International Journal of Clinical Medicine, 2012, 3, 341-343 Published Online September 2012 ( 1
Acute Normalization of Thyroxine Induced Hallucinations
and Delusions
Yuko Furuhashi1, Masaya Ishikawa2
1Medical Center, Shizuoka University, Shizuoka, Japan; 2Saginuma Park Clinic, Kawasaki, Japan.
Received June 15th, 2012; revised July 16th, 2012; accepted July 25th, 2012
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
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Acute Normalization of Thyroxine Induced Hallucinations and Delusions
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
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
4. Conclusion
General practitioners should bear in mind the possibility
of psychotic symptoms following aggressive treatment of
severe Graves’ disease.
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