RICHARD C. W. HALL, M.D.

Psychiatric effects of thyroid hormone disturbance

Psychosomatic illness review: No. 5 in a series
ABSTRACT:

ma seems to be decreasing, perhaps because of better and more avail associated with psychiatric signs and symptoms.. The author able medical care, which interrupts reviews the literature on psychiatric findings in hypothyroidism the disease at an earlier stage. Early and hyperthyroidism and provides recommendations for reviews of the literature suggested diagnostic and treatment procedures. that psychosis did indeed occur in the 50% range reported by the Clinical Society.6'8 More recent Disturbances of endocrine function frequently associated with this con studies, however, suggest that the dition. Ten years later, the Clinical are among the most common phys current incidence of psychosis in Society of London6 published a de ical causes for the production of tailed report that defined the myxedematous patients is between what appears to be primary psychi symptoms of 109 patients with 5% and 15%. As described in the atric disease.'3 This paper reviews myxedema. The majority of their literature (there are several psychiatric, physical, and laborato findings remain valid. The Society hundred case reports on the psy ry findings associated with hypo concluded that delusions hal and chiatric course and symptoms),9-2' thyroidism and hyperthyroidism, lucinations occurred in nearly half the characteristic course of slowly and presents recommendations for of the cases, nd that insanity a progressive myxedema seems to be diagnosis and treatment. was seen in an equal number of one of progressive mental slowing, HYPOTHYROIDISM patients. The report defined the with a decline in memory function, History and symptoms characteristic insanity of myx speech, and learning ability. Per edema as acutechronic mania or In 1874, Gull4 reported on a cre ceptual changes progress, with dis tinoid state occurring in an adult or dementia melancholia with a tortion of hearing, taste, vision, and smell. Delusions and frank halluci female had psychiatric symp who marked preponderance of suspi cion and self-accusation. nations or psychosis occur as the toms. Four years later, Ord5coined the term myxedema com and The frequency of an initial psy disease becomes more advanced. chiatric presentation for myxede mented that mental changes were The typical manifestations of myxedema madness were de scribed in 1949 by Ascher,2 ho w Dr. Hall is chief of staff of the VA Medical Center, Memphis, associate dean for emphasized the prominence of veterans affairs, and proftssor ofpsychiatry and of internal medicine at the University psychiatric symptoms in his classic of Tennessee College of Medicine. Reprint requests to him at VA Medical Center, 1030 Jefferson A ye., Memphis, TN 38104. review of 14 cases in which the
Neuroendocrine disorders often present and/or are JANUARY 1983 . VOL 24@ NO 1 7

Thyroid hormone

disturbance

diagnosis of myxedema had not been previously established. All of these patients presented with psy chotic changes, and ten had been admitted to a mental ward for ob servation under the Lunacy Act. In nine of the 14, there a dra was matic and complete recovery of sanity with thyroid treatment. Two patients partially improved when treated, one remained un changed, and two died. In discussing the cases, Ascher called attention to the very impor tant fact that myxedema causes psychosis: If one observer can encounter this number in four years, it must mean that there are many others. Possibly thereare manycasesin mentalhospi talswhichhavenotbeendiagnosed.If the diagnosisis bornein mindby psy chiatrists a number of otherwise hopelesspsychosesmay be cured, and the awareness of an organic causefor one psychosismay lead to the discoveryof physical causes for otherswhichare at presentdismissed as of psychologicalor idiopathic ori gin. Ascher suggested that the pa tient's history was of little help in initially establishing the diagnosis, although it was of great utility in
confirming the diagnosis once it

cold intolerance. He noted that changes in facial appearance, alter ations of voice, and snoring were often complained of by the pa tient's relatives. Most of his cases were women. Although no charac teristic psychosis occurred, in all cases he noted that the most fre quent presentation was depression or an agitated paranoid state. Other

introversion and failing memory are conspicuous.Ruhberg22 be lieved that every of uncom case plicated myxedema presents with a mental state, the essential features of which are fatigability and psy chomotor retardation. Etiology of mental symptoms A variety of theories have been developed to explain the occur rence of mental changes in hypo thyroid patients. Early theories25 suggested that myxedematous psy chosis was a direct result of cerebral hypometabolism or of the produc tion of central nervous system toxins. Other theories26-'@7 surmised that the psychosis was due to cere bral edema, enzymatic changes in the brain, or diminished cerebral blood flow. Easson28 proposed that mental symptoms were related to a change in internal stimuli rapid and external perception which may not allow the physiological and

presentationsfor the conditionde

scribed in the literature are: chronic insidious personality change with lability of mood, anxiety, and emo tional withdrawal; gradually pro gressive depressive disorder simu lating psychogenic depression; a paranoid schizophrenia-like syn drome; rapidly developing psy

