WILLIAM H. WILSON, M.D.

JAMES W. JEFFERSON, M.D.

No.5 in a series

Thyroid disease, behavior,

and psychopharmacology
ABSTRACT: The authors review psychiatric complications of thyroid Patients usually complain of some
disease and the use of psychotropic agents in hyper- and combination of weakness, fatigue,
hypothyroid patients. Neuropsychiatric symptoms of heat intolerance, palpitations, tremor,
hyperthyroidism tend to resolve with treatment of excessive thyroid dyspnea, polyphagia, insomnia, in-
production; those of hypothyroidism respond in a variable manner to creased stool frequency, and weight
loss. Physical examination reveals
thyroid replacement, but most patients improve substantially after
warm, moist skin, and a rapid hean
becoming euthyroid. The judicious use of most psychotropics has its rate, sometimes with atrial fibrilla-
place even in the presence of overt thyroid disease. The important tion. Stare and lid lag are common in
antithyroid effects of lithium should be noted when treating patients thyrotoxic patients. Marked exoph-
with thyroid disease. Routine monitoring of thyroid function in thalmos may occur in Graves' dis-
otherwise healthy patients taking antipsychotic agents, tricyclic ease.
antidepressants, or monoamine oxidase inhibitors (MAOls) is not Studies of unselected hypenhyroid
believed necessary. patients have demonstrated that the
hypenhyroid state is usually accom-
panied by significant mental distur-
Diseases affecting the thyroid gland psychiatric aspects of thyroid disease bance, characterized by hyperactivity
are often accompanied by psychiatric and its treatment, and then the interac- and anxiety. > These patients are jit-
symptoms.'" Medical and surgical tion of the thyroid gland and its hor- tery, irritable, and emotionally labile.
treatment of thyroid disease can also mones with psychiatric medications. Although they believe that their ener-
have psychiatric sequelae. Psychiatric gy is increased, their ability to work
medications may, in tum, alter thy- THYROID DISEASE productively is decreased owing to
roid structure and function, while AND BEHAVIOR shortened attention span and other
thyroid metabolism plays a role in the Hyperthyroidism cognitive dysfunctions. These psy-
effects of some psychiatric medica- The hypenhyroid state has numerous chological and behavioral symptoms
tions. This review first addresses the physical and mental concomitants. ',' usually resolve as the hyperthyroid
state is corrected by appropriate ther-
Dr. Wilson is a resident in psychiatry and Dr. Jefferson is professor ofpsychiarry, both at apy.
the University ofWisconsin Medical School, Madison, Wisconsin. Reprint requests to Dr. A number of atypical psychiatric
Wilson, University ofWisconsin Hospitals and Clinics, 600 Highland Ave.• Madison. WI presentations of hyperthyroidism
53792. have been reported.s-o "Apathetic" or

