International Journal of Clinical Medicine

International Journal of Clinical Medicine, 2012, 3, 341-343 1
http://dx.doi.org/10.4236/ijcm.2012.35066 Published Online September 2012

(http://www.SciRP.org/journal/ijcm)
Acute Normalization of Thyroxine Induced Hallucinations and Delusions
Yuko Furuhashi1, Masaya Ishikawa2

1Medical Center, Shizuoka University, Shizuoka, Japan; 2Saginuma Park Clinic,
Kawasaki, Japan. Email: [email protected]
Received June 15th, 2012; revised July 16th, 2012; accepted July 25th, 2012
ABSTRACT
The association between disorders of thyroid function and psychiatric symptoms is
well established. Generally, hypo- thyroidism is recognized as being able to induce
psychotic symptoms. However, psychotic symptoms without affective and cognitive
disturbances are rare in hyperthyroidism. We presented a patient with Graves’ disease
who suffered from delusions and hallucinations without affective and cognitive
disturbances following abrupt normalization of thyroid function. Furthermore, the
patient was clinically and biochemically euthyroid when the psychotic symptoms
developed. There was resolution of psychotic symptoms in this case. It is suggested
that the abrupt change of thyroxine may cause susceptible individuals to become
transient psychotic state.
Keywords: Graves’ Disease; Hallucination, Delusion
1. Introduction
Graves’ disease is a form of hyperthyroidism associated with diffuse goiter,
ophthalmopathy, and dermopahty. This is believed to be an autoimmune disease that
is multifactorial in organ [1]. Patients with Graves’ disease may experience emotional
lability, tremors, sinus tachycardia, restlessness, excessive sweating, and impaired
ability to concentrate [1-3].
While the association between disorders of thyroid function and affective symptoms
is well established [1-6], it is rare that psychotic symptoms without affective and
cognitive disturbances in patients with Graves’ disease [7,8]. The following is a case
of new-onset psychosis in a woman who underwent isotope irradiation therapy of
Graves’ disease.
2. Case
Ms. A is a 36-year-old woman, who had married and had three children, complained
of palpitation, excessive sweating, and finger tremors. Laboratory tests at that time
showed serum level of free thyroxine (free T4) was 6.4 ng/dL (normal range 0.9 - 2.0
ng/dL) and serum thyroid-stimulating hormone (TSH) level was under the de-
tection level (<0.05 μU/mL, normal range 0.3 - 4.1 μU/mL). Serum antibodies to
thyroglobulin, microsomes, and thyrotropin were positive. She was diagnosed as
Graves’ disease. Thiamazole (MMI) 30 mg a day was administrated with good
compliance, but the white blood
cell counts were reduced to 980/mm3. The MMI was replaced with Propylthiouracil
(PTU). She exhibited poor control (free T4 6.0 ng/dL) even when PTU was adminis-
trated 1200 mg a day. Her symptoms such as irritability and general fatigue
deteriorated in parallel with an in- crease of serum free T4 level (9.8 ng/dL). She was
sent to our hospital to be treated by isotope irradiation therapy.
On admission, the patient was a slightly thin woman with finger tremors but no
exophthalmos. She was alert. She had a family history of hyperthyroidism in her
father. She had no prior psychiatric history and did not receive a psychiatric
treatment. There was no history of recent or past alcohol or illegal drug use. At that
time of admission, she had routine laboratory tests and imaging studies. Al- though
her free T4 level was 10.4 ng/dL and TSH level was under the detection level, other
data including elec- trolytes and brain magnetic resonance were all normal. A week
after her admission, isotope irradiation therapy on the thyroid was tried for in place of
medication. At that time the irradiation therapy was ended, her serum free T4 level
was 13.4 ng/dL. She complained severe general fatigue and palpitation. Four weeks
after irradiation therapy, her serum free T4 level was 2.0 ng/dL. Along with the
improvement of thyroid hormone level, physical symptoms such as palpitation,
sweating, and hand tremors fully improved. Then, she suddenly suffered an abrupt
ongoing auditory hallucinations of multiple and indistinct voices. She reported that
someone had been talking critically of her and sometimes commanded her
Copyright © 2012 SciRes.
IJCM342 Acute Normalization of Thyroxine Induced Hallucinations and Delusions
to kill herself. In addition, she insisted that her conversa- tions were recorded all the
time and she was watched by surveillance cameras. In spite of hallucinations and