Psychiatric symptoms may be the earliest or most prominent signsor symptomsreportedby the hypothyroidpatient.
chotic depression; and a mania-like presentation with paranoid idea tion and agitation.8-'1-14.21.24 The most characteristic picture of rapidly developing myxedema is one of generalized agitation, with progressive disorientation, perse cutory delusions, hallucinations,

emotional readjustment necessary

to maintain an integrated concept of body stability. This theory had the added advantage of explaining the fact that some patients became worse when treatment was initiat ed: Further internal adjustment, albeit towards normality, often caused a worsening of the myxede matous patient's emotional state. Other authors29have noted that the severity of mental symptoms is greater in elderly patients and in persons with rapidly changing levels of thyroid hormone. The cerebral effects of the hy pothyroid state were well depicted by Scheinberg and associates26 in their study of eight myxedematous patients with sensory impairment. He documented a 38% decrease in cerebral blood flow, a 27% decrease in cerebral oxygen and glucose consumption, and a 91%increase in
PSYCHOSOMATICS

had been suspected. That was be cause symptoms are admitted rather than complained of. - .. The mental slowness of the illness itself smothers self-criticism. In fact, you get no history of myxedema if you are not thinking of myxedema when you take that history. Ascher defined the following symptoms as most common in his patients: general tiredness, weight gain, vague aching pains in the legs, memory impairment, constipation, deafness, loss of hair, dry skin, and
8

and intermittent bouts of lethargy

and extreme restlessness. Patients are often extremely irritable, delu sional, paranoid, and complain of auditory and/or visual hallucina tions. Hypersexuality during these states has also been reported)9 Stoll2' describes the classic person ality changes as follows: One is impressed by the marked personal ity changes present in advanced cases: irritability, untruthfulness, suspicion, delusions, retarded cere bration, inability to concentrate,

cerebrovascular resistance in these

patients. He suggested that there was a specific correlation between

disturbed metabolism and altered mental state. Ofnote to the practicing clinician are the findings of Blume and Gra bow3nd Crevasse and Logue,3' a who established that unusual neu
rologic symptoms may precede other signs of myxedema. These authors reported on the early oc currence of cerebellar ataxia and peripheral neuropathy as present ing symptoms of hypothyroidism. The EEG effects of myxedema have been studied by a variety of authors, with mixed findings. Browning and associates32 were un able to correlate the EEG pattern and the clinical symptoms of hy pothyroid patients. Libow and

A lack of thyroid hormones can lower the threshold for depression; an ex cess can contribute to a state of tense dysphoria. Thyroid function in some persons also appears to influence the course of affective disorders. Ade quate mobilization of thyroid hor mones favors recovery from depres sion; excess mobilization increases the risk of mania in vulnerable individ uals.37 These authors, in reviewing

have unexplained menstrual dis orders, weight gain, or macrocytic anemia. The condition should also be included in the differential diag nosis of unexplained ascites, re fractory heart failure, and idio pathic hyperlipemia. Various effu
sions, all of which have high pro

tein content, may occur in hypothyroid patients. The hypo thyroid patient's thick tongue may
suggest amyloidosis. Hypothyroid ism should also be considered in

available information, propose that

thyroid hormones modulate the ac tivity of central fl-adrenergic re

Discontinuation of therapy by the patient typically leads to a return of symptoms within a short period of time.
ceptors in their response to the presence of catecholamines. They suggest that thyroid hormone in creases the ability of these central /3-adrenergic receptors to receive stimulation from norepinephrine. Thyroid hormone, by modulating catecholamine neurotransmission in the CNS, would therefore serve as a mechanism for physiologic ad justment and defense during times of adaptive demand. This hypothesis is important, since it ex plains a wide variety of clinical findings and suggests important new areas of research. Differential diagnosis

Durell33demonstrated slowing and

flattening of the EEG in delirious myxedematous patients. Logothe tis34also reported EEG slowing and flattening, and suggested that these changes were associated with hy perthyroid psychosis. He noted the resolution of these abnormalities when the patient was returned to the euthyroid state. Using a care fully controlled research model in hypothyroid patients who had little functional thyroid tissue, Lansing and Trunnell35 deprived patients of thyroid replacement and obtained serial EEGs. These investigators found slowing of dominant alpha rhythms, but were unable to docu ment significant changes in ampli tude. When thyroid replacment was reinstituted, the EEG abnor malities disappeared. New research by Whybrow and

patients who present with what ap pear to be myasthenic or rheumatic syndromes. The clinician should remember that cerebrospinal fluid protein levels are high in myxede matous patients. The major complications of the disease are cardiac in nature, and occasionally a patient may develop refractory hyponatremia resulting
from inappropriate secretion of an

tidiuretic hormone. The clinician should also remember that myx edematous patients are unusually sensitive to opiates and that the administration of average doses of these drugs may prove fatal.38 Treatment Following appropriate diagnosis, thyroid replacement treatment
should be initiated cautiously. If

the myxedema is severe, if myx edematous heart disease exists, or if the patient is elderly, the clinician
should begin treatment with ex treme caution, as rapid physiologic changes in thyroid levels may be associated with worsening of cardi ac symptoms or the development of a mania-like or organic psychosis. If replacement therapy is used,