JUNE 1985' VOL 26' NO 6 481

Thyroid disease

"masked" hyperthyroidism occurs gery. The infiltrative ophthalmopathy and 60. Except for those patients who
most often in the elderly. These pa- and dermopathy of Graves' disease have been treated for thyroid disease
tients, rather than being hyperactive, are not affected by this treatment. by surgery or radioiodine, the cause in
present with psychomotor retardation, The principal complication of treat- most cases is unknown. The presence
confusion, and apathy. Such patients ment is hypothyroidism, which may of antithyroid gland antibodies in
may even lapse into coma and die. It be induced by any of the treatment most of these patients suggests that the
thus is important to assess thyroid modalities. Often replacement hor- destruction of the thyroid gland is due
function in elderly patients who pre- mone is given to prevent this compli- to autoimmunity. It has even been pro-
sent with depression, dementia, or de- cation. Since radioiodine ablates the posed'2 that Graves' disease, which
lirium. Hyperthyroidism has also pre- thyroid gland over a period of months has some features of autoimmunity,
sented with overt psychosis, mimick- and years, patients treated with an iso- Hashimoto's disease, and primary hy-
ing schizophrenia, paranoid states, tope remain at risk of developing hy- pothyroidism, represents the spec-
and affective disorders. Occasionally pothyroidism months to years after trum of a single disorder. In addition
hyperthyroidism may result in a non- treatment, and thus need long-term to the iatrogenic causes mentioned
psychotic depression. above, certain drugs may cause hypo-
Although these presentations are thyroidism. Among these are lithium
rare, accurate diagnosis has marked Hypothyroidism usually and carbamazepine.
benefits for the patient, so thyroid In adults, the onset of hypothyroid-
results in progressive
function tests are an essential part of ism is usually insidious. Early symp-
the comprehensive evaluation of pa-
cognitive impairment toms include fatigue, cold intoler-
tients with psychotic and affective dis- accompanied by lethargy ance, constipation, and menorrhagia.
orders. The usual screening studies and depression. As the disease progresses, intellectual
are of serum thyroxine by radioim- and motor activity slow. Appetite les-
munoassay (T.RIA) and triiodothy- sens, although there may be moderate
ronine resin uptake (T,RU), along follow-up. Similarly, patients treated weight gain. Other symptoms include
with the calculated free thyroxine in- with surgical thyroidectomy remain at dry skin, hair loss or dryness, muscle
dex (FfI). High values should be con- risk for developing hypothyroidism aches, and a deepening of the voice.
finned by a T, assay, low values by an over a period of years. The full-blown syndrome of hypothy-
assay of thyroid-stimulating hormone Several reports'O-I2 have discussed roidism includes a dull, expression-
(TSH). Some authorities now suggest psychoses developing during treat- less face, periorbital puffiness, dry
more extensive evaluation to detect ment with antithyroid drugs. In addi- sparse hair, a large tongue, and pale,
more subtle abnormalities. We will tion to hypothyroidism, surgery occa- rough, doughy skin. Untreated, the
return to this unsettled subject when sionally causes psychiatric symptoms patient may lapse into a fatal coma,
discussing subclinical dysfunction. due to hypoparathyroidism resulting especially if stressed with concurrent
The definitive treatment of hyper- from damage to the parathyroid illnesses such as infection.
thyroidism is directed at blocking the glands or hypoxia secondary to laryn- Hypothyroidism usually results in
synthesis of excessive thyroid hor- geal nerve damage (see the section on progressive cognitive impairment ac-
mone. The neuropsychiatric symp- thyroid neoplasia). companied by lethargy and depres-
toms tend to resolve with treatment of sion, although a wide variety of psy-
the thyroid disorder. Beta-blockers, Hypothyroidism chiatric symptoms have been reported
particularly propranolol, are used to Hypothyroidism may derive from fail- in isolated cases.' Practically all pa-
block the sympathomimetic effects of ure of the thyroid gland itself (primary tients with the physical symptoms of
excess thyroid hormone pending the hypothyroidism) or from pituitary or hypothyroidism have at least mild
outcome of definitive treatment. The hypothalamic disease (secondary hy- cognitive impairment, manifested as
production of thyroid hormones is pothyroidism). Primary hypothyroid- forgetfulness, carelessness in every-
controlled either by use of antithyroid ism is much more common than the day activities, and difficulty concen-
drugs (propylthiouracil, methima- secondary form. Primary hypothy- trating. Patients initially find their
zole, carbimazole) to block hormone roidism is several times more com- cognitive dysfunction quite frustrat-
synthesis or by ablation of the thyroid mon in women than in men and most ing but may become indifferent to it as
gland with radioactive iodine or sur- often occurs between the ages of 40 it increases in severity. The spectrum

