His most recent assessment reveals: unlikely. Bendroflumethiazide can cause mild
hypertriglyceridaemia, but not with this severity
Reference and it is rarely clinically significant.
Results
interval
Blood 145/85 Reference:
pressure mmHg Dyslipidaemia and atypical antipsychotic drugs
Weight 95 kg
BMI 30 kg/m2 [ Q: 322 ] Question ID #3373
Total
7.0 mmol/L A 60 year old man with a three year history of diet
cholesterol
controlled type 2 diabetes mellitus and a previous
HDL myocardial infarction (MI) 3 years ago attends for
0.7 mmol/L >1.0
cholesterol review. He stopped smoking at the time of his MI.
Triglycerides 3.2 mmol/L 0.1-2.0 He has had difficulty tolerating a statin due to
Calculated troublesome muscle aches and pains. His
4.7 mmol/L symptoms settle following discontinuation of
LDL
therapy but return within a week of
Fasting recommencement. His serum creatine kinase has
6.3 mmol/L 3.5-5.5
glucose always been within the reference range. You have
39 mmol/mol tried to use the following drug therapies, using the
HbA1c 20-42
Hb minimum dose indicated in the BNF: simvastatin,
atorvastatin and rosuvastatin. He has tolerated
The most likely reason for the change in his pravastatin 40 mg once daily. His current
metabolic parameters is biochemistry:
Reference
1- Bendroflumethiazide induced dyslipidaemia Results
interval
2- Diabetes mellitus Total
6 mmol/L
cholesterol
3- Lipoprotein lipase deficiency
HDL
4- Olanzapine induced dyslipidaemia 1.0 mmol/L >1.0
cholesterol

Triglycerides 1.5 mmol/L 0.1-2.0 [ Q: 323 ] Question ID #3374

Calculated
4.3 mmol/L A 39 year old man attends clinic asking for advice
LDL
as his older brother has recently had a myocardial
Creatinine 125 mmol/L 70-120
infarction at the age of 44. His father died of an MI
54 mL/min/ at the age of 43. He is a very fit non-smoker, and
eGFR >90
1.73 m2 has a healthy diet. He runs about 10 miles weekly
and has no symptoms whatsoever. He has no
What would be the most appropriate next step to other medical problems or takes any medication.
manage his lipid profile? Physical examination is normal with a blood
(Please select 1 option) pressure of 120/68 mmHg. You organise
investigations with the following results:
1- Add ezetimibe 10 mg once daily
2- Add fenofibrate 160 mg once daily Reference
Results
interval
3- Add omega 3 fatty acids
Total 10.7
4- Continue current therapy cholesterol mmol/L
5- Increase pravastatin to 80 mg once daily HDL 1.5
>1.0
cholesterol mmol/L
Answer & Comments 0.6
mmol/L
Answer: 1- Add ezetimibe 10 mg once daily
8.9
Calculated LDL
mmol/L
This patient is at high risk of cardiovascular events
4.3
due to diabetes mellitus, previous MI and smoking Fasting glucose 3.5-5.5
mmol/L
history. In this patient we are dealing with
secondary prevention and the aim should be to Liver profile normal
reduce his LDL cholesterol, ideally to <2 mmol/L.
The maximum recommended dose of pravastatin Which of the following is the most likely diagnosis?
is 40 mg once daily. But even at maximum dose (Please select 1 option)
Pravastatin is a low intensity statin, ie; reduceas
LDLc by 29% from baseline. Ezetimibe can 1- Familial hypercholesterolaemia
effectively reduce LDL cholesterol by blocking 2- Hypercholesterolaemia secondary to diet
intestinal absorption of dietary and biliary
cholesterol, particularly in conjunction with a 3- Hyperlipidaemia secondary to alcohol excess
statin. Both omega 3 fatty acids and fenofibrate 4- Hypothyroidism
have a limited effect in reducing LDL cholesterol.
Fenofibrate should be used with caution in renal 5- Polygenic hypercholesterolaemia
dysfunction, particularly in conjunction with a
statin. NICE CG181 does not recommend fibrates Answer & Comments
or omega 3 fatty acids for the prevention of
cardiovascular disease. Answer: 1- Familial hypercholesterolaemia
Reference: Heterozygous familial hypercholesterolaemia (FH)

NICE guidelines for type 2 diabetes is estimated to affect 1 in 500 of the population
NICE technology appraisal for ezetimibe and causes significantly elevated LDL cholesterol
dominant fashion, meaning that for any individual
with the condition 50% of relatives will be

affected. If untreated it is estimated that 50% of Answer & Comments

men will develop cardiovascular disease by the
age of 60, but lipid lowering therapies are very Answer: 5- Triglycerides and LDL cholesterol may
effective at reducing this risk. NICE guidelines for be affected by fasting
FH recommend treating with a statin and then
ezetimibe if required. Most laboratories measure total cholesterol, HDL
cholesterol and triglycerides and calculate LDL
Reference: cholesterol by using the following formula (all
NICE guidelines for familial parameters in mmol/L):
HEART UK- the cholesterol charity- Information LDL cholesterol= total cholesterol- HDL
on FH for patients and healthcare cholesterol- (triglycerides/2.2)
professionals
Triglycerides can increase in the non-fasting state
FH Wales- information from a service which
and therefore also affect calculated LDL
offers comprehensive clinical and family
cholesterol. Current NICE guidance recommends
testing
using non-fasting parameters such as non-HDL
http://www.fhservice.wales.nhs.uk/home cholesterol (i.e. total cholesterol -HDL cholesterol)
as these parameters are less affected by fasting
[ Q: 324 ] Question ID #3375 status.
The above equation is not applicable when the

triglycerides are >4.4 mmol/L
diabetes and hypertension is due to have a routine
measurement of her full lipid profile as part of her
annual review. She takes metformin 500 mg twice Reference:
daily, simvastatin 40 mg once daily and ramipril 10 JBS-3 guidance
mg once daily. She asks if this must be a fasting NICE CG 181
test and if the results will be interpretable if she
does not fast. [ Q: 325 ] Question ID #3376
A 50 year old man attends clinic. He works as a civil
approach to measuring her lipid profile?
servant and is generally well. He has felt
(Please select 1 option) increasingly tired over the last year, but has
1- All the parameters within a lipid profile are attributed this to difficulties at work. He has also
significantly affected by fasting status gained about 5kgs in weight over the last six
months. He has no relevant medical history, takes
2- Fasting is only relevant when the no regular medication and is physically active.
triglycerides are >4.4mmol/L Both of his parents are healthy octogenarians. His
sister takes medication for her thyroid. On
3- HDL cholesterol is the only parameter
examination, his pulse is 56/min, blood pressure is
affected by fasting status 122/72 mmHg with no other obvious findings and
4- Total cholesterol and HDL cholesterol only has a BMI of 28 kg/m2. Investigations reveal:
are affected by fasting status
Reference
5- Triglycerides and LDL cholesterol may be Results
interval
affected by fasting
Total 10.0
cholesterol mmol/L
HDL 1.2
>1.0
cholesterol mmol/L

1.1 requested the arrest team. She is now drowsy. Her

Triglycerides 0.1-2.0 past medical history is unremarkable.
mmol/L
8.3
Calculated LDL On examination, she is drowsy with a GCS of 13.
mmol/L
Her pulse is 88 bpm and blood pressure 132/88
4.8 mmHg with oxygen sats of 100% on air. There is no
mmol/L focal neurology and her plantar responses are
equivocal.
(Please select 1 option) Of note, her blood results reveal:
2- Hypercholesterolaemia secondary to diet Potassium 3.5 mmol/l (3.5-5)
3- Hyperlipidaemia secondary to alcohol excess Urea 3.8 mmol/l (3-8)
4- Hypothyroidism induced Creatinine 70 micromol/l (50-100)
hypercholesterolaemia Glucose 4.1 mmol/l (3.5-6)
initial treatment for this patient?
Answer & Comments
Answer: 4- Hypothyroidism induced
1- 15mg oral Tolvaptan
2- 100mg IV Hydrocortisone stat
Untreated hypothyroidism can cause a significant 3- 150mls of 3% hypertonic saline over 20 mins
hormones are involved with hepatic lipid 4- 1litre Normal saline infused over 4 hrs
metabolism. Secondary causes of dyslipidaemia 5- Fluid restriction to 500mls per day
should always be considered and include
medications, alcohol, obesity, obstructive liver
disease and nephrotic syndrome. Inherited causes Answer & Comments
of dyslipidaemia are less likely in the absence of a Answer: 3- 150mls of 3% hypertonic saline over 20
relevant family history. Dietary indiscretion alone mins
rarely causes such a profound
hypercholesterolaemia.
This patient is likely to have hyponatraemic
Reference: encephalopathy which is life threatening and has
Further reading on secondary causes of presented with a fit. Post-operative
hyperlipidaemia hyponatraemia is not uncommon and is likely to
be due to a combination of SIADH which develops
[ Q: 326 ] Question ID #3451 inappropriate IVIs. The European Endocrine
Society Guidelines on severe hyponatraemic
You are called via the arrest bleep to a 43 year old encephalopathy recommend a rapid correction of
woman who is on the surgical ward. She had a sodium by approximately 5 mmol/l. This can
laparoscopic cholecystectomy performed two ameliorate the cerebral oedema that underlies
days ago and has since had nausea and vomiting this disorder.
and has been receiving IV dextrose. It transpires
that she had a fit for which the nursing staff For more information on how to correct and what

European Journal of Endocrinology (2014) 3- 125 mmol/l

Clinical Practice Guideline on the diagnosis
4- 130 mmol/l
and management of hyponatraemia,
5- 135 mmol/l
[ Q: 327 ] Question ID #3452
Answer & Comments
A 55 year old man with chronic hyponatraemia
Answer: 2- 120 mmol/l
associated with bronchial carcinoma is receiving
treatment with Tolvaptan.
A decision has been taken to treat this patient with
Which class of drug is Tolvaptan? hypertonic saline as she has acute symptomatic
hyponatraemia which reflects underlying cerebral
oedema. In this context, treatment with 150mls
1- Aldosterone receptor agonist 3% hypertonic saline given over three hours can be
lifesaving. The target sodium by which one should
2- Sodium-potassium channel blocker
elevate the sodium is 5 mmol/l over the first hour.
3- Vasopressin receptor agonist The increase in sodium should be then limited to
10mmol/l over the next 24hrs based on a clinical
4- Vasopressin receptor antagonist improvement.
5- Vasopressinase analogue
Reference:
European Journal of Endocrinology (2014)
Answer & Comments
Clinical practice guideline on diagnosis and
Answer: 4- Vasopressin receptor antagonist treatment of hyponatraemia
Tolvaptan is a drug developed for the treatment of [ Q: 329 ] Question ID #3564

hyponatraemia associated with SIADH and is a
vasopressin receptor antagonist. Initial dose is You are called to see a 42 year old female who has
usually 15mg daily and doses can be titrated become particularly confused. She was admitted
depending on response to treatment. three days prior following an accident on her bike
and had sustained a cerebral contusion. This did
Medscape tolvaptan (Rx) Samsca. Dosing and not require any neurosurgical intervention. On
usess examination, she was drowsy with a GCS of 13 and
bilateral upgoing plantars but no focal neurology.
[ Q: 328 ] Question ID #3453 Her pulse is 68 bpm with a blood pressure of
128/80 mmHg. Oxygen saturations are 99% on air.
A 62 year old woman with acute symptomatic Her blood results reveal the following:
hyponatraemia likely due to SIADH and associated
with drowsiness is considered to be appropriate
for immediate treatment with hypertonic saline. Sodium 118 mmol/l (134-144)
Her serum sodium is 115 mmol/l. Potassium 3.8 mmol/l (3.5-5.5)
What is the target sodium to which you would
treat this patient over the next 1hr?
Glucose 4.8 mmol/l (3.5-5.5)
1- 116 mmol/l Which of the following would be the most

2- 120 mmol/l appropriate initial treatment for this patient?

1- 100mg IV hydrocortisone stat Sodium 125 mmol/l (134-144)

2- 150 mls of 3% hypertonic saline given over Potassium 4.5 mmol/l (3.5-5.5)
20 mins Urea 6.8 mmol/l (3-8)
3- 1g phenytoin IV over 30 mins Urine Osmolality 620 mosmol/l
4- 1l N saline over 4 hrs Urine Sodium 125 mmol/l
5- Fluid restriction to 500 mls per day

Checking through his records, the previous days
his U+Es were normal. He had been allowed to eat
Answer & Comments and drink normally and had stopped IV fluids 2
days ago. He was on dexamethasone the dose of
Answer: 2- 150 mls of 3% hypertonic saline given which had been reduced to 4mg daily from 8 mg
over 20 mins daily over the last day but he was on no other
treatment.
This patient appears to have developed a
hyponatraemic encephalopathy associated with On examination, he had Glasgow Coma Scale of
the severe and acute hyponatraemia. This seems 15, though seemed confused with him being
likely due to either SIADH or indeed cerebral salt disorientated. Oxygen saturations were 97% on air
wasting. In this scenario, the acute development and his blood pressure was 110/80 with a pulse of
of hyponatraemia results in cerebral oedema 88 bpm.
associated with an osmotic influx of water into the
brain cells and swamping of the counter – Which of the following is the most likely diagnosis?
regulatory sodium-potassium pump. The resulting (Please select 1 option)
cerebral oedema is life threatening and manifests
as headache, drowsiness, seizure and potentially 1- Acute hypoadrenalism
death. Therefore, urgent treatment is required 2- Cerebral Salt Wasting
and guidance recommends rapid increase in
sodium by approx 5 mmol/l through use of 150 ml 3- Pituitary apoplexy
boluses of 3% hypertonic saline.M 4- Syndrome of inappropriate ADH secretion
Steroids will not help in this scenario despite the 5- Type IV renal Tubular acidosis
cerebral oedema. The patient does not have
hypoadrenalism as reflected by normal potassium Answer & Comments
and blood pressure.
Answer: 2- Cerebral Salt Wasting
Reference:
Goce Spasovski et al (2014) European Society of The most likely diagnosis in this patient with head
Endocrinology Clinical Practice Guidelines on injury who then develops acute symptomatic
diagnosis and treatment of hyponatraemia hyponatraemia and grossly elevated urine sodium
is cerebral salt wasting. The grossly elevated urine
[ Q: 330 ] Question ID #3565 sodium (>100) is highly suggestive as the sodium is
usually less with SIADH. Similarly with SIADH,
You are called to see a 42 year old male patient on there is a dilutional element so urea and
the neurosurgical ward. He was admitted with a potassium typically reflect this dilution being
head injury 3 days ago which required only themselves low normal in contrast to CSW where
observation. However, he has become more there is hypovolaemia and hence higher
confused in the last 12 hours and his most recent concentrations. Hypoadrenalism is an incorrect
U+Es performed this morning reveal: answer as the patient is already on a high dose of
steroids – dexamethasone 4mg/d.

Reference: Reference:
Cerebral Salt Wasting Medscape Resuscitation Council Guidelines on Anaphylaxis
An 18 year old female is admitted as an emergency An 18 year old student is admitted after having
with acute facial swelling and difficulty breathing. had a strange reaction where she became acutely
She is not known to have any allergy but does unwell after going to a Chinese restaurant. She
suffer from mild asthma for which she occasionally became light headed and short of breath and she
uses a salbutamol inhaler. She was out having a thinks she momentarily passed out. An ambulance
picnic with her friends, eating various foods, when was called and she was given oxygen and
she suddenly became unwell, feeling particularly recovered. She has a history of eczema but
anxious and itchy, while developing facial/mouth nothing else. On examination, there is nothing to
swelling with difficulty breathing. Her friends find and she seems fine. Blood results are normal.
called 999.
Which of the following tests could be used to
On examination, she has swelling of the face assess if this were an anaphylactic reaction?
particularly around the eyes and lips. There are (Please select 1 option)
wheals around the neck. Pulse is 100 bpm and
blood pressure 128/80 mmHg. She has an audible 1- Alpha-1 antitrypsin
wheeze and oxygen saturations are 96% on air.
2- C1-esterase
Which of the following is the most appropriate 3- C4 complement
treatment for this patient? 4- C-reactive protein
5- Mast cell tryptase
1- 0.5 mg adrenaline IV
2- 0.5 mg adrenaline IM Answer & Comments
3- 10mg chlorpheniramine IM Answer: 5- Mast cell tryptase
4- 100mg hydrocortisone IV
Mast cell tryptase is the molecule to measure in
5- 40mg oral prednisolone
suspected anaphylaxis as the mast cells release
this in abundance in anaphylaxis with
Answer & Comments concentrations rising abruptly within 30 minutes
to 1 hour. C1 esterase deficiency is a cause of
Answer: 2- 0.5 mg adrenaline IM repeated episodes of anaphylaxis but this is not
the molecule to measure. As in this case, the
This patient has developed angioedema, urticarial measurement of mast cell tryptase may
and breathing difficulties typical of anaphylaxis. differentiate between a faint and anaphylaxis
The patient should be treated with 0.5 mg IM where doubt exists.
adrenaline as the initial treatment as per the
resuscitation council guidelines. Other treatments Reference:
include IM/IV hydrocortisone and IM Resuscitation Council Guidelines anaphylaxis
chlorpheniramine but the IM adrenaline and fluids
is the initial treatment. The use of IV adrenaline is [ Q: 333 ] Question ID #3775
reserved for severe cases in whom expert
understanding of IV adrenaline is understood.
A 72 year old man with a 12 year history of
diabetes being treated with metformin is seen as

he is lethargic and the GP is concerned about his [ Q: 334 ] Question ID #4133

persistent hyperkalaemia. His HbA1c 7.5% (<7). He
also has a history of hypertension for which he A 45 year old female presents with a 3 month
takes bisoprolol 5 mg daily, amlodipine 10 mg/d, history of sweats and diarrhoea. She has watery
simvastatin 40mg/d and aspirin 75 mg/d. diarrhoea 5-6 times daily and is also aware of
flushes which occur daily without any obvious
He has been re-referred to clinic by his GP as he precipitant. She feels these symptoms have
has been noted to have a persistent become more obvious and has been associated
hyperkalaemia. Previously he was taking an ACE with some weight loss of 2kg over the last 3
inhibitor but this was stopped one year ago. months. There is no past history of note and she
takes no medication. There is nothing to note on
Sodium 132 mmol/l (134-144) examination with a BMI of 24.5 kg/m2. Stool
Potassium 5.8 mmol/l (3.5 – 5) culture is negative. FBC, Electrolytes, LFTs, Calcium
and thyroid function are all normal. CT scan of the
abdomen reveals numerous small metastatic
Creatinine 100 micromol/l (50-100) deposits in the liver and some thickening around
Glucose 14.1 mmol/l (3.5-5.5) the appendix/ileocecal junction.
Which of the following is the likely cause of this Which of the following tumour markers would be
man’s hyperkalaemia? most helpful in this patient?
1- Auto-immune hypoadrenalism 1- CA 19-9
2- Bisoprolol 2- CA 125
3- Chronic renal failure 3- CEA
4- Metformin 4- Chromogranin A and B
5- Renal artery stenosis 5- HCG
Answer: 2- Bisoprolol Answer: 4- Chromogranin A and B
This patient has a long history of hypertension and This patient presents with a classical history of
hyperkalaemia. He has a mild hyponatraemia flushes and diarrhoea together with metastatic
associated with the hyperkalaemia and the most deposits in the liver suggesting metastatic
likely diagnosis is type 4 renal tubular acidosis or neuroendocrine tumour (carcinoid syndrome).
hyporeninaemic hypoaldosteronism. The most Useful tumour markers in this condition include
likely drug to cause this is the beta blocker and this chromogranin A and B and urinary 5-HIAA with
should be stopped. Other drugs implicated include 85% sensitivity and 95% sensitivity.
ACE inhibitors and NSAIDs.
Chromogranin A: Is it a useful tumour marker in
Reference: NETs
Hyporeninemic hypoaldosteronism
[ Q: 335 ] Question ID #4134
A 45 year old woman is diagnosed with

acromegaly. Her IGF-1 concentration is elevated at
110 nmol/l (14-30) and she fails to suppress

growth hormone concentrations on an oral 1- Niacin deficiency

glucose tolerance test. MRI of the pituitary
2- Pyridoxine deficiency
confirms a pituitary macroadenoma which is
distinct from the optic chiasm. 3- Riboflavin deficiency
She is acromegalic in appearance, has a blood 4- Selenium deficiency

pressure of 140/80 mmHg. There is nothing else of 5- Vitamin C deficiency
note on examination and visual fields are full.
Answer & Comments
All other tests including FBC, U+Es, LFTs and TFTs
are normal. Answer: 1- Niacin deficiency
She is to have pituitary surgery in due course.

Carcinoid syndrome is associated with the pellagra
as the tumour elaborates serotonin from
Which of the following investigations of the GI
tryptophan, a component of niacin (vitamin B3).
tract should also be undertaken on this patient?
(Please select 1 option) DermnetNZ Pellagra
1- Chromogranin A and B
2- Colonoscopy
3- CT scan of abdomen
4- Endoscopy
5- Fasting gut peptides
Answer & Comments

Answer: 2- Colonoscopy
This woman with active acromegaly should have a

colonoscopy according to guidance. Individuals
over the age of 40 with acromegaly should be
screened with further interval screening
performed at 3 years for those not cured or with
polyps present.
Screening guidelines for acromegaly
[ Q: 336 ] Question ID #4135
A 55 year old man is diagnosed with metastatic

small bowel neuroendocrine tumour. He is noted
to have a reddened scaly rash around neck in a
necklace like effect.
Which of the following is likely to be responsible for

this rash?


diabetes has been converted from twice daily
Novomix to a basal bolus insulin regimen
comprising of insulin glargine and novorapid three
months previously at a total daily dose of 72 units.
On review in the clinic her glycaemic control has
improved since her insulin regimen change with
her current Hba1c measuring 8.1 % (<6) compared
with 8.9% (<6) prior to her regimen change. She is
however unclear as to how to modify her prandial
[ Q: 337 ] DM - Question ID #4 insulin doses according to her diet.
A 45 year old lady recently diagnosed with type 2 Which of the following is the most appropriate
diabetes is managed by diet and exercise alone initial advice for this lady with respect to adjusting
and has an HbA1c of 6.5% (<6). Her BMI is 32 kg / her prandial insulin dose?
m 2 and her blood pressure is 144 / 74 mmHg. (Please select 1 option)
1- 0.5 units of insulin per 10 gram of dietary

She has a 13 year old daughter and is concerned
about the potential risk of her daughter carbohydrate
subsequently developing type 2 diabetes. 2- 1 units of insulin per 10 gram of dietary
carbohydrate
Which of the following is the correct lifetime risk of
type 2 diabetes for this lady’s daughter? 3- 2 units of insulin per 10 grams of dietary
carbohydrate
1- 1 in 2
carbohydrate
2- 1 in 3
3- 1 in 10 carbohydrate
4- 1 in 20
Answer & Comments
5- 1 in 40
Answer: 2- 1 units of insulin per 10 gram of dietary
Answer & Comments carbohydrate
Answer: 3- 1 in 10
The DAFNE patient education program suggests
that patients should initially adjust prandial insulin
The incident diabetes risk in siblings and offspring doses by 1 unit according to each 10 gram of
of patients with type 2 diabetes is approximately dietary carbohydrate. This initial ratio may
10%. The background population risk for type 2 subsequently be modified according to response
diabetes is around 2-5%, while the risk of incident and the influence of other factors such as exercise.
type 2 diabetes in a monozygotic twin of a patient
with type 2 diabetes is around 1 in 3.
A 21 year old man has a 4 year history of type 1

diabetes with good glycaemic control exemplified
by a most recent HbA1c measurement of 6.5%

(<6). His current medication includes once daily Investigations reveal:

insulin glargine at a dose of 8 units combined with
pre-prandial humalog at a dose of 4 units prior to 12.9 mmol/l (3.5 -
each meal. He experiences occasional Fasting plasma glucose
5.6)
hypoglycaemic episodes and questions his
Random plasma 14.7 mmol/l (3.5 -
diagnosis. Reviewing his notes he was found to
glucose 5.6)
have presented with ketoacidosis but cytoplasmic
islet cell antibody serology was negative. Cholesterol 4.8 mmol/l (<5)
Triglyceride 1.7 mmol/l (0.9 - 2.2)
What percentage of patients with type 1 diabetes
HDL-C 1.4 mmol/l (0.9 - 1.9)
will exhibit high titres of cytoplasmic islet cell
antibodies? LDL-C 2.9 mmol/l (<2)
(Please select 1 option) TSH 0.7 mu/l (0.32 - 5)
GAD Antibodies Positive
1- 5 - 10%
2- 20 - 25% Which of the following is the correct diagnosis for
3- 30 - 40% this lady?
4- 60 - 80%
1- Impaired glucose tolerance
5- 100%
2- Latent Autoimmune Diabetes in Adults
(LADA)
Answer & Comments
3- Metabolic Syndrome
Answer: 4- 60 - 80%
4- Type 1 diabetes
Cytoplasmic islet cell antibodies (ICA) are IgG 5- Type 2 diabetes
antibodies which can react on frozen sections of
human, rat or mouse pancreas. High titres of ICA
Answer & Comments
are found in up to 80% of newly diagnosed
patients with type 1 diabetes, in approximately 3% Answer: 2- Latent Autoimmune Diabetes in Adults
of first degree relatives and in 0.2% of the general (LADA)
population. The great majority of patients
developing type 1 diabetes express
autoantibodies reacting to more than one antigen. Positive glutamic acid decarboxylase antibody
Relatives expressing a single autoantibody (e.g. (GAD) serology suggests the diagnosis to be LADA
Anti-GAD, with restricted ICA) show a lower rate - latent autoimmune diabetes in adults. This lady
and slower progression to overt diabetes. has no features of the metabolic syndrome or type
2 diabetes and is unlikely to have type 1 diabetes
Placental Insuffiicency as she reports no weight loss which is a cardinal
feature of absolute insulin deficiency. LADA is a
form of type 1 diabetes with slow progression to
[ Q: 340 ] Question ID #8 insulin dependency and can be distinguished from
people with type 2 diabetes by the presence of
A 41 year old lady is referred to the diabetes clinic GAD autoantibodies. There is no consensus on the
following presentation to her primary care optimum treatment of LADA, however a recent
physician with a 5 month history of lethargy and Cochrane review concluded that a sulphonylurea
increasing thirst but denies any weight loss. On should not be the first line treatment since it may
examination, her blood pressure is 125/70 mmHg, be associated with a more rapid progression to
her BMI is 25 kg /m2 and her waist circumference insulin dependence.
is 73.4 cm.

