Acta Psychiatr Scand 2001: 104: 7275 Copyright # Munksgaard 2001

Printed in UK. All rights reserved

ACTA PSYCHIATRICA
SCANDINAVICA
ISSN 0001-690X

Case report
Late-onset bipolar disorder due to
hyperthyroidism
Nath J, Sagar R. Late-onset bipolar disorder due to hyperthyroidism.
Acta Psychiatr Scand 2001: 104: 7275. # Munksgaard 2001.
Objective: Bipolar disorder starts typically in early age and late-onset
cases are rare. Late-onset cases are more likely to have comorbid medical
illnesses responsible for them. This case report highlights late-onset
bipolar disorder due to hyperthyroidism.
Method: A 65-year-old patient of bipolar disorder has been described.
Result: Physical examination and laboratory investigations detected
presence of hyperthyroidism and the patient was treated with antithyroid
and anxiolytics.
Conclusion: A thorough examination and investigation are required in
late-onset cases of bipolar disorder to rule out secondary causes.
Definitive antimanic agents or mood stabilizers may not be required in
such cases.
Jisu Nath1, Rajesh Sagar2
1
Department of Psychiatry, Government Medical
College Hospital, Chandigarh, India and 2Department
of Psychiatry, All India Institute of Medical Sciences,
New Delhi 110 029, India
Key words: bipolar disorder; mood disorder; mania;
hyperthyroidism
Dr Rajesh Sagar, Assistant Professor, Department of
Psychiatry, All India Institute of Medical Sciences, New
Delhi 110 02, India
Accepted for publication January 31, 2001

Introduction stressor present. There was no history of head injury,

It is well known that bipolar disorder typically has an
early age of onset and the late onset cases are rare. In a
secondary analysis of the ECA (Epidemiological
Catchment Area) data it was found that the lifetime
prevalence of subsyndromal mania is 6%, compared
to 1% for bipolar I disorder in patients over 65 years
of age. The prevalence of bipolar disorder in admitted
patients over 60 years of age has been found to be
4.7% in one study (2). The definition of late-onset
varies from study to study and in a case report, a first
episode of mania has been reported after the age of 80
with successful treatment with carbamazepine (3).
Diagnosis of mania in the elderly may be difficult
and exclusion of secondary causes are required to
make a diagnosis of primary bipolar disorder.
Elderly patients with mania are more likely to
have CNS pathology or other systemic causes and a
negative family history (4).
Case report
A 65-year-old retired male from North India
presented with a 1-month history of acute onset
irritability, increased energy, talkativeness, grandi-
osity and decreased sleep followed by 11 days
history of sadness of mood, restlessness and
disturbed sleep. The total duration of the illness
was approximately 1.5 months and there was no
fever, convulsion or progressive memory impair-
ment. His history of first-rank symptoms and
substance abuse was also negative. Before present-
ing to us he was treated with very low dosage of
haloperidol, thioridazine and chlordiazepoxide at
different times without significant improvement. A
premorbid history and family history was unre-
markable. On examination at admission, he had lean
and thin habitus, pulse 158/mn, temperature 37uC
and no neurological deficit. Grade I goitre, moist
palm and staring look were present. Mental state
examination revealed restlessness, sudden crying
spells, increased volume of speech, anxious affect,
depressive cognition without suicidal ideation, guilt
and impaired attention and concentration. A
provisional diagnosis of bipolar disorder due to a
general medical condition was made and lorazepam
4 mg started because of anxiety and restlessness. A
complete blood count including ESR and peripheral
smear, blood sugar, renal function test, liver
function test, electrolytes and alkaline phosphatase
were found to be normal. Thyroid profile was done
on the third day of admission and the result was:
FT3-8.5 (normal 4.07.8) pmol/l, FT4-28.0 (normal
13.023.0) pmol/l and TSH-0.17 (normal 0.274.2)
uIU/ml. MMSE (Mini Mental State Examination)
was tried on the same day but the patient was not co-
operative. He scored 7 out of 10 in the orientation