482 PSYCHOSOMATICS
 -

of cognitive dysfunction runs from that chronic deficiency of thyroid hor- or an abnormal TRH stimulation test
minimal to profound. Although de- mone leaves a residual CNS deficit. suggestive of hypothyroidism is found
mentia may develop acutely, the usual Some patients who do not improve in a patient who appears to be euthy-
course is for mild cognitive deficits to with replacement therapy may be roid by physical examination and has
progress insidiously in a manner clini- showing the symptoms of a relatively normal levels of circulating thyroid
cally indistinguishable from Alz- independent psychiatric disorder. In hormones. A common occurrence,
heimer's disease. Thus, it is important many patients, however, improve- with an overall prevalence of 2% to
that physicians keep their indices of ment in all aspects of hypothyroidism, 5%, it is particularly frequent in wom-
suspicion high in demented patients. including psychiatric symptoms, con- en over the age of 60. At times, sub-
Hypothyroidism is relatively common tinues for many months after they clinical hypothyroidism represents the
and usually reversible, especially if have regained the euthyroid state ac- earliest stage of thyroid failure. For
treatment is begun early in its course. ,. cording to laboratory examinations. example, a significant proportion of
The affective sphere is also signifi- Little has been written about treating clinically euthyroid patients who have
cantly altered by hypothyroidism. hypothyroid patients whose psychiat- elevated TSH levels and positive anti-
Depression is mentioned in almost all thyroid antibody titers subsequently
clinical reports""'" and is often promi- develop overt hypothyroidism. 23 The
nent on psychological testing. In cases Some hypothyroid patients role of subclinical hypothyroidism in
presenting with psychiatric symp- psychiatric disorders is the subject of
who do not improve with
toms, the initial clinical diagnosis is current research and speculation.
frequently severe or psychotic depres-
replacement therapy may Some investigators believe that sub-
sion. Affective disturbance may take be showing the symptoms of clinical hypothyroidism can present
other forms, such as irritability and la- a relatively independent clinically as depression, and that such
bility of affect. Occasional patients psychiatric disorder. depression responds to exogenous
have been hyperactive or hypomanic thyroid hormone, or to a combination
rather than apathetic and withdrawn. of thyroid hormone and antidepres-
Psychosis may accompany hypo- ric symptoms prove refractory to re- sant medication. At this time the data
thyroidism, and is, at times, the pre- placement therapy, but reports 21 •22 of are insufficient to state definitively
senting symptom. 11 The psychosis successful outcomes in several cases how vigorously subclinical hypothy-
usually occurs in the context of severe indicate that psychiatric treatment roidism should be sought in depressed
hypothyroidism of several months' to (antipsychotics, antidepressants, patients, and how it should be man-
several years' duration, associated ECT) directed at the remaining symp- aged clinically. A full exploration of
with marked cognitive impairment toms may be helpful once the patient is this topic is beyond the scope of this
and/or depression. Visual and audi- maintained in a euthyroid state. article, but the subject has been well
tory hallucinations, persecutory delu- A few reports"'" describe acute de- reviewed in the recent literature.',2A-26
sions, and other paranoid ideation are terioration, in cognitive and affective Overt or subclinical hypothyroid-
the most common psychotic symp- function, sometimes of psychotic pro- ism may be involved in the pathogene-
toms. The relationship of psychotic portions, occurring during replace- sis of rapid cycling bipolar disorders.
symptoms to laboratory values has ment hormone therapy. This deterior- While such studies are intriguing,
been the subject of research, but is not ation may occur in response to the they remain in the realm of research,
yet clearly delineated.'· abruptly changing levels of thyroid and the clinical implications have not
The response of neuropsychiatric hormone. Although some authors rec- been confirmed. 27
symptoms to thyroid replacement is ommend continuing full replacement
variable. 7 ,.",,20 Most patients show therapy in the face of heightened dis- Thyroid neoplasia
substantial improvement after regain- turbance, it is likely that more gradual Neoplasia forms the third major cate-
ing a euthyroid state. Improvement is replacement schedules decrease the gory of thyroid disease. 2.3,28 The large
greatest among patients whose mental severity of these episodes and lead to a majority of thyroid nodules are be-
changes were mild and of recent on- smoother course of recovery . nign, or so indolent that they never
set. Persons with psychosis or long- The term "subclinical hypothy- come to medical attention. Nodules
standing hypothyroidism are less like- roidism" has been used to refer to that concentrate radioiodine more
ly to show improvement, suggesting cases in which an elevated TSH level than surrounding tissue ("hot no-
(continued)