[ Q: 341 ] Question ID #9 The most likely diagnosis for this patient is MODY,
suggested by the presence of a first degree
A 35 year old school teacher is referred to clinic for relative presenting with diabetes < 25 years
assessment of and management of his diabetes. coupled with the fact that this patient has no
He was diagnosed with diabetes 3 years previously evidence of ketosis and has corrected fasting
on the basis of elevated fasting blood glucose blood glucose for at least 2 years without insulin.
levels and has subsequently experienced good The diagnosis of MODY in this case is also
glycaemic control on oral hypoglycaemic therapy. supported by the absence of features of the
metabolic syndrome, obesity and negative GAD
He denies any weight loss, has never experienced
ketosis and has an elder sister who was diagnosed serology.
with diabetes 12 years previously at the age of 24.
On examination his blood pressure is 135/75 [ Q: 342 ] Question ID #12
mmHg, his body weight is 75 kg and his BMI is 25.5
kg / m2. His current medication includes metfomin A 51 year old man with recently identified type 2
1 gram twice daily and gliclazide 80 mg twice daily. diabetes currently managed with lifestyle
modification alone undergoes a mixed meal
Investigations reveal: tolerance test with measurement of glucose,
insulin and glucagon profiles over a 4 hour period.
HbAlc 7.5% (<6)
Fasting Plasma Which of the following glucose, insulin and
6.9 mmol/l (<6) glucagon profiles would you expect to occur in this
Glucose
Total cholesterol 4.5 mmol/l (<4) gentleman compared to an age matched healthy
volunteer following a mixed meal tolerance test?
TSH 0.1 mu/l (032 - 5.5)
TSH receptor
Negative 1- Increased plasma glucose, reduced early
antibodies
phase insulin secretion, reduced glucagon
96 ml/min/1.73 m2 (90 -
eGFR secretion
110)
GAD antibodies Negative 2- Increased plasma glucose, reduced early
phase insulin secretion, elevated glucagon
Which of the following is the most likely correct secretion
diagnosis for this young man?
3- Increased plasma glucose, exaggerated early
(Please select 1 option) phase insulin secretion, reduced glucagon
1- Latent Autoimmune Diabetes in Adults secretion
(LADA) 4- Increased plasma glucose, delayed early
2- Maturity onset diabetes of the young phase insulin secretion, no difference in
(MODY) glucagon secretion
3- Schmidt syndrome 5- Increased plasma glucose, no difference in

insulin secretion, elevated glucagon
4- Type 1 diabetes
secretion.
5- Type 2 diabetes
Answer & Comments
Answer & Comments
Answer: 2- Increased plasma glucose, reduced
Answer: 2- Maturity onset diabetes of the young early phase insulin secretion, elevated
(MODY) glucagon secretion

Beta and alpha cell dysfunction are characteristic together with insulin in a 1:1 molar ratio. Beta cells
features of the pathophysiology of type 2 account for between 70 – 80% of the endocrine
diabetes. Beta cell function is reduced by up to cell mass of the pancreas and contain
70% according to data from UKPDS at the point of chromogranin A which is an acidic 48KDa protein
type 2 diabetes diagnosis. The earliest which has a putative function as a pro-hormone.
manifestation of beta cell dysfunction occurs in Delayed, but exaggerated early phase insulin
the form of reduced and delayed post-prandial secretion is a feature of early glucose intolerance,
early phase insulin secretion. Alpha cell as glucose intolerance progresses to type 2
dysfunction is manifest as elevated plasma diabetes, with associated progressive beta cell
glucagon levels compared to healthy subjects dysfunction, early phase postprandial insulin
which remain inappropriately elevated following secretion becomes both delayed and blunted.
meal ingestion.
A 45 year old man with a 6 month history of diet diabetes is reviewed in clinic. On examination her
controlled type 2 diabetes undergoes a 2,500 kcal BMI is 33 kg / m2 and her blood pressure is 145 /
4 hour mixed meal tolerance test as part of a 65 mmHg. She is generally well but is concerned
research program. Peak insulin concentrations are about the possibility of cardiovascular disease
measured after 2 hours with a level of 48 pmol/l since her father suffered with a myocardial
being achieved with a peak glucose concentration infarction at the age of 61 years and she has
of 14. 8 mmol/l being achieved after 90 minutes recently read an article outlining the link between
diabetes and cardiovascular disease.
Which of the following is a feature of pancreatic
beta cell function? Investigations reveal:
total Cholesterol 4.8 mmol/l (<5)
1- Beta cells account for 30% of the Endocrine
cell mass. LDL-Cholesterol 2.8 mmol/l (< 3)
HDL-Cholesterol 1.1 mmol/l (0.9 - 1.9)
2- C-Peptide is secreted with insulin in a 2:1
molar ratio Hba1c 7.1% (<6)
3- C-peptide is a by-product of insulin
proteolysis TSH 1.9 mu/l (0.32 - 5)
4- Early phase insulin secretion is delayed and Which of the following parameters is the most
diminished in people with impaired glucose important coronary heart disease risk factor in this
tolerance lady?
5- Insulin is produced by proteolytic cleavage (Please select 1 option)
from proinsulin 1- Hba1c
2- HDL-Cholesterol
Answer & Comments
3- LDL-Cholesterol
Answer: 5- Insulin is produced by proteolytic
cleavage from proinsulin 4- Total cholesterol
5- Systolic Blood pressure
Insulin is produced in the pancreatic beta cell by
proteolytic cleavage from pro-insulin resulting in a
by-product, namely c-peptide which is secreted

Answer & Comments patients with type 1 diabetes which contributes to

challenges in the clinical management of such
Answer: 3- LDL-Cholesterol patients. Immune mediated islet cell destruction
in type 1 diabetes is primarily CD 4 +T-cell
The UKPDS cardiovascular risk assessment model mediated, with class II HLA molecules being critical
for patients with type 2 diabetes identified LDL-C to the presentation of antigens to CD4+ T cells. It
as the most important individual determinant of has been postulated that the predisposing DR3 /
coronary heart disease, followed in sequential DR4 alleles for type 1 diabetes arises as a result of
order by HDL-C, Hba1c, systolic blood pressure the more efficient presentation and binding of a
and smoking. specific ‘diabetogenic’ peptide. Intrauterine
malnutrition is a recognised risk factor in the
aetiology of type 2 diabetes – the so called Barker
hypothesis.
A 28 year old man is referred by his GP following

presentation with polydypsia, weight loss and [ Q: 346 ] Question ID #22
general malaise. He has no previous medical
history of note and no family history of note. On A 44 year old lady has recently been diagnosed
examination his BMI is 27 kg / m2 and his blood with type 2 diabetes. She is currently receiving no
pressure is 133 / 73 mmHg. medication and has an HbA1c of 6.9% (<6). Her GP
contacts you for advice regarding whether he
Investigations reveal should screen this lady’s identical (monozygotic)
twin for diabetes.
Fasting plasma glucose 15.9 mmol/l (<5.6)
What is the life time risk of this lady’s twin sister
Hba1c 10.1% (<6)
having type 2 diabetes or any abnormality of
glucose metabolism?
Which of the following is a feature of the
pathophysiology of type 1 diabetes? (Please select 1 option)
(Please select 1 option) 1- 5%

1- Has a single susceptibility locus 2- 5 - 10%
2- HLA genes on chromosome 6 are closely 3- 10 - 20%
linked to autoimmune process 4- 30 - 50%
3- Malnutrition in utero is a risk factor 5- 70%
4- Mechanism of autoimmunity is B-cell
mediated Answer & Comments
5- Obesity is a major risk factor Answer: 5- 70%
Answer & Comments Using clinical diabetes as the criterion, most twin
Answer: 2- HLA genes on chromosome 6 are studies have demonstrated a concordance rate for
monozygotic twins of between 45 – 95% and for
closely linked to autoimmune process
dizygotic twins between 3 and 37%. When glucose
tolerance tests are performed in ‘non-diabetic’
Multiple HLA loci on chromosome 6 are linked monozygotic co-twins available data suggests that
with the pathophyisology of type 1 diabetes. the concordance rate is usually over 70%.
Obesity is not a contributory factor to the
pathophysiology of type 1 diabetes, however Concordance rate for type II diabetes mellitus in
there is an increasing incidence of obesity in monozygotic twins: actuarial analysis.

[ Q: 347 ] Question ID #23 include the integrity of the glucose monitoring

equipment, whether there are problems with the
A 48 year old man with a 4 year history of type 2 actual technique of glucose monitoring and
diabetes attends clinic for review. His current whether or not the observed discrepancy between
medication includes metform 500 mg three times glucose monitoring and HbA1c may be related to
a day, gliclazide 160 mg twice a day, ramipril 10 mg a haemoglobinopathy.
once a day and simvastatin 20 mg once a day. He
conducts frequent home blood glucose [ Q: 348 ] Question ID #24
monitoring and his average capillary glucose over
the last month shown on his meter is 9 mmol/l. A 55 year old man undergoes a 75 gram oral
glucose tolerance subsequent to a fasting plasma
Based on this average glucose profile which of the glucose measurement of 8.3 mmol/l (< 6)
following is the most likely HbA1c concentration conducted by his GP. The results of his 75 gram
for this patient? oral glucose tolerance test reveal a fasting plasma
(Please select 1 option) glucose of 7.1 mmol/l (<5.6) and a 2 hour post-
challenge plasma glucose of 12.2 mmol/l (< 7.8)
1- 6%
2- 6.5% Which of the following is a recognised feature of
type 2 diabetes?
3- 7%
4- 8%
1- 30% of patients presenting with acute
5- 9% coronary syndrome will have undiagnosed
type 2 diabetes
Answer & Comments 2- C-Peptide is usually low or absent at
Answer: 3- 7% diagnosis
3- Genetic mutation has been identified in up
7% is the most likely HbA1c concentration for this to 30% of patients at diagnosis
patient, based on the ADAG formula (A1c derived
Average Glucose) of Average glucose = 1.583 X 4- Has a low identical twin concordance
HbA1c - 2.52. 5- Insulin levels are elevated comparable to the
degree of glycaemia at diagnosis
Av. glucose = 1.583 X HbA1c – 2.52
9 = 1.583 X HbA1c - 2.52 Answer & Comments

Answer: 1- 30% of patients presenting with acute
HbA1c X 1.583 = 9 + 2.52 coronary syndrome will have undiagnosed
type 2 diabetes
HbA1c = 11.52 ÷ 1.583
HbA1c = 7.28% Up to 1/ 3 of patients presenting with acute

coronary syndromes, including myocardial
Discrepancies between average glucose levels infarction will on screening, despite having no
obtained from self monitoring and measured previous history of glucose intolerance, have type
HbA1c values require further evaluation. When 2 diabetes. A similar proportion of patients
Hba1c levels are disproportionately low compared presenting with acute cerebrovascular syndromes
to measured average glucose values this may (stroke / TIA) will also have previously unidentified
suggest periods of unrecognised or unmeasured type 2 diabetes. C-peptide levels are usually
hypoglycaemia. Further factors to consider present or may even be elevated at diagnosis in

patients with type 2 diabetes as consequence of In this scenario, the addition of ezetimibe to a
hyperinsulinaemia related to insulin resistance. simvastatin is supported by the IMPROVE-IT study
This hyperinulinaemia is not however appropriate and are included in guidance. Current guidelines
to the level of glycaemia. Identical twin do not advocate the use of fibrate therapy as an
concordance is high (45 – 95%) in twin studies of add on to statin therapy. ( < 2mmol/l).
patients with type 2 diabetes.
Lipid Modifying Drugs NICE
A 49 year old man attends clinic for review. He has
a 2 year history of type 2 diabetes which was A 53 year old lady with a 3 year history of type 2
diagnosed following admission to hospital with a diabetes is reviewed in clinic; she has a previous
troponin positive cardiac event. His current history of hypothyroidism but has no other
medication includes simvasatin 40 mg at night, medical history of note. Her current medication
metformin 500 mg three times daily, aspirin 75 mg includes metformin 500mg three times a day,
once daily, Perindopril 4 mg once daily and simvatatin 20 mg at night, ramipirl 2.5 mg once a
Bisoprolol 2.5 mg once daily. day and thyroxine 100 mcg once a day.
On examination, his BMI is 30 kg /m2, his blood On examination her BMI is 32 kg /m2 blood
pressure is 141/79 mmHg and his pulse is 62 beats pressure 135/85 mmHg and her pulse is 62 beats
per minute. per minute.
Investigations reveal: Investigations reveal:
Hba1c 6.9% (<6) Hba1c 7.5% (<6)

Total Cholesterol 3.9 mmol/l (<5) total
6.3 mmol/l (<5)
LDL-C 1.8 mmol/l (<2) cholesterol
HDL-C 0.8 mmol/l (0.9 - 1.8) LDL-C 4.1 mmol/l (<2)
Fasting Plasma TG 2.7 mmol/l (0.9 - 2.2) triglyceride 2.1 mmol/l (0.9 - 2.2)
TSH 4.3 mu/l (0.32 - 5) eGFR > 96 /min / 1.73 m2 (90 - 110)
TSH 8.6 mu / l (0.32 - 5.5)
Which of the following would be the most Free T4 10.9 pmol/l (9.3 - 23.4)
appropriate treatment option to optimise this
patient’s lipid profile? Which of the following is the most appropriate
(Please select 1 option) treatment option to optimise this lady’s lipid
1- Switch Simvastatin to Atorvastatin profile?
2- Add Ezetemibe
1- Add Fenofibrate
3- Add Fenofibrate
2- Commence Atorvastatin
4- Add Omega-3 fish oil
3- Increase Simvastatin
5- Switch Simavastatin to Rosuvastatin
4- Increase Metformin
Answer & Comments 5- Increase thyroxine
Answer: 2- Add Ezetemibe


Answer: 5- Increase thyroxine Answer: 1- Once daily insulin long acting analogue
This lady appears to have sub-optimal thyroid This lady’s primary concern with respect to insulin
hormone replacement which is likely to contribute therapy is minimising hypoglycaemia risk. Her BMI
to her dyslipidaemia. Hypothyroidism is a is also elevated thus a secondary consideration
recognised risk factor for lipid lowering therapy would relate to the minimization of any weight
associated myoptoxicity, therefore prior to gain associated with exogenous insulin therapy.
escalating her specific lipid lowering medications Basal insulin analogues such as Insulin Detemir
it is important to correct her thyroid profile. and Glargine are associated with reduced
hypoglycaemia risk compared with NPH insulin,
while results of the 4T study demonstrated that
insulin initiation with Detemir in patients receiving
on-going metformin and sulphonylurea
A 65 year old lady is referred to the clinic for combination therapy was associated with reduced
insulin initiation. She has a 7 year history of type 2 hypoglycaemia and less weight gain compared
diabetes with deteriorating glycaemic control over with either TDS pre-prandial novorapid or twice
the last 2 years resulting in a most recent Hba1c daily novomix 30 regimens.
measuring 9.1%. Her current medication includes
metformin 1g BD, Gliclazide 16 mg BD, Ramipril
5mg OD, furosemide 40mg OD, simvastatin 40mg [ Q: 352 ] Question ID #50
od and bisoprolol 1.25mg OD. She has a previous
history of ischaemic heart disease having been A 42 year old South Asian gentleman is referred to
admitted to hospital 8 months previously with an the diabetic clinic by his GP. He has a 5 year history
episode of heart failure. of type 2 diabetes. He complains of feeling tired
and has a previous history of ischemic heart
On examination, her BMI measures 35 kg/m2, her disease.
blood pressure 140/80 mmHg and she has
evidence of background retinopathy on retinal On examination BMI 34 kg m2, pulse 52 bpm,
screening. She has been previously intolerant of blood pressure 148/78 mm/Hg. Current
exenetide due to nausea and had no significant medication consists of 'Novomix 30/70' mixed
response when commenced on sitagliptin. You insulin - 42 IU twice daily, metformin 500 mg twice
contemplate insulin initiation for her but she daily, simvastatin 20 mg od, aspirin 75 mg od,
informs you that she is worried about enalapril 20 mg od, atenalol 50 mg od.
commencing insulin as she lives alone and is
worried about hypoglycaemia when commenced Investigations –
on insulin.
Hbalc 7.9% (<6)
Which of the following insulin regimens would be
the most appropriate for this lady in terms of
hypoglycaemia avoidance? LDL-Cholesterol 4.5 mol/l (< 3)
(Please select 1 option) Triglyceride 2.9 mmol/l (0.9 - 2.2)
1- Once daily insulin long acting analogue U + Es Normal

TSH 32.8 mu / l (0.3 - 5.5)
2- Once daily NPH insulin
Free T4 6.9 pmol / l (9.8 - 23.6)
3- Thrice daily pre-prandial novorapid
4- Twice daily biphasic insulin aspart Which of the following is the most appropriate
approach to optimise this patient’s lipid profile?
5- Twice daily NPH insulin

1- Improve glycaemic control 98 ml/ min / 1.73 m 2 (90

eGFR
2- Commence thyroxine - 110)
TSH 0.4 mu / l (0.32 - 5.5)
3- Commence fenofibrate
albumin/creatinine
4- Commence Omega 3 fish oil 0.4 mg / mmol (<2.5)
ration
5- Increase Simvastatin dose
approach for the management of this patient’s
Answer & Comments
blood glucose control?
Answer: 2- Commence thyroxine (Please select 1 option)
1- Convert to a three times daily Mix 50

This patient is hypothyroid and correction of his regimen
thyroid status will also improve both his glucose
control and lipid profile. Increasing the statin dose 2- Add Metformin
or commencing a fibrate is not appropriate as 3- Continuous subcutaneous insulin infusion
hypothyroidism is a risk factor for dyslipidaemia
(insulin pump)
per se and is also associated with increased risk of
myotoxicity with lipid-lowering therapies. Omega- 4- Convert basal insulin glargine to insulin
3 fish oils are not routinely recommended for use detemir
in this setting.
5- Convert once daily basal insulin glargine to
twice daily insulin glargine
Answer & Comments

A 35 year old lecturer with a 14 year history of type
1 diabetes attends clinic for review. He describes Answer: 3- Continuous subcutaneous insulin
an erratic blood glucose profile on self blood infusion (insulin pump)
glucose monitoring with unpredictable episodes
of hypoglycaemia occurring at a frequency of up
to 3 to 4 episodes per week despite optimal This patient fulfils current NICE guideline criteria
education which has resulted in recent loss of for CSII therapy, in that he is failing to archive
hypo awareness. optimal blood glucose control despite appropriate
education and insulin therapy in the setting of
variable blood glucose profiles and frequent
On examination blood pressure 125 / 75 mm/hg,
hypoglycaemic episodes.
fundoscopy reveals background retinopathy in the
left eye and examination of injection sites revelas
no evidence of lipohypertrophy. Current [ Q: 354 ] Question ID #52
medication includes basal insulin glargine
combined with pre-prandial insulin aspart A 51 year old gentleman is referred by his GP for
(novorapid) with dose adjustment of both insulins review of his glucose control and insulin dosage.
according to self monitored blood glucose levels He has a 7 year history of type 2 diabetes. He has
and dietary carbohydrate content. a previous history of ischemic heart disease having
been commenced on insulin following his
Investigations reveal: myocardial infarction 3 years previously.
Hbalc 8.1% (<6) On examination, body weight is 144 kg, BMI 51 Kg

Total Choleseterol 3.9 mmol/l (<5) / m2 pulse 67 bpm, blood pressure 160/88 mmHg.
He has already tried an exercise regime and other
Plasma Triglyceride 1.2 mmol/l (0.9 - 2.2) weight loss measures recommended by his doctor
with little effect. His current mediation includes

metformin 1 gram twice daily, simvastatin 40 mg [ Q: 355 ] Question ID #53

daily, Novomix 30/70 mixed insulin 114 units in
the morning, 120 units evening time, ramipril 10 A 70 year old lady is referred to clinic for specialist
mg daily, bisoprolol 5 mg daily and Aspirin 75 mg assessment. She has a 7 year history of type 2
daily having been previously intolerant of orlistat. diabetes and has a background history of ischemic
heart disease having suffered a myocardial
Investigations reveal infarction 2 years previously and had an
echocardiogram at this point revealing impaired
Hba1c 9.8% (<6) left ventricular ejection fraction of 40%. Her
Total Cholesterol 4.1 mmol/l (<5) current treatment includes metformin 1 gram bd,
glicalzide 160 mg bd, simvastatin 40 mg od, aspirin
75 mg od, lisinopril 20 mg od, frusemiode 40 mg
TSH 2.9 mu l (0.32 - 5.5) od, bisoprolol 5 mg od.
58 ml / min / 1.73 m2 (90
eGFR Clinical examination reveals BMI 33 kg /m2, blood
- 110)
pressure 143/67 mmHg, pulse 65 bpm, her chest
albumin creatinine
5.5 mg / mmol (<2.5) is clear to auscultation and there is no evidence of
Ratio
heart failure.
therapy option for this patient?
(Please select 1 option) Hba1c 9.1%
1- Conversion to insulin detemir Cholesterol 4.4 mmol/l (< 5)
2- Conversion from insulin to exenetide LDL-C 2.4 mmol/l (< 3)
3- Addition of Exenatide Triglyceride 2.2 mmol/l (0.9 - 2.2)
eGFR 43 ml / min/ 1.73 m2 (90 - 110)
4- Addition of Orlistat
TSH 2.5 mu / l (0.3 - 5.5)
5- Referral for Bariatric surgery.
Answer & Comments treatment option for reducing this patient’s blood
glucose?
Answer: 5- Referral for Bariatric surgery.
This patient fulfils referral criteria for bariatric 1- Exenatide

surgery in that he is morbidly obese (BMI above 2- Insulin glargine
40) with associated co-morbidities including
poorly controlled diabetes, hypertension and 3- Liraglutide
ischaemic heart disease. Conversion to another
4- Pioglitazone
insulin regimen is unlikely to have additional
benefit while sibutramine is contraindicated due 5- Vildagliptin
to his hypertension. Long-term weight loss
response to gastroplasty or banding is between 16
Answer & Comments
and 25% at 10 years. Bariatric surgery has been
shown to result in a 39% relative risk reduction in Answer: 2- Insulin glargine
all cause mortality at 10 years post surgery, while
diabetes remission rate at 10 years is around 40%.
Insulin initiation represents the most appropriate
therapy choice for this lady.

BNF recommendations: Which of the following is the most appropriate oral

hypoglycaemic agent for this lady?
 Exenatide: for standard-release injection, (Please select 1 option)
use with caution if eGFR 30–50
mL/minute/1.73 m2; avoid if eGFR less 1- Glicalzide
than 30 mL/minute/1.73m2 for modified- 2- Metformin
release injection, avoid if eGFR less than
50 mL/minute/1.73 m2 3- Repaglinide
4- Rosiglitazone
 Liraglutide: avoid if eGFR less than 60
mL/minute/1.73 m2—limited experience 5- Sitagliptin
 Vildagliptin: caution in heart failure (avoid Answer & Comments

if moderate or severe)
Answer: 2- Metformin
 Pioglitazone: caution in cardiovascular
disease or in combination with insulin (risk Most guidelines recommend Metformin as first
of heart failure line therapy in type 2 Diabetes provided eGFR is
greater than 30ml/min/1.73m2. In this patient the
[ Q: 356 ] Question ID #54 eGFR is 56 and the modestly elevated creatinine is
not a contra-indication to treatment. Metformin
A 60 year old lady with a 6 month history of type 2 in this patient would offer potential reductions in
diabetes and past history of hypertension attends mortality according to published data and would
a community diabetes clinic for review. She is be the first choice for treatment.
generally well and is currently receiving no oral
hypoglycaemic therapy. On examination BP 150 / Reference:
78 mm/hg, BMI 28 Kg / m2 Body weight 63 kg, NICE guidance as pdf
waist circumference 78 cm and no evidence of
microvascular complications can be identified. [ Q: 357 ] Question ID #55
Current medication includes Lisinopril 20 mg OD,
Simvastatin 20 mg OD and Aspirin 75 mg OD. You are contacted by a GP colleague regarding an
elderly lady with a history of type 2 diabetes,
Investigations reveal: hypertension, ischaemic heart disease and
features of vascular dementia. She is receiving
Hba1c 7.3% (<6) multiple medications and her GP is concerned
Total Cholesterol 4.8 mmol/l (<5) about the risk of drug interactions particularly
with respect to the risk of hypoglycaemia.
Plasma triglyceride 1.7 mmol/l (<1.7)
56 ml /min / 1.73 m2 Which of the following drugs taken by this lady
eGFR
(90- 110) may result in an increase risk of hypoglycaemia in
Fasting Plasma patients with diabetes?
6.1 mmol/l (3.5 - 5.5)
Glucose (Please select 1 option)
Albumin/creatinine
4.1 mg / mmol (<3.5) 1- Isosorbide mono-nitrate
ratio
128 micromol/l (50 - 2- Nifedipine
Serum creatinine
110) 3- Low dose aspirin
TSH 1.2 mu / l (0.32 - 5.5)
4- Omeprazole
5- Simvasatin

Answer & Comments in such a patient in whom HBA1c remains above

48 mmol/mol (6.5%). Consideration should be
Answer: 3- Low dose aspirin given to swapping the sulphonylurea for a TZD or
a DPP-IV inhibitor if the SU is contraindicated or if
Low dose aspirin has been associated with the there is significant risk of hypoglycaemia. In this
development of hypoglycaemia related to a postmenopausal woman pioglitazone is relatively
stimulatory effect of aspirin on the beta cell contra-indicated due to fracture risk.
mediated via inhibition of prostaglandin synthesis.
In larger doses salicylates can have detrimental The mechanism of action of the sulphonylurea
effects on glucose homeostasis resulting from class of drugs resulting in glucose independent
inhibition of oxidative phosphorylation with a insulin release. Consequently sulphonylurea
consequent impairment in glucose oxidation. therapy may be associated with both
Other commonly used agents which may increase hypoglycaemia and weight gain. Glibenclamide
the risk of hypoglycaemia, particularly in the has the longest half life (approximately 16 hours)
elderly include ACE-inihbitors via mechanisms of all sulphonylureas with breakdown into
involving improved insulin sensitivity. Statins may metabolically active metabolites so that
have a diabetogenic risk. Nitrates and PPIs have no glibenclamide is the agent associated with the
effect on glucose homeostasis, while nifedipine highest risk of hypoglycaemia.
may have detrimental effects on glucose
homeostasis. NICE Algorithm for treating T2DM
A 69 year old lady with a 4 year history of type 2 A 51 year old man with a 12 month history of diet
diabetes attends the clinic for annual review. She controlled type 2 diabetes has an Hba1c of 7.4%
is currently taking metformin 1 g bd together with (<6). On examination his BMI is 33 kg/m2 and his
lisinopril 20mg daily. She is well and little is noted blood pressure is 134/88 mmHg. He is
on examination other than a BMI of 31.8 kg/m2 consequently commenced on metformin at a
and a blood pressure of 144/84 mmHg. She has an staring dose of 500mg BD.
HbA1c of 58 mmol/mol (7.5% (<6)).
Which of the following is a recognized feature of
Which of the following would be the most metformin therapy?
appropriate approach to the further management (Please select 1 option)
of her hyperglycaemia?
1- Metformin improves hepatic glucagon
sensitivity
1- Add Exenatide
2- Metformin undergoes both hepatic and
2- Add Gliclazide renal clearance
3- Add Pioglitazone 3- Metformin decreases splanchnic glucose
4- Add Liraglutide turnover
5- Continue with metformin alone 4- Metformin reduces hepatic and peripheral

fatty acid synthesis
Answer & Comments 5- Metformin may undergo significant drug

interactions with warfarin, cimetidine and
Answer: 2- Add Gliclazide
ACE-inhibitors.
NICE would recommend the addition of a

sulphonylurea/DPP-IV/pioglitazone to metformin

Answer & Comments 3- Contraindicated in established diabetic

nephropathy
Answer: 4- Metformin reduces hepatic and
peripheral fatty acid synthesis 4- Has no effect on microalbuminuria in
patients with type 1 diabetes
Metformin has a variety of metabolic effects, 5- Has no effect on systemic vascular resistance
although its complete mechanism of action is yet
to be fully understood. Metformin improves
insulin sensitivity, with recent data suggesting an Answer & Comments
increase in AMP kinase activity mediating an Answer: 1- Causes a reduction in intraglomerular
increase in glucose utilization and fatty acid pressure
oxidation both in the liver and peripheral tissues.
The primary site of action of metformin appears to
be the liver with suppression of hepatic ACE inhibitors act by blocking the renin-
glycogenolysis, gluconeogenesis and an increase angiotensin-aldosterone system (RAAS). They are
in splanchnic glucose turnover all being involved in competitive inhibitors of angiotensin converting
the glucose lowering effects of metformin. enzyme (ACE), which catalyse the conversion of
Metformin reduces hepatic and peripheral fatty the inactive angiotensin I to the powerful
acid oxidation It is excreted almost unchanged in vasoconstrictor and stimulator of aldosterone
the urine, more by tubular secretion than by release, angiotensin II. Inhibition of ACE thus
glomerular filtration; hence metformin is results in a decrease in the production of
contraindicated in significant renal impairment angiotensin II and hence a decrease in
due to an increase risk of metabolic acidosis, vasoconstriction and a decrease in the levels of
particularly in the presence of an inter-current aldosterone, with resulting reduction in
illness or in the context of other conditions intraglomerular pressure. The result is a decrease
associated with tissue hypoxia. Consequently in peripheral resistance and a decrease in the
conditions associated with an increase risk of retention of salt and water, hence decreasing
tissue hypoxia such as severe heart failure and blood pressure. ACE inhibitors also reduce the
respiratory diseases represent contraindications breakdown of the potent vasodilator bradykinin.
to metformin. Metformin may reduce intestinal Increased levels of bradykinin may further
vitamin B12 absorption and only undergoes drug enhance vasodilation and contribute to blood
interactions with cimetidine. pressure reduction.
ARBs act by blocking the RAAS further

[ Q: 360 ] Question ID #58 downstream than ACE inhibitors. They block the
actions of angiotensin II by competitively binding
A 49 year old man with a 12 month history of diet to the angiotensin type 1 (AT1) receptor. It is via
controlled type 2 diabetes has an Hba1c of 6.9% this receptor that angiotensin II normally exerts its
(<6),a BMI of 31 kg /m2 and blood pressure of effects. These effects are an increase in
165/89 mmHg. He is consequently commenced on vasoconstriction leading to increased total
ramipril at a starting dose of 2.5 mg once daily. peripheral resistance and an increase in the
production of aldosterone leading to the retention
Which of the following is a recognised feature of of salt and water and hence increased blood
ACE-inhibitor therapy? volume. The result is an increase in blood
pressure. By blocking the AT1 receptor, ARBs
prevent these effects of angiotensin II and hence
1- Causes a reduction in intraglomerular decrease blood pressure. As ARBs, unlike ACE
pressure inhibitors, do not block the action of the enzyme
ACE, they do not inhibit the breakdown of
2- Causes relaxation of afferent arterioles of
bradykinin. ARBs therefore are not associated
the glomerulus with the persistent dry cough, often seen with ACE
inhibitor therapy.