delusions, she did not present any predominant affective symptoms. She was fully
orientated for time and place, and her cognitive functions were not disturbed. She was
treated with haloperidol (HPD) 9 mg a day. Immediately her psychotic symptoms
responded to HPD. She was discharged seven weeks after the irradiation therapy was
ended. At her discharge, her serum free T4 level was 1.0 ng/dl. Consecutive
examinations revealed that her serum TSH level had been under the detection level
until she was discharged. Two weeks after her discharge, HPD was discontinued
because her psychotic symptoms were improved. Six months after her initial
presentation in our hospital, she has remained in a euthyroid state and symptom free
with no return of psychotic symptoms.
3. Discussion
Patients with Graves’ disease may experience emotional lability, tremors, sinus
tachycardia, restlessness, excessive sweating, and impaired ability to concentrate. A
minority of patients, usually the elderly, are apathetic, depressed, and withdrawn [1].
Recent prospective studies suggest that there is an association between abnormalities
of thyroid function and affective illness [2-4]. A lack of thyroid hormones can lower
the threshold for depressive state, on the other hand, an excess of thyroid hormones
can contribute to manic state. These findings suggest a possible central effect, either
due to alterations of brain thyroid hormone homeostasis or, perhaps, to autoimmunity
involvement in the brain. On the contrary, various studies have reported that
psychiatric symptoms do not correlate with the de- gree of elevation of thyroid
hormone levels [1,5-6]. For example, Trzepacz et al. [1] reported that there were no
relationships between the clinical assessment of disease severity and serum levels of
thyroid hormone. This discrepancy may arise if serum levels do not reflect intra-
cellular thyroid hormone concentrations, or if there are cellular variations in nuclear
thyroid hormone receptor sensitivity.
Thus, the association between disorders of thyroid function and psychiatric symptoms
is well established [1-6], it is rare that psychotic symptoms in patients with Graves’
disease [7-15].
A Medline search was performed using the search terms, “Graves’ disease and
psychosis”, “Graves’ disease and delusions”, “Graves’ disease and hallucinations”,
“Graves’ disease and paranoia”. Our search revealed only eight case reports of
psychotic symptoms linked to Graves’ disease [8-15]. Of these, three cases [8-10]
have a certain similarity to our case. Katsigiannopoulos et al. [8] reported the patient
who developed a psychotic dis-
order without affective and cognitive disturbances in thyrotoxic state. Bewher et al.
[9] and Irwin et al. [10] reported the case of a patient with Graves’ disease who
suffered from psychotic symptoms with manic features following abrupt
normalization of thyroid functions.
Our case is especially interesting as the patient with Graves’ disease who suffered
from delusions and hallucinations without affective and cognitive disturbances
following abrupt normalization of thyroid function. It seems possible that a rapid
reduction in high ambient thyroid hormone tissue levels could lead to alteration, or
recovery, of cellular function at different rates in different regions of the brain. This
process may have triggered the transient psychotic features seen in our case. In those
reports [9,10] and our case, it is suggested that the rapid change in thyroid hormone
levels might induce psychotic symptoms in susceptible individuals. Thyroid
hormones and their receptors spread widely in the human brain, and thyroid hormones
act on neural transmission as direct neurotransmitters by themselves [2]. These data
suggest that a small change of serum thyroid hormone may induce a change in
mental condition, however, the reason for this discrepancy and the pathogenesis of
psychosis in Graves’ disease are still elusive. The molecular mecha- nisms and
functional pathways underlying the modula- tory effects of thyroid hormones on
mental status remain to be fully elucidated. Further studies and the accumula- tion of
data of thyroid hormones on mental status are required.
4. Conclusion
General practitioners should bear in mind the possibility of psychotic symptoms
following aggressive treatment of severe Graves’ disease.

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International Journal of Clinical Medicine, 2012, 3, 341-343 1

http://dx.doi.org/10.4236/ijcm.2012.35066 Published Online September 2012

Yuko Furuhashi1, Masaya Ishikawa2

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