JUNE 1985· VOL 26· NO 6 483

 Thyroid disease

dules"). multinodular lesions. cystic order can be anxiety and cognitive ed TSH and normal or near normal T,
nodules. and nodules in the elderly are dysfunction secondary to air hunger and T. values had spontaneous nor-
usually benign. Nodules in children and hypoxia. Treatment consists of malization of TSH levels despite con-
and young men. nodules that do not surgical restoration of the airway. tinuation of lithium treatment.)) Pre-
take up radioiodine (••cold nodules"). existing thyroid pathology may pre-
fast-growing nodules. and nodules in THYROID HORMONES AND dispose patients to develop hypo-
persons exposed to head and neck irra- PSYCHOTROPIC DRUGS thyroidism, but clearly is not a pre-
diation have a greater likelihood of Lithium requisite.
malignancy. Diagnosis is confirmed Lithium has important effects on thy- Hypothyroidism has been report-
by biopsy. Prognosis depends on the roid function. JO.)2 It is concentrated in ed JO•34 to occur in 5% to 30% of patients
histologic type. The most common the thyroid gland. reaching a level 1.5 taking lithium (compared with 0.5%
fonn. papillary carcinoma. carries an to 5 times that in the serum. Systema- to 1.3% of the general population),
excellent prognosis. while follicular tic biopsy studies similar to those done nine times more frequently in women
carcinoma has a slightly less favorable with the kidney have not been done than men, and usually after at least 18
one. Both forms are well-differentiat- months of lithium treatment. Infants
ed and slow-growing. have developed goiter when exposed
Much less common are anaplastic The role of subclinical to lithium prenatally. A retrospective
tumors that. in contrast. are rapidly in- review" of 876 lithium patients found
hypothyroidism in
vasive and carry a grim prognosis. a 6.1 % incidence of euthyroid goiter
Other fonns of thyroid cancer include
psychiatric disorders is the and a 3.7% incidence of goiter with
medullary carcinoma. lymphoma. subject of current research hypothyroidism. Another retrospec-
squamous cell carcinoma. and metas- and speculation. tive study,)2 which did not distinguish
tases from other sites. Thyroid neo- euthyroid and hypothyroid goiter, re-
plasms may spread beyond the gland ported goiter in 5% of 800 patients
by local invasion and metastatic pro- with the thyroid. Such information taking lithium. Most of these patients
cesses. The psychiatrist needs to be would help resolve the question of developed goiter after years of treat-
aware ofthe possibility ofCNS metas- whether the occasional case of lith- ment, although some developed goiter
tases and their neuropsychiatric con- ium-associated hypothyroidism that after only a few weeks of lithium ther-
sequences in patients with thyroid does not remit with drug discontinua- apy.
neoplasia. tion is drug-induced or coincidental. In a recent prospective study,"
Treatment consist of thyroidec- Lithium blocks a number of steps in thyroid function tests of 51 patients
tomy. suppression of TSH secretion the synthesis and release ofT•. It may were evaluated before starting lith-
with exogenous thyroid hormone. or also inhibit the action ofTSH. Elevat- ium, at four months, and atone year of
ablation of lesions with iodine 131. ed antithyroid antibody titers have therapy. After four months of treat-
These treatments have several possi- been associated with lithium-induced ment, T, and T. had uniformly de-
ble psychiatric sequelae. Patients may hypothyroidism in 10% to 60% of pa- creased and TSH had increased. All of
become clinically hypothyroid if they tients. these parameters, however, remained
receive insufficient replacement hor- Abnonnal thyroid function tests oc- within the normal range, except in one
mone. Excessive replacement results cur in most patients at some time dur- patient who became hypothyroid and
in hyperthyroidism. ing the course of lithium therapy. Re- received replacement treatment. After
Thyroidectomy can damage the su- duced T, and T•• elevated TSH, and 12 months. T, and T. had returned to
perior and recurrent laryngeal nerves exaggerated TSH responses to thyro- pretreatment levels, although TSH re-
to varying degrees. Surgical trauma to tropin-releasing honnone (TRH) are mained higher than before lithium
the recurrent laryngeal nerves can re- frequently found in clinically euthy- therapy. No other patients developed
sult in the "bilateral abductor vocal roid patients. The more sensitive the hypothyroidism.
cord paralysis syndrome." character- test. the greater the incidence of ab- Subclinical hypothyroidism in-
ized by nonnal phonation with inspi- normalities and also the less likeli- duced by lithium has been associated27
ratory stridor that may progress to hood that these abnonnalities will be with rapid cycling in bipolar patients,
complete respiratory obstruction. 2" clinically important. For example, a especially with the concurrent use of
The presenting symptoms of this dis" number of patients with mildly elevat- tricyclic antidepressants. Unfor-