Direct renin inhibitors, such as aliskiren, act to pancreatitis in the general population (0.44- 0.47
block the action of renin in converting cases per 1000 patient years). Neutralizing
angiotensinogen to angiotensin I. antibodies to exenatide have been infrequently
identified, with a maximum incidence of around
[ Q: 361 ] Question ID #59 3%. Anti-exenatide antibodies are however
identified in up to 40% of patients, the clinical
relevance of this finding is unclear.
diabetes has a Hba1c of 8.2% (<6), a BMI of 36 kg/
m2 and blood pressure of 155/78 mmHg. His [ Q: 362 ] Question ID #77
current medication includes metformin 850 mg
tds, glicalzide 160 mg bd, simvaststin 20 mg daily, A publication reports the outcome of a new statin
ramipril 5 mg daily and bendrofluazide 2.5 mg therapy in a placebo controlled primary
daily. Based on current NICE guidelines he is prevention of ischaemic heart disease in a diabetic
commenced on exenatide at a starting dose of 5µg population. 1000 patients were randomised to
bd. receive the new therapy and 1000 allocated to
placebo. The study was completed over a five year
Which of the following is a feature of the period. In the placebo group there were 150
therapeutic profile of exenatide? myocardial infarcts and in the group treated with
the new statin there were 100 myocardial infarcts.
1- Exenatide has over 90% homology to human What is the number needed to treat with the new
GLP-1 statin versus the conventional statin to prevent
2- Exenatide undergoes hepatic and renal one MI over the course of this study?
clearance (Please select 1 option)
3- Exenatide has a terminal half life of 2.5 hours 1- 10
4- Exenatide is causally linked to an increase 2- 20

risk of pancreatitis 3- 30
5- 20% of patients will develop neutralizing 4- 40
antibodies to exenetide.
5- 50
Answer & Comments

Answer & Comments
Answer: 3- Exenatide has a terminal half life of 2.5
hours Answer: 2- 20
Exenetide is an exendin derived peptide with 53 % In the new statin group, there were 100 MIs in a
homology to human GLP-1 and is consequently 1000 patients treated. In the conventional statin
resistant to degradation by human DPP-IV. It is group there were 150 MIs in a 1000 treated
predominantly cleared via renal excretion and is patients. Therefore treating 1000 patients one
therefore not recommended in patients with an would have 50 fewer MIs. Thus the Number
eGFR < 30. Exenatide has a half-life of around 2.5 needed to treat with the new statin to prevent 1
hours and therefore is given twice daily by MI is 1000/50 = 20.
subcutaneous injection. No causal link between
exenatide and pancreatitis has to date been [ Q: 363 ] Question ID #78
identified, although a higher incidence of
pancreatitis has been reported in association with A new antiplatelet agent has been proven to
exenatide (0.49 cases per 1000 patient years) reduce the risk of stroke in a year from 10% in
compared with the background rate of

patients treated with conventional treatment to Triglycerides 4.1 (0.8 - 2.2)

6% in patients treated with conventional
Free T4 12.1 pmol/l (10 - 22)
treatment plus the new agent. The cost of this new
drug is £10 per month extra than conventional 4.8 mu/l 90.5 - 5)
therapy. Thyroid
>1300 iu/l (<200)
autoantibodies
How much extra would a hospital need to spend
Albumin:creatinine
per year to prevent one stroke? 2.6 (<2.5)
ratio
1- 1200 Which of the following is the most likely cause for

this patient’s dyslipidaemia?
2- 3000
3- 4800
1- Hypothyroidism
4- 6000
2- Nephrotic syndrome
5- 12000
3- Poor glycaemic control
4- Type III hyperlipidaemia
Answer & Comments
5- Type V hyperlipidaemia
Answer: 2- 3000
Answer & Comments

To answer this question firstly one needs to
calculate the number needed to treat to prevent Answer: 3- Poor glycaemic control
one stroke. In this case the annual number of
strokes with the new agent per 100 patients
This patient has a typical dyslipidaemia of type 2
treated is 6 and in the conventional treatment it is
diabetes with poor glycaemic control. With a
10. Therefore there are 4 fewer strokes per
HbA1c above 8%, this reflects defective
hundred patients treated with the new drug giving
chylomicron metabolism contributing to excess
an NNT of 25. Therefore, you would need to treat
triglyceridaemia and increased cholesterol.
25 patients for one year to prevent 1 stroke each
Improving glycaemic control by reducing HBA1c by
of which costs an extra £120. Therefore, it would
1% would be expected to reduce triglycerides by
cost the hospital an extra 25 x 120 = £3000 to
up to 0.5 mmol/l. This is not hypothyroidism as
prevent one stroke with the newer treatment.
TSH levels are normal and the thyroid
autoantibodies mean nothing other than a 30%
[ Q: 364 ] Question ID #114 lifetime risk of developing hypothyroidism.
A 54 year old male attends the diabetic clinic for [ Q: 365 ] Question ID #115
routine review. He has had diabetes for ten years
and is currently receiving metformin 1g bd
A 62 year old male, who has been newly diagnosed
combined with biphasic insulin – novomix 30. He
with diabetes by his GP, is referred to clinic. He is
also takes simvastatin 40 mg daily. Investigations
on a diet, but currently taking no medication. His
reveal:
blood pressure is 136/82 mmHg, his BMI is 32
kg/m2 and his investigations reveal:
87 mmol/mol (10.1%)
HbAlc
(<6)
U+Es Normal
HbA1c 6.65 (<6)
hdL 0.8 mmol/l (0.9 - 1.9)

HDL Cholesterol 0.9 mmol/l (0.9 - 2.2) HbAlc 5.2% (<6)

Triglyicerides 3.3 mmol/l (0.9 - 2.2) ICA 0.0 iu/l (<0.1)
GAD antibody 0.01 iu/l (<0.5)
Which is the most appropriate agent to treat his
Triglyceride 0.7 mmol/l (0.9 - 2.2)
dyslipidaemia?
1- Atorvastatin Which of the following is the diagnosis?

2- Fenofibrate (Please select 1 option)
3- Nicotinic acid 1- Type 1 diabetes
4- Omega-3 fatty acids 2- Type 2 diabetes
5- Weight reduction 3- LADA

4- MODY type 1
Answer & Comments
5- MODY type 2
Answer: 1- Atorvastatin
Answer & Comments
Since this patient is over the age of 40 years old
Answer: 2- Type 2 diabetes
and has a normal to high cardiovascular risk for
someone with type 2 diabetes, the most
appropriate treatment for his elevated cholesterol Afro-Caribbeans may present with type 2 diabetes
(target total cholesterol and LDL cholesterol below with marked hyperglycaemia which is particularly
4 and 2 respectively) would be a statin. If his sensitive to insulin therapy. The patient should be
triglycerides remain elevated (2.3 - 4.5 mmol/l) treated with withdrawal of insulin and
despite the use of a statin, then consider the commencement of diet alone and monitoring.
addition of a fibrate.
NICE clinical guidelines 87: The management of
type 2 diabetes
A study embarks on a new method of measuring
insulin resistance in a group of obese subjects. It
[ Q: 366 ] Question ID #116 utilises mathematical modelling of certain new
serological markers.
A 38 year old Afro-caribbean lady attends diabetic
clinic for annual review. She was diagnosed with Which of the following would be the appropriate
diabetes 4 years previously and was treated standard measure of insulin resistance against
immediately on Novomix 30 twice daily due to her which this new technique should be compared?
presentation with a fasting plasma glucose of 21 (Please select 1 option)
mmol/l and osmotic symptoms. Her glycaemic
control has been excellent with an HbA1c range of 1- Homeostatic model assessment (HOMA)
between 5.5 – 6.5%. Over the last 12 months her
2- Hyperinsulinaemic euglycaemic clamps
insulin dose requirements have fallen such that
she is receiving insulin 4 iu twice daily. Her BMI is 3- Insulin tolerance test
28kg/m2.
4- Oral glucose tolerance test
Investigations reveal: 5- Quantitative insulin sensitivity check index
(QUICKI)

Answer & Comments 1- Glucose tolerance test

Answer: 2- Hyperinsulinaemic euglycaemic clamps 2- Glycaemic load
3- Glycaemic index
Hyperinsulinaemic euglycaemic clamp is the gold
4- Prolonged glucose tolerance test
standard technique against which other
techniques, as listed above may be used. 5- The standard meal test
[ Q: 368 ] Question ID #118 Answer & Comments

Answer: 3- Glycaemic index
A technique of measuring insulin resistance
whereby the product of the fasting values of
glucose and insulin are divided by a constant of This description of the measurement of glucose
22.5. concentrations following a specific carbohydrate
compared with glucose itself is that of the
To which technique does this description refer? glycaemic index. High GI index foods have a value
of 70 or above, medium 56-69 and low <55.
1- Glucose/Insulin ratio (GI ratio)

2- Glycaemic index
From which of the following is Glucagon-like
3- Homeostatic model assessment (HOMA)
Peptide 1 (GLP-1) produced?
4- Quantitative insulin sensitivity check index (Please select 1 option)
(QUICKI)
1- Body of stomach
5- Score for insulin sensitivity index (ISI)
2- Ileum
Answer & Comments 3- Liver
Answer: 3- Homeostatic model assessment 4- Pancreas

(HOMA) 5- Pylorus
HOMA is one of the most widely used and easiest Answer & Comments
techniques of measuring insulin
sensitivity/resistance. It generally correlates well Answer: 2- Ileum
with insulin clamp studies.
GLP-1 is a hormone produced by the L-cells of the
[ Q: 369 ] Question ID #119 ileum and has effects on insulin and glucagon
secretion by the pancreatic islets, as well as having
central effects regulating caloric intake.
‘Healthy fasted subjects are given a 50g
carbohydrate meal and glucose concentrations
are measured every 15mins for the first hour and [ Q: 371 ] Question ID #121
every 30 mins up to 2 hours. These glucose
concentrations are then compared with values Which of the following effects are mediated by
after the consumption of 50g of glucose’. GLP-1?
To which of the following does this methodology
refer? 1- Delayed gastric emptying time
(Please select 1 option) 2- Increased jejunal transit time

3- Increased gastric acid secretion 5- Type IV renal tubular acidosis

4- Increased pancreatic exocrine enzyme
secretion Answer & Comments
5- Increased bile acid secretion Answer: 1- Citalopram
Answer & Comments The patient has a hyponatraemia with

inappropriate conservation of urine sodium and
Answer: 1- Delayed gastric emptying time highish urine osmolality versus a plasma
osmolality of approx 269 mosmol/l - Claculated as
GLP-1 produces satiety through a number of - 2x (sodium+potassium) + Urea + Glucose. The
mechanisms including reduced gastric emptying most likely explanation for this is SIADH and the
and is also felt to act through central effects most likely precipitant of SIADH is Citalopram.
reducing hunger. SSRIs are a common cause of hyponatraemia due
to SIADH. Type IV RTA (hyporeninaemic
hypoalosteronism) is unlikely as this is usually
[ Q: 372 ] Question ID #125 associated with a higher potassium concentration.
A 58 year old female is referred by the GP who is

concerned about her hyponantraemia. He
recently performed U+Es which reveal:
A 28 year old female presents at 14 weeks in her
second pregnancy. She previously gave birth to a
Sodium 124 mmol/l (134 - 144)
healthy baby boy 2 years ago who weighed 4Kg.
Potassium 3.6 mmol/l (3.5 - 5) The patient has a history of polycystic ovarian
Urea 5.5 mmol/l (3 - 8) syndrome and has previously been treated with
metformin to assist with conception. The only
Creatinine 120 micromol/l (50 - 100)
other issue of note is that her cousin has type 1
Glucose 9.2 mmol/l (3.5 - 5.5) diabetes. She has a BMI of 32.3 kg/m2 and is
HbA1c 7.2% (<5.5) otherwise fine.
She is generally well and has a history of diabetes, Which of the following would be a reason for
depression and hypertension for which she is screening this patient for gestational diabetes?
receiving gliclazide 80mg bd, metformin 500 mg (Please select 1 option)
tds, Lisinopril 20 mg daily, amlodipine 10mg daily
and citalopram 20mg daily. Her hyponatraemia is 1- Her age
confirmed and the following results are returned: 2- Her BMI
3- Her family history of diabetes
Urine sodium 22 mmol/l
Urine osmolality 610 nmosmol/l 4- Her history of polycystic ovarian syndrome
5- The previous weight of her infant
Which of the following is the likely cause of her
hyponantraemia?
Answer & Comments
Answer: 2- Her BMI
1- Citalopram
2- Gliclazide Screening for gestational diabetes is hotly debated
3- Hypoadrenalism with the general acceptance of case selection
being advocated. NICE advise testing for GDM in
4- Lisinopril the following scenarios:

 1st degree relative with diabetes (her Which of the following foods has the highest GI
cousin is not a first degree relative) value?
 Previous pregnancy with macrosomia (Please select 1 option)
(>4.5kg)
 Previous gestational diabetes 1- Apples
 BMI above 30
2- Baked Potatoes
 Family origin with a high prevalence of
diabetes 3- Boiled Potates
4- Peaches
5- Spaghetti
A 68 year old man has a long history of type 2

diabetes with end stage renal disease. He has had Answer & Comments
some problems with associated hyperkalaemia Answer: 2- Baked Potatoes
and has been advised a low potassium diet.
Which of the following foods should he specifically The Glycaemic Index (GI) relates solely to
avoid? carbohydrates and is a measure of by how quickly
a food raises plasma glucose compared with
glucose itself. Carbohydrates can be scored from 0
1- Apples to100 where glucose has a GI of 100. Thus, the GI
index provides information on whether a food
2- Grapefruits raises blood sugar levels dramatically, moderately
3- Oranges or minimally - high, moderate or low GI values.
Apples, peaches Oranges and even Chocolate are
4- Peaches considered low GI (less than 55). Yet, through
5- Pineapple different preparation, the GI can alter –mashed
potatoes (70) and baked potatoes (85) have a high
GI (above 70) whilst boiled potatoes have a
Answer & Comments moderate GI of 58. Foods only appear if they
Answer: 3- Oranges contain carbohydrate hence meats, eggs and fish
do not appear in the GI index. The GI is important
in diabetes and conditions related to post-prandial
Hyperkalaemia is a common biochemical hypoglycaemia or dumping syndrome. Generally,
abnormality in chronic renal failure and a low the lower the GI index the ‘better’ the
potassium diet is frequently required. Foods with carbohydrate.
a high potassium content which should be avoided
include Avocado, Banana, Tomato, Oranges,
Orange juice and Potato. Also canned fruits have a [ Q: 376 ] Question ID #167
high potassium content.
A 52 year old male is seen 6 weeks after being
admitted to hospital with an inferior myocardial
infarction. He was diagnosed with type 2 diabetes
two years ago and was taking metformin 500 mg
A 23 year old type 1 diabetic man has noticed tds, ramipril 10mg daily and simvastatin 40mg
some problems in relation to his post-prandial daily. He had received thrombolysis and made an
glucose excursions after eating certain foods. He uneventful recovery. He was a smoker of 10
has read about the glycaemic index (GI) of foods cigarettes per day but has since given up. After his
and its impact on post-prandial glucose MI, he was also prescribed atenolol 25 mg daily
concentrations. and aspirin 75mg daily.

On examination he is well, his blood pressure is [2008, amended 2014]

128/78 mmHg and pulse 64 bpm. https://www.nice.org.uk/guidance/cg181/ch
apter/1-recommendations#lipid-
Investigations reveal: modification-therapy-for-the-primary-and-
secondary-prevention-of-cvd-2
HDL 1.5 mmol/l (0.9-1.9) [ Q: 377 ] Question ID #168
Plasma Triglycerides 1.4 mmol/l (0.9 – 2.2)
A 55 year old male develops muscle aches and
HbA1c 7.1% (<6)
pains. He has a history of ischaemic heart disease
and has been taking simvastatin for the last 3 years
Which of the following is the most appropriate without any particular problems. However, most
management concerning further cardiovascular recently he has started to lead a healthier lifestyle
risk reduction? and has been taking some health supplements.
Consumption of which of the following
1- Add Ezetimibe
supplements may have precipitated this statin-
2- Add Fenofibrate induced myalgia?
3- Add Niacin (Please select 1 option)
4- No changes required 1- Cranberry Juice
5- Switch Simvastatin to Atorvastatin (80 mg) 2- Garlic Capsuls

3- Ginseng
Answer & Comments
4- Grapefruit Juice
Answer: 5- Switch Simvastatin to Atorvastatin (80 5- Vitimin C
mg)
Answer & Comments

This patient has appropriate cholesterol
concentrations with his current statin therapy, yet Answer: 4- Grapefruit Juice
the GISSI-III study revealed that the use of omega-
3 fatty acids in patients following MI treated with Grapefruit juice is a recognised hepatic enzyme
all conventional post-MI therapy was associated inhibitor and statin-induced mylagia/myositis is
with a further 25% reduction in cardiovascular described following regular consumption of
mortality. grapefruit juice.
________________ Secondary prevention 1.3.20

Start statin treatment in people with CVD with [ Q: 378 ] Question ID #170
atorvastatin 80 mg[6]. Use a lower dose of
atorvastatin if any of the following apply: potential A 41 year old gentleman attends his GP for a
drug interactions high risk of adverse effects routine life insurance medical. He has no past
patient preference. [new 2014] For information medical history of note and feels generally well.
about implementing this recommendation, see On examination his blood pressure is 155 / 85
Implementation: getting started. 1.3.21 Do not mmHG, his BMI is 32 kg / m2, his waist
delay statin treatment in secondary prevention to circumference is 102 cm and his body weight is
manage modifiable risk factors. [2014] 1.3.22 If a 98.4 kg.
person has acute coronary syndrome, do not delay
statin treatment. Take a lipid sample on admission Investigations reveal:
and about 3 months after the start of treatment.

Fasting Plasma Glucose 5.3 mmol/l (3.5 - 6) HDL

< 1.29 (Women)
Total Cholesterol 5.4 mmol/l (<5.5) Cholesterol
Plasma Triglyceride 2.1 mmol/l ().9 - 2.2) Fasting

Plasma ≥ 5.5 mmol/l
HDL Cholesterol 0.9 mmol/l (0.9-1.9) Glucose
LDL Cholesterol 3.3 mmol/l (<2) Blood ≥ 130/85 mm Hg or recieving
Pressure Anti-Hypertensive Treatment
Based upon the IDF criteria, which of the following
would support a diagnosis of the metabolic Reference:
syndrome in this man? http://www.idf.org/webdata/docs/MetSyndro
(Please select 1 option) me_FINAL.pdf
1- His BMI, triglyceride concentration and
fasting glucose [ Q: 379 ] Question ID #171
2- His BMI, blood pressure and triglyceride
A 49 year old man attends the medical outpatient
concentration
clinic for review of his blood pressure control. His
3- His Waist circumference, blood pressure and current medication includes perindopril 8 mg
fasting glucose daily, amlodipine 5 mg daily and doxazosin 4 mg
daily. On examination, his blood pressure is 156 /
4- His Waist circumference, blood pressure and 88 mm Hg, his BMI is 34 kg / m2 and his waist
HDL concentration circumference is 96 cm.
5- His Waist circumference, HDL-cholesterol
and total cholesterol Fasting Plasma Glucose 5.4 mmol/l (3.5 - 6)
Total Cholesterol 4.6 mmol/l (<5.5)
Answer & Comments Plasma Triglycerides 1.8 mmol/l (0.9 - 2.2)
Answer: 4- His Waist circumference, blood HDL Cholestgerol 0.8 mmol/l (0.9 - 1.9)
pressure and HDL concentration LDL Cholesterol 3.2 mmol/l (< 3)
This gentleman meets the criteria for the Which of the following criteria would suggest a
metabolic syndrome, as defined by the diagnosis of metabolic syndrome in this gentleman
International Diabetes Federation, since he has according to the International Diabetes
central obesity (waist circumference ≥94 cm), a Federation?
plasma triglyceride ≥1.7 mmol/l, blood pressure (Please select 1 option)
≥130 / 85 mm Hg and a HDL-cholesterol < 1.04
mmol/l. 1- BMI, LDL-C concentration and blood
pressure
The IDF definition of the metabolic syndrome is 2- BMI, fasting plasma glucose and plasma
based on the presence of central obesity (waist triglyceride concentration
≥80 cm in women) combined with any two of the 3- Waist circumference, HDL-cholesterol
following: concentration and blood pressure
4- Waist circumference, triglyceride
Plasma
≥1.7 mmol/l concentration and LDL-cholesterol
Triglyceride
concentration
HDL
< 1.04 ( Men) 5- Waist circumference, HDL-cholesterol and
Cholesterol
LDL-cholesterol concentration

Answer & Comments Which of the following is associated with the use
of CGM during pregnancy?
Answer: 3- Waist circumference, HDL-cholesterol
concentration and blood pressure (Please select 1 option)
1- Reduced risk of fetal trisomy 21

This gentleman meets the criteria for the 2- Reduced risk of neural tube defects
metabolic syndrome, as defined by the
International Diabetes Federation, since he has 3- Reduced risk of shoulder dystocia
central obesity (waist circumference ≥94 cm), a 4- Reduced risk of fetal malformation
plasma triglyceride ≥1.7 mmol/l, blood pressure
≥130 / 85 mm Hg and a HDL-cholesterol < 1.04 5- Reduced risk of neonatal hypoglycaemia
mmol/l.
Answer & Comments
The IDF definition of the metabolic syndrome is
based on the presence of central obesity (waist Answer: 3- Reduced risk of shoulder dystocia
≥80 cm in women) combined with any two of the A recent study has suggested that CGM improves
following: glucose control in the third trimester of
pregnancy, leads to decreased mean birth weight,
Plasma thus reducing the incidence of macrosomia and
≥1.7 mmol/l
Triglyceride hence shoulder dystocia which is common
HDL problem with macrosomic babies.
< 1.04 ( Men)
Cholesterol
CGM in pregnancy
HDL
< 1.29 (Women)
Cholesterol
Fasting [ Q: 381 ] Question ID #173
Plasma ≥ 5.6 mmol/l
Glucose A 78 year old man attends clinic for review. He has
Blood ≥ 130/85 mm Hg or recieving a 5 year history of type 2 diabetes and his current
medication includes metformin 1 gram twice daily,
Pressure Anti-Hypertensive Treatment
perindopril 4 mg daily and Aspirin 75 mg once
daily. He has a past history hypertension and was
Reference: admitted to hospital 3 years previously with
http://www.idf.org/webdata/docs/MetSyndro congestive heart failure. On examination, his BMI
me_FINAL.pdf is 31 kg/m2, his blood pressure is 166/86 mm/Hg,
cardiovascular and respiratory system
[ Q: 380 ] Question ID #172 examinations are both normal. He feels generally
well although complains of feeling tired and gets
A 24 year old lady with an 8 year history of type 1 up at least twice a night to pass water. He is self-
diabetes attends antenatal clinic, with her first caring, independent and has normal cognitive
pregnancy at 10 weeks gestation. Her pre- function.
conception Hba1c was 8.2% (<6) and her current
medication includes Novomix 30 32 units in the Haemogobin 13.1 g dl (11 - 16)
morning and 34 units in the evening. She is Hba1c 8.7% (<6)
subsequently converted to a basal bolus insulin
regimen comprising of novorapid and levemir at
an initial total daily dose of 74 units. Subsequent Plasma Triglyceride 2.1 mmol/l (0.9 - 2.2)
dose modifications are conducted on the basis of TSH 1.35 mu / l (0.32 - 5.5)
continuous capillary glucose monitoring (CGM)
eGFR 53 ml/min/1.73m²

In accordance with NICE guidelines, which of the Which of the following methodologies is outlined
following would be the most appropriate above?
management with respect this man’s glycaemic (Please select 1 option)
control?
1- Homeostatic Model Assessment (HOMA)
2- Hyperinsulinaemic euglycaemic clamp
1- Add Gliclazide 80 mg once a day
3- Intravenous glucose tolerance test
2- Add pioglitazone 30 mg once daily
4- Quantitative insulin sensitivity check index
3- Add vildagliptin 50 mg twice daily
5- Hyperglycaemic clamp
4- No other intervention required
5- Start once daily insulin glargine Answer & Comments
Answer: 2- Hyperinsulinaemic euglycaemic clamp
Answer & Comments
Answer: 1- Add Gliclazide 80 mg once a day This is the classical example of the
hyperinsulinaemic euglycaemic clamp used as the
This man has poor glucose control with associated gold standard to assess insulin sensitivity. Clamp
symptoms. According to current NICE guidance a techniques are relied upon in research studies as
sulphonylurea would eb the most appropriate well as phase 3 and 4 interventions to assess the
additional therapy (May 2009) Vildagliptin would impact of pharmacological agents and
be an appropriate alternative is problemtaic interventions impact on insulin sensitivity.
hypoglycaemia should occur. He is not a candidate
for Pioglitazone since he has a previous history of [ Q: 383 ] Question ID #175
heart failure, even though there is no current
clinical evidence of heart failure.
A 48 year old Asian lady is referred to the diabetes
clinic. She has a 4 year history of type 2 diabetes
[ Q: 382 ] Question ID #174 and speaks very little English. Her current
medication includes Metformin 1 gram twice
The following description summarizes a daily, Gliclazide 160 mg twice daily, Lisinopril 10
standardized technique outlined in a research mg daily and Simvastatin 20 mg daily. On
proposal that you are submitting for local ethical examination, her BMI is 28 kg/m2, her body weight
approval: is 71 kg and her blood pressure is 136/76 mmHg.
"Through a peripheral vein, insulin is infused at 10- Investigations reveal:

120 mU per m2per minute. Glucose 20% is infused
to maintain blood sugar levels between 5 and 5.5 Hba1c 8.2% ( <6)
mmol/l. The rate of glucose infusion is determined
by checking the blood glucose levels every 5 to 10
minutes. The rate of glucose infusion during the Plasma Triglyceride 1.8 mmol/l (0.9 - 2.2)
last 30 minutes of the test determines insulin Thyroid Function
Normal
sensitivity. If high levels (7.5 mg/min or higher) are Tests
required, the patient is insulin-sensitive. Very low 62 ml/min/1.73m² (90-
levels (4.0 mg/min or lower) indicate insulin eGFR
110)
resistance. Levels between 4.0 and 7.5 mg/min are
not definitive and suggest impaired glucose
Which of the following patient education
tolerance."
programmes would be the most appropriate for
this lady?