72

Table 1. Mania secondary to thyrotoxicosis
Age and sex of the
Year Author(s) patient
1979 Villani et al. (10) 43 years/female
1983 Corn et al. (11) 46 years/female
1991 Lee et al. (12) 29 years/female
section and failed to copy the intersecting pentagon
correctly. Subsequently he scored 26, 25 and 21 out
of 30 on the fifth, seventh and twelfth days of
admission, respectively, without any apparent
deterioration in cognition clinically. A plain CT
head scan was also performed, with suspected mild
bilateral frontal lobe atrophy. By that time he was
started on 15 mg buspirone and lorazepam was
being slowly tapered. He showed rapid improvement
and was discharged on the 15th day by request of his
family members. After discharge, he underwent a
radioactive iodine uptake test from endocrinology
OPD (out-patient department) which showed
increased uptake, and was put on carbimazole
30 mg/day. In his first follow-up in psychiatry
OPD, 3 weeks after discharge, he was symptoma-
tically fine except for tremor and tachycardia and
had high FT3 and FT4 and his MMSE score was 26/
30. Subsequently lorazepam was stopped as the
patient continued to show improvement, and he was
maintained on only 15 mg of buspirone. At 9
months after discharge, MMSE score improved to
28/30 and the thyroid profile came within normal
limits. The patient was progressing well with
carbimazole 30 mg and buspirone 15 mg.
Discussion
This case highlights the importance of extensive
history and investigations in elderly patients who
present with mania for the first time. A number of
neurological as well as medical causes of secondary
mania have been reported such as stroke, head
injury, infections, metabolic causes and drugs (5).
Frontal lobe dementia may initially present with
such disinhibition syndromes (6), but the possibility
is less likely in this case because of the absence of
evidence of prominent cognitive impairment in both
history and follow-up and good subsequent recov-
ery. An admixture of organic psychiatric features
may be common in these cases (7).
A review of the published English-language
literature revealed few cases where mania was
judged to be due to hyperthyroidism (Table 1). All
the cases reported were females in the young to
middle-aged group. Gravess disease is rare in males.
To the best of our knowledge this is the first
published case report of bipolar disorder in a male
Bipolar disorder due to hyperthyroidism
Diagnosis Treatment given
Secondary mania Propranolol and propylthiouracil
Recurrent mania Haloperidol and tricyclic antidepressants
Mania Propranolol and propylthiouracil
geriatric patient secondary to hyperthroidism. Few
cases reported co-existence of bipolar disorder and
hyperthyroidism due to thyroid adenoma; however,
an aetiological role could not be established because
of past history of psychiatric illness and treatment
with lithium, which itself can induce hyperthyroid-
ism (8, 9). The absence of past or family history of
psychiatric illness, presence of temporal relation
between onset of mania and detection of hyperthy-
roidism, good recovery with antithyroid medication
without using mood stabilizer or antipsychotic
drugs, all make our diagnosis relatively confident.
In conclusion, we emphasize relevant investiga-
tions of elderly bipolar patients. Furthermore, mood
stabilizers may not be required for acute treatment
of late-onset bipolar disorder due to hyperthyroid-
ism.
References
1. JUDD LL, KUNOVAC JL. Bipolar and unipolar depressive
disorders. In: BRUNELLO N et al., eds. Mental disorders in the
elderly new therapeutic approaches. Karger, 1998;110.
2. YASSA R, NAIR V, NATASE C et al. Prevalence of bipolar
disorder in a psychogeriatric population. J Affect Disord
1988;14:197201.
3. KELLNER MB, NEHER F. A first episode of mania after age 80.
Can J Psychiatry 1991;36:607608.
4. YASSA R, NAIR NP, ISKANDAR H. Late-onset bipolar disorder.
Psychiatr Clin North Am 1988;11:117131.
5. KRAUTHAMMER C, KLERMAN GL. Secondary mania manic
syndromes associated with antecedent physical illness or
drugs. Arch Gen Psychiatry 1978;35:13331339.
6. SHULMAN KI. Dis-inhibition syndromes, secondary mania
and bipolar disorder in old age. J Affect Disord
1997;46:175182.
7. LISHMAN WA. Organic psychiatry the psychological
consequences of cerebral disorder, 3rd edn. Blackwell
Science, 1998;509.
8. PARKER PE, WALTER RYAN WG, PITTMAN CS et al. Lithium
treatment of hyperthyroidism and mania. J Clin Psychiatry
1986;47:264266.
9. WALTER-RYAN WG, FAHS JJ. The problem with parsimony:
mania and hyperthyroidism. J Clin Psychiatry
1987;48:289290.
10. VILLANI S, WEITEL WD. Secondary mania. Arch Gen
Psychiatry 1979;36:1031.
11. CORN TH, CHECKLEY SA. A case of recurrent mania with
recurrent hyperthyroidism. Br J Psychiatry 1983;143:7476.
12. LEE S, CHOW CC, WING YK et al. Mania secondary to
thyrotoxicosis. Br J Psychiatry 1991;159:712713.
73
Nath and Sagar
Invited comment
In this issue of Acta Psychiatrica Scandinavica, Nath
and Sagar (1) report a case of a manic syndrome
appearing for the first time in a person over 65 years
of age and describe how proper diagnosis of
thyrotoxicosis and treatment tailored to the primary
thyroid disorder allowed for resolution of the mood
disorder without the use of mood stabilizers or
antidepressants. This case illustrates both the clarity
with which hyperthyroid disease can mimic the
manic state seen in classic bipolar disorder and the
necessity of a thorough physical examination,
history and laboratory work-up in order to identify
possible underlying medical causes of patients who
present with manic syndromes.
Primary thyroid disorder has long been recog-
nized as presenting with psychological disturbances
and these disturbances are, in the case of hyperthy-
roid disorder, ubiquitous, if not universal (2).
Restlessness, hyperactivity, distractibility and irrit-
ability are common manifestations of hyperthyroid-
ism, and other key elements of mania, such as
grandiosity, insomnia and pressured speech may
also present simultaneously, secondary to the hyper-
aroused state that seems to be induced by elevated
levels of thyroxine. Certain individuals may also
develop paranoid states and acute psychosis during
thyrotoxic states (3), and confusional states also
abound. For this reason, thyroid disorder should
automatically be part of the differential diagnosis in
any person presenting with a new onset of mania,
regardless of their age. A careful physical examina-
tion and history will often pick up key signs (such as
cardiac arrythmias, exopthalmos and enlarged
thyroid gland) or symptoms (intolerance to heat)
(4), but assessment of TSH, T4 and T3 levels are
critical, even in the absence of other features of
thyroid disease. Although it is recognized that
primary bipolar disorder and thyroid disease may
present at any time in life (5), a late first onset of
manic disorder after age 50, as seen in the case
described by Nath and Sagar (1), is atypical and is
much more likely to be secondary to a primary
medical disturbance (6).
The interplay between thyroid function and
mood function is not unidirectional, and some
have theorized that thyroid function may change
(perhaps at the subclinical level) as an adaptive
response to the physiological effects of primary
mood disorders (7). In primary depression,
thyroxine levels have been shown to increase in
some individuals during a depressive state, and
approximately one-third of depressed patients
show decreased response to TRH (thyroid releas-
ing hormone) (7). Furthermore, thyroid hormone
supplementation is an efficacious treatment for
74
many euthyroid patients who suffer from depres-
sion, often in the context of bipolar disorder (8) .
Lithium, one of the main treatments for bipolar
disorder, is widely known to have both acute and
chronic effects on the thyroid gland, and mon-
itoring of thyroid functions in people receiving
lithium is now standard practice (9), but
hypothyoidism is also present in up to 9% of
bipolar patients who have not been treated with
lithium or carbamazepine (10). Recent findings
correlating the intensity of manic symptoms with
levels of free thyroxine in clinically euthymic
bipolar patients treated with lithium suggest that
the efficacy of lithium in treatment of acute mania
may be due in part to a direct action on
decreasing thyroid levels (11). At the genetic
level, lithium has been shown to regulate the
expression of the thyroid hormone receptor gene
in specific regions of the brain (12). Current
efforts to identify the genes which underly the
biology of bipolar disorder (13) are aimed at
eventually understanding the primary cause of
manias, which will ultimately illuminate the exact
role of thyroid regulation in primary bipolar
disorders.
In a case as clearcut as that of Nath and Sagar
(1), it is straightforward to diagnose the manic
syndrome as a Mood Disorder Secondary to
Hyperthyroid Disease. Under certain diagnostic
systems, such as the DSM-IV (14), bipolar
disorder cannot be diagnosed if the manic
symptoms are due to the direct physiological
effects of a ... general medical condition (e.g.
hyperthyroidism). With current advances in
understanding the genetic mechanisms underlying
the cause of bipolar disorder already well under
way, it may be only a matter of time before many
of the patients who we currently diagnose as
having bipolar disorder will actually have more
specific designations that describe in detail their
underlying pathology.
Michael Escamilla MD
Department of Psychiatry (7792)
University of Texas Health Science Center
7703 Floyd Curl Drive
San Antonio, TX 782293900
USA
References
1. NATH J, SAGAR R. Late-onset bipolar disorder due to
hyperthyroidism. Acta Psychiatr Scand 2001;104:7275.
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Publications, 1987;428436.