JUNE 1985· VOL 26· NO 6 487

Thyroid disease

tunately, the response of these pa- vated by lithium administration, re- nonresponders. This study suggests
tients to supplemental thyroid hor- quiring increased dosage of re- that the mechanisms responsible for
mone has been inconsistent. placement thyroid hormone to main- carbamazepine decreasing thyroid
Although irreversible hypothyroid- tain a euthyroid state. The action of hormone levels without inducing
ism following prolonged lithium ther- lithium is additive with other drugs compensatory increases in TSH may
apy has been reported,,,,J· lithium-in- that block thyroid function, such that be related to its therapeutic efficacy
duced hypothyroidism and goiter are patients treated with thioamide anti- and that exploration of the mechanism
almost always fully reversed follow- thyroid drugs show additional de- of this effect could be a fruitful area
ing discontinuation of lithium. Sup- creases in thyroid function if lithium is for research. Although carbamaze-
plemental thyroid hormone can be added to the therapeutic regimen. pine has not been reported to cause
given to produce a euthyroid state if The antithyroid effects of lithium clinical hypothyroidism, the in-
discontinuation of lithium is not feasi- have been used therapeutically in creased use of this drug and our grow-
ble. combination with other antithyroid ing appreciation of the effects of
Hyperthyroidism has been report- drugs. 40 •• 2 Lithium has been used in "subclinical" hypothyroidism neces-
ed" in a small number of patients treat- sitate continuing assessment of the in-
ed with lithium and may simply be co- teraction of the thyroid gland, its hor-
incidental. Some of the patients clear- Monitoring of thyroid mones, and carbamazepine.
ly had preexisting Graves' disease. In function is an important Carbamazepine has been used with-
such patients lithium withdrawal or aspect of lithium therapy. out adverse effects in patients taking
dosage reduction may precipitate hy- replacement thyroid hormone, and
perthyroidism, probably because the without necessitating change in the
condition has been controlled until conjunction with radioiodine to treat dosage of thyroid hormone." After the
that time by lithium's antithyroid ef- hyperthyroidism and thyroid cancer. start of carbamazepine therapy the se-
fects. These applications remain largely ex- rum T. and T, concentrations of these
Monitoring of thyroid function is an perimental, as neither efficacy nor patients declined within the normal
important aspect of lithium therapy. safety has been well established. range, TSH concentration remained
While there is some disagreement as unchanged, and the patients remained
to indications for, frequency of, and Carbamazepine clinically euthyroid. Thus, as with pa-
types of testing, assessment of func- Carbamazepine has been shown' J'" re- tients not taking thyroid replacement,
tion prior to starting lithium is consi- peatedly to decrease total serum T. mildly decreased values of T J and T.
dered a necessity. Determination of and T,. The effect is dose-related, are to be expected and in the presence
the FrJ is often adequate, although with larger doses of carbamazepine of normal FrJ and TSH values do not
TSH measurement, while more ex- resulting in lower serum levels of the indicate hypothyroidism.
pensive, is a more sensitive index of thyroid hormones. These levels usual-
primary hypothyroidism. Once lith- ly remain within the "normal" range, Antipsychotic agents
ium therapy has begun, thyroid func- but in some patients drop to "abnor- Scattered reports" in the clinical liter-
tion testing can be done either on mally" low levels. The above studies ature pertain to thyroid test abnormali-
schedule (eg, every six or 12 months) have shown that despite this decrease ties associated with antipsychotic
or as needed, based on the clinical in total serum hormone levels, the FrJ drug use, but their clinical signifi-
state of the patient. Our practice is to is only mildly decreased, while serum cance is unclear. Several clinical stud-
evaluate thyroid function whenever TSH and the TRH stimulation test re- ies have shown no effect of neurolep-
our clinical suspicion is aroused. We sults remain normal during carbama- tics on thyroid function tests. Assess-
do not believe that the TRH infusion zepine therapy. None of the patients in ment of a number of endocrine func-
test currently has a role in the routine these studies developed clinical signs tions in 62 chronic schizophrenic men
clinical testing of thyroid function in of hypothyroidism. treated for a month with 6 mg/d I.M.
lithium patients. A recent study'" of 50 affectively ill of haloperidol found no change in
The antithyroid effects of lithium patients treated with carbamazepine plasma T. before or after TSH stimula-
are important to note when treating pa- found that the decreases in serum T. tion compared with pretreatment lev-
tients with preexisting thyroid dis- and free T. were significantly greater els.·9 Similarly, no abnormalities were
ease. Hypothyroidism can be aggra- in carbamazepine responders than found in thyroid function tests, in-

488 PSYCHOSOMATICS
cluding TSH, in 22 chronic schizo- severe dystonic reactions after receiv- presence of hyperthyroidism. The
phrenic patients receiving long-term ing haloperidol or fluphenazine. In principal treatment of the psychosis of
treatment with various antipsychotic one of these, laryngeal-pharyngeal hyperthyroidism is restoration of the
drugs." These studies leave some dystonia resulted in death due to respi- euthyroid state.
doubt about the effects of antipsychot- ratory compromise. Although similar The possible induction of thyroid
ics on thyroid function, since the sam- dystonic reactions occur with these storm by a neuroleptic in a hyperthy-
ple sizes were rather small, the drug agents in euthyroid patients, this ef- roid patient has been the subject of a
doses were lower than those that many fect seems to be potentiated by hyper- case report. ss Thyroid storm is an
patients typically receive. and the thyroidism, as demonstrated by the acute exaggeration of hyperthyroid-
most sensitive tests of thyroid func- case" of a man who tolerated haloperi- ism manifested by marked tachycar-
tion were not employed. However, dol well while euthyroid, but had dia, hyperthermia, and dysfunction of
the data strongly support the clinical marked dystonia during two hyperthy- the gastrointestinal and central ner-
impression that in the absence of thy- roid episodes. This probable in- vous systems. It occurs in patients
roid disease antipsychotics do not in- creased risk of severe dystonia should who are hyperthyroid, but beyond that
duce thyroid dysfunction. In our opin- there is a low correlation between the
ion, therefore, routine monitoring of clinical picture and the plasma levels
thyroid function in otherwise healthy In our opinion, routine of thyroid hormones. It is relatively
patients taking antipsychotic drugs is monitoring of thyroid uncommon in children. The c~urse in
not necessary. the 13-year-old girl in the case report
The action of antipsychotic agents
function in otherwise suggests that the thyroid storm was
is, in ways not well characterized, de- healthy patients taking due to haloperidol and supports the
pendent on the level of thyroid hor- antipsychotic drugs is not authors' speculation that the thyroid
mones, as demonstrated both experi- necessary. storm was not due to increased thyroid
mentally and in the clinical setting of hormone secretion, but rather to sensi-
hyperthyroidism and hypothyroid- tization to its effects. Of course, the
ism. An intriguing but preliminary be taken into account in the treatment thyroid storm could have been coinci-
double-blind, placebo-controlled of psychosis accompanying hyperthy- dental, or the patient's reaction to
clinical trial" showed an enhancement roidism, although the degree of cau- haloperidol could have been idiosyn-
of the antipsychotic effects of chlor- tion necessary is unclear since the fre- cratic. Physicians should be aware of
promazine by T). In this study 20 quency and severity of the risk is poor- this possible interaction, and also that
adult, euthyroid, acutely psychotic ly defined. Since this reaction has not there are insufficient data on which to
schizophrenic patients were treated been reported in association with oth- generalize.
with either chlorpromazine or chlor- er antipsychotics, there may be less Treating symptoms of hypothyroid-
promazine and 25 mcg/d ofT). Pa- risk involved with their use in this set- ism with antipsychotics may be prob-
tients receiving T) required less chlor- ting. However, there are no firm data lematic, since adverse reactions have
promazine to control their symptoms to support this supposition. been reported, although there are little
than did those receiving only chlor- A possible problem that could be firm data on which to rely. At times,
promazine (mean dose, 1190 mg/d vs encountered with neuroleptics in hy- hypothyroid patients show agitation
1650 mg/d). The experimental group perthyroid patients is the intensifica- that warrants pharmacologic treat-
also had quicker onset of the therapeu- tion of tachycardia, and/or potentia- ment. Some authors'" believe that hy-
tic effects of chlorpromazine and tion of cardiac arrhythmias, probably pothyroid patients are more suscepti-
greater clinical improvement. Since due to the anticholinergic effects of ble to the sedative effects of all drugs.
only this preliminary investigation has these drugs. However, with careful It is possible that chlorpromazine was
been carried out, no firm clinical im- monitoring and cardiovascular eval- responsible for inducing hypothermic
plications can be derived. uation, neuroleptics have been suc- coma in a myxedematous patient. 54
Several clinically important prob- cessfully used in controlling symp- Although not well documented, such
lems have arisen with the use of anti- toms of hyperthyroidism such as agi- concerns suggest that if antipsychotics
psychotics in hyperthyroid patients. tation." Another approach would be are used in patients with hypothyroid-
At least five case reports" pertain to to manage agitation with benzodiaze- ism, low doses should be initially em-
hyperthyroid patients who developed pines, which appear safe to use in the ployed, the effects should be carefully

JUNE 1985· VOL 26 • NO 6 489

Thyroid disease

monitored, and less sedating drugs effect is uncertain. The T, dose used ments. Recent reviews 7l · n of MAOI
may be better tolerated. results in only small shifts of the thy- pharmacology make no mention of
roid state within what is usually consi- changes in thyroid function test values
Tricyclic antidepressants dered the euthyroid range. One hy- in association with MAOI therapy,
We are not aware of clinically signifi- pothesis·' is that the effect derives nor do other reviews'"·" of pharmaco-
cant morphologic or functional from interaction of T, and the TCA at logic agents affecting thyroid func-
changes induced by tricyclic antide- central, noradrenergic receptors. Pa- tion. One might conclude that if there
pressants (TCAs) in the thyroid sys- tients who respond to TCAs only after are effects, they are not marked. Rou-
tem of animals or humans, so from the addition of thyroid hormone may tine monitoring of thyroid function
this standpoint the routine monitoring represent a subgroup of depressed pa- during MAOI therapy, therefore, does
of thyroid function in patients taking tients who have subclinical hypothy- not appear to be necessary.
these agents is not necessary. The ob- roidism, evident only by increased It is interesting to speculate that the
servation that 12 of 19 lithium patients TSH response to TRH stimulation." therapeutic effect of MAOIs might be
with underactive thyroid function While some optimal level of thyroid potentiated by exogenous thyroid hor-
were also receiving TCAs led to the mone, in a way similar to that occur-
speculation that these drugs may have ring with TCAs. However, we are not
additive antithyroid effects." This It seems prudent not to use aware of any relevant studies.
finding has yet to be substantiated. MAOIs in the presence of Very little has been written con-
TCAs do not appear to interact signifi- unarrested hyperthyroidism cerning the use of MAOls in the pres-
cantly with the drugs used to treat or hypothyroidism. ence of thyroid disease in humans.
thyroid diseases.." However, the tox- The literature makes no mention of in-
icity of TCAs is increased in the pres- teractions between MAOls and anti-
ence of hyperthyroidism. ,. TCAs may activity seems necessary for TCA re- thyroid drugs. The Physicians' Desk
exacerbate tachycardia and cardiac ar- sponse, exceeding that level does not Reference" cautions about use of the
rhythmias in hyperthyroid patients.'" seem helpful, as evidenced by re- MAOI tranylcypromine in hyperthy-
Treating the thyroid abnormality will ports·' that the depression of some roid patients because of their in-
often effectively treat the affective frankly hyperthyroid patients has not creased sensitivity to pressor amines.
symptoms without requiring the use of responded well to TCAs. Increased thyroid hormone concentra-
antidepressant medication. Therapy with TCAs has induced tions result in increased myocardial
In some patients, the addition of rapid cycling in some bipolar pa- sensitivity to a number of central and
thyroid hormone enhances the antide- tients." A recent study" suggests that peripheral mediators of cardiac activi-
pressant activity of the TCA. Clinical bipolar patients in whom tricyclics in- ty, including catecholamines, hista-
reports6G-03 indicate that this hormone duce rapid cycling are likely to be sub- mine, serotonin, acetylcholine, and
accelerates therapeutic response, clinically hypothyroid, as demonstrat- exogenous pressors.'· Although the
especially in women, and that it may ed by an augmented TSH response to clinical data are insufficient to evalu-
aid in the treatment of drug-resistant TRH, and/or by increased basal TSH ate the level of caution that is warrant-
depression. A well-controlled double- levels. However, supplemental thy- ed, these theoretical concerns give
blind clinical trial·' confirmed this roid hormone has had inconsistent reason to suspect that cardiac arrhyth-
finding in that a significant number therapeutic effects. mias, hypertension, or hypotension
(nine of 12) of severely depressed men could result from MAOI use in pa-
and women who had not responded to Monoamine oxidase inhibitors tients with abormally high levels of
imipramine or amitriptyline showed Remarkably little clinical literature thyroid hormone, and that hyperthy-
prompt, marked, and sustained im- exists concerning monoamine oxidase roid patients taking MAOIs might be
provement with the addition of 25 to inhibitors (MAOIs) and thyroid me- more sensitive to the effects of exoge-
50 mcgld of T,. This phenomenon is tabolism, even though interactions nous pressor agents. The animal liter-
now well enough established that a could theoretically be suspected be- ature cited above adds the additional
TCA trial in a depressed adult cannot cause thyroid hormone and MAOls concern of thermoregulatory dysfunc-
be considered a failure until T, poten- both affect the adrenergic nervous tion. It seems prudent not to use
tiation has been tried. system, and because interactions have MAOls in the presence of unarrested
The mechanism of the potentiation been reported···'o in animal experi- hyperthyroidism or hypothyroidism.