(Please select 1 option) 3- DAFNE

1- BERTIE 4- DESMOND
2- Conversation mapping 5- EXPERT
3- DAFNE
Answer & Comments
4- DESMOND
5- EXPERT Answer: 3- DAFNE
Answer & Comments The DAFNE (Dose Adjustment For Normal Eating)
patient education programme is designed for
Answer: 2- Conversation mapping people with type 1 diabetes. It is a course running
over 5 consecutive days primarily focusing diet
composition and insulin dose changes.
Conversation mapping would be the most
appropriate for this lady, as it is a primarily visually
based patient education course and as such it can [ Q: 385 ] Question ID #177
be effectively delivered with the support of
interpreters. It is probably the most useful of the A 56 year old man is admitted to hospital with a
listed educational techniques for patients with lower respiratory tract infection. He is noted on
limited English speaking capacity. admission to have a random plasma glucose of
15.6 mmol/l (3.5-5.5). He is treated with oral
[ Q: 384 ] Question ID #176 antibiotic therapy, 3 months following his
discharge he undergoes a 75 gram oral glucose
tolerance test, the results of which are outlined
below:
diabetes is seen in the clinic. She is generally well
and expresses a wish to be referred to a structured
education programme as a means of improving Fasting plasma glucose 7.5 mmol/l (< 5.6)
her blood glucose control. On examination her
BMI is 25 kg/m2, her body weight is 68 kg and her 2-hour post challenge plasma glucose 13.1 mmol/l
blood pressure is 125/75 mmHg. Her current (<11.1)
mediation includes Novorapid and Levemir at a
total daily dose of 84 units. Which of the following education programmes
would be most appropriate for this man?
Investigations reveal: (Please select 1 option)
1- BERTIE
Hba1c 8.9% (<6)
2- Conversation mapping
Total 4.1 mmol/l (<4)
Plasma Triglyceride 1.1 mmol/l (0.9 - 2.2) 3- DAFNE
Thyroid Function Normal 4- DESMOND
5- X-PERT
Which of the following structured patient
education programmes would be the most
appropriate for this lady? Answer & Comments
(Please select 1 option) Answer: 4- DESMOND
1- BERTIE
This man has a new diagnosis of type 2 diabetes
2- Conversation mapping based on his oral glucose tolerance test. The

DESMOND education programme is a foundation supplementation on beta cell function in people

course for people newly diagnosed with type 2 with treatment naive type 2 diabetes.
diabetes and comprises 2 half days over a two
week period. X-pert is a programme for either type Which of the following is the most appropriate
1 or type 2's requiring insulin. DAFNE and BERTIE method of assessing first phase insulin secretion?
are also for type 1 patients.
1- 100 gram oral glucose tolerance test

2- Frequently sampled IV glucose tolerance test
A 61 year old man with a 6 year history of type 2 (FSIVGTT)
diabetes is reviewed in the clinic. On examination 3- Hyperinsulinaemic euglycaemic calmp
his blood pressure is 155/81 mmHg, his BMI is 32
kg/m2 and his body weight is 86 kg. His current 4- HOMA beta estimation
medication includes Metformin 1 g twice daily,
5- 4 hour mixed meal tolerance test
Glicalzide 160 mg twice daily, Atorvastatin 20mg
daily, Enalapril 20 mg once daily and Amlodipine 5
mg once daily. His most recent Hba1c is 9.1% (< 6) Answer & Comments
so you decide to commence a once daily insulin
Answer: 2- Frequently sampled IV glucose
analogue.
tolerance test (FSIVGTT)
Which of the following patient education
programmes would be the most appropriate for The FSIVGTT allows for very rapid collection of
this man? blood for insulin estimation during the early
period following glucose injection. First phase
insulin secretion is defective early in the natural
1- BERTIE history of type 2 diabetes, while the restoration of
early phase insulin secretion may be a feature if
2- Conversation mapping
improved beta cell function.
3- DAFNE
4- DESMOND [ Q: 388 ] Question ID #180
5- X-PERT
A 69 year old woman undergoes a right
hemicolectomy for ulcerative colitis. She has a 5
Answer & Comments year history of type 2 diabetes with her pre-
operative medication including metformin 500 mg
Answer: 5- X-PERT
three tds, pioglitazone 30 mg od and gliclazide 80
mg bd, with her pre-operative Hba1c being 7.5% (
The X-PERT patient education programme is <6). (58 mmol/mol). The surgical procedure is
primarily designed for patients with relatively successful and the immediate post-operative
recently diagnosed type 2 diabetes. It is also period unremarkable, during which time she has
however, suitable for patients with type 2 been managed with intravenous Variable Rate
diabetes of longer duration and in particular Insulin Infusion. Her appetite remains poor and
patients with type 2 diabetes commencing on the surgical team is concerned with respect to her
insulin. nutritional status since at one week post surgery
she is noticed to have lost 4.4 kg in weight
[ Q: 387 ] Question ID #179 compared to her admission body weight. She is
consequently commenced on an 18 hour enteral
feeding regimen.
You have established a research project to assess
the effect of dietary conjugated linoloeic acid

Which of the following is the most appropriate months ago due to progressive weight gain; he has
method of managing this lady’s blood glucose also been intolerant of orlistat due to abdominal
during this period? discomfort and diarrhoea. On examination, his
BMI is 43 kg/m2 and his blood pressure is 166/88
mmHg.
1- Continue with intravenous sliding scale
insulin Investigations reveal:
2- Commence sub-cutaneous sliding scale
Hba1c 8.9% (<6)
insulin
3- Introduce sub-cuatneous basal insulin
regimen Plasma Triglyceride 3.1 mmol/l (0.9 - 2.2)
TFTs Normal
4- Introduce a subcutaneous GLP-1 analogue
5- Re-introduce gliclazide in association with Which of the following treatments is associated
her enteral feed with the greatest reduction in future
morbidity/mortality for this man?
Answer & Comments (Please select 1 option)
Answer: 3- Introduce sub-cuatneous basal insulin 1- Bariatric surgery

regimen 2- Gliclazide 80mg twice daily
3- Exenetide 5 micrograms twice daily
According to the JBDS guidelines 2012:
4- Sitagliptin 100 mg once daily
Maintaining euglycaemia in patients receiving 5- Pioglitazone 30 mg daily
enteral feeding is often challenging. Aim to keep
Blood Glucose with in target range 6-12 mmols
Answer & Comments
Carbohydrate in enteral feeds is often absorbed Answer: 1- Bariatric surgery
quickly leading to hyperglycaemia and so insulin
requirements often increase.
Data from the Swedish obesity study coupled with
The catabolic state that occurs after major surgery long term follow up data post-bariatrc surgery
and the patient's poor nutritional state mean it is have demonstrated diabetes remission in up to
important to achieve good glucose control. 70% of patients at 5 years following bariatric
surgery, with up to 40 % of patients demonstrating
It is often impractical to use intravenous insulin for remission of diabetes at 10 years post surgery.
a prolonged period of time and so a simple These observations are coupled with a 29%
subcutaneous regime using basal insulin is often reduction in all cause mortality associated with 16
preferred. – 25% excess weight loss at 10 years post bariatric
surgery, along with a 92% reduction in diabetes
related mortality.
A 39 year old gentleman is referred to clinic for
review. He has a 2 year history of type 2 diabetes
and his current medication includes Metformin 1 You are contacted by a cardiology SpR to a review
gram twice daily, perindopril 8 mg daily and a 64 year old man who was recently admitted with
simvastatin 40 mg daily. He was also taking an episode of troponin positive chest pain. He has
rosiglitazone 4 mg daily, but discontinued this 4 a 7 year history of type 2 diabetes and his current

glicalzide 160 mg twice daily, Warfarin as per INR, exists, however, GLP-1 has been shown to exert
atorvastatin 40 mg daily, perindopril 4 mg daily beneficial effects on left ventricular function.
and bisoprolol 5 mg daily.
Reference:
On examination his blood pressure is 155/75 Renal failure and exenatide
mmHg, his BMI is 38 kg/m2 and he has no evidence
of cardiac failure. The cardiology team are thus
considering the possibility of exenatide, but are
unsure of the any specific contraindications.
A 56 year old man with a body mass index of 34
Further investigations reveal: kg/m2 is found to have a random plasma glucose
of 12.1 mmol/l during a recent admission to
hospital with a lower respiratory tract infection.
Hba1c 8.9% (<6)
One month later he has his fasting plasma glucose
Total Cholesterol 4.9 mmol/l (<5) measured on two occasions over a 5 day period
Plasma revealing fasting plasma glucose levels of 6.7
3.9 mmol/l (0.9 - 2.2) mmol/l and 6.9 mmol/l respectively.
Triglyceride
55 ml/min/1.73m2; (90-
eGFR Which of the following would be the most
110)
appropriate approach regarding this patient's
glucose concentrations?
Trans thoracic echo LV ejection fraction of 35%
with an LV mural thrombus (Please select 1 option)
1- Arrange oral glucose tolerance test

Which of the following is a specific
contraindication to exenatide therapy? 2- Measure HbA1c
(Please select 1 option) 3- No further investigation required

1- Concomitant Warfarin therapy 4- Repeat fasting glucose in three months
2- LV ejection fraction < 30% 5- Repeat fasting glucose in six months
3- Type III hyperlipoproteinaemia
Answer & Comments
4- Type V hyperlipoproteinaemia
Answer: 1- Arrange oral glucose tolerance test
5- eGFR < 30 m l / min /1.73 m2
This man has, by definition, impaired fasting

Answer & Comments glucose (IFG) (glucose between 6.1-6.9) and initial
Answer: 5- eGFR < 30 m l / min /1.73 m2 management includes lifestyle modification. IFG
also has a high incident risk of type 2 diabetes and
patients should undergo an oral glucose tolerance
Exenatide is contraindicated in people with test as up to 30% will have overt diabetes.
significant renal impairment. Exenatide has no
direct drug interaction with warfarin, but may
impact on INR through effecting warfarin [ Q: 392 ] Question ID #185
absorption due to delayed gastric emptying.
Exenatide is associated with an increase incidence A 65 year old man with a 6 year history of type 2
of reported pancreatitis, but diabetes is reviewed in clinic. His current
hypertriglyceridaemia (also a risk factor for medication includes metformin 850 mg twice
pancreatitis) is not a contraindication to daily, gliclazide 80 mg twice daily, rosuvastatin 10
exenatide. There is limited experience with mg once daily and perindopril 2 mg a day. On
exenatide, although no specific contraindication examination, his blood pressure is 156/86 mmHg

and his BMI is 33 kg/m2. Urinalysis reveals 3+ Which of the following is the most appropriate
protein and 1+ glucose and a 24 hour urinary approach to improving this young man's glucose
collection is subsequently arranged. control?
Which of the following urine albumin
concentrations signifies overt proteinuria? 1- Administer correction bolus at 7 am
(Please select 1 option) 2- Increase basal insulin rate between 11 pm
1- 20 mg / 24 hours and 8 am
2- 50 mg / 24 hours 3- Increase basal rate between 5am and 8 am
3- 100 mg / 24 hours 4- Increase basal rate between 6pm and 11 pm
4- 1 gram / 24 hours 5- Omit bed time snack
5- 300 mg / 24 hours
Answer & Comments
Answer & Comments Answer: 3- Increase basal rate between 5am and 8
am
Answer: 5- 300 mg / 24 hours
This man's glucose profile is typical of the dawn
Microalbuminuria = Urine albumin: 20- phenomenon with progressive increase in early
200 mg/g creatinine (men); 30-300 mg/g morning plasma glucose levels in the absence of
creatinine (women). nocturnal hypoglycaemia. This phenomenon is
primarily related to hepatic gluconeogenesis and
Overt albuminuria = Urine albumin: >300 glycogenolysis, hence the correct management
mg/day. would be to increase the basal insulin infusion rate
Overt proteinuria = Urine total protein: during this period in order to suppress hepatic
glucose release.
=300 mg/day.
Nephrotic range proteinuria = Urine total [ Q: 394 ] Question ID #187

protein: =3.5 g/day; Serum albumin: <3.0>
A GP colleague contacts you regarding referral of
Reference:
patients to the X-PERT patient programme which
BMJ best practice: Proteinuria has been recently commenced by your diabetes
service.
Which of the following patients would be the most
A 25 year old final year medical student with a 10 appropriate to refer to this patient education
year history of type 1 diabetes is reviewed in clinic programme?
4 months following conversion form a basal bolus
insulin regimen to an insulin pump. His frequent HbA1c Normal range less than 42 mmol/mol or 6%
nocturnal hypoglycaemic episodes have stopped (Please select 1 option)
and his Hba1c is now 67 mmol/mol (8.3%). On
1- A 15 year old girl with a 3 year history of type
review of his dietary history he has his main
evening meal between 8 and 9 pm, has a light 1 diabetes, taking a basal bolus insulin
breakfast at around 7 pm, a light lunch at around regimen with a most recent HbA1c of 67
1 pm and frequently has a bed time snack. mmol/mol (8.3 %)
Continuous glucose monitoring reveals glucose 2- A 58 year old man with a 2 year history of
levels of between 7 and 14 mmol/l between 5 and
type 2 diabetes taking metformin 1 gram
8 am, with no evidence of hypoglycemia.

twice daily with a most recent HbA1c of 57 Plasma

2.1 mmol/l (0.9 -2.2)
mmol/mol (7.4%) Triglyceride
3- A 33 year old man with a 12 year history of TSH 1.7 mu/l (0.32 - 5.5)
type 1 diabetes taking twice daily biphasic 68 ml/min/1.73m² ( 90-
eGFR
insulin with a most recent HbA1c of 73 110)
mmol/mol (8.8%)
4- A 48 year old man with a 3 year history of
approach to improve this lady’s blood glucose
type 2 diabetes secondary to Pancreatitis
control?
taking biphasic insulin with a most recent
HbA1c of 61 mmol/mol (7.7%)
1- Commence Exenatide
5- A 61 year old man with a recent diagnosis of
impaired glucose tolerance following a 75 2- Commence sitagliptin
gram oral glucose tolerance test.
3- Commence once daily glicalzide
4- Commence once daily Insulin glargine
Answer & Comments
5- Commence once daily biphasic insulin
Answer: 2- A 58 year old man with a 2 year history
of type 2 diabetes taking metformin 1 gram
twice daily with a most recent HbA1c of 57 Answer & Comments
mmol/mol (7.4%) Answer: 2- Commence sitagliptin
The X-PERT (and DESMOND) patient programme is This lady is at an increased risk of hypoglycaemia
6 week educational programme specifically during the month of Ramadan, therefore glucose
designed for patients with type 2 diabetes. It has independent insulin providing therapies such as
been shown to be effective in improving a number exogenous insulin and sulphonylureas do not
of parameters in diabetes care in trained represent the most appropriate treatment option.
individuals. Exenatide’s mechanism of action utilises the
incretin effect, resulting in glucose dependent
[ Q: 395 ] Question ID #188 stimulation of beta cell insulin release and would
thus be associated with a reduced risk of
hypoglycaemia, particularly in the absence of
A 55 year old Asian lady with a 5 year history of
concomitant sulphonylureas therapy. Exenatide is
type 2 diabetes is reviewed in clinic. Her current
however associated with appetite suppression
and is therefore not acceptable during Ramadan.
pioglitazone 30 mg once daily, simvastatin 20 mg
Sitagliptin is a DPPIV-enzyme inhibitor and thus
once daily and perindopril 4 mg once daily. On
also utilises the incretin effect to produce glucose
examination her blood pressure is 144/78 mmHg,
reduction, but does not have an effect on appetite
her BMI is 36.8 Kg/m2 and her body weight is 75.8
suppression and is thus acceptable.
kg. She is a devout Muslim and wishes to fast
during daylight hours during the month of
Ramadan. [ Q: 396 ] Question ID #189
Investigations reveal A 17 year old young man is reviewed in the

adolescent clinic. He has a five year history of type
Hba1c 8.6% (<6) 1 diabetes managed with a basal bolus insulin
Total Cholesterol 4.7 mmol/l (<5) regimen at a total daily dose of 62 units / day and
a most recent Hba1c of 8.1 % (<6). He is planning
a major night out with his friends to celebrate his

18th birthday and requests some advice on the On examination his body weight is 88 kg, his BMI
effect of alcohol on his diabetes management. is 28 kg / m2 and his blood pressure is 110 / 70
mmHg. His most recent Hba1c was 65 mmol/mol
Which of the following is the most appropriate (8.1%) (<6) and his main current concern is how to
advice for this young man? optimally manage his diabetes in relationship to
his sporting activities, since he is a keen rugby
player having recently been included in the
1- Alcohol increases blood glucose levels and national under 21 squad. As his level of exercise
insulin doses should be increased has increased, he has noticed increased variability
in his blood glucose profile and an increased
2- Alcohol produces reductions in blood
frequency of both elevated and low blood sugars,
glucose in the short term so that insulin which is starting to adversely affect his athletic
doses should be reduced performances.
3- Alcohol reduces blood glucose levels for
several hours after and insulin doses should Which of the following is the most appropriate
be 75% advice for this young man?>
4- Spirits have less effect on blood glucose than
beer 1- Consume energy drinks immediately before
and during exercise
5- Alcohol produces reductions in blood
glucose levels for several hours after 2- Increase his dose of prandial insulin with his
drinking a pre bed meal is advised in meal following playing rugby to facilitate
conjunction with a modest reduction in normalisation of elevated blood glucose
insulin dose levels which may have occurred as a
consequence of exercis
Answer & Comments 3- Omit his dose of prandial insulin with his
meal prior exercise or playing a rugby game,
Answer: 5- Alcohol produces reductions in blood
while increasing his basal insulin dose on the
glucose levels for several hours after drinking
evening following playing rugby a game of
a pre bed meal is advised in conjunction with
rugby
a modest reduction in insulin dose
4- Reduce his dose of basal insulin on the
Alcohol produces short term elevations in blood evening following playing a game of rugby
glucose followed by longer term reduction in and also reduce his dose of prandial insulin
blood glucose levels after drinking. It is therefore with his meal prior to playing rugby
important to advise patients of this possibility and
5- Reduce his dose of basal insulin on the
the need for pre bed food in conjunction with a
evening before he plays a rugby game
modest dose reduction following drinking.
[ Q: 397 ] Question ID #190 Answer & Comments

Answer: 4- Reduce his dose of basal insulin on the
A 20 year old young man is reviewed in the young evening following playing a game of rugby and
adult diabetes clinic. He has a 7 year history of also reduce his dose of prandial insulin with
type 1 diabetes and is currently taking a basal his meal prior to playing rugby
bolus insulin regimen comprised of once daily
insulin detemir at night combined with pre-
Strenuous exercise such as that related to playing
prandial novorapid at a total daily insulin dose of
rugby is associated with a depletion in glycogen
82 units.
stores which may result in hypoglycaemia and

glucose variability following strenuous exercise. Answer & Comments

Omitting prandial insulin, or the consumption of
energy drinks will result in hyperglycaemia which Answer: 3- Focus on reducing 2 hour post prandial
may adversely affect sporting performance. The blood glucose levels
optimal approach to managing this young man’s
glucose profile would be to modestly reduce his At Hba1c concentrations < 7.5%, post-prandial
pre prandial and post exercise insulin doses on a glucose levels become a more important
match day in order to minimise hypoglycaemia determinant of Hba1c than fasting or pre-meal
risk, while advising a meal containing complex blood glucose levels, thus targeting post-prandial
carbohydrates 2-4 hours prior to playing a match. blood glucose levels to < 8.5 mmol/l would be the
optimal approach to improving this lady’s glucose
[ Q: 398 ] Question ID #191 control based on her current Hba1c level.
A 27 year old lady attends clinic for review. She has [ Q: 399 ] Question ID #192
a 10 year history of type 1 diabetes and her
current insulin regimen includes once daily insulin A 38 year old man is referred to you for
glargine at a dose of 34 units at night along with assessment following his recent diagnosis of
variable doses of pre-prandial novorapid. Her diabetes, based on two fasting plasma glucose
most recent Hba1c is 57 mmol/mol (7.4%) (<6), levels of 7.9 mmol/l and 8.1 mmol/l. On
but she is keen to achieve an HbA1c of < 48 examination his blood pressure is 146/76 mmHg,
mmol/mol (6.5%) prior to attempting to conceive his BMI is 31 kg /m2 , his body weight is 90 kg and
since during a first unplanned pregnancy 2 years his waist circumference is 97 cm. He is currently
previously she had experienced a miscarriage receiving no medication; he is a non-smoker and
which she attributed to her poor blood glucose drinks alcohol infrequently. He has no family
control at that time. She conducts regular blood history of note and his main complaint is that of
glucose monitoring and is motivated to modify her feeling a little lethargic with some loss of libido.
insulin doses according to her blood glucose
profile. HbA1c 6.8% (<6)
Which of the following is the most appropriate Total Cholesterol 4.2 mmol/l (<5)
advice for this lady in order to achieve a reduction Plasma Triglyceride 1.5 mmol/l (0.9 - 2.2)
in her Hba1c? TSH 0.98 mu/l (0.32 - 5.5)
(Please select 1 option) Testosterone 8.1 nmol/l (9 - 30)
1- Focus on reducing fasting blood glucose Prolactin 175 mu/l (50-450)
levels AST 92 iu/l (5-40)
2- Focus on reducing pre-meal blood glucose Alkaline Phosphatase 295 iu/l (50-110)
levels
3- Focus on reducing 2 hour post prandial blood
investigation for this gentleman?
glucose levels
4- Focus on reducing pre-bed blood glucose
levels 1- Islet cell antibody serology
5- Focus on reducing pre bed and fasting blood 2- GAD antibody serology
glucose levels 3- Serum ferritin
4- Transferrin saturation
5- Overnight dexamethasone suppression test

Answer & Comments Which of the following is the most appropriate

advice relating to glycaemic index for this
Answer: 4- Transferrin saturation
gentleman?
This gentleman is likely to have
haemochromatosis based on the clinical features 1- Addition of vinegar will increase the
of diabetes, deranged liver function tests and low glycaemic index
testosterone levels. The diagnosis of
2- The glycaemic index is a measure of insulin
haemochromatosis is often made following the
incidental finding on routine blood screening of response to food ingestion
elevated serum liver enzymes. Arthropathy with 3- A baked potato is an example of a low
stiff joints, diabetes, or fatigue, may be the glycaemic index food
presenting complaint. Other presenting features
may include hypogonadism, erectile dysfunction 4- Low glycaemic index foods characteristically
and loss of libido. have a low carbohydrate content.
5- Low glycaemic index foods are associated
Serum transferrin and transferrin saturation are
with slower rates of carbohydrate digestion
commonly used as screening for
haemochromatosis. Transferrin binds iron and is and greater hepatic and peripheral tissue
responsible for iron transport in the blood. carbohydrate extraction.
Measuring transferrin provides a crude measure
of iron stores, saturation values in excess of 45% Answer & Comments
are recognized as a threshold for further
evaluation of haemochromatosis. Transferrin Answer: 5- Low glycaemic index foods are
saturation greater than 62% is suggestive of associated with slower rates of carbohydrate
homozygosity for mutations in the HFE gene. digestion and greater hepatic and peripheral
tissue carbohydrate extraction.
Ferritin, a protein synthesized by the liver is the
primary form of iron storage within cells and
The Glycemic index or GI is a measure of the
tissues. Measuring ferritin provides another crude
effects of carbohydrates on blood glucose levels.
estimate of whole body iron stores though many
Carbohydrates that break down rapidly during
conditions notably inflammation can elevate
digestion releasing glucose rapidly into the
serum ferritin. Serum ferritin in excess of 1000 ng/
bloodstream have a high GI; carbohydrates that
ml is almost always attributable to
break down slowly, releasing glucose gradually
haemochromatosis.
into the bloodstream, have a low GI. For most
people, foods with a low GI have significant health
[ Q: 400 ] Question ID #193 benefits. The concept was developed by Dr. David
J. Jenkins and colleagues in 1980–1981.
A 52 year old man has been recently diagnosed
with type 2 diabetes. He is currently managed with A lower glycemic index suggests slower rates of
diet and lifestyle modification. On examination his digestion and absorption of the foods'
blood pressure is 144 / 75 mmHg, his BMI is 33 kg carbohydrates and may also indicate greater
/ m2, his body weight is 93 kg and his waist extraction from the liver and periphery of the
circumference is 102 cm. He has just completed products of carbohydrate digestion. A lower
the EXPERT patient education program and his glycemic response is often thought to equate to a
most recent Hba1c is 6.7 % (<6). On review in the lower insulin demand, better long-term blood
clinic he is well but requests some further glucose control and a reduction in blood lipids. The
information relating to the glycaemic index of food insulin index may therefore also be useful as it
to the management of his diabetes. provides a direct measure of the insulin response
to a food.

