Acute Normalization of Thyroxine Induced Hallucinations and Delusions

doi:10.4236/ijcm.2012.35066

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

http://dx.doi.org/10.4236/ijcm.2012.35066 Published Online September 2012 (http://www.SciRP.org/journal/ijcm) 1

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 bein g able to induce psychotic symptoms. However, psychotic symptoms without affectiv e

and cognitive disturb ances are rare in hyperthyroidism. We presented a patient with Graves’ disease who su ffered 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 th is case. It is suggested that the abrupt change of thyrox ine 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 tachy-

cardia, restlessness, excessive sweating, and impaired ab i-

lity to concentrate [1-3].

While the association between disorders of thyroid

function and affective symptoms is well establish ed [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 thy-

roid-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 Propylthiou r acil (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 isotop e 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 dru g use. At that time of ad mission,

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 trem-

ors 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

Acute Normalization of Thyroxine Induced Hallucinations and Delusions

342

to kill herself. In add ition, she insisted that her conv ersa-

tions were recorded all the time and she was watched by

surveillance cameras. In spite of hallu cinations and delu-

sions, 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, exces-

sive 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 as-

sociation 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 dis-

crepancy 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 hallu-

cinations 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 differ-

ent 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 in-

duce a change in mental condition, however, the reason

for this discrepanc y 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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