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BMJ 1960;1:7890.
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6. STONE K. Mania in the elderly. Br J Psychiatry 1989;155:
220224.
7. WHYBROW PC, AKISKAL H, MCKINNEY WT. Mood disorders.
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8. SACHS GS, PRINTZ DJ, KAHN DA, CARPENTER D, DOCHERTY JP.
The expert consensus guideline series: medication treatment
of bipolar disorder [review]. Postgrad Med 2000;1:104.
9. EAGLES JM, MCCANN I, MACLEOD TN, PATERSON N. Lithium
monitoring before and after the distribution of clinical
practice guidelines. Acta Psychiatr Scand 2000;101:349353.
Bipolar disorder due to hyperthyroidism
10. VALLE J, AYUSO-GUTIERREZ JL, ABRIL A, AYUSO-MATEOS JL.
Evaluation of thyroid function in lithium-naive bipolar
patients. Eur Psychiatry 1999;14:341345.
11. LEE S, CHOW CC, WING YK et al. Thyroid function and psy-
chiatric morbidity in patients with manic disorder receiving
lithium therapy. J Clin Psychopharmacol 2000;20::204209.
12. HAHN CG, PAWLYK AC, WHYBROW PC, GYULAI L, TEJANI-BUTT
SM. Lithium administration affects gene expression of thy-
roid hormone receptors in rat brain. Life Sci 1999;64:1793
1802.
13. ESCAMILLA MA, FREIMER NB, REUS VI. The genetics of bipolar
disorder and schizophrenia. In: The molecular and genetic
basis of neurological disease, 2nd edn. Boston: Butterworth-
Heinemann, 1997;13431362.
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manual of mental disorders, 4th edn. Washington: American
Psychiatric Association, 1994;332.
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