The glycemic index of a food is defined as the area or without additions, there is still a higher blood
under the two hour blood glucose response curve glucose curve after white bread than after a low GI
(AUC) following the ingestion of a fixed portion of bread.
carbohydrate (usually 50 g). The AUC of the test
food is divided by the AUC of the standard (either The glycemic index can only be applied to foods
glucose or white bread, giving two different with reasonable carbohydrate content, as the test
definitions) and multiplied by 100. relies on subjects consuming enough of the test
food to yield about 50 g of available carbohydrate.
The average GI value is calculated from data Many fruits and vegetables (but not potatoes)
collected in 10 human subjects. Both the standard contain very little carbohydrate per serving and
and test food must contain an equal amount of thus the GI is negligible. This also applies to
available carbohydrate. The result gives a relative carrots, which were originally and incorrectly
ranking for each tested food. reported as having a high GI. Alcoholic beverages
have been reported to have low GI values, but it
The current validated methods use glucose as the should be noted that beer has a moderate GI.
reference food, giving it a glycemic index value of Recent studies have shown that the consumption
100 by definition. This has the advantages that it is of an alcoholic drink prior to a meal reduces the GI
universal and it results in maximum GI values of of the meal by approximately 15%. Moderate
approximately 100. White bread can also be used alcohol consumption more than 12 hours prior to
as a reference food, giving a different set of GI a test does not affect the GI
values (if white bread = 100, then glucose ≈ 140).
For people whose staple carbohydrate source is The GI concept has been criticized for a variety of
white bread, this has the advantage of conveying reasons –
directly whether replacement of the dietary staple
with a different food would result in faster or  The glycemic index does not take into
slower blood glucose response. The disadvantages account other factors besides glycemic
with this system are that the reference food is not response, such as insulin response, which
well-defined, and the GI scale is culture is measured by the insulin index and can
dependent. A low GI food will release glucose be more appropriate in representing the
more slowly and steadily. A high GI food causes a effects from some food contents other
more rapid rise in blood glucose levels and is than carbohydrates.
suitable for energy recovery after endurance  The glycemic index is significantly altered
exercise or for a person with diabetes by the type of food, its ripeness,
experiencing hypoglycemia. processing, the length of storage, cooking
methods, and its variety (white potatoes
The glycemic effect of foods depends on a number are a notable example, ranging from
of factors such as the type of starch (amylose vs moderate to very high GI even within the
amylopectin), physical entrapment of the starch same variety)
molecules within the food, fat and protein content  The glycemic response is different from
of the food and organic acids or their salts in the one person to another, and even in the
meal — adding vinegar for example, will lower the same person from day to day, depending
GI. The presence of fat or soluble dietary fibre can on blood glucose levels, insulin resistance,
slow the gastric emptying rate thus lowering the and other factors.
GI. Unrefined breads with higher amounts of fiber  High-glycemic-index foods may have a low
generally have a lower GI value than white breads. carbohydrate content, and low-glycemic-
Many brown breads, however, are treated with index foods may have a high carbohydrate
enzymes to soften the crust, which makes the content. This criticism can be addressed
starch more accessible (high GI). by taking into account the glycemic load
 Low GI foods (GI range <55) include most
While adding butter or oil will lower the GI of a fruit and vegetables (except potatoes,
meal, the GI ranking does not change. That is, with watermelon), grainy breads, pasta,

legumes/pulses, milk, products extremely Answer & Comments

low in carbohydrates (fish, eggs, meat,
nuts, oils), brown rice Answer: 3- The glycaemic load of a serving of food
 Medium GI foods ( GI range 55 – 69) can be calculated from its carbohydrate
include whole wheat products, basmati content, multiplied by its glycaemic index, and
rice, sweet potato, table sugar, most divided by 100
white rices (eg, jasmine).
 High GI foods (GI range >70) include corn The glycemic load (GL) is a ranking system for
flakes, baked potato, watermelon, carbohydrate content in food portions based on
croissant, white bread, extruded cereals their glycemic index (GI) and the portion size.
(eg, Rice Krispies), straight glucose (100)
The usefulness of glycemic load is based on the
[ Q: 401 ] Question ID #194 idea that a high glycemic index food consumed in
small quantities would give the same effect as
larger quantities of a low glycemic index food on
diabetes is reviewed in clinic. She is currently blood sugar. For example, white rice has a
managed with a basal bolus insulin regimen somewhat high GI, so eating 50g of white rice at
comprising of insulin glargine at a dose of 38 units one sitting would give a particular glucose curve in
at night coupled with variable pre-prandial doses the blood, while 25g would give the same curve
of humalog. She has recently completed the but half the height. Since the peak height is
DAFNE patient education program and her most probably the most important parameter for
recent Hba1c is 7.9% (<6). Her frequency of diabetes control, multiplying the amount of
hypoglycaemia has significantly reduced since she carbohydrates in a food serving by the glycemic
completed the DAFNE course, but she is still index gives an idea of how much effect an actual
experiencing some high blood sugar levels in the portion of food has on blood sugar level.
afternoon and early evening and requests further
information on the glycaemic load of food in Glycemic load is generally a useful concept in
relation to her glycaemic control. programs targeting health maintenance. Studies
have shown that sustained spikes in blood sugar
Which of the following is the most appropriate and insulin levels may lead to increased diabetes
risk. The Shanghai Women's Health Study
advice relating to glycaemic load for this lady?
concluded that women whose diets had the
(Please select 1 option) highest glycemic index were 21 percent more
1- The glycaemic load is closely related to the likely to develop type 2 diabetes than women
glycaemic index of food whose diets had the lowest glycemic index. Similar
findings were reported in the Black Women's
2- The glycaemic load of a serving of food can Health Study. A diet program that manages the
be calculated by its carbohydrate content glycemic load aims to avoid sustained blood sugar
divided by its glycaemic index and multiplied spikes, and can help avoid onset of type 2
by 100 diabetes. For people with diabetes, glycemic load
is a highly recommended tool for managing blood
3- The glycaemic load of a serving of food can sugar.
be calculated from its carbohydrate content,
multiplied by its glycaemic index, and Glycemic load for a single serving of a food can be
divided by 100 calculated as the quantity (in grams) of its
carbohydrate content, multiplied by its GI, and
4- The glycaemic index and glycaemic load of a
divided by 100. For example, a 100g slice serving
serving of food have the same effect on of watermelon with a GI of 72 and a carbohydrate
post-prandial glucose excursions content of 5g (it contains a lot of water) makes the
5- The glycaemic load of food reflects of insulin calculation 5*0.72=3.6, so the GL is 3.6. A food
with a GI of 100 and a carbohydrate content of 10g
sensitivity

has a GL of 10 (10*1=10), while a food with 100g (Please select 1 option)

carbohydrate and a GI of just 10 also has a GL of 1- Faulty blood glucose monitoring equipment
10 (100*0.1=10).
2- Incorrect self blood glucose monitoring
Glycaemic load does not reflect insulin sensitivity technique
but since different foods contain different
3- The presence of a Haemoglobinopthy
amounts of carbohydrate it is a more useful
measure of the effect of an individual serving of 4- Unrecognised hypoglycaemia
food on post-prandial glucose levels than the
5- Vitamin B12 deficiency
glycaemic index of food alone . Glycemic Load also
has a scale. Low is 10 or less, Medium is 11-19 and
20 or greater is considered high. Answer & Comments
Answer: 4- Unrecognised hypoglycaemia
Based on this lady’s self monitored average
A 56 year old lady with a five year history of type glucose measurement you would expect this
2 diabetes is reviewed in the clinic following lady’s Hba1c to be approximately 10%. This lady is
conversion to insulin 6 months previously by her unlikely to have a haemoglobinopathy as her
GP. Her current medication includes metformin 1 haematological parameters are normal, while
gram twice daily, glicalzide 80 mg twice daily, vitamin B12 deficiency would not interfere with
insulin glargine 38 units at night, simvastatin 20 the Hba1c assay. Incorrect blood glucose
mg at night and ramipril 5 mg at night. On her monitoring technique or defective blood glucose
examination blood pressure is 150 / 85 mmHg, her monitoring could account for the observed
BMI is 35 kg/m2 and her body weight is 84 kg. She discrepancy between this lady’s blood glucose
attended the EXPERT patient education monitoring data and her Hba1c measurement.
programme 3 months previously at which time her Over a 3 month period this lady has achieved an
body weight was 77.2 kg and her Hba1c at this Hba1c reduction of 1%, which would be associated
time measured 8.1%. Her 3 month average blood with an expected weight gain of 2.5 to 3.5 kg. This
glucose level on review of her glucose monitor is lady has gained nearly 7 kg suggesting that she
15.1 mmol/l. may be eating in response to hypoglycaemia or to
avoid hypoglycaemia.
Haemoglobin 13.8 g/dl (11 - 16)
4.17 x1012 (3.8 - [ Q: 403 ] Question ID #197
RBC
5.6)
MCV 84fl (80 - 98) A 32 year old lady with a 21 year history of type 1
Mean Cell Haemoglobin diabetes is reviewed in clinic. She is currently
29.5 pg (27 - 34) taking a basal bolus insulin regimen with an
Concentrate
average total daily dose of 81 units. Her glycaemic
Hba1c 7.1% (<6)
control is poor with a most recent hab1c of 9.1%
Total Cholesterol 4.1 mmol/l (<4) (<6). She has been unable to obtain an Hba1c <
4.5 mu/l (0.32 - 8.5% despite completing the DAFNE program and
TSH trying multiple different insulin regimens. She was
5.5)
unable to manage CSII therapy successfully and
67 ml/min/1.73 m²
eGFR has evidence of bilateral background diabetic
(90 - 110)
retinopathy and peripheral sensory neuropathy.
She is therefore keen to pursue the possibility of
Which of the following is the most likely
islet cell transplantation.
explanation for the discrepancy between this
lady’s self monitored blood glucose levels and her
Hba1c?

Which of the following is the most appropriate the portal vein of the liver. The islets are then
information for this lady regarding islet cell infused slowly through the catheter into the liver.
transplantation? Specialized enzymes are used to remove islets
from the pancreas of a deceased donor. Because
the islets are fragile, transplantation occurs soon
1- 50% of patients who receive islet cell after they are removed. Typically a patient
transplantation will demonstrate insulin receives at least 10,000 islet “equivalents” per
independence 2 years following their final kilogram of body weight, extracted from two
islet cell infusion donor pancreases. Patients often require two
transplants to achieve insulin independence
2- Around 10% of patients remain free of
insulin injections five years after Rejection is the biggest problem with any
transplantation. transplant, the use of immunosuppressive
corticosteroid based immunosuppression may
3- islet cell transplantation requires an open
have a detrimental metabolic effect, due to
surgical procedure increased insulin resistance. Currently the
4- Long term post-transplantation Edmonton protocol of immunosuppressive drugs
corticosteroid based immunosuppressant is used, which includes including daclizumab,
therapy is required sirolimus, and tacrolimus.
5- Nearly all patients who receive islet cell

transplantation will achieve insulin
independence at 1 year following
You see a 58 year old man with type 2 diabetes in
transplantation
the clinic. His HbA1c is 7.2% (< 6) and he has had
diabetes for 16 years. He has pre-proliferative
Answer & Comments retinopathy in his right eye and has had 1000 laser
burns to treat this. He has not had any treatment
Answer: 2- Around 10% of patients remain free of
to his left eye which shows severe background
insulin injections five years after retinopathy. He has recently been diagnosed with
transplantation. angina and has been advised to take aspirin 150mg
once daily.
Experience to date with islet cell transplantation
suggests that nearly two-thirds of recipients What advice would you give him?
achieve “insulin independence”—defined as being (Please select 1 option)
able to stop insulin injections for at least 14 days—
during the year following transplantation. Insulin 1- He should not take aspirin as this will lead to
independence is however difficult to maintain an increased risk of bleeding into his eyes.
over time. Six months after their last infusion of 2- He should take clopidogrel not aspirin
islets, more than half of recipients are free of the
need for insulin injections, but at 2-year follow-up, 3- He should take aspirin with tranexamic acid
the proportion drops to about one-third of to reduce the risk of bleeding into his eyes
recipients. 5 years after transplantation only
4- He should take aspirin as recommended as
around 10% of patients demonstrate insulin
independence. Other reported benefits of islet cell there is no increased risk of bleeding into his
transplantation include improved blood glucose eyes.
control, and greatly reduced risk of episodes of 5- He should take aspirin as recommended as it
severe hypoglycemia.
will reduce the risk of his retinopathy
progressing
Transplants are often performed by a radiologist,
using x rays and ultrasound to guide placement of
a catheter through the upper abdomen and into


Answer: 4- He should take aspirin as Answer: 1- The best corrected visual acuity must
recommended as there is no increased risk of be 6/12 or better in one eye
bleeding into his eyes.
The best corrected acuity should be better than
Aspirin is safe in severe non-proliferative DR and 6/12 in one eye only as long as the unaided acuity
does not appear to increase the risk of bleeding, is not worse than 6/60 in the other eye. A visual
nor however does it protect from retinopathy field defect should be covered by the other eye to
progression. There is no evidence to make a be able to drive but does not in itself stop driving,
comment on whether clopidogrel is any different nor does proliferative retinopathy as long as the
in its effect than aspirin. Equally there is no acuity is satisfactory. The patient needs to be able
evidence to support using tranexamic acid. to read a number plate at 20 meters.
A 53 year old man with a 4 year history of type 2 A 27 year old lady has developed gestational
diabetes who is currently self-employed as a taxi diabetes during her first pregnancy. She has no
driver is reviewed in clinic. His current medication family history of diabetes. She has required insulin
includes metformin 1 g od, rosiglitazone 4 mg od, therapy from 28 weeks gestation in the form of a
simvastatin 20 mg od and enalpril 5 mg od. On basal bolus regimen with an insulin requirement of
examination, his blood pressure is 146/76 mmHg, 70 units over 24 hours. Following an uneventful
his BMI is 33 kg/m2, his visual acuity is 6/9 in the delivery, which of the following should she be
right eye and 6/6 in the left eye. His metabolic advised to do?
control is good with his most recent HbA1c being
6.9% (<6). His main concern relates to the effect
diabetes may have on his eye sight and in (Please select 1 option)
particular how this may influence his ability to
drive. 1- Continue with her present insulin
2- Commence low dose once daily basal insulin
When assessing a patient’s fitness to drive which
of the following is most accurate? 3- Stop insulin and commence metformin
(Please select 1 option) 4- Stop Insulin and commence on a
sulphonylurea
1- The best corrected visual acuity must be
6/12 or better in one eye 5- Stop all treatment
2- The best corrected visual acuity should be
6/9 or better in both eyes Answer & Comments
3- The patient may not drive if there is a visual Answer: 5- Stop all treatment
field defect in one eye
4- Proliferative retinopathy is an automatic bar Gestational diabetes generally resolves once the
baby is born. Based on different studies, the
to driving
chances of developing GDM in a second pregnancy
5- The patient should be able to read a number are between 30 and 84%, depending on ethnic
plate at 25 meters background and presence of other risk factors for
diabetes such as obesity, metabolic syndrome and
family history. This patient should be re-screened
with a fasting plasma glucose measurement at the
6-week postnatal health check and annually

thereafter, as she is at a high risk of developing Diagnose gestational diabetes if the woman has
subsequent diabetes since women who required either:
insulin treatment or who have positive glutamate
decarboxylase (GAD) or islet cell antibodies (ICA)  a fasting plasma glucose level of 5.6
are at higher risk of future diabetes. mmol/litre or above
 a 2- hour plasma glucose level of 7.8
Reference: mmol/litre or above.
NICE clinical guidelines 63: Diabetes in
pregnancy Offer a trial of changes in diet and exercise to
women with gestational diabetes who have a
[ Q: 407 ] Question ID #205 fasting plasma glucose level below 7 mmol/litre at
diagnosis.
A 24 year old Asian lady with a strong family Offer metformin[2] to women with gestational
history of type 2 diabetes undergoes an oral diabetes if blood glucose targets are not met using
glucose tolerance test at 24 weeks gestation changes in diet and exercise within 1–2 weeks.
during her first pregnancy. The results of her 75 g
oral glucose tolerance test are outlined below. Offer insulin instead of metformin to women with
Fasting and 2 hour self blood glucose monitoring gestational diabetes if metformin is
over the subsequent 2 weeks reveal an average contraindicated or unacceptable to the woman.
fasting glucose of 5.4 mmol/l and 2-hour value of Offer addition of insulin to the treatments of
6.7 mmol/l. changes in diet, exercise and metformin[2] for
women with gestational diabetes if blood glucose
Fasting Blood Glucose 5.8 mmol/L (5.3 targets are not met.
Level mmol/l)
1 Hour Blood Glucose 10.1 mmol/l (<10 [ Q: 408 ] Question ID #206
Level mmol/L)
2 Hour Blood Glucose 9.3 mmol/l (<8.6 A 23 year old lady with a previous history of
Level mmol/L) gestational diabetes during her first pregnancy 18
3 Hour Blood Glucose 8.2 mmol/l (<7.8 months previously undergoes a 75 gram oral
Level mmol/L) glucose tolerance test at week 24 of her second
pregnancy. This reveals a 2hr post OGTT glucose of
Which is the most appropriate initial management 14.5 mmol/l. She is subsequently commenced on
for this lady? a basal bolus insulin regimen at an initial total daily
dosage of 64 units.
1- Dietary / lifestyle modification According to NICE guidelines, which of the

following are appropriate capillary blood glucose
2- Basal bolus insulin
targets for this lady?
3- Metformin (Please select 1 option)
4- Once daily basal insulin 1- Fasting <5 mmol/l and 1 hour post-prandial
5- Sulphonylurea < 7.1 mmol/l
2- Fasting <5.3 mmol/l and 1 hour post-prandial
Answer & Comments < 7.8 mmol/l
Answer: 1- Dietary / lifestyle modification 3- Fasting <5.9 mmol/l and 1 hour post-prandial
< 8.1 mmol/l
We currently follorw the NICE Guidelines for 4- Fasting <6.1 mmol/l and 1 hour post-prandial
gestational Diabetes 2015: < 8.5 mmol/l

5- Fasting <6.9 mmol/l and 1 hour post-prandial Answer & Comments

< 8.5 mmol/l
Answer: 4- Continue Metformin
Answer & Comments

A recent randomized controlled trial of metformin
Answer: 2- Fasting <5.3 mmol/l and 1 hour post- versus insulin showed that women preferred
prandial < 7.8 mmol/l metformin tablets to insulin injections, and that
metformin is safe and equally effective as insulin.
Metfomin in this case would also have additional
In accordance with NICE guidelines, blood glucose potential benefits of a low risk of hypoglycaemia
targets during pregnancy for women with diabetes coupled with no detrimental weight effect.
(including gestational diabetes) care:
 A fasting value of <5.3> [ Q: 410 ] Question ID #208

 A 1 hour postprandial value of less than
7.8 mmol/l A 32 year old lady with a strong family history of
type 2 diabetes is referred by her GP at 14 weeks
The recommendations for self-monitoring of gestation during her first pregnancy. She is
blood glucose during pregnancy are to: concerned about the possibility of developing
diabetes during her pregnancy. She undergoes a
 Test fasting blood glucose levels 75 gram oral glucose tolerance test the results of
 Test blood glucose 1 hour after eating which are outlined below.
Reference: 5.3
NICE clinical guidelines 63: diabetes in pregnancy Fasting Plasma Glucose
mmol/l
1-hour post challenge plasma 8.1
[ Q: 409 ] Question ID #207 glucose mmol/l
2-hour post challenge plasma 7.7
A 32 year old Asian lady with a 2 year history of glucose mmol/l
type 2 diabetes is referred by her GP following a
positive pregnancy test subsequent to a two Which of the following is the correct interpretation
month period of ammenorrhea. Her glycaemic of these data?
control has been good, with a most recent HbA1c
of 6.3% (<6). She is currently only taking
metformin 500 mg twice daily and on examination 1- Gestational diabetes
her BMI is33 kg /m2 and her blood pressure is
132/70 mm/hg. 2- Impaired glucose tolerance
3- Impaired fasting plasma glucose
4- Normal Glucose tolerance
initial approach for managing this lady’s diabetes?
(Please select 1 option) 5- Combined impaired fasting glucose and
impaired glucose tolerance
1- Commence Basal Insulin
2- Commence Basal-Bolus Insulin Answer & Comments
3- Commence Bihpasic Insulin Answer: 4- Normal Glucose tolerance
4- Continue Metformin
5- Commence Sulphonylurea Diagnose gestational diabetes if the woman has
either:

A fasting plasma glucose level of 5.6 Depending on the population studied, the
mmol/litre or above or diagnostic criteria and the length of follow-up, the
risk can vary enormously. The risk appears to be
A 2-hour plasma glucose level of 7.8 highest in the first 5 years, reaching a plateau
mmol/litre or above. thereafter. In populations with a low risk for type
2 diabetes, in lean subjects and in patients with
Diabetes in pregnancy NICE guidelines (2015)
auto-antibodies, there is a higher rate of women
NG3, gestational diabetes: risk assessment,
developing type 1 diabetes.
testing, diagnosis and management
Reference:
[ Q: 411 ] Question ID #209 Impact of gestational diabetes on the risk of
diabetes following pregnancy among Chinese
A 21 year Asian lady has developed gestational and South Asian women.
diabetes during her first pregnancy. She has no
family history of diabetes. She has required insulin [ Q: 412 ] Question ID #210
therapy from 28 weeks gestation in the form of a
basal bolus regimen with an insulin requirement of
A 35 year old lay with a 3 year history of type 2
68 units over 24 hours. 2 weeks subsequent to an
diabetes is referred to ante-natal clinic at 14
uneventful delivery she no longer requires insulin
weeks gestation. Her current medication includes
and has a fasting plasma glucose of 5.5 mmol/l and
metformin 500 mg three times a day only. On
random self measured capillary glucose levels no
examination, her blood pressure is 136/74 mmHg,
greater than 7.9 mmol/l.
her BMI is 35 kg/m 2 and she has no clinical
evidence of microvascular complications.
What is the risk of this lady progressing to develop
diabetes over the next 5 years?
HbA1c 7.5% (<6)
TSH 0.98 mu/l (0.32 - 5.5)
1- 1 %
U+E Normal
2- 5 - 10% eGFR 96 ml/min/1.73m² (90-110)
3- 10 - 20%
4- 25 - 35% appropriate method of managing this lady’s
5- 80% glycaemic control?
Answer & Comments 1- Increase metformin dose
Answer: 4- 25 - 35% 2- Add GLP1 analogue
3- Add Thiazolidinedione
Women diagnosed with gestational diabetes have
an increased risk of developing diabetes mellitus 4- Commence basal-bolus insulin
in the future. The risk is highest in women who 5- Commence twice daily biphasic insulin
needed insulin treatment, had antibodies
associated with diabetes (such as antibodies
against glutamate decarboxylase and islet cell Answer & Comments
antibodies), women with more than two previous
Answer: 4- Commence basal-bolus insulin
pregnancies, and women who were obese and
exhibiting features of the metabolic syndrome (in
order of importance). Women requiring insulin to This lady has suboptimal glycaemic control on
manage gestational diabetes have a 25-35% risk of metformin monotherapy. An optimal level of
developing diabetes within the next five years. glucose control should be defined by an HbA1c

target < 6.5%. This would be best achieved with Answer & Comments
conversion to a basal bolus insulin regimen. GLP1
and Thaizolidinediones are not recommended Answer: 1- Diabetes
during pregnancy, while biphasic insulin would not
represent the most effective means of managing Based on this lady’s average glucose of 8.6 mmol/l
both fasting and post-prandial glucose levels. she is likely to have a HbA1c of around 7 – 7.5%
Analogue basal and prandial insulins may be safely based on the A1c derived average glucose
used in such a regimen. Current evidence suggests calculation (Av Glucose = 1.583 X A1c – 2.52). She
that continuing with metformin in combination is at high risk of subsequent diabetes following her
with insulin may be appropriate to reduce insulin pregnancy since she required around 0.8 u / kg of
requirements as there is no evidence of a insulin, although she has no family history of
detrimental effect of metformin on pregnancy diabetes and is GAD negative. Positive family
outcome. history, GAD positivity and features of the
metabolic syndrome further increase the risk of
[ Q: 413 ] Question ID #211 incident diabetes following gestational diabetes.
Based on this glucose profile alone it is unclear
whether this lady has type 1 or type 2 diabetes.
A 24 year old lady attends clinic 6-8 weeks
following the birth of her first baby. The delivery Reference:
was uncomplicated, but during her pregnancy she NICE clinical guidelines 63: Diabetes in
developed gestational diabetes and was pregnancy
commenced on basal bolus insulin at 22 weeks
requiring a total of 54 units daily. On examination,
her blood pressure is 122/66 mmHg, her BMI is 29 [ Q: 414 ] Question ID #212
kg/m2 her body weight is 65 kg and her waist
circumference is 81 cm. She was found to be GAD A 25 year old lady attends ante-natal clinic at 14
antibody negative when she initially developed weeks gestation, having recently been
gestational diabetes and has no family history of commenced on basal bolus insulin following a
diabetes. She is concerned about the possibility of diagnosis of gestational diabetes. She has no
developing diabetes in the future and since family history of diabetes, but was diagnosed with
discontinuing insulin after her delivery she has gestational diabetes during her first pregnancy 2
been monitoring her blood glucose levels two to years previously which resulted in the successful
three times daily. On review of her meter, she has birth of a 5.3 kg baby boy. On examination her
an average glucose level of 8.9 mmol/l. She blood pressure is 135/75 mmHg, her BMI is 31
returns to clinic the next morning and her fasting kg/m2 her waist circumference is 84 cm and
plasma glucose is taken and found to be 7.6 fundoscopy reveals no evidence of retinopathy
mmol/l.
What should be the HbA1c target for this lady
What is the current diagnosis for this lady based during her pregnancy?
on her self monitored glucose profile?
1- 5.5%
1- Diabetes
2- 6.1%
2- Impaired glucose tolerance
3- 6.5%
3- Impaired fasting glucose
4- 7%
4- Combined impaired glucose tolerance and
5- Do not measure Hba1c.
impaired fasting glycaemia
5- Normal glucose tolerance


Answer: 5- Do not measure Hba1c.
A 27 year lady with a 14 year history of type 1
diabetes attends the antenatal clinic at around 12
Current NICE guidelines do not recommend using weeks gestation during her first pregnancy. Her
HbA1c during pregnancy, as physiological changes current medication includes Novorapid and insulin
mean that lower levels of HbA1c are obtained for detemir at a total daily dose of 72 units via a basal
equivalent blood glucose profiles. NICE guidelines bolus regimen.
recommend fasting blood glucose targets
between 3.5-5.9 mmol/L, and 1-hour post- On examination her blood pressure is 115 / 75
prandial levels <7.8 mmol/l during pregnancy. mmHg, her BMI is 28.5 kg / m2and her body weight
is 77 kg. Her Hba1c is 57 mmol/mol (7.4%) (<6) and
[ Q: 415 ] Question ID #213 retinal screening carried out 6 months previously
revealed the presence of background retinopathy
A 26 year old nurse attends the diabetes clinic to in both eyes.
discuss pre-conception advice. She has a 12 year
What frequency of retinal screening should be
history of type 1 diabetes with her most recent
HbA1c being 8.1% (<6), her current medication offered to this lady during her pregnancy?
includes humalog and insulin glargine via a basal (Please select 1 option)
bolus regimen amount to a total of 66 units per 1- Screen once at 20 weeks gestation
day.
2- Screen once at 28 weeks gestation
On examination her blood pressure is 125 / 65
3- Screen at initial antenatal visit and again at
mmHg, her BMI is 25 kg / m2, her body weight is
28 weeks
69 kg and she has no clinical evidence of
microvascular complications. 4- Screen at initial antenatal visit and again at
16 - 20 weeks and then at 28 weeks
What would be target HbA1c for this lady to safely
achieve prior to conceiving (according to the NICE 5- Screen at 28 weeks and then at 12 weeks
guidelines)? post-partum

Answer & Comments
1- 6.1%
Answer: 4- Screen at initial antenatal visit and
2- 6.5%
again at 16 - 20 weeks and then at 28 weeks
3- 7%
4- 7.5% Progression of diabetic retinopathy may occur
during pregnancy. The worsening of retinopathy
5- 8% during pregnancy can be quite significant and may
require
Answer & Comments
Photocoagulation during pregnancy, more
Answer: 2- 6.5% frequently in those patients with preexisting
diabetic retinopathy. The known risk factors for
NICE guidelines recommend an optimal HbA1c progression of diabetic retinopathy in pregnancy
below 6.5% if this can be safely achieved. An are summarized below:
HbA1c below 7% is satisfactory, unless lower
results could be safely obtained with more 1. Pregnancy is independently associated
intensive therapy. NICE recommend that women with progression of diabetic
with HbA1c above 10% avoid pregnancy. 2. Baseline severity of retinopathy