490 PSYCHOSOMATICS
Benzodiazepines treatment for hyperthyroidism; how- Conclusion
In the late 1960s, preliminary investi- ever, some patients remain irritable The interaction of the thyroid gland
gations" suggested that the benzodi- and anxious despite adrenergic (P) and its honnones in health and disease
azepines decreased thyroid gland ac- blockade.· 2 The benzodiazepines, with psychiatric medications is a com-
tivity. In addition, diazepam was used in conjunction with p-blockers, plex matter. Thyroid diseases have
shown'· in vitro to compete with T. for provide additional relief from these protean psychiatric manifestations,
binding sites on thyroxine-binding symptoms. The benzodiazepines do recognition of which can lead to
globulin. However, several carefully not affect antithyroid drug treatment prompt treatment of the underlying
controlled clinical trials"'" found no or in other ways interfere with the pri- disorder. Still, the judicious use of
effect of usual clinical doses of diaze- mary treatment undertaken for this psychotropic medications has its place
pam or chlordiazepoxide on thyroid disorder. even in the setting of frank thyroid dis-
function tests in both normal volun- The benzodiazepines may also be ease. Subclinical thyroid disease has
teers and hyperthyroid patients. We useful for symptomatic treatment of received much attention recently. We
would anticipate no problems with agitation or anxiety in hypothyroid pa- are gradually acquiring an under-
other benzodiazepines and see no tients. Although throughout the litera- standing of this condition, and this is
need for the routine monitoring of ture there are suggestions that hypo- beginning to result in improved diag-
thyroid function in those patients who thyroid patients have an increased nosis and treatment. Many psychiatric
are being treated with this class of sensitivity to the sedative-hypnotic medications have important interac-
drugs. drugs," we have not found studies to tions with the thyroid hormones or
The benzodiazepines are not a pri- support these clinical observations. have the potential for adversely affect-
mary treatment for the symptoms of Nonetheless, it seems prudent to be- ing thyroid function. Comprehension
thyroid disease but can be useful ad- gin treatment with lower-than-usual of these effects aIJows the develop-
juncts. Propranolol and other p- doses and to titrate gradually upward ment of treatment strategies that will
blockers are the primary symptomatic as tolerated. maximally benefit our patients. 0

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