Prange36-37 focusing on the thyroid

axis and catecholamine interaction suggests that thyroid function plays a role in the expression of certain affective disorders:
JANUARY 1983 - VOL 24- NO 1

As stated earlier, psychiatric symp toms may be the earliest or most prominent signs or symptoms re ported by the hypothyroid patient. The essential diagnostic features are shown in Table 1. Hypothy roidism should be considered in the differential diagnosis of patients who appear neurasthenic and/or

doses in the range of 8 to 15 mg/d for a week, then increased by 15 mg/d up to a total of 100 to 200 mg/d, are usually effective. Levothyroxine sodium given in
9

Thyroid hormone

disturbance

the range of 0.15 to 0.3 mg/d is

probably the medication of choice for the majority of hypothyroid pa tients because of its predictable ac tion. Dosage should be adjusted upward until the T4 rises to high normal levels. When a rapid re sponse is necessary, the clinician may wish to consider liothyronine sodium (T3). Lower doses, begin ning in the 5-@sgrange, should be used because of this agent's rapidi ty of action. The level should be

that represent a mixture of T4 and T3 in 4-to- 1 ratio (liotrix) are thought by some to represent a more completeand balanced product for replacement.38 Course following treatment If treatment is initiated slowly and the patient is followed carefully, most mental and physical symp toms abate over a period of days to months. Some physicians have the mistaken belief that if psychologi cal symptoms have not abated

increased slowly. New medications

Table 1Diagnostic Featuresof Hypothyroidism5

,SymptomsWeaknessHoarsenessFatiguePathological

madeMental sleep)Cold slowingworse

fatigue (ie, by

intoleranceLethargyConstipationHeadacheConfusionJoint
painDepressionNervousnessAgitated gainMenorrhagia paranoiaWeight or amenorrheaDecreased taste and smell Schizophreniform or mania-like psychosesSignsSkindry,

heartThick

paleBradycardiayellowishDelayed cold, puffy, tendonScant return of deep eyebrowsreflexesCoarse, brittle hairi nailsLaboratory brittle tongueThin,
iWater bottle

within five days following treat ment, an underlying thought dis order must be present. In fact, many behavioral and mental symptoms may persist for consid erable periods after resolution of the physical complaints. It is not unusual for patients to report that from two to six months elapsed before they felt that their mental function had fully returned to nor mal. Sleep and consequently human-growth-hormone release during sleep may remain disturbed for several weeks to months follow ing replacement of thyroid hor mone. Patients who have been psychot ic usually experience the disap pearance of delusions and halluci nations within the first week. This is particularly true if antipsychotics are added when thyroid hormone replacement is begun. Gradually, over the next week to ten days, the patient becomes more alert and the physical signs of myxedema begin to resolve.39 Kales and associates4 have shown that improvement in clinical condition tends to parallel restoration ofnormal sleep patterns and, in fact, suggested that the re turn of normal sleep may be an excellent predictor of treatment

outcome.
Discontinuation of therapy by the patient typically leads to a re turn of symptoms within a short period.33 If the patient is taking T4 or a mixed T3 plus T4 preparation, psychotic symptoms usually reap pear over four to seven days. Psy chosis may reappear within 12 to 18 hours when T3 is discontinued. Some patients become worse fol lowing initiation of treatment. Mason4' suggests that small changes in thyroid levels produce dramatic effects' on brain function. If mental symptoms are worsened

findings T4less than 3.5 @g/100mL Radioiodine uptake below 10% in 24 hours T3uptake usually low Plasmacholesterol elevated in primary hypothyroidism Macrocytic anemia possibly present 17-ketosteroids may be low Thyroid-stimulating hormone (TSH) radioassay elevated in primary hypothyroidism
Adapled with permission from Current Medical Diagnosis and Treatment, 1978, pp 67O@672 (Kolb

FO@).
I;

10

PSYCHOSOMATICS

by treatment, the reinstitution of therapy at lower dosages is recom

mended. Phenothiazines (chlorpro mazine or thioridazine) are useful

in moderate dosages (100 to 300 mg/d) for the treatment of myx edematous psychosis. HYPERTHYROIDISM