3. Poor metabolic control at conception Total Cholesterol 4.2 mmol/l (<4)

4. Rapid improvement of glycaemic control
1.9 mmol/l (0.9 -
5. Poor metabolic control during pregnancy Plasma Triglyceride
2.2)
or the early post partum period
6. Duration of diabetes 76 ml/min 1.73
eGFR
7. Chronic hypertension and pregnancy m2; (90-110)
induced hypertension Urine Albumin to 1.9 mg/mmol
Creatinine Ratio (ACR) (<2.5)
NICE guidelines recommend retinal assessment
should be carried out by digital imaging with When eGFR >60 ml/min/1.73m2 , what increase in
mydriasis using tropicamide. Recommendations SeCr denotes significant renal function reduction ?
from the National Screening Program are:
1. Annual Screening for diabetic retinopathy 1- 5%

is recommended in the preconception
period using two-field mydriatic digital 2- 10%
photography using Tropicamide. 3- 20%
2. Women with type 1 and type 2 diabetes
should be offered two-field mydriatic 4- 50%
digital photography to National Standards 5- Changes in serum creatinine are not accurate
at (or soon after) their first antenatal clinic
visit and again at 28 weeks’ gestation.
3. If background diabetic retinopathy is Answer & Comments
found to be present, an additional screen Answer: 3- 20%
should be performed at 16-20 weeks.
4. If referable diabetic retinopathy is found
to be present in early pregnancy, careful An increase in serum creatinine > 20%, when
ophthalmological supervision is required eGFR > 60 ml/min/1.73 m2 suggests a significant
depending on the level of retinopathy deterioration in renal function, indicating the need
both during pregnancy and for at least 6 for further investigation. However a rise in serum
months post-partum. creatinine of up to 20% on initiation of ACE-I or
5. Because, like many drugs that are used in ARB therapy is considered to represent a normal
pregnancy, Tropicamide is only licensed physiological response, a greater increase may be
for use in pregnancy under the direction indicative of renovascular disease.
of a registered medical practitioner, care
pathways should be set up in such a way [ Q: 418 ] Question ID #222
as to enable this to be undertaken.
A 49 year old lady with 32 year history of type 1
[ Q: 417 ] Question ID #220 diabetes on review in the clinic complains of
persisting burning sensation in both feet which
A 56 year old man with a 4 year history of type 2 has been an ongoing problem for the last 2 years
diabetes attends clinic for routine review. His and has shown no symptomatic response to
current medication includes Metformin 500 mg codydramol and non-steroidal based analgesia.
three times daily, Glicalazide 80 mg twice daily, She has had chronic sub-optimal glucose control
Simvastatin 20 mg once daily and Lisionopril 10 mg with a most recent Hba1c measuring 8.9% (< 6).
once daily. On examination, his blood pressure is
146/76 mmHg, his BMI is 32 kg / m2 and visual On examination her blood pressure is 145/75
acuity is 6 / 9 in both eyes. mmHg, her BMI is 29 kg/m2 examination of her
feet reveals preserved dorsalis pedis pulses and
posterior tibial pulses with reduced vibration and
HbA1c 7.7% (<6)

proprioception sensation along with a current medication includes Metformin 500 mg

biosthesiometer reading of 20V. three times daily, gliclazide 160mg twice daily,
rosiglitazone 4 mg once daily, simvastatin 20 mg
Which of the following would be the most once daily and lisinopril 20 mg once daily.
appropriate therapy option for managing this
lady’s symptoms? On examination his blood pressure is 145/85
mmHg and his BMI is 35 kg/m2. Lower limb
neurological examination reveals reduced
1- Carbemazepine 100 mg daily vibration, proprioception, thermosensation and
10 g microfilament sensation in the left foot along
2- Duloxetine 60 mg daily
with an absent left ankle jerk. Sensory modalities
3- Fluoxetine 20 mg daily appear preserved as are all reflexes in the right
foot. There is no evidence of muscle wasting and
4- Gabapentin 900 mg daily both dorsalis pedis and posterior tibial pulses are
5- Improve glycaemic control palpable bilaterally.
Answer & Comments
Answer: 2- Duloxetine 60 mg daily HbA1c 8.3% (<6)
Total Choleseterol 4.7 mmol/l (<4)
In accordance with NICE guidelines 173, for people Plasma TG 1.9 mmol/l (0.9 - 2.2)
with painful diabetic neuropathy, offer oral
duloxetine 60mg, amitriptyline, pregabalin or 78 ml/min/1.73 m2;
eGFR
gabapentin. If satisfactory pain reduction is still (0.9 - 2.2)
not achieved with maximisation then switch to Urine
1.8 mg/mmol creat
another 1st line agent. In this case duloxteine is Albumin:Creatinine
(<2.5)
the right answer as the dose for gabapentin is too Ratio
high for initiation.
What is the most likely cause of this man’s
Tight control of blood glucose can reverse the symptoms?
changes of diabetic neuropathy, but only if the
neuropathy and diabetes is recent in onset.
Conversely, painful symptoms of neuropathy in 1- Diabetic peripheral neuropathy
2- Cauda equina syndrome
disease and numbness progress. Of course, these
uncontrolled patients are at great risk for diabetic 3- Mononeuritis multplex
foot ulcers and amputation.
4- Peripheral vascular disease
Reference: 5- Prolapsed intervetebral disc
NICE clinical guidelines 173: Neuropathic pain
Answer & Comments
Answer: 5- Prolapsed intervetebral disc
A 65 year old gentelman with a 6 year history of
type 2 diabetes is reviewed in clinic and complains Mononeuritis multiplex involves damage to at
of a dead feeling in his left foot a that over the last least 2 separate nerve areas. This condition can
few weeks has become increasingly painful with become progressively worse over time. The
episodes of stabbing pain and electric shock like damage to the nerves involves destruction of the
symptoms, which do not appear to be related to axon, thus interfering with nerve conduction.
exercise. He also complains of low back pain. His Common causes of damage include a lack of

oxygen from decreased blood flow or 88 mmol/l (15 -

inflammation of blood vessels. Pain is usually an Ferritin
300)
initial presenting feature of mononeuritis
38 ml/min/1.73
multiplex, which is usually described as deep and eGFR
m² (90 - 110)
acing with superimposed lancating jabs. Loss of
sensation and movement may be associated with Urine Albumin to 7.9 mg/mmol
dysfunction of specific nerves. Creatinine Ratio (ACR) creat (<2.5)
Corda equina syndrome results from acute loss of Which of the following is the most appropriate
function of the neurologic elements (nerve roots) approach for the management of this gentleman’s
of the spinal canal below the termination (conus) anemia?
of the spinal cord, with signs arising due loss of (Please select 1 option)
function related to the injured nerves.
1- EPO should not be considered until his eGFR
Diabetic peripheral neuropathy usually produces is < 30 ml/min/1.73 m2
bilateral signs and symptoms and the fact that
2- EPO would be contra-indicated due to sub-
peripheral pulses are present and that the
optimal blood pressure control
symptoms are not in keeping with claudication
make a diagnosis of peripheral vascular disease 3- He should receive iron supplementation only
also unlikely in this case.
4- He should receive iron supplementation
A prolapsed inetervetbral disc resulting in prior to considering therapy with EPO
lumbosacral nerve root compression would 5- He does not require any treatment for his
produce symptoms and signs such as those anaemia at current levels
demonstrated by this gentleman and further
investigation with a lumbosacral MRI would be
appropriate. Answer & Comments
Answer: 4- He should receive iron
[ Q: 420 ] Question ID #234 supplementation prior to considering therapy
with EPO
diabetes is reviewed in clinic he feels tired but The failure of erythropoietin production and
denies any osmotic symptoms. His current therapy subsequent development of anemia is more
includes ‘novomix 30’ 32 units in the morning and common in patients with diabetes, particularly
24 units in the evening, ramipril 5 mg daily, females with type 1 diabetes. Co-existent
simvastatin 40 mg daily, indapamide 1.5 mg daily autonomic neuropathy may be an important
and aspirin 75 mg daily. On examination his blood factor as release of erythropoietin is modulated by
pressure is 134 /66 mmHg, his body weight is the sympathetic nervous system. Urinary
stable at 86 kg, his BMI is 32 kg / m2 and he has erythropoietin losses, interstitial fibrosis (90% of
reduced vibration and proprioception sensation in erythropoietin is produced by peri-tubular
both feet. fibroblasts) and angiotensin converting enzyme
inhibition may also be factors.
Patients with anemia secondary to diabetic kidney
Hab1c 7.7% (<6) disease, however demonstrate no difference in
Total Cholesterol 4.4 mmol/l (<5) response to exogenous erythropoietin compared
with patients with non diabetic kidney disease.
Haemoglobin 10.1 g/dl (12-16) Exogenous erythropoietin has been shown to
MCV 86 pl (76-98) reduce Hba1c levels, thus when evaluating
glycaemic control in patients undergoing therapy

for renal anemia, Hba1c estimation alone may be Which of the following is the most appropriate
insufficient. It has long been postulated that approach to the evaluation of this gentleman’s
correction of renal anemia will have a positive renal function?
effect on mortality. This seems likely but at what
level of haemoglobin (Hb) this benefit would
become evident is less clear. 1- His renal function can be assessed by
monitoring his serum creatinine since serum
Raising haematocrit by 25% has been shown to creatinine bears a linear relationship with
reduce left ventricular mass and cross sectional glomerular function
analyses have demonstrated increased mortality
in patients with Hb < 11 g / dl compared to those 2- eGFR measurements would not be an
with Hb levels > 11 g /dl. Patietns treated to a Hb accurate means of following his renal
level > 13.5 g / dl have been shown to experience function as eGFR underestimates true GFR
higher incidence of congestive heart failure, in people with diabetes with GFR values GFR
stroke, myocardial infarction and death. < 60 ml/min/1.73m2
Consequently, current guidelines advocate that
treatment should maintain stable Hb 3- eGFR calculations for this gentleman require
concentrations between 10.5 and 12.5 g / dl, with correction by multiplying by a factor of 1.2.
adjustments to treatment considered when Hb 4- This gentleman has chronic kidney disease
levels < 11.0 g / dl or >12.0 g / dl. Age alone should
stage 3 and should be treated to a blood
not be determinant of treatment for renal anemia.
pressure target of 130 / 80
Appropriate iron stores are required for the
optimal management of renal anemia with EPO 5- Blood pressure is the primary determinant of
and this is defined by a serum ferritin this gentleman's kidney function
concentration of between 200 and 500 µg / l
combined with either a transferrin saturation >
20% ( unless ferritin > 800 µg / l) or percentage Answer & Comments
hypochromic red cells < 6%( unless ferritin > 800 Answer: 3- eGFR calculations for this gentleman
µg / l). require correction by multiplying by a factor of
1.2.
Glomerular filtration rate (GFR) is the gold
A 46 year old man of Afro-Caribbean origin has standard measure of renal function and has a non
recently been diagnosed type 2 diabetes managed linear relationship with serum creatinine. There
by lifestyle modification. He has no previous are three physiological determinants of GFR
medical history of note. On examination his blood namely, Ultrafiltration pressure, permeability of
pressure is 155 / 80 mmHg, his body weight is 94 the glomerular wall and surface area of capillary
Kg, his BMI is 34 kg/m2 and direct fundoscopy is available for filtration. GFR is important because
normal. as it reduces, for reasons not completely clear,
there is an associated increase risk of
Investigations reveal: cardiovascular disease. In the South Tees
Mortality study the adjusted hazard ratio for
Hba1c 6.9% (<6) ischemic heart disease was 3.6 and 8.1 fold higher
for those with eGFR 30 – 59 and < 30 ml/ min/1.73
m2 respectively. Consequently, all patients with an
58 ml/min/1.73m² eGFR < 60 ml/min/1.73 m2are defined as having
eGFR
(90 - 110) chronic kidney disease irrespective of their
Serum Creatinine 128 µmol/l (56 - 102) urinalysis. The MDRD equation is used to calculate
eGFR and this under estimates GFR particularly in
Urine Albumin 1.9 mg.mmol/creat
patients with values > 60 ml/min /1.73 m2. GFR
Creatinine Ratio (<2.5)
varies according to gender, muscle mass and other

factors such as physical exertion. MDRD derived Answer & Comments

eGFR values require correction by multiplying by
0.742 if female and by 1.212 if Afro-Caribbean. Answer: 4- Alter her lunchtime insulin to
carbohydrate ratio to 1 unit to 15g
This gentleman does not have CKD stage 3 as his
corrected eGFR is 69 (58 X 1.2). Clinical Meal time insulin requirements (bolus rates) are
determinants of renal function in people with assessed by measuring the glucoses 2 hours post-
diabetes include numerous factors including both prandially to ensure limited glucose excursion. She
blood pressure and blood glucose control. has lost 2 stone in weight and has therefore
probably increased insulin sensitivity and needs
[ Q: 422 ] Question ID #238 less insulin for food at lunchtime. The other
mealtime insulin requirements should also be
assessed by measuring post-prandial glucoses. If
A 32 year old woman comes to clinic. She has been the basal rates are reduced, this may result in
using continuous subcutaneous insulin infusion glucoses too low at other times of the day. Many
therapy for 3 years. Over the last 18 months her modern pumps can give boluses of insulin over a
HbA1c has been < 7.5%. She has lost 2 stone in protracted period of time e.g. over 1 hour to
weight and her BMI is now 23. She has the accommodate lower glycaemic index meals.
following basal rates of insulin:

Midnight-6am 0.5 units/hour
6am-1pm 0.8 units/hour
A 23 year old woman has been on continuous
1pm-6pm 0.7 units/hour subcutaneous insulin infusion for 1 year
6pm-mitnight 0.9 units/hour commenced 3 months into a pregnancy. Her
control throughout pregnancy was acceptable
Her insulin to carbohydrate ratios are 1 unit to 10g with an HbA1c between 6.2 to 6.6%. She is now 6
at breakfast and lunch, 1unit to 15g at evening months post-partum. Her latest HbA1c is 9.5%.
meal. She attends with a 2 day history of polyuria,
abdominal pain and vomiting. She has given
herself repeated boluses of insulin via the pump
She has recently developed recurrent
but her glucoses remain >28mmol/l. She is
hypoglycaemia 1 – 2 hours after lunch and finds
this very difficult as she works as a secondary admitted to hospital with diabetic ketoacidosis
school teacher. and treated according to local policy.
How would you advise her? Once she has recovered the following is the
appropriate course of action?
1- Lower all basal rates by 0.1units/hour
1- Cessation of continuous subcutaneous
2- Lower her basal rates by 0.1units/hour 1pm insulin infusion therapy is indicated as she
to 6pm has had an episode of diabetic ketoacidosis
3- Lower her basal rates by 0.1units / hour 6am 2- Her insulin via the pump needs to be
- 1pm increased by 20%
4- Alter her lunchtime insulin to carbohydrate 3- She should return to a basal bolus regime for
ratio to 1 unit to 15g 3 months to allow her insulin requirements
5- Increase the "low glycaemic index" to be recalculated.
carbohydrate content of her lunch

4- She should be advised to temporarily 2- Continue the pump therapy with the
override to 150% of her usual basal rates if anaesthetist monitoring the blood glucoses
the situation recurs. intra-operatively and giving intravenous
glucose if needed.
5- She should be advised that if an initial bolus
via the pump for hyperglycaemia does not 3- Switch to intravenous glucose and insulin the
lower her glucose then a bolus should be night before the procedure and continue
given by an insulin pen and the pump until eating and drinking
removed and the set up procedure
4- Discontinue the pump on induction of
repeated.
anaesthesia and observe glucoses. Start
intravenous insulin if needed.
Answer & Comments
5- Anaesthetist to alter the pump during the
Answer: 5- She should be advised that if an initial procedure and post-operatively.
bolus via the pump for hyperglycaemia does
not lower her glucose then a bolus should be Answer & Comments
given by an insulin pen and the pump removed
and the set up procedure repeated. Answer: 2- Continue the pump therapy with the
anaesthetist monitoring the blood glucoses
Insulin delivery may become discontinued if there intra-operatively and giving intravenous
is a mechanical fault with the pump or if a cannula glucose if needed.
has become blocked or kinked and this can result
in diabetic ketoacidosis. This can be prevented if Hysteroscopy is a procedure requiring a short
the patient is educated to give an insulin bolus by anaesthetic with an expected rapid recovery
pen or syringe if hyperglycaemia is not responding usually performed as a day case. If continuous
to boluses from the pump. This patient may have subcutaneous insulin infusion therapy is stopped
forgotten this rule particularly if the pump was alternative insulin therapy should be started
commenced in an urgent manner when she had within 1 hour, ideally immediately. If the cessation
poor control or problems in pregnancy. is protracted hyperglycaemia is inevitable and
diabetic ketoacidosis could result. Although using
[ Q: 424 ] Question ID #240 intravenous glucose and insulin therapy from the
night before is not wrong, it is unlikely to be
necessary and will result in an unnecessary
A 53 year old on continuous subcutaneous insulin hospital admission and hourly glucose estimations
therapy is due to be admitted for a hysteroscopy overnight which is disruptive. The anaesthetist is
and endometrial biopsy under general unlikely to be familiar enough with the pump
anaesthetic. She has been on continuous mechanism to alter this and could monitor the
subcutaneous insulin infusion therapy for 5 years glucoses and ensure hypoglycaemia does not
and has an HbA1c of 5.5%. The anaesthetist occur during anaesthesia when it will not be
contacts you for advice on glycaemic management detected.
during surgery.
What will you advise? [ Q: 425 ] Question ID #241

A 19 year old woman on continuous subcutaneous
1- Stop the pump at midnight before the insulin infusion for 6 months comes to clinic. Her
procedure and commence intravenous HbA1c is 8%. She is due to go to Australia for 2
insulin and glucose at 6 am to cover the months and has not previously travelled
intra-operative procedure and restart the internationally with her pump. She asks for advice
pump when eating and drinking. on monitoring her pump on the journey to
Australia.

How will you advise her? correction bolus of 8units of insulin after training
(Please select 1 option) but finds that overnight he is having
hypoglycaemic episodes.
1- Continue with the usual basal rates as per UK
time and temporarily override as needed. How would you advise him?
2- Set the pump at the lowest basal rate for the (Please select 1 option)
duration of the flight, bolus for food as usual 1- Give a bolus of insulin at the start of his
and set the clock on the pump to local time squash match or training and reduce the
on arrival basal rate throughout
3- Switch back to a basal bolus regime using 2- Give a bigger bolus of insulin with his post
insulin glargine and insulin aspart for the squash meal and increase basal rates to
journey bedtime
4- Set the basal rate to 0.2unit / hour and check 3- Increase the basal rates during the squash
blood glucoses every 2 hours and give match / training
insulin boluses as necessary
4- Give a smaller bolus e.g. 4 units and keep the
5- Set the pump to 50% of usual basal rates and basal rates the same across the evening and
give insulin boluses as needed. night.
5- Increase the basal rates leading up to the
Answer & Comments
squash match / training
Answer: 2- Set the pump at the lowest basal rate
for the duration of the flight, bolus for food as Answer & Comments
usual and set the clock on the pump to local
time on arrival Answer: 1- Give a bolus of insulin at the start of his
squash match or training and reduce the basal
rate throughout
The usual basal rates alter depending on the time
of day, the diurnal hormonal variations and usual
routine and travel across several time zones will Giving more insulin as a bolus or by increasing the
disrupt these factors. Setting the pump to the basal rates before exercise may cause
lowest usual basal rate allows travel to be safely hypoglycaemia during exercise. The
undertaken and food boluses and correction catecholamines released during exercise may
boluses can be given as needed. If the pump clock cause hyperglycaemia and the extent may vary
is switched to local time on arrival the usual basal depending on the activity. Hypoglycaemia up to 24
daily rates can resume with minimal disruption. hours after activity may occur. His bolus of 8 units
of insulin is probably excessive for him and
injecting the Insulin just prior to exercise may help
[ Q: 426 ] Question ID #242 to reduce his post exercise hyperglycaemia;
generally 1 unit of insulin will reduce the glucose
A 28 year old man with type 1 diabetes mellitus is by 2.5mmol/l although this will vary depending on
on continuous subcutaneous insulin infusion and insulin sensitivity. Reducing his basal rates post
presents for urgent review as he has developed exercise should help to prevent hypoglycaemia.
problems with erratic glucose levels. He trains
regularly in the gym and plays squash three times
a week. He has found his glucoses need to be
greater than 8mmol/l prior to training or squash to
prevent hypoglycaemia but that post training they A 30 year old man takes insulin lispro 6 units three
are usually greater than 18mmol/l. He eats a high times a day and insulin glargine 16units. Despite
carbohydrate meal with a usual bolus plus a efforts from the patient and diabetes team, his

HbA1c remains greater than 9%. Any increase in (Please select 1 option)
his insulin causes recurrent severe hypoglycaemia. 1- Arrange for a district nurse to visit the school
He is to commence continuous subcutaneous
to inject the child using a needle and syringe
insulin infusion.
prior to lunch.
His starting basal rates should be: 2- Continue without a lunchtime bolus and
(Please select 1 option) encourage low glycaemic index food for this
meal
1- 0.5 units / hour
3- Continue without a bolus until the child is
2- 1.0 units / hour
able to administer his own bolus which will
3- 1.5 units / hour probably be within 1 to 2 years
4- 0.1 units / hour 4- Increase the basal rate for an hour over the
5- 0.8 units / hour period following lunch
5- Switch to a different insulin regime such as a
Answer & Comments twice daily pre-mixed regime until the child
is able to manage his own pump
Answer: 1- 0.5 units / hour
Answer & Comments

The initial basal rate is calculated by adding the
total daily insulin and subtracting 25 to 30 %. This Answer: 4- Increase the basal rate for an hour over
dose is then halved and this result divided by 24 to the period following lunch
give the starting basal rate.
This can be a difficult issue when children have
e.g. total daily dose = 34
good glycaemic control but need to move to a
situation where this may be compromised. Many
Subtract 30% = 24 children are competent to manage their pump by
the age of 6 to 7. Switching to a pre-mixed insulin
50% of 24 = 12 regime would usually worsen the glycaemic
control and be too restrictive to be acceptable.
Hourly rate = 12 / 24 = 0.5 units / hour Leaving the child without a bolus is possible but
will probably lead to hyperglycaemia and may
[ Q: 428 ] Question ID #247 cause polyuria and other symptoms of
hyperglycaemia in the afternoon. A district nurse
visiting to give an injection of insulin would not be
A child of 5 years of age has been on a continuous
wrong but would be restrictive and the injection is
subcutaneous insulin infusion for 18 months. He is
likely to be unwelcome. Increasing the basal rate
starting primary school and his mother is returning
is a compromise as it will not account accurately
to work. His parents usually manage his pump and
for the amount of food eaten and may cause a
calculate and give his bolus doses. They have
problem if the child refuses to eat when the only
discussed his pump at length with his school staff
option for the school may be to unclip the pump
who are comfortable with recognising and
for an hour.
treating any hypoglycaemic episodes and also
agree to unclip the pump for sports and re-attach
the pump once the activity is concluded. The [ Q: 429 ] Question ID #300
remaining issue is giving a bolus to cover his lunch
as the school staff are unhappy to accept this A 55 year old male presents with a two day history
responsibility. of pain in the left leg and fever. He has had type 2
diabetes diagnosed for three years and is treated
What would you advise? with metformin 1g bd. On examination, he has a

temperature of 37.5oC and has an erythematous 2- Metformin

swelling of the skin of the foot to the mid shin. It is
3- Pioglitazone
noted that he has a small abrasion between the
great toe and 2nd toe. 4- Once daily basal insulin
Which of the following is the most likely infective 5- Twice daily biphasic insulin
organism in this case?
Answer & Comments
1- E Coli Answer: 2- Metformin
2- H. Influenzae
The current NICE guideline update on blood
3- Methicillin resistant Staph Aureus glucose control (CG 87, May 2009) advocates
metformin as the first line oral therapy in people
4- Pseudomonas aeruginosa
with type 2 diabetes with sub-optimal glucose
5- Strep Pyogenes control (Hba1c ≥6.5%) unless the person is not
overweight, metformin is contraindicated or not
Answer & Comments tolerated or the person requires rapid therapeutic
response due to hyperglycaemic symptoms. This
Answer: 5- Strep Pyogenes gentleman describes classic hyperglycaemic
symptoms and the absence of any weight loss
suggests that this patient does not currently
The patient has a classical description of cellulitis
require exogenous insulin.
which is most likely to be due to either Staph
Aureus (not typically MRSA) or Streptococcus.
A 65 year old gentleman with a 3 year history of
type 2 diabetes is reviewed in clinic. He feels
A 52 year man presents with a 3 month history of
generally well and has a fairly predictable lifestyle
general lethargy and polyuria over the last month,
having been retired for the last 2 years. His current
but he denies any obvious weight loss. He has no
medication includes metformin 1 gram bd,
past medical history or family history of note.
ramipril 5 mg od and simvastatin 20 mg od.
On examination his body weight is 83 kg, his BMI
On examination there is no evidence of any
is 30 kg /m2 and his blood pressure measures
microvascular complications, his blood pressure
144/77 mmHg.
measures 145/75 mmHg, his body weight is 88 kg
and his BMI is 31 kg/m2.
U+E Normal
Fasting glucose 14.9 mmol/l 3.5-6
55 mmol/mol
HbA1c 8.3% <6% HbA1c <6
(7.2%)
U+Es Normal
79
eGFR >90
mls/min/1.73m2
Urine analysis - Glucose +++ Ketones +
Total
4.5 mmol/l <5
cholesterol
treatment for this man? LDL cholesterol 2.9 mmol/l <3
(Please select 1 option) HDL cholesterol 0.9 mmol/l 0.9-2
1- Gliclazide

0.9- eGFR 64 ml/min/1.73m2 >90

Triglyceride 1.9 mmol/l
2.1 Total cholesterol 4.1 mmol/l <5
Which of the following is the most appropriate LDL cholesterol 2.2 mmol/l <3
management for this patient? 0.9-
HDL cholesterol 0.8 mmol/l
2
1.1-
1- Add Exenatide Triglycerides 2.1 mmol/l
2.
2- Add Empagliflozin
3- Add Gliclazide
appropriate therapeutic option for managing this
4- Add Sitagliptin man's glycaemic control?
5- Continue with metformin alone (Please select 1 option)
1- Add Exenatide
Answer & Comments 2- Add tds Humalog Insulin
Answer: 5- Continue with metformin alone 3- Add once daily NPH insulin
4- Add once daily insulin glargine
glucose control (NG 28) advocates the use of a 2nd 5- Add twice daily biphasic insulin
line oral hypoglycaemic agent in people with type
2 diabetes with sub-optimal control (Hba1c ≥ 58 Answer & Comments
mmol/mol 7.5%) receiving maximum tolerated
metformin monotherapy. A TZD/DPP-4i/SU or Answer: 1- Add Exenatide
SGLT2 inhibitor are recommended. In this case,
with the Hba1c at 54 mmol/mol the guidance does
not suggest any requirmeent to optimise
glucose control (CG 87, May 2009) suggests that in
treatment.
people failing to maintain adequate blood glucose
control (Hba1c 7.5%) insulin should be initiated in
[ Q: 432 ] Question ID #304 the form of either once or twice daily NPH insulin
according to need, in the context of appropriate
A 52 year old bus driver is reviewed in clinic. He structured education. A basal insulin analogue is
has an 8 year history of type 2 diabetes and has recommended if the person can not use the device
background retinopathy affecting both eyes. He is to deliver NPH insulin, optimal dose titration of
generally well and denies any osmotic symptoms NPH insulin is limited by hypoglycaemia, the
or weight loss. His current medication includes person needs help with injecting insulin and a
metformin 1 gram twice daily, glicalzide 160 mg once daily analogue insulin would replace twice
twice daily, simvastatin 40 mg once daily and daily NPH. Exenatide is currently recommended
perindopril 4 mg once daily. according to the NICE guidance as an alternative
to exogenous insulin where insulin use would have
On examination his body weight is 91 kg, his BMI detrimental effects on employment, or in people
is 31 kg/m2 and his blood pressure measures with a BMI 35 Kg /m2 of European descent where
148/78 mmHg. further weight gain would exacerbate problems
associated with high body weight or in people with
Investigations reveal: BMI 35 Kg /m2 where insulin is unacceptable due
to occupational implications or where weight
reduction would benefit other co-morbidities.
U+Es Normal Biphasic insulin within the current NICE guidance
HbA1c 8.7% <6

may be considered as an option in people who are (HbA1c ≥ 6.5%) unless it is contraindicated or not
markedly hyperglycaemic e.g. Hba1c > 9.0%. tolerated. In such situations a sulphonylurea of
lowest acquisition cost – but not glibenclamide –
[ Q: 433 ] Question ID #305 is recommended. Sitagliptin is currently not
recommended in people with moderate renal
impairment defined as a creatinine clearance < 50
A 69 year old lady is reviewed in clinic. She has a ml / min.
six month history of type 2 diabetes which has
been initially managed with lifestyle modification.
She also has a five year history of treated [ Q: 434 ] Question ID #306
hypertension. Her current medication includes
amlodipine 5 mg once daily, simvastatin 20 mg A 44 year old male is referred by his GP as he is
once daily and Aspirin 75 mg once daily. concerned regarding a fasting plasma glucose
value of 5.9 mmol/l and wonders what needs to be
On examination her body weight is 71 kg, her BMI done about this. The patient informs you that he
is 29 Kg/m2 and her blood pressure is 155/75 went to the GP as he was concerned about
mmHg. Investigations reveal: developing diabetes and he tells you that he has
been thristy on occassions and may get up in the
HbA1c 7.1% <6 night twice to urinate. He has a strong family
history of diabetes with his mother and maternal
49 90- uncle suffering from the disorder. He takes no
eGFR
mls/min/1.73m2 110 medication
50-
Creatinine 128 micromol/l
100 On examination, he has a BMI of 32.2 kg/m2, blood
Albumin/creatinine pressure of 132/78 mmHg and he has central
4.1 mg/mmol <3.5 adiposity. A repeat fasting plasma glucose returns
ratio
as 6.1 mmol/l (3.5-6).
Fasting plasma 3.5-
6.1 mmol/l
glucose 6
You give the patient advice concerning the
importance of diet and exercise with emphasis
Which of the following would be the most placed on weight loss.
appropriate approach for managing this lady’s
blood glucose? Which of the following would you suggest
(Please select 1 option) regarding further investigation of his glucose
1- Glibenclamide concentration?
2- Gliclazide
1- Arrange oral glucose tolerance test
3- Metformin
2- Check HbA1c
4- Pioglitazone
3- Check fructosamine
5- Persist with current lifestyle changes alone
4- No further investigation required
Answer & Comments 5- Repeat fasting glucose in 3 months
Answer & Comments
The current NICE guideline update on blood Answer: 1- Arrange oral glucose tolerance test
glucose control (CG 87, May 2009) advocates the
use of metformin as a first line oral hypoglycaemic
This patient has impaired fasting glucose
agent in people with suboptimal glycaemic control
according to the IDF criteria with a glucose at or

above 6.1 mmol/l and below 7.1 mmol/l. The and her pregnancy is progressing normally.
recommendation would be for an OGTT with up to According to NICE guidelines, what is the most
30% of such cases having a diagnosis of diabetes appropriate time for her Gestational Diabetes
on OGTT. He may have the metabolic syndrome Mellitus (GDM) screening?
although we are not told his waist circumference
which is a criterion measurement.
1- As early as possible
[ Q: 435 ] Question ID #361 2- At 24 weeks
3- At 28 weeks
diabetes was referred by his GP for conversion to 4- At 36 weeks
insulin. He was taking metformin 850 mg tds,
5- No indication to check for GDM
gliclazide 160 mg bd and pioglitazone 45 mg od.
He does not smoke and denies any alcohol
consumption. Answer & Comments
Answer: 1- As early as possible
On examination, BMI is 41.2 kg/m2, blood pressure
142/68 mmHg and abdominal examination reveals
2 cm smooth non-tender hepatomegaly. According to NICE guidelines on gestational
diabetes (NICE clinical guidelines 63), the following
In type 2 diabetes, elevations of which liver groups of patients should be screened for GDM:
enzymes are most correlated with non-alcoholic
fatty liver disease?  Previous history of GDM
 Certain ethnic groups (e.g. south east
Asians, black Caribbean and middle
1- AST alone eastern)
 Previous birth weight of a child > 4.5 Kg
2- ALT and AST
 Body mass index > 30 kg/m2
3- ALT and gamma-GT  Family history of a first degree relative
with GDM
4- AST and gamma-GT
5- gamma-GT and alkaline phosphatase Screening for GDM in the above mentioned high
risk group patients should be arranged at the
booking appointment.
Answer & Comments
Answer: 3- ALT and gamma-GT [ Q: 437 ] Question ID #475
Up to 20% of patients with T2DM have changes of Which of the following oral hypoglycaemic agents
fatty liver. Elevated concentrations of ALT more is associated with Vitamin B12 deficiency?
than AST (unlike alcoholic liver disease where AST (Please select 1 option)
is usually higher) is typical and gamma-GT is
usually moderately elevated. Bilirubin and alkaline 1- Acarbose
phosphatase are usually normal. 2- Gliclazide
3- Glibenclamide
4- Metformin
An Asian lady with previous history of gestational 5- Pioglitazone
diabetes presents around 16 week pregnant in
antenatal clinic. She is otherwise asymptomatic


According to the NICE lipid guidelines CG181,
which of the following QRISK2 10 year risk
Long term Metformin use has been linked with predictions of CVD should be the threshold for the
Vitamin B12 deficiency according to results of a
introduction of statin therapy in a 45 year old man
multicenter randomised, placebo controlled trial
with type 2 diabetes?
published in BMJ (online publication on May 20,
2010), although the mechanism for the deficiency (Please select 1 option)
remains unclear. It has been suggested that 1- There is no threshold risk; the patient should
patients being initiated on long term Metformin
be treated with a statin
therapy should receive dietary counselling on start
of the therapy and then randomised to systemic 2- 5%
serum B12 screening or routine care groups for
3- 10%
follow up purposes as a cost effective measure.
4- 15%
[ Q: 438 ] Question ID #476 5- 20%
What is the risk of Type I DM in a baby born to a

Answer & Comments
mother with Type 1 DM?
(Please select 1 option) Answer: 3- 10%
1- 1%
According to the NICE guidelines, patients should
2- 1-2% be considered to be at high risk for cardiovascular
disease if one or more of the following are
3- 3-4%
present:
4- 5-10%
 Increased BMI
5- 20-25%
 Hypertensive (> 140/80 mm of Hg)
 Microalbuminuria
Answer & Comments  Smoker
 Deranged lipid profile
Answer: 2- 1-2%  Past medical history of cardiovascular
disease
The following table sums up the risk of  Family history of cardiovascular disease
development of Type 1 Diabetes in a child with
family history of Type 1 Diabetes: A cardiovascular risk of >10% on QRISK2 warrants
therapy with statin therapy (atorvastatin as
Type of DM Type 1 recommended by NICE).