History
In 1918, Woodbury2 described the manifestations of Graves' disease as involving fatigue, irritability, in tolerance to cold, fine tremor, rest lessness, insomnia, excitability, la bile emotional disposition, ner vousness, weight loss, palpitations, doubts, and fears. Amburg and Lunde43 later depicted the hyper thyroid patient as characterized by hyperexcitability, irritability, restlessness, increased sexual mo tivation, exaggerated response to environmental stimuli, emotional instability and ultimately psycho sis. here seems to be a consensus T in the literature concerning the oc currence of fatigue, irritability, and instability of personality, but psy chosis associated with hyperthy roidism remains a much less com mon finding. The prevalence of psychosis in severe hyperthyroid states has been reported to range between 1% and

20%. In 1928, Johnson44 studied

2,286 patients with operative goiter and found only 24 cases of psycho sis. However, many clinicians be lieve that the incidence of psychosis in hyperthyroid states is consider ably higher. Lidz and Whitehorn,24 Kleinschmidt and associates,45 and Deutsch46 stated that the rate of psychosis in hyperthyroid patients approximated 20%. Bursten47 re ported an 18.5% rate of psychosis among hospitalized hyperthyroid patients, but noted that this was a selected population. In another
JANUARY 1983. VOL 24- NO 1

sis occurring in hyperthyroid states, which were subsequently reversed by surgery. Rulison and associates5' describe a case characterized by psychosis with hallucinations and delusions that cleared following It is interesting to note that the thyroidectomy. Bluestone48 report majority of the existing literature ed on three cases each which of concerning the mental effects of responded to thyroidectomy with hyperthyroidism explores possible abrupt cessation of psychotic psychogenic etiologies for this syn symptoms. Greer and Parsons52 drome, rather than defining clear described a hyperthyroid patient cut mental changes of the type that who presented as a paranoid occur with hypothyroidism. In re schizophrenic. Consistent agree viewing the literature, one is left ment can be found in the literature that fatigue, irritability, emotional instability, and excitability are all The prevalence of psychosis common features of the hyperthy in severe hyperthyroidism is roid state, as are episodes of severe between 1% and 20%. and often disabling anxiety. No clear picture, however, exists con with the impression that psychotic cerning any fixed psychotic con mental changes in the hyperthyroid stellation of symptoms or progres state are not only less common but sion of psychiatric disease. Some less extreme in their manifestation individuals become delirious, while than those occurring with hypothy others experience periods of hy roidism. perexcitability simulating mania Ettigi and Brown49 note that hy that alternate with periods of ex perthyroidism is almost inevitably haustion and depression. associated with mental changes. Other symptoms The most common presenting symptoms includenervousness, The most frequent office presenta manifested as apprehension, rest tion of hyperthyroidism is a hy lessness, and inability to concen peractive individual complaining trate; marked emotional lability; of anxiety and nervousness. Often a and hyperkinesia.5 fine generalized tremor is present,

study'7f8,000 psychotic and 2,500 o schizophrenic patients, he found an overall incidence of hyperthyroid ism of less than 1%; these figures are in fundamental agreement with findings by Bluestone.48

Psychosis
The typical psychosis of hyper thyroidism is reported by most au thors42-44 to simulate a manic-de

and the patient will report feeling shakyorjittery. Familymembers

often remark about personality changes and marked increases in both irritability and emotional la bility. Jefferson and Marshall53 point out that this nervousness is

pressive psychosis. Other presen

tations reported in the litera ture24-'1'4749 include simple, cata tonic, and paranoid schizophrenia; psychotic depression; functional psychosis; organic brain syn drome; and psychoses of undeter mined type. Reports are available of psycho

dissimilar to that seen in the patient

with anxiety neurosis, in that it is characterized by restlessness,

shortness ofattention span, and a

need to move about.

Popkin and Mackenzie2 state

that the behavioral changes of hy
(continued)

11

Thyroid hormone disturbance

perthyroidism are numerous and frequently suggest a diagnosis of either anxiety neurosis or neurasthenia. Hyperthyroidism can be differentiated from these latter conditions by the following findings: In thyroid dysfunction, sleeping pulse will remain acceler ated; sedated pulse will exceed 80; palms will be dry and warm, not cool and clammy; fatigue will be accompanied by a desire to be ac tive; and cognitive dysfunction is more prominent than in neurasth enia. Restlessness, increased work ac tivity, and emotional explosiveness occur fairly frequently, as does marked emotional lability with un expected tearfulness and crying, which often produce a sense of shame and bewilderment in the patient. When questioned, patients report that they are unaware of why they are crying. Often they describe diminished frustration tolerance, and although their work energy seems increased, their actual ability to complete tasks is diminished owing to shortened attention span and heightened distractibility.