Concordance In
36 %
Monozygotic twins
What is the chronology of appearance of
hypoglycaemic symptoms?
1-2% chance of
Mother Diabetic (Please select 1 option)
having Type 1 DM
1- Autonomic symptoms - Counter regulatory
hormones - Neuroglycopenia

2- Autonomic symptoms - Neuroglycopenia - glargine insulin at night time. She is using an

Counter regulatory hormones injectable device with which she is having trouble
injecting, being aware that often the insulin oozing
3- Counter regulatory hormones - Autonomic out of the injection site.
symptoms - Neuroglycopenia
4- Counter regulatory hormones - What is the most appropriate advice to improve
Neuroglycopenia -autonomic symptoms her glycaemic control?
5- Neuroglycopenia - Counter regulatory
hormones - Autonomic symptoms 1- Reduce insulin dose
2- Refer for DAFNE
Answer & Comments
3- Switch to insulin analogues
Answer: 3- Counter regulatory hormones -
4- Switch to pen device
Autonomic symptoms - Neuroglycopenia
5- Switch to premix BD insulin
A fall in plasma glucose level evokes a rapid
response by the body and includes the following Answer & Comments
steps:
Answer: 4- Switch to pen device
 Release of counter-regulatory hormones
such as glucagon, cortisol and growth Clearly she is facing difficulties as far as injecting
hormones takes place at a plasma glucose insulin is concerned with oozing of insulin from the
level of < 3.8 mmol/L. These hormones injection site. In the first instance, her delivery
induce gluconeogenesis and device can be changed to pen device. According to
glycogenolysis to bring up the plasma NICE guidelines on Type 2 DM (NICE clinical
glucose level guideline 87):
 Autonomic symptoms including tremors,
anxiety, sweating and palpitations appear Reference:
when the plasma glucose level falls below Education should be offered to a Diabetic who
3.4 mmol/L, as a result of increased requires insulin about using an injection device
sympathetic nervous system activity In Diabetics with manual or visual disability, an
(symptom of hunger is evoked due to appropriate device or adaptation should be
parasympathetic nervous system offered
activation). Appropriate local arrangements should be in place for
 Neuroglycopenic symptoms are evoked disposal of sharps
when plasma glucose levels fall below 2.6
mmol/L and include confusion, lethargy, [ Q: 442 ] Question ID #616
incoordination and blurred vision. A
further decline in blood sugar or a lack of
counter-regulatory response may result in A 28 year old woman is diagnosed with gestational
loss of consciousness, convulsions and diabetes in her first pregnancy. She is treated with
coma. metformin in the first instance.
Which of the following is the appropriate advice

[ Q: 441 ] Question ID #491 regarding blood sugar monitoring according to
guidance for this patient?
A 64 year old Type 2 diabetic is reviewed in clinic
with poor glycaemic control. She is currently on
basal bolus insulin regimen comprising of 12 units 1- Check blood sugars before every meal
of aspart insulin three times a day and 22 units of

2- Check fasting and 2-hours post meal blood or haemorrhage. This gentleman has suboptimal
sugars glycaemic control as reflected by his home blood
sugar readings but his HbA1C is inappropriately
3- Check fasting and 1-hour post prandial blood low as a result of recent blood loss. As a result his
sugars insulin dose needs to be increased to control
4- Check blood sugars twice a day impaired home blood sugar readings.
5- Check blood sugar every alternate day In contrast falsely elevated HbA1c values can be
seen in uraemia (Carbamoylated Hb) or in
Answer & Comments presence of Hb F.
Answer: 3- Check fasting and 1-hour post prandial

blood sugars
An 18 year old presents with symptoms of weight

According to NICE guidance, women with loss, polyuria and polydipsia. On examination he
gestational diabetes who are being treated with has optic atrophy and sensory neural deafness. He
lifestyle advice or oral therapy are advised to test has a strong family history of Diabetes Mellitus
fasting and 1-hour post prandial blood glucose and sensorineural deafness. His biochemical
levels after every meal. investigations reveal high blood sugars and
glycosuria.
What should be the next investigation to further
A 55 year old, Type 2 Diabetic, on basal bolus establish the diagnosis of his underlying familial
insulin regimen, recently lost blood through an condition?
episode of haemetmesis, with a fall in the (Please select 1 option)
haemoglobin concentration of 2.5 g/l. He is
reviewed in the Diabetic clinic, where it is noticed 1- Anti-GAD antibodies
that his home blood sugar readings are mostly 8- 2- Bone profile
14 mmol/L. While his HbA1C value as checked in
Diabetic clinic is 6.5%. 3- CT abdomen
4- Prolactin
What is the next best step in his management?
5- Screen for Diabetes insipidus
1- Decrease his insulin dose Answer & Comments

2- Educate him regarding blood sugar
Answer: 5- Screen for Diabetes insipidus
monitoring technique
3- Increase his insulin dose This 18 year old is likely to have Wolfram`s
4- No change required syndrome (DIDMOAD), which is a rare genetic
disorder associated with non immune mediated
5- Recheck his HbA1C in 6-8 weeks time pancreatic β cell destruction, diabetes insipidus,
optic atrophy and neural deafness. The affected
Answer & Comments individuals have abnormalities in process of
myelination and mitochondrial malfunction. The
Answer: 3- Increase his insulin dose life expectancy of affected individuals is about 3
decades.
Falsely low values of HbA1C are associated with
haemoglobinopathies (such as Hb C, D and S) and
reduced survival of RBC secondary to haemolysis

A 44 year old gentleman with a body mass index A 25 year old woman with a 7 year history of type
of 47kg/m2 presents to the clinic with poorly 1 diabetes presents to clinic being 8 weeks
controlled Type 2 DM. He has multiple co- pregnant. Her glycaemic control has been
morbidities including sleep apnoea, hypertension excellent with a HbA1c of around 6-6.5% on basal
and osteoarthritis. bolus insulin. She enquiries about possible risk of
major congenital malformations in her offspring.
According to NICE guidelines what is the next best
step in his management? What are the chances of major congenital
(Please select 1 option) malformation in her child?
1- Bariatric surgery
1- 1%
2- Exenetide
2- 1%
3- Insulin
3- 5-7%
4- Orlistat
4- 10%
5- Sibutramine
5- Same as background population
Answer & Comments
Answer & Comments
Answer: 1- Bariatric surgery
Answer: 5- Same as background population
According to NICE guidelines on management of
overweight and obese adults (NICE clinical The risk of congenital abnormalities and perinatal
guidelines 43), consider surgery for people with mortality is increased in babies born to diabetic
severe obesity if: mothers by two- folds and three -folds
respectively. A good glycaemic control around
 They have a BMI of 40 kg/m2 or more, or conception and early pregnancy can reduce the
between 35 kg/m2 and other significant incidence of both the above mentioned
disease ( for example, type 2 diabetes, complications. The major congenital
high blood pressure) that could be abnormalities detected in neonates include
improved if they lost weight congenital heart disease (x 3.4 times higher risk)
 All appropriate non-surgical measures and neural tube defects (x3-4 times higher risk)
have failed to achieve or maintain (1). According to the results from The Diabetes
adequate clinically beneficial weight loss Control and Complications Trial (DCCT) a good
for at least 6 months glycaemic control is associated with rates of
 They are receiving or will receive intensive spontaneous abortion and congenital
specialist management malformations similar to those seen in non
 They are generally fit for anaesthesia and diabetic population (2).
surgery
 They commit for long term follow up Reference:
 Consider surgery as a first line option for Perinatal mortality and congenital anomalies in
adults with a BMI > 50 kg/m2 in whom babies of women with Type 1 or Type 2
surgical intervention is considered Diabetes in England, Wales and Northern
appropriate; consider Orlistat before Ireland: population based study by Macintosh
surgery if the waiting time is long et al., BMJ 2006;333:177(22 July)

Pregnancy outcomes in the Diabetic Control and 4- Fasting and before every meal
Complication Trial - Am J Obstetrics and
5- Once a day
Gynaecology, 1996 Apr;174(4):1343-53
Answer & Comments

Answer: 3- Fasting and 1 hour post prandial
According to NICE, which of the following is a
target range for blood glucose during pregnancy? According to current NICE guidelines for
(Please select 1 option) management of diabetes during pregnancy
(February 2015), advise pregnant women with
1- 1 hour post-prandial <7.8 mmol/l
type 2 diabetes or gestational diabetes -who are
2- 1 hour post-prandial <9 mmol/l on a multiple daily insulin injection regimen to test
their fasting, pre-meal, 1-hour post-meal and
3- 2 hour post-prandial <7.8 mmol/l
bedtime blood glucose levels daily during
4- 2 hour post-prandial <9 mmol/l pregnancy.
5- Fasting plasma glucose <5.5 mmol/l
Advise pregnant women with type 2 diabetes or
gestational diabetes to test their fasting and 1-
Answer & Comments hour post-meal blood glucose levels daily during
pregnancy if they are on diet and exercise therapy
Answer: 1- 1 hour post-prandial <7.8 mmol/l or taking oral therapy (with or without diet and
exercise therapy) or single-dose intermediate-
In accordance with NICE guidelines (February acting or long-acting insulin.
2015):
Advise pregnant women with any form of diabetes
to maintain their capillary plasma glucose below
the following target levels, if these are achievable A 32 year old woman with gestational diabetes in
without causing problematic hypoglycaemia: her second pregnancy treated with twice daily
fasting: 5.3 mmol/litre and 1 hour after meals: 7.8 insulin delivers a healthy child via vaginal delivery.
mmol/litre or 2 hours after meals: 6.4 mmol/litre Post delivery her blood glucose concentrations
quickly revert to normal and she no longer
Advise pregnant women with diabetes who are on requires insulin.
insulin or glibenclamide to maintain their capillary
plasma glucose level above 4 mmol/litre. Which of the following applies regarding post-
partum screening for diabetes in thia woman?
1- Arrange for a fasting blood glucose 6 weeks
According to NICE guidelines, in women with post delivery
gestational DM, (who are on dietary control/oral
2- Arrange for an OGTT 6 weeks post delivery
hypoglycaemic agent) what are the
recommendations regarding frequency of blood 3- Arrange for an OGTT 3 months post delivery
sugar monitoring? 4- Arrange post prandial glucose measurement
(Please select 1 option) 6 weeks post delivery
1- Every 4 hourly 5- Check HbA1c 6 weeks post partum
2- Fasting and 2 hour post prandial
3- Fasting and 1 hour post prandial

Answer & Comments located on chromosome 12. It is the commonest

type of maturity onset diabetes of the young,
Answer: 1- Arrange for a fasting blood glucose 6 accounting for approximately 70% of all the
weeks post delivery MODY. It is characterised by severe
hyperglycaemia and about one third of patients
In accordance with NICE Clinical Guidelines 63, require insulin therapy for control of diabetes.
women who were diagnosed with gestational Early on in disease patients may display an
diabetes should be offered lifestyle advice exaggerated response to sulfonylurea therapy.
(including weight control, diet and exercise) and
offered a fasting plasma glucose measurement [ Q: 451 ] Question ID #673
(but not an OGTT) at the 6-week postnatal check
and annually thereafter. Women who were
diagnosed with gestational diabetes (including A 25 year old man of Caucasian origin was recently
those with ongoing impaired glucose regulation) diagnosed to have Diabetes and started on insulin
should be offered early self-monitoring of blood therapy. In last 6 weeks he is having multiple
glucose or an OGTT in future pregnancies. A episodes of hypoglycaemia and his insulin
subsequent OGTT should be offered if the test requirement has reduced to 12 units per day.
results in early pregnancy are normal.
His clinical examination is normal and he has a
Reference: body mass index of 22kg/m2. A recent renal scan
NICE CG63: diabetes in pregnancy had shown presence of renal cysts. He has a strong
family history of Diabetes with his father and 3
first cousins developing diabetes in their 3rd to 4th
[ Q: 450 ] Question ID #672 decade.
A 25 year old male is recently diagnosed to have Which of the following test is likely to reveal his
Diabetes Mellitus based on routine screening. His underlying diagnosis?
BMI is 24kg/m2 and there are no ketone bodies in (Please select 1 option)
urine with only 2+ sugars. His recent ultrasound
abdomen did not show any abnormalities. He has 1- Anti GAD antibodies
strong family history of Type 2 DM with few of the 2- Anti islet cells antibodies
family members requiring insulin therapy for
control. 3- Insulin, C peptide levels
4- Renin levels
What's the likely underlying genetic mutation?
5- Screening for monogenetic diabetes
1- Glucokinase
Answer & Comments
2- HNF 1α
Answer: 5- Screening for monogenetic diabetes
3- HNF 4α
4- IPF The patient has MODY 5, which is secondary to
mutation of HNF-1? and is characterised by onset
5- NeuroD1
of diabetes in the third decade and association
with renal cysts or uterine abnormalities in
Answer & Comments females.
Answer: 2- HNF 1α
The patient is likely to have MODY type 3, caused

by mutation of Hepatocyte nuclear factor- 1α,

[ Q: 452 ] Question ID #675  Cardiomyopathy

 Arthritis
A 55 year old man with type 2 Diabetes is reviewed
in the clinic. His biochemistry results are as shown: [ Q: 453 ] Question ID #676
Albumin 38 g/L (30-50 g/L) A 45 year old man with Type 2 DM for 8 years
(50-125 presents to clinic with lack of libido and erectile
ALP 175 U/L dysfunction. His BMI is 32 kg/m2 and there is no
U/L)
loss of secondary sexual characteristics. He denies
ALT 125 mU/L (05-58 U/L)
usage of any substance of abuse and his alcohol
35 intake is 14 units in a week. His biochemistry
Bilirubin (0-18)
micromol/L shows:
Proteins 66 g/L (60-80 g/L)
(10-300 FSH 2.2 U/L (1-10)
Ferritin 550 pmol/L
ng/mL) LH 3.5 U/L (3-10)
Transferrin Testosterone 7.5 nmol/L (9-28.5)
52% (15-50%)
saturation Prolactin 350 mU/L (45-400)
HbA1c 8.2% (<6) LFT Normal
Hb 12.8 g/L (12-16)
He undergoes a MRI which shows no obvious
Which of the following is the likely underlying abnormality.
diagnosis?
(Please select 1 option) What is the likely explanation for his low libido?
1- Glycogen storage disease
1- Anabolic steroid usage
2- Haemochromatosis
2- Haemochromatosis
3- LADA
3- Kallmann syndrome
4- Mitochondrial disease
4- Kleinfelter`s syndrome
5- MODY
5- Obesity
Answer & Comments
Answer & Comments
Answer: 2- Haemochromatosis
Answer: 5- Obesity
Haemochromatosis (Bronze diabetes) is a
hereditary (HFE/haemojvelin/hepcidin and other Erectile dysfunction is defined as inability to
gene mutations) or acquired (e.g. secondary to achieve or maintain an erection for sufficient time
repeated blood transfusions) condition leading to duration and firmness resulting in incomplete
pathological effects of iron accumulation on sexual activity in > 25% of the attempts. About
multiple organs and can present with one or more 10% of men are affected by low libido and erectile
of the following features: dysfunction and the prevalence increases with
age.
 Deranged LFT/cirrhosis
 Diabetes due to pancreatic β cell failure The following is a list of main causes for erectile
 Hypogonadism dysfunction:
 Skin pigmentation

 Medications such as diuretics, β blockers, (Please select 1 option)

MAO inhibitors, opioids, glucocorticoids, 1- Continue the antibiotics
tranquilizers, digoxin, antiandrogens,
gemfibrozil 2- Debride the ulcer
 Systemic illness (heart failure, cirrhosis,
uraemia etc.)
 Neurological conditions such as 4- Silver containing dressing
autonomic neuropathy, cord compression
5- Vascular review
 Vascular conditions such a peripheral
vascular disease
 Endocrine disease (hypogonadism, Answer & Comments
diabetes, thyroid dysfunction)
Answer: 5- Vascular review
 Psychological
 Urogenital abnormalities like trauma,
priapism and Peyronie`s disease This gentleman has a satisfactory glycaemic
 Alcohol, substance of abuse like heroin, control as reflected by HbA1C of 6.8%. His ulcer
marijuana seems to have responded to antibiotic therapy as
evidenced by a clear serous discharge from the
This gentleman has features of secondary gonadal ulcer and the superficial nature of ulcer makes
failure as evidenced by low testosterone and low debridement a less attractive option. As he has
FSH/LH levels. His age group and normal evidence of peripheral vascular disease (taking
secondary sexual characteristics make it unlikely pentoxifylline tablets), he should be referred for a
for him to have any genetic abnormality like vascular review to assess if the blood flow to the
Kallmann syndrome. A normal MRI rules out any extremity could be improved.
not on any medication and systemically well. A According to the NICE guidelines regarding
normal LFT and transferrin saturation makes it management of diabetic foot ulcer (NICE clinical
unlikely for him to have Haemochromatosis. guideline 10), examination of patient`s feet should
include;
Obese individuals have increased activity of
aromatase which converts testosterone to  Testing of foot sensation using a 10 g
estrogens which in turn suppress FSH/LH levels. monofilament or vibration
Total testosterone concentrations are influenced  Palpation of foot pulses
by sex hormone-binding globulin (SHBG)  Inspection of any foot deformity and
concentrations, which are decreased by obesity footwear
and increased with ageing.
The foot risks are classified as:
 At low risk (need annual review)
 At increased risk: In presence of
A 65 year old male diabetic presents with a peripheral neuropathy or vascular
superficial ulcer under the second toe of right foot. insufficiency (arrange regular review at 3-
He has been on antibiotics for the last 2 weeks and 6 monthly interval, by foot protection
the discharge from ulcer is clean. His HbA1C is team)
6.8% and medications include aspirin, clopidogrel,  At high risk: In presence of peripheral
ramipril, amlodipine, simvastatin, pregablin and neuropathy or vascular insufficiency along
pentoxifylline. On examination, his dorsalis pedis with deformity or previous ulcer or skin
pulse is feebly palpable. change (arrange frequent review ; 1-3
monthly)
Which of the following is the most appropriate  Foot care emergencies including new
step in his management? ulceration, swelling or discolouration

(review by multidisciplinary foot care  Deranged lipid profile

team within 24 hours)  Past medical history of cardiovascular
disease
 Family history of cardiovascular disease
Patients aged 40 and above with normal to high
A 54 year old type 2 Diabetic male, with a body risk for cardiovascular disease should be offered
mass index of 28kg/m2, undergoes annual review generic simvastatin or a statin of similar efficacy or
in the diabetic clinic. The following are the cost.
biochemical results from the screening:

Albumin 34 g/L (30-50)
(50-
ALP 108 U/L A 25 year old man with type 1 diabetes is reviewed
125)
in clinic. He is currently on basal bolus insulin
ALT 22 mU/L (5-58) therapy. His home blood sugar readings are
Bilirubin 12 micromol/L (0-18) generally high (>10 mmol/mol). He has not
suffered from any hypoglycaemic episodes in the
Proteins 64 g/L (60-80)
last 1 year.
HbA1c 7.6% (<6)
Total Cholesterol 5.4 mmol/L (<5) According to NICE guidelines, what is the cut off
value for HbA1C in patients with Type 1 DM for use
Triglycerides 1.9 mmol/L (1.1-2)
of insulin pumps?
LDL Cholesterol 2.9 mmol/L (<3)
Which one of the following is the most appropriate 1- 7.5%

advice regarding his lipid control?
2- 8.0%
3- 8.5%
1- Diet and exercise
4- 9.0%
2- Ezetimibe
5- 9.5%
3- Fibrates
4- Niaspan Answer & Comments
5- Statins Answer: 3- 8.5%
Answer & Comments According to NICE guidelines insulin pump therapy

Answer: 5- Statins should be considered in Type 1 diabetic who are
DAFNE trained and are on basal bolus insulin
regimen if their glycaemic control remains
According to the NICE guidelines on Type 2 unsatisfactory HbA1C > 8.5% or they are having
Diabetes (NICE clinical guideline 87), patients frequent hypoglycaemic episodes.
should be considered to be at high risk for
cardiovascular disease if one or more of the
following are present: [ Q: 457 ] Question ID #684
 Increased BMI A 45 year old type 2 diabetic male is referred with

 Hypertensive (> 140/80 mm of Hg) episodes of epigastric pain and nausea for the last
 Microalbuminuria few weeks. His blood test results were as detailed
 Smoker below:

Albumin 35 g/L (30-50) [ Q: 458 ] Question ID #685

ALP 72 U/L (50-125)
A 21 year old male shift worker, who has been a
ALT 41 mU/L (5-58)
diabetic for 14 years, presents with recurrent
Bilirubin 10 micromol/L (0-18) episodes of hypoglycaemia. He is taking 12 units of
Proteins 64 g/L (60-80) short acting insulin analogue (insulin aspart) three
times a day and on 22 units of long acting insulin
FT4 18.4 pmol/L (9-23)
analogue (glargine insulin). His home blood sugar
(0.35- monitoring shows blood sugar values varying from
TSH 1.1 mU/L
5.5) 2-20.
LDL 2.5 mmol/L (<3)
What is the next most appropriate step in his
Total Cholesterol 4.4 mmol/L (<5)
management?
Triglycerides 16.3 mmol/L (1.1-2)
HbA1C 7.1% (<6)
1- Acarbose
Which lipid lowering agent should be started in his 2- Decrease his insulin dose
case?
3- Metformin
4- Refer to a course on carbohydrate counting
1- Atorvastatin
(DAFNE)
2- Ezetimibe
5- Start him on insulin pump
3- Fenofibrate
4- Niaspan Answer & Comments
5- Rosuvastatin Answer: 4- Refer to a course on carbohydrate
counting (DAFNE)
Answer & Comments
This 21 year old has suboptimal glycaemic control
Answer: 3- Fenofibrate
and massive fluctuations in his blood sugar values,
despite being on an intensive basal bolus insulin
According to the NICE guidelines on Type 2 regimen. As he works in a shift pattern the
Diabetes (NICE clinical guideline 87), a Type 2 DM fluctuations in blood sugar readings can be
patient with high serum triglyceride levels should improved if he varies his short acting insulin dose
be initially assessed for a possible secondary cause depending upon the carbohydrate content of the
of hypertriglyceridaemia (including poorly meal. If these measures are not helpful, he should
controlled diabetes, hypothyroidism, Cushing`s be referred for continuous subcutaneous insulin
syndrome, chronic renal failure, drugs such as infusion (CSII).
steroids, estrogens, isotretinoin) and treated if
such a cause is identified. If the TG levels remain
elevated then Fibrates should be offered. These
may be started before the statin in scenario of
acute need (e.g. impending pancreatitis). If A 38 year old type 1 diabetic female, who has been
lifestyle measures and Fibrates are ineffective in on insulin pump for last 6 months, presents to
controlling TG levels a trial of omega-3 fish oils is clinic with recurrent hypoglycaemic episodes. She
recommended. confesses that she is not checking her blood sugars
and does not maintain a calorie intake diary. The
pump also has come out on numerous occasions
while she is asleep.

What is the most appropriate step in her 3- The risk of colon cancer is increased 2.3 fold
management? in patients on insulin glargine.
(Please select 1 option) 4- There is an increased risk of colon cancer for
1- Dietary advice patients taking insulin but not
sulphonylureas.
2- Intensify the control
5- There is no evidence to suggest
3- Remove insulin pump
sulphonylureas increase the risk of cancer.
4- Replace the tubing of pump
5- Offer more education about Insulin pump Answer & Comments
use
Answer: 1- Population-based cohort studies
support her concerns, showing a higher
Answer & Comments cancer-related mortality in those treated with
insulin or sulphonylureas but not metformin.
Answer: 5- Offer more education about Insulin
pump use
Therapies used to treat patients with diabetes
may increase or decrease their cancer risk.
This lady is on insulin pump and her glycaemic
Population-based cohort studies support this,
control is suboptimal, reflecting a lack of
showing a higher cancer-related mortality in those
monitoring and awareness on her part. In this case
treated with insulin or sulphonylureas compared
it is so important to get this woman to understand
with patients on metformin therapy.
the importance of glycaemic control and
adherance t the pump. She should be offered
further education regarding carbohydrate [ Q: 461 ] Question ID #847
counting, regular blood sugar monitoring and
adjustment of insulin pump basal rate. A 49-year old barrister with a 2 year history of type
2 diabetes mellitus, controlled on diet, attends
[ Q: 460 ] Question ID #846 clinic asking to be prescribed metformin. She has
a family history of colorectal cancer, which has
affected both her parents and a maternal aunty.
A 52 year old solicitor with a 7 year history of type
She has read an article that metformin maybe
2 diabetes presents to clinic concerned about her
protective against cancer in diabetes.
treatment. She is on gliclazide 160mg b.i.d., and
insulin glargine 24 units taken in the evening. She
Which of the following is correct?
has read there may be an increased risk of cancer
associated with her diabetic medications. (Please select 1 option)
1- There is no evidence to suggest that

Which of the following is correct? metformin is protective against colorectal
(Please select 1 option) cancer.
1- Population-based cohort studies support her 2- Metformin reduces the risk of bowel
concerns, showing a higher cancer-related adenocarinoma but not squamous cell
mortality in those treated with insulin or carcinoma.
sulphonylureas but not metformin.
3- Metformin in combination with gliclazide
2- There is an increased risk of cancer reduces the risk of colorectal cancer by a
associated with gliclazide, which is not a factor of 1.8.
class effect matched by other
sulphonylureas.

4- Metformin activates adenosine 4- The risk of bowel, breast and pancreatic

monophosphate-activated protein kinase, cancer in type 2 diabetes is 1.6 times greater
which may suppress tumour formation. than that for type 1 diabetes.
5- Metformin has been shown in vitro to inhibit 5- The risk of bowel, breast and pancreatic
the effects of tumour suppressor genes such cancer is 3 times more common in type 2
as p53. diabetes than type 1 diabetes.

Answer: 4- Metformin activates adenosine Answer: 2- Type 2 diabetes is associated with a
monophosphate-activated protein kinase, greater incidence of cancer, particularly of the
which may suppress tumour formation. pancreas, breast and colon.
Metformin may have a protective effect against The greater incidence of breast, pancreatic and
cancer and pilot studies from a diabetes database colon cancer in patients with type 2 diabetes may
support this. The potential mechanism is that be multifactorial, possibly linked to obesity, insulin
metformin activates adenosine monophosphate- resistance or hyperglycaemia. For example,
activated protein kinase which may suppress carcinoma of the colon is associated with obesity,
tumour formation. hyperglycaemia, metabolic syndrome,
hypertriglyceridaemia, insulin treatment and
raised insulin-like growth factor levels.
A 57-year old petro-chemical engineer attends [ Q: 463 ] Question ID #849

diabetes clinic having recently been diagnosed
with type 2 diabetes. She has spent most of her You have recently started a 61 year old teacher
working life exposed to benzene derivatives. Aged with a 5 year history of type 2 diabetes on
49 she was diagnosed with breast cancer, which exenatide. Her colleague at school also has type 2
was treated with a lumpectomy. Her husband is diabetes and is on liraglutide and has told her it is
undergoing chemotherapy for disseminated “better than exenatide.” The patient contacts you
colorectal cancer. asking for your advice on this as she is keen to
change to liraglutide.
She has read in a Sunday-magazine that diabetes
maybe associated with an increased risk of cancer How do you advise her?
and asks for your opinion on this article. (Please select 1 option)
What do you advise? 1- Liraglutide has demonstrated non-inferiority

compared to exenatide.
1- She should not believe what she reads in the 2- In a head-to-head comparative study against
Sunday press? exenatide, liraglutide was associated with a
0.3% superior HbA1c reduction.
2- Type 2 diabetes is associated with a greater
incidence of cancer, particularly of the 3- In a head-to-head comparative study against
pancreas, breast and colon. exenatide, liraglutide was associated with a
0.9% superior HbA1c reduction.
3- Type 2 diabetes is associated with a greater
incidence of cancer, particularly of the 4- In an open-labelled study exenatide has
pancreas, lung and brain. demonstrated a 0.4% superior HbA1c
reduction compared to liraglutide.

5- Exenatide has demonstrated non-inferiority perceived disease severity; injection related

compared to liraglutide. anxiety; a perceived lack of positive gain.
4- A perceived loss of control over one’s life;
Answer & Comments poor self-efficacy; personal failure;
Answer: 2- In a head-to-head comparative study perceived disease severity; injection related
against exenatide, liraglutide was associated anxiety; depression.
with a 0.3% superior HbA1c reduction. 5- A perceived loss of control over one’s life;
poor self-efficacy; hysteria; perceived
In comparative studies, liraglutide has disease severity; injection related anxiety; a
demonstrated superior HbA1c reductions perceived lack of positive gain.
compared to glimepiride, metformin,
rosiglitazone, and insulin glargine. In a head-to-
Answer & Comments
head comparative study against exenatide,
liraglutide was associated with superior HbA1c Answer: 3- A perceived loss of control over one’s
reductions of 0.3%. life; poor self-efficacy; personal failure;
perceived disease severity; injection related
[ Q: 464 ] Question ID #850 anxiety; a perceived lack of positive gain.
A 58 year old patient with a 14 year history of type Patients with T2DM are often reluctant to begin
2 diabetes presents to clinic. His HbA1c is 13.6% insulin and, in many cases, delay the start of
despite taking metformin 1g bd., gliclazide 160mg insulin therapy for quite lengthy periods of time.
bd., and exenatide 10mcg bd. His BMI is 35 kg/m2, This has led to the development of the concept of
his blood pressure is 164/98 mmHg and he has “psychological insulin resistance” (PIR).
pre-proliferative retinopathy, microalbuminuria,
and a distal sensori-motor neuropathy. While clinical lore suggests that PIR is quite
common, there has been little formal study in this
He refuses to consider insulin therapy and is not area. In the United Kingdom Prospective Diabetes
keen on attending a recommended EXPERT Study (UKPDS), of those with T2DM randomized to
patient education programme as he doesn’t like insulin therapy, 27% initially refused. Early reports
talking to other “diabetics”. You diagnose him with from the international Diabetes Attitudes, Wishes,
‘Psychological Insulin Resistance.’ and Needs (DAWN) study indicate that the
majority (54.9%) of insulin-naïve patients worry
Which factor constitute Psychological Insulin about the possibility of insulin therapy. The six
Resistance? features of PIR are as listed in answer C, which is
the best answer.
1- A perceived loss of control over one’s life;

poor self-efficacy; anxiety; perceived
disease severity; injection related anxiety; a
A 45-year old builder with a 12 year history of type
perceived lack of positive gain.
2 diabetes has an HbA1c of 11.5% despite taking
2- A perceived loss of control over one’s life; metformin 1g bd., gliclazide 160mg bd., and
neurosis; personal failure; perceived disease sitagliptin 100mg od. He has refused exenatide or
severity; injection related anxiety; a insulin due to a needle phobia.
perceived lack of positive gain.
According to research on the concept of
3- A perceived loss of control over one’s life; ‘Psychological Insulin Resistance’ what percentage
poor self-efficacy; personal failure; of patients who are reluctant to start insulin have
a needle phobia?

(Please select 1 option) circadian neuroendocrine oscillations.

1- 10% Bromocriptine modulates neurotransmitter
action in the brain and is associated with
2- 40%
HbA1c reductions of 0.56%.
3- 50%
4- Hyperprolactinaemia is associated with type
4- 60% 2 diabetes and by treating
hyperprolactinaemia plasma glucose levels
5- 80%
improve.
Answer & Comments 5- Bromocriptine reduces glucagon secretion.
Answer: 3- 50%
Answer & Comments
The fifth factor in the concept of psychological Answer: 3- Body fat stores and insulin action are
insulin resistance (PIR) concerns injection related controlled by the temporal interaction of
anxiety. Approximately 50% of patients report circadian neuroendocrine oscillations.
being fearful of injections. Although this is often Bromocriptine modulates neurotransmitter
presumed to be the single, or single largest, action in the brain and is associated with
contributor to PIR, it may be overstated. True HbA1c reductions of 0.56%.
injection phobia is rare, even among insulin-using
patients with diabetes.
Body fat stores and insulin action are controlled by
the temporal interaction of circadian
[ Q: 466 ] Question ID #852 neuroendocrine oscillations. Bromocriptine
modulates neurotransmitter action in the brain.
A 72 year old American tourist with a 4 year Studies using bromocriptine in type 2 diabetes
history of type 2 diabetes is admitted to the acute have shown improvements in glycaemic control
assessment unit with haematemesis. The House- and glucose tolerance with HbA1creductions of
Officer / Foundation Year 1 doctor admits the ~0.56%.
patient and erroneously informs you that the
management of the patients’ diabetes is ‘diet- Despite receiving FDA approval, bromocriptine is
control’. not part of the type 2 diabetes management
guidelines from the National Institute for Health
Upon reviewing the drug chart you note the and Clinical Excellence. It is commonly used in the
patient is on bromocriptine. management of T2DM in the USA.
How can bromocriptine be used in the [ Q: 467 ] Question ID #853

management of type 2 diabetes?
(Please select 1 option) A 40 year old lady with a 2 year history of type 2
1- By inhibiting central D2 receptors diabetes is reviewed in diabetes clinic in the
summer. Six months prior to this appointment,
bromocriptine increases systemic insulin
during the winter, your colleagues started her on
sensitisation.
sitagliptin 100mg o.d.
2- By reducing serum prolactin levels
bromocriptine augments the effects of The patient has a past medical history of eczema,
endogenous incretins on reducing satiety asthma and perennial rhinitis. She comments that
and slowing gastric emptying. since she started sitagliptin she has noticed a
‘blocked and stuffy’ sensation in her nose and
3- Body fat stores and insulin action are throat.
controlled by the temporal interaction of

What do you advise? What do you advise?

1- Her symptoms are most likely related to 1- Exenatide acts in a glucose dependent
hayfever in the summer months. manner. Therefore there is negligible risk of
hypoglycaemia.
2- Sitagliptin is associated with nasopharyngitis
and may be contributory. 2- The risk of hypoglycaemia is increased in
patients on exenatide who are also taking a
3- She should be referred to an allergy clinic in
sulphonylurea.
view of her past medical history of atopy.
3- The risk of hypoglycaemia is increased in
4- She should be prescribed an anti-histamine
patients on exenatide who are also taking
and nasal decongestants.
metformin.
5- She should monitor her PEFR twice daily as
4- The risk of hypoglycaemia is increased in
her asthma may have decompensated.
thiazolidienedione.
Answer & Comments
5- The risk of hypoglycaemia in decreased if
Answer: 2- Sitagliptin is associated with exenatide is administered one hour before
nasopharyngitis and may be contributory. oral hypoglycaemic agent therapy.
Several selective inhibitors of DPP-4 have been Answer & Comments

developed and those that are licensed include
sitagliptin, vildagliptin, and more recently, Answer: 2- The risk of hypoglycaemia is increased
saxagliptin. They offer an alternative oral in patients on exenatide who are also taking a
treatment for T2DM, which unlike the sulphonylurea.
sulphonylureas, are not associated with
hypoglycaemia or weight gain. They achieve a 0.4-
The most common side-effects associated with
0.7% HbA1c reduction over 12 months.
exenatide include nausea, vomiting, and
diarrhoea, which are dose-dependent and more
Adverse effects include nasopharyngitis, urinary
common during drug initiation but subside over
tract infections and pancreatitis. However, no
time. The risk of hypoglycaemia is increased in
study on DPP-4 inhibitors has reported on patient-
centred parameters such as mortality, diabetic
sulphonylurea.
complications, health economics and health-
related quality of life. This has focused the
In contrast, the risk of hypoglycaemia is not
development of novel DDP-4 inhibitors towards
increased when exenatide is combined with
overcoming these short-comings. Such agents,
metformin or a thiazolidiedione.
which are in clinical trial phase, include linagliptin,
dutogliptin and alogliptin.
You review a 22 year old lady who was found to
have a fasting blood glucose of 15mmol/L, which
You review a 55 year old male patient with a 12
when repeated was 14.5mmol/L. Her 21 year old
year history of type 2 diabetes. He is on metformin
sister was recently diagnosed with diabetes and
1g b.i.d., gliclazide 160mg b.i.d., and pioglitazone
her 24 year old brother was diagnosed with
30mg o.d. His BMI is 36kg/m2. You consider adding
diabetes aged 22.
in exenatide. The patient is concerned that
exenatide may increase the risk of hypoglycaemia.

You look back through her medical records and Answer & Comments
note that she has a history of pelvic inflammatory
disease. A urinary Chlamydia antigen test was Answer: 3- Grade 3
positive. An ultrasound scan of her pelvis was
reported as showing bilateral renal cysts and a Wagner’s classification of diabetic foot lesions is as
unicornuate uterus. She also has a history of gout follows:
and is known to binge drink.
 Grade 0 – high-risk foot, no ulcer present.
What is the underlying diagnosis?  Grade 1 – Superficial ulcer, not infected.
(Please select 1 option)  Grade 2 – deep ulcer with or without
cellulitis but no abscess or bone
1- Type 1 diabetes involvement.
2- Polycystic ovarian syndrome  Grade 3 – deep ulcer with bone
involvement or abscess formation.
3- MODY 1  Grade 4 – localised gangrene (toe,
4- MODY 3 forefoot, heel).
 Grade 5 – gangrene of the whole foot.
5- MODY 5
Answer & Comments
Answer: 5- MODY 5 A 25 year old model with a 17 year history of type
1 diabetes presents to clinic concerned about her
finger nails. She has noticed an area of redness
MODY 5 is due to a mutation in HNF1-ß and over her nail folds, which have been present for
accounts for 3% of cases of MODY. The average the last month. She is concerned as this may affect
age of presentation is 22 years associated with her employment prospects.
renal cysts often with uterine abnormalities, gout
and insulin resistance. What is the most likely diagnosis?
1- Bullosis diabeticorum
A 74 year old patient with a 28 year history of type 2- Diabetic thick skin
2 diabetes presents to the diabetic foot clinic with
3- Folliculitis
a deep ulcer on his right forefoot. The podiatrist is
able to prod down to bone and there is clinical 4- ANCA negative small vessel vasculitis
evidence of abscess formation.
5- Periungual telangectasia
According to the Wagner classification of diabetic
foot lesions, what grade ulcer does this patient Answer & Comments
have?
Answer: 5- Periungual telangectasia
1- Grade 1 Skin conditions specific to diabetes include:

pretibial diabetic dermopathy, bullosis
2- Grade 2
diabeticorum, diabetic thick skin, and periungual
3- Grade 3 telangectasia. Periungual telangectasia is
characterised by venous capillary dilatation at the
4- Grade 4
nail fold seen in up to 50% of people with diabetes.
5- Grade 5 Note that necrobiosis lipoidica, vitiligo, and
granuloma annulare are skin conditions seen more

commonly in those with diabetes but are not What is the average delay between starting oral
specific to diabetes. hypoglycaemic therapy to initiating insulin?
1- 2 years.
A 42 year old patient with a 29 year history of type 2- 5 years.

1 diabetes presents to clinic. He works as a builder 3- 8 years.
and operates heavy drilling machinery. He is
concerned that the skin on his hands is thickening 4- 11 years.
and feels tight. This has resulted in reduced joint 5- 15 years.
mobility in his hands. He drinks 35 units of alcohol
weekly. On examination you note that he is unable
to place the palms of the hands flat together and Answer & Comments
make the ‘prayer sign.’ Answer: 4- 11 years.
What is the most likely diagnosis?

Recent data have shown that patients with T2DM
in the UK delay initiating insulin on average for
1- Dupuytren’s contracture. over 11 years after first being prescribed an oral
medication. It was found that for patients
2- Diabetic cheiroarthropathy.
immediately initiating insulin there were increases
3- Limited cutaneous scleroderma. in (undiscounted) life expectancy of 0.61 years and
quality-adjusted life expectancy of 0.34 quality-
4- Diabetic thick skin. adjusted life years versus delaying initiation for 8
5- Diabetic bullae. years. There were also substantial reductions in
cumulative incidence and time to onset of all
diabetes-related complications with immediate
Answer & Comments versus delayed insulin initiation.
Answer: 2- Diabetic cheiroarthropathy.
Diabetes is associated with an increased incidence
of pseudogout and osteoarthritis but the classical What percentage of patients do not achieve the
condition to consider is the ‘stiff hand syndrome’ target HbA1c of <7% recommended by the
or diabetic cheiroarthropathy. In this the skin American Diabetes Association on oral
thickens and tightens which, in association with hypoglycaemic agent therapy?
sclerosis of the tendon sheaths, results in limited
joint mobility in the hands and less commonly the
feet. This reduced joint mobility gives an inability 1- 10%
to place the palms of the hand flat together and
2- 20%
make the ‘prayer sign.’ No specific treatment for
this currently exists. 3- 40%
4- 60%
5- 70%
Patients with T2DM are at increased risk of a large

number of diabetes-related complications due to Answer & Comments
an unnecessary delay in insulin initiation.
Answer: 4- 60%

Despite the availability of many anti-diabetic capsule form by people with diabetes. Many
agents, approximately 60% of patients do not natural products and herbal medicines are not
achieve the target HbA1C level of <7%. Reasons safe when used in conjunction with other
for this include: noncompliance; side-effects of pharmaceutical medicines and can cause
treatments; fear of hypoglycaemia; weight-gain; problems.
problems with dose titration of anti-diabetic
agents; and more stringent HbA1C targets set by
[ Q: 476 ] Question ID #3454
healthcare organisations which tend to change.
A 55 year old man is commenced on treatment

[ Q: 475 ] Question ID #861 with simvastatin 40 mg daily.
You review a 45 year old ecologist who has been Risk from which of the following is increased with
found to have fasting plasma glucose of 8.4 the use of statin therapy?
mmol/L and 9.1 mmol/L on two occasions. She has
not lost weight and her GAD antibodies are
negative. Her HbA1c is 7.3%, her blood pressure is 1- Diabetes mellitus
130/78mmHg and her BMI is 29 kg/m 2.
2- Erectile dysfunction
You diagnose her with type 2 diabetes with the 3- Immune hypoadrenalism
recommendation that she commences metformin
4- Ischaemic heart disease
500mg b.i.d. in the first instance. She refuses
treatment preferring to use herbal medicines. She 5- Multiple sclerosis
has read that Karela supplements are of value in
type 2 diabetes and would like to try them first.
Answer & Comments
How do Karela supplements benefit patients with Answer: 1- Diabetes mellitus
type 2 diabetes?
(Please select 1 option) Statins have been shown through meta-analyses
1- Karela reduces peripheral insulin resistance. to be associated with a 23% increased risk of new
onset diabetes and the FDA warned of this
2- Karela inhibits hepatic gluconeogenesis. phenomenon in 2012 following results of the
JUPITER study. However, statins are without
3- Karela inhibits free fatty acid oxidation.
question drugs that reduce CV risk and appear to
4- Karela has hypoglycaemic effects. offer beneficial effects in ED.
5- Karela has incretin like effects.
Journal of Pharmacotherapy and
pharmacotherapeutics (2014)Statin induced
Answer & Comments diabetes and its clinical implications
Answer: 4- Karela has hypoglycaemic effects.
[ Q: 477 ] Question ID #3455
The hypoglycaemic effects of Karela are well
documented. It is used traditionally in Asian A 55 year old man with type 2 diabetes is being
cookery and as a traditional medicine to lower treated with metformin and gliclazide. His HbA1c
blood glucose levels. In practice it is difficult to is 76 mmol/mol (9.1%). It is decided to commence
take enough of the Karela plant to have a him on empagliflozin.
significant effect. Karela capsules are an unknown
entity. While certain components of Karela do Which of the following describe this class of drug?
have hypoglycaemic effects there have been no (Please select 1 option)
formal studies to indicate if it can be used safely in
1- Dipeptidyl peptidase –IV inhibitor

2- Glucagon-like peptide agonist 1- No change in HbA1c but reduced progression

of nephropathy
3- Potassium channel inhibitor
2- Reduced cardiovascular events and all-cause
4- Sodium glucose co-transporter-1 inhibitor
mortality
5- Sodium glucose co-transporter-2 inhibitor
3- Reduced HbA1c with reductions in all
microvascular complications
Answer & Comments
4- Reduced HbA1c yet increased risk of major
Answer: 5- Sodium glucose co-transporter-2 acute cardiovascular event (MACE)
inhibitor
5- Reduced microvascular complications but
unchanged all-cause mortality
Empagliflozin like canagliflozin and dapagliflozin is
a SGLT-2 inhibitor which prevents the
reabsorption of glucose from the proximal tubule Answer & Comments
of the nephron. Consequently it increases renal
Answer: 2- Reduced cardiovascular events and all-
losses of glucose and the class of agents pose an
exciting development in the treatment of cause mortality
diabetes.
EMPA-REG was an outcome study in over 7000
Medline Plus (2016) Empagliflozin type 2 subjects treated with empagliflozin in
addition to standard care versus standard care.
[ Q: 478 ] Question ID #3456 The primary outcome measure was death from
cardiovascular causes, nonfatal myocardial
infarction or nonfatal stroke and was reduced
Empagliflozin was used in the landmark EMPA- from 12.1% to 10.5%. Roughly 25% reduction in
REG study as an adjunctive treatment to standard the composite end-point. Death from any causes
care in subjects with type 2 diabetes. fell from 8.3% to 5.7%
Which of the following were the reported results of The New England Journal of Medicine, Zinman B
EMPA-REG? et al (2015) Empagliflozin, Cardiovascular
(Please select 1 option) Outcomes, and Mortality in Type 2 Diabetes

Endocrinology
Endocrinology and Diabetes - Mock
Exam
A 24 year old female has received a six month course of carbimazole for Graves disease. She recently stopped
treatment and attends two months later for subsequent review and complains of recurrence of her previous
symptoms. On examination, she has a modest goitre with pulse of 80 bpm and has a fine tremor of the
outstretched hands. The results of her thyroid function tests reveal:
Free T4 32.3 pmol/l (9 - 22)

TSH <0.02 mu/l (0.5 - 5)
She informs you that she is keen on getting pregnant at some stage in the future but currently takes the oral
contraceptive, microgynon.
Which of the following would be the most appropriate action for this patient?
1- Continue with further six months propylthiouracil

2- Continue with long term propylthiouracil
3- Continue to treat with long term carbimazole
4- Radioactive iodine
5- Refer for thyroid surgery
Answer & Comments

Answer: 4- Radioactive iodine
The most appropriate first line treatment for this patient who has recurrent thyrotoxicosis following anti-
thyroid treatment would be radioactive iodine. She should ensure that she does not become pregnant for
four months after treatment but she is already taking the OCP. There is no report of eye disease associated
with the Graves’ so concomitant steroids is probably unnecessary. Following radioiodine treatment,
approximately 80% of patients become hypothyroid.

A 71 year old gentleman is admitted to hospital following admission to hospital with a mechanical fall. On
admission, his random plasma glucose is 12.4 mmol/l (<7.8) and a subsequent fasting plasma glucose
measures 7.9 mmol/l (<6). He is generally well, taking no regular medications and on examination his blood
pressure is 146/86 mmHg and his BMI is 31 kg / m2.
Further investigations reveal:
Hba1c 7.1% (<6)

LDL Cholesterol 3.7 mmol/l (<2)
HDL Cholesterol 0.9 mmol/l (0.9 - 1.9)
Which of the following is the most important determinant of the future risk of cardiovascular events in this
gentleman?
1- Total cholesterol level

2- LDL-cholesterol level
3- HDL-cholesterol level
4- Plasma Triglyceride Level
5- Non-HDL-cholesterol level
Answer & Comments

Answer: 5- Non-HDL-cholesterol level
The results of the Strong Heart Study indicate that non-HDL-C may be a superior predictor of cardiovascular
events than LDL-C; HDL-C or plasma TG levels alone in both men and women with type 2 diabetes. The utility
of non-HDL-C in predicting cardiovascular events in non-diabetic subjects is supported by data from the SHEP
(Systolic Hypertension in the Elderly Program) and Lipid Research Clinics (LRC) studies, in which non-HDL-C
was found to be a better predictor than LDL-C of cardiovascular events in patients followed over 4.5 years
and 19 years respectively.

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El-Zohry

Endocrinology and Diabetes – SCE

Complications of diabetes 45 31-75

Diabetes mellitus (diagnosis and general management,

Diabetic emergencies and management during acute

Hypothalamus and Pituitary 46 203-248

Page | 2 Dr. Khalid Yusuf (FB: Sohag Endocrine Group)

[ Q: 1 ] Adrenal - Question ID #63 [ Q: 2 ] Question ID #64

1- 24hr urine collection for catecholamines Urea 5.5 mmol/l (3-8)

Answer & Comments 2- Arrange MRI abdomen

Answer: 1- 24hr urine collection for 3- Check 24 hr urine catecholamines

Page | 3 Dr. Khalid Yusuf (FB: Sohag Endocrine Group)

initial PRA:Aldo ratio is suggestive of Conn's 230

Answer & Comments

Although the investigations would suggest that

A 42 year old female is co-incidentally noted to AACE guidelines: management of adrenal

Page | 4 Dr. Khalid Yusuf (FB: Sohag Endocrine Group)

[ Q: 6 ] Question ID #85 A 44 year old female is investigated for

U+Es Normal Urine free

Page | 5 Dr. Khalid Yusuf (FB: Sohag Endocrine Group)

Which adjuvant therapy would most likely prolong

Page | 6 Dr. Khalid Yusuf (FB: Sohag Endocrine Group)

[ Q: 10 ] Question ID #146 [ Q: 11 ] Question ID #160

5- Phaeochromocytoma Answer: 2- Atenolol

Answer & Comments Beta blockers are well recognised to cause a

Page | 7 Dr. Khalid Yusuf (FB: Sohag Endocrine Group)

http://www.ncbi.nlm.nih.gov/pubmed/17315030 and low renin. This is unlikely to be essential

A 22 year old woman was referred to clinic by her [ Q: 13 ] Question ID #345

Which of the following is the correct diagnosis? 1- Apparent mineralocorticoid excess

Page | 8 Dr. Khalid Yusuf (FB: Sohag Endocrine Group)

Answer & Comments A 32 year old female presents with hypokalaemia

21-hydroxylase is involved in the cholesterol

1- 3 ß HSD 2- Congenital adrenal hyperplasia

2- 11 ß HSD 3- Conn's syndrome

3- 11 ß hydroxylase 4- Gitelman`s syndrome

4- 17 ß hydroxylase 5- Liddle`s syndrome

Answer & Comments Answer: 4- Gitelman`s syndrome

Page | 9 Dr. Khalid Yusuf (FB: Sohag Endocrine Group)

aldosterone levels. The main differential diagnosis [ Q: 18 ] Question ID #646

1- Apparent mineralocorticoid excess

1- Autosomal dominant Answer & Comments

Page | 10 Dr. Khalid Yusuf (FB: Sohag Endocrine Group)

Which of the following concerning peri and post- 124

Answer & Comments 1- Adrenal leukodystrophy

Answer: 5- Peri and post operative hydrocortisone 2- Adrenal tuberculosis

The perioperative management of a cortisol 5- Sarcoidosis

An Asian man is admitted with a history of weight [ Q: 21 ] Question ID #650

Page | 11 Dr. Khalid Yusuf (FB: Sohag Endocrine Group)

Which of the following is likely to improve the Answer & Comments

1- Aminglutethimide The 2004 WHO classification of endocrine

Page | 12 Dr. Khalid Yusuf (FB: Sohag Endocrine Group)

2- Loss of function of MAX mutation seemingly adequate replacement with

[ Q: 24 ] Question ID #654 143 (135-

Page | 13 Dr. Khalid Yusuf (FB: Sohag Endocrine Group)

Creatinine 72 µmol/L (60-115) PRA:Aldo interpretations and need to be stopped

Answer & Comments [ Q: 26 ] Question ID #656

Page | 14 Dr. Khalid Yusuf (FB: Sohag Endocrine Group)

What is the most appropriate next step in his

Page | 15 Dr. Khalid Yusuf (FB: Sohag Endocrine Group)