and quantitatively less severe than depression in hypothyroid patients. Most patients with hyperthyroid ism do not report significant de pression. When it does occur, it is more likely to be of the agitated type rather than the retarded type, and to be associated with marked variability of mood rather than consistently depressed mood. Apathetic hyperthyroidism, de scribed by Lackey57 in 1931 (and also referred to as silentor masked thyrotoxicosis because these patients do not appear to be

only one hyperthyroid patient in a group of 1,000 patients at a large public mental institution. Although there is no characteris tic, single psychosis associated with hyperthyroidism, paranoid symp toms, suspiciousness, and manic like states are most frequently re ported. Whybrow and associates59 report that both the schizophrenia and paranoia scales of the MMPI are consistently elevated in hyper thyroid patients with psychosis. These authors stress that the men

tal changes

encountered

clear

The behavioral changes of hyperthyroidism are many and often simulate anxiety neurosis or neurasthenia.
in a hypermetabolic state), may present as retarded or stuporous depression or apathetic dementia. This presentation is most frequent in the elderly. Initially the patient may complain of confusion, fa tigue, weakness, profound weight loss, and cardiovascular complica tions. Later, depressive features be come more marked. The depression deriving from apathetic hyperthy roidism simulates that seen in some cases of hypothyroidism. Often these patients appear to have ad vanced psychomotor retardation and to be totally detached and dis interested in any attempt to reach them 58 While hypothyroidism frequent ly coexists with major psychiatric symptoms in hospitalized mental patients, hyperthyroidism does not seem to be particularly prevalent in this population. Bursten47 reported only ten cases of thyrotoxicosis in 8,000 overtly psychotic patients, while Bluestone48 was able to find

quickly following treatment, sug gesting that the behavioral mani festations of hyperthyroidism are

toxic phenomena rather than some

form of liberated latent psycho sis. These findings are supported by the work of MacCrimmon and associates,6 who demonstrated

MMPI scale deviations in hyper thyroid patients suggestive of hys

terical somatization. These patterns returned rapidly to normal follow ing treatment. This study indicates that the behavioral, neurotic, and psychotic manifestations of hyper thyroidism are related more to the biochemical abnormalities asso ciated with the disease than they are to the patient's previous per sonality pattern. Physical diagnosis

Subtle cognitive

changes

are

clearly demonstrable in the hyper thyroid patient.54 Cognitive dis orders present on testing disappear as thyroid levels return to normal. Wilson and associates55 were able to show that the experimental ad ministration of T3 to 11 normal vol unteers, simulating an acute hyper thyroid state, produced marked changes in interpersonal function ing and caused dysphoria, depres sion, jitteriness, and decreased friendliness.

Physical signs and symptoms that

occur in 70% or more of hyperthy roid patients include tachycardia, goiter, nervousness, soft moist skin, fine tremor, hyperhidrosis, heat hy persensitivity, exophthalmos, stare, dyspnea, weight loss, bruit over the thyroid, palpitations, fatigue, mus cular weakness, and loose stools. The disease has its highest inci dence in women between the ages of 20 and 40. When hyperthyroid ism is associated with a diffuse 15

Several investigators45-56 have re

ported depression to be associated with the hyperthyroid state. When depression does occur in the hyper thyroid patient, it is qualitatively
JANUARY 1983 . VOL 24@ NO 1

Thyroid hormone disturbance

goiter and ocular signs, the condi tion is termed Graves' disease. Cli nicians should remember that spider angiomas and gynecomastia,

sis, manic

phase;

anxiety

neurosis, disorders:

particularly
women;

in

menopausal

with a hypermetabolic state such as leukemia, polycythemia vera, and

severe anemias. Pheochromocyto

schizoaffective

which might otherwise suggest he

patic disease or alcoholism, occur commonly in hyperthyroid pa tients. Other physical signs that the clinician may not routinely asso ciate with the condition, but which in fact are common, include a harsh pulmonary systolic (Means') mur

and drug abuse (stimulants, am phetamines. cocaine, phencycli dine). Other medical problems that should be included in the differen tial diagnosis are acute and sub acute thyroiditis, pituitary tumor, and other conditions associated

ma and acromegaly may be asso ciated with hypermetabolism and

an enlarged thyroid gland!@

Treatment Controversy
most

still exists as to the

treatment for a

efficacious

mur, lymphadenopathy, and splen

omegaly. Osteoporosis also occurs commonly in patients with long standing disease. Additional skin signs include pretibial myxedema (a localized, nonpitting, hard, bi lateral swelling over the tibia), and

Table2Diagnostic Featuresof Hyperthyroidism5

Symptoms
intoleranceIrritabilityRestlessnessNervousnessEasy WeaknessHeat
fatigabilityPersonality

an infiltrative

dermopathy

with

similar infiltrations over the dor sum of the feet. Clubbing and swelling of the fingers may also

appetiteAnxiety changeIncreased quickenedLoose statesSpeech

stoolsSignsSweatingPretibial
myxedemaWeight edemaTachycardiaLid lossPeriorbital lagSkinsoft, accommodationTremorHair of pupillary moist, warm, thinLack silkyStareSpider fine and angiomasExophthalmosGynecomastiaGoiterMeans' murmurBruit thyroidSplenomegalyClubbing over fingersLymphadenopathyInfiltrative of wastingDyspneaOsteoporosisPalpitationsLaboratory dermopathyMuscle

occur (see Table 2).

Laboratory diagnosis Laboratory findings

characteristic

of the disease include elevated

radio-T3 resin uptake, and elevated T4 and radioiodine uptake. The ra

dioiodine uptake characteristically

cannot be suppressed by T3 admin

istration.

An unusual

condition

called T3 toxicosis evidences nor mal T4 levels with elevated serum T3. Serum cholesterol may be low and postprandial glucosuria may be present. Urinary creatinine levels are usually increased. Lym phocytosis is generally present. Hy pokalemia may also occur. Thy roid-stimulating hormone (TSH) levels are usually low, while long acting thyroid stimulator (LATS) and thyroid stimulating immuno globulin (TSI) are elevated.38 Differential diagnosis The major psychiatric differentials include manic-depressive psycho
16

findings
Elevated 14 Elevated radio-T3 resin uptake Radioiodine uptake elevated (Failure of suppression by T3 administration). Serum cholesterol usually low Urinary creatine increased Postprandial glycosuria may occur
Lymphocytosis

Urinary and serum calcium may be elevated TSH can be low while LATS and TSI are elevated
Adaptedwith permission from CurrentMedicalDiagnosisand Treatment. 980,pp 687-694(KoIb 1 FO,CamargocA7t).

PSYCHOSOMATICS

particular patient. The literature today suggests an increased ten dency toward long-term medical treatment, followed by radioiodine therapy, rather than surgical thyroidectomy. Medical treatment is performed with drugs of the thiouracil type, often combined with iodine. In addition, particu larly for patients being prepared for surgery, the use of propranolol in doses of 80 to 240 mg/d seems an effective and rapid way of reversing the toxic manifestations of the dis ease. Because propranolol merely controls the symptoms rather than reversing the hypermetabolic state, escape and thyroid storm may occur. Radioactive iodine has pro vided excellent results in the treat ment of diffuse or toxic nodular goiter. The clinician needs to remember that lithium, which acts as a colloid trap, is effective in reducing the severity of hyperthyroidism. This is particularly important in psychia try, since one of the most frequent psychiatric misdiagnoses is that of manic-depressive disorder. If this diagnosis is accepted in a hyper thyroid patient without appro priate study, lithium administra tion often produces dramatic short term results and thereby errone ously confirms in the clinician's mind the diagnosis of mania. The dilemma with lithium therapy is REFERENCES
1. Hall RCW. Gardner ER. Popkin MK, ef al:

that it is only an adjunctive treat ment for hyperthyroidism, and misdiagnosis may predispose the patient to the subsequent develop ment of thyroid storm.

Twenty of these patients were de

termined to be hypothyroid. The thyrotropin-releasing hormone test was the most useful in establishing the proper diagnosis. In a study of 480 newly admitted psychiatric patients, conducted at

If a hyperthyroid patient devel

ops psychotic symptoms, these can often be controlled with either re

the Yale-New Haven Psychiatric

Evaluation Unit, Cohen and Swi gar7demonstrated elevations in effective free thyroxin (EFT) in 43 patients (9%). Twenty-seven of these patients were thought to be suffering from acute stress hyper thyroidism. The EFT levels of this group spontaneously reverted to normal within two weeks following admission.

serpine or chlorpromazine.6' Halo

peridol has also been reported62 to be effective in treating psychosis associated with thyrotoxicosis that is unresponsive to chlorpromazine. However, several case reports63'66 indicate that there may be in creased neurotoxicity associated with haloperidol in hyperthyroid patients. Finally, several reports67'68 exist of nonpsychotic hyperthyroid pa tients developing what appears to be either a schizophreniform psy chosis or an agitated organic psy chosis following the initiation of treatment with antithyroid drugs. Consequently, vigilance is needed during the treatment phase.

In addition, the EFT level was

diminished in 42 patients admitted

to the unit (9%). In 16 of these patients the EFT level subsequent ly had returned to normal, A pre
sumptive diagnosis of secondary hypothyroidism was made in eight

patients. An additional nine pa tients with known thyroid disease

were found to be taking inadequate
or excessive replacement therapy.

Thyroid screening in psychiatric patients

Gold and associates69 recently demonstrated the value of endo crine screening in psychiatric pa tients. In their study of 250 consec utive patients admitted to a psychi atric hospital with the diagnosis of depression and anergia, endocrine diseases were a frequent finding.

Cohen and Swigar7 concluded that

thyroid function tests are of value in psychiatric patients, but they caution that diagnosis and treat ment should not be based on a single laboratory value. Rather, careful physical and laboratory ex amination is necessary to ensure

proper diagnosis and treatment. 0

Mental changes accompanying thyroid gland dysfunction. Arch Gen Psychiatry 20:48-63, 1969. 11. Jam VK: Affective disturbance in hypothy roidism. Br J Psychiatry 119:279-289, 1971. 12. Clower CG, Young AG, Kepas D: Psychotic

Unrecognized physical illness prompting psy chiatric admission:A prospective study. Am J

Psychiatry 138:629-635, 1981. 2. Popkin MK. Mackenzie TB: Psychiatric pre sentations of endocrine dysfunction, in Hall

RCW(ed): Psychiatric Presentationsof Medi cal/I/ness. New York, Spectrum Books, 1980, pp 142-143.
3. Lavis VR: Psychiatric manifestations of endo

crine disease in the elderly, in Levenson AF,

Hall RCW (eds). Aging. vol 14: Neuropsy chiatric Disease in the Elderly. New York,

adult life in women. Trans C/in Soc London 7.180-185, 1874. 5. Ord WM: On myxedema, R Med Chirg Soc Trans 61:57-58, 1878. 6. Report on myxedema. Trans C/in Soc London 21 (suppl):31. 1888. 7. Von Juaregg JW: Myxodem und Kretinismus, in: Aschaffenburg s Handbuch der Psychia trie, pad 2, section I. Leipzig, Halfte, 1912, 8. Hayward EP, Woods AH: Mental derange ments in hypothyroidism. JAMA 97:64, 1931. 9. Ziegler LH: Psychosis associated with myx

states resulting from disorders of thyroid

function. Johns Hopkins MedJ 124:305-31 0,
1969.

13. Akelaitis AJ: Psychiatric aspects of myxede

ma. J Nerv Ment Dis 83:22-36, 1936.

14. Savage GH: Myxedema and its nervous
symptoms. J Ment Sd 25:51 7-519, 1980. 15. Tonks CM: Mental illness in hypothyroid pa

edema. J Neurol Psychopathol 11:20-27,

1930. 10. Whybrow PC, Prange JR. Treadway CR:

Raven Press, 1981, pp 59-81.

4. Gull W: On a cretinoid state supervening in

tients. Br J Psychiatry 110:706-710,

1964.

JANIJARY

1983 VOL24- NO 1

17

Thyroid hormone disturbance

16. Pomeranze

J, King EF: Psychosis

as first sign

thyroid-catecholamine-receptor interaction,
its relevance to affective illness. Arch Gen Psychiatry 38:106-1 13, 1981.

c/is in hyperthyroidism. Psychosom Med

41:331-340, 1979. 55. Wilson WP, Johnson JE, Feist FW: Thyroid

of thyroid dysfunction. 212, 1966.

Geriatrics 21 :21 1-

17. Treadway CR, Prange AJ Jr. Doehne EF, et al: Myxedema psychosis: Clinical and bio chemical changes during recovery. J Psy

37.PrangeAJ: The Thyroid Axis,Drugs and

Behavior. New York, Raven Press, 1974. 38. KoIb FO: Endocrine disorders, in Krupp MA,

hormone in brain function. 2. Changes in

photically elicited EEG responses following

the administration of triiodothyronine to nor

mal subjects 56. Whybrow . Electroencephalogr C/in OR:

chiatr Res 5:289-296, 1967. 18. Ward DJ, Rastall ML: Prognosis in myxede ma madness.J Psychiatry 113:149-151, Br 1967. 19. Hall RCW, Popkin MK, DeVaul R, et al: Psy chiatric manifestations of Hashimoto's thy roiditis. Psychosomatics 23:337-342, 1982. 20. Ascher R: Myxedematousmadness.BrMedJ 2:555-562, 1949. 21. Stoll HF: Chronic invalidismwith marked per sonality changes due to myxedema. Ann In tern Med6:806-814, 1932. 22. Ruhberg GN: Myxedemaitsnervous and mental manifestations. Minn Med 19:637641, 1936. 23. Davidoff F, Gill J: Myxedema madness: Psy chosis as an early manifestation of hypothy
roidism. Conn Med 41 :618-621, 1977.

Chatton MJ (eds): Current Medical Diagnosis and Treatment.Los Altos, Calif., Lange Medi cal Publications, 1978, pp 670-677.
39. Youmans JB, Riven 55: Hypothyroidism with out myxedema. Annlntern Med5:1 497-1505, 1932. 40. Kales A, Heuser G, Jacobson A, et al: All night sleep studies in hypothyroid patients

Neurophysio/ 16:329-331, 1964.

PT, Prange AJ, Treadway

Mentalchanges accompanying thyroid gland

dysfunction. Arch Gen Psychiatry 20:48-63, 1969. 57. Lackey FH: Non-activated (apathetic) type of hyperthyroidism. N EngI J Med 294:747-748, 1931. 58. Thomas FB, Mazzanerri EL, Skaloman TG: Apathetic thyrotoxicosis: A distinctive clinical and laboratory entity. Ann Intern Med 72:679-685, 1970. 59. Whybrow PC, Prange AJ, Treadway CR:

before and after treatment. J C/in Endocrinol

27:1593-1 599, 1967.

41. Mason JW: A review of psychoendocrine re

search on the pituitary-thyroid system. Psy

chosom Med 30:666-681, 1968.

42. Woodbury MS: The psycho-neurotic syn drome of hyperthyroidism. J Nerv Ment Dis 47:401-410, 1918. 43. Hamburg DA, Lunde DT: Relation of behav ioral, genetic, and neuroendocrine factors to thyroid function, in Spuhler JN (ed): Genetic Diversity and Human Behavior. Chicago, Al dine Publishing. 44. Johnson WO: Psychosis and hyperthyroid ism. J Nerv Ment Dis 67:558, 1928.

Mental changes accompanying thyroid gland dysfunction. Arch Gen Psychiatry 20:48-63, 1969.
60. MacCrimmon DJ, Wallace JE, Goldberg W, et al: Emotional disturbance and cognitive del i cits in hyperthyroid/sm. Psychosom Med 41:331-340, 1979. 61 . Burch EA Jr. Messervy TW: Psychiatric

24. Lidz T, Whitehorn JO: Psychiatric problems in a thyroid clinic. JAMA 139:698-701, 1949. 25. Osler W: An acute myxedematous condition with tachycardia, glycosuria, melaena, mania and death. J Nerv Ment Dis 26:65, 1899. 26. Scheinberg P. Stead EA, Brannon ES, et al: Oorrelativeobservationson cerebral metabo lism and cardiac output in myxedema. J C/in Invest 29:1139, 950. 1 27. ScheinbergP, Stead EA Jr: Cerebral metabo lism in hyperthyroidism and myxedema, ab
stracted. Fed Proc 9:113, 1950.

45. Kleinschmidt HJ, Waxenberg SE, Cuker R: Psychophysiology and psychiatric manage
ment of thyrotoxicosis: A two year follow-up in psy 9:127-

symptomsin medical illness: Hyperthyroidism revisited. Psychosomatics 19:71-75, 1978.

62. Bianco FJ, Lerro FA: Schizophrenic chosomatics 13:120-121, 1972. syn

drome, thyrotoxicosis and haloperidol. Psy 63. Lake CR, Fann WE: Possible potentiation of
haloperidol neurotoxicity in acute hyperthy

study. J Mt Sinai Hosp 23:131-153, 1956.

46. Deutsch SF: Recent contributions choendocrinology. Psychosomatics 134, 1968.

28. EassonWM: Myxedemawith psychosis. Arch Gen Psychiatry 14:277-283, 1966. 29. Savin CT, Chopra D, Azizi F, et al: The aging
thyroid: Increased prevalence of elevated

47. Bursten B: Psychoses associated with thyro toxicosis. Arch Gen Psychiatry 4:267-273,
1961. 48. Bluestone H: Hyperthyroidism masquerading

roid/sm.Br J Psychiatry 123:523-525, 1973. 64. Yosselson 5, Kaplan A: Neurotoxic reaction

to haloperidol in a thyrotoxic patient. N EngIJ

Med 293:201, 1975. 65. HoffmanWH, Chodoroff G, Piggott LR: Halo

peridol and thyroid storm. Am J Psychiatry

serum thyrotropin levels in the elderly. JAMA 242:247-250, 1979. 30. BlumeWT,Grabow JD: The cerebellar' signs
of myxedema. Dis Nerv Syst 30:55-57, 1969. 31. Crevasse LE, Logue RB: Peripheral neuropa

as functional psychosis. Am Prac Dig Tr

8:557-558, 1957. 49. Ettigi TG, Brown GM: Brain disorders asso ciated with endocrine dysfunction, in Hendrie

135:484-486, 1978. 66. Weiner MF: Haloperidol, hyperthyroid/sm and

sudden death. Am J Psychiatry 136:717-718, 1979. 67. Herridge OF, Abey-Wickrama I: Acute iatro

thy in myxedema. Ann Intern Med 50:14331437, 1959. 32. Browning TB, Atkins RN, Weiner H: Cerebral metabolic disturbances in hypothyroidism. ArchIntern 93:938-950, Med 1954.
33. Libow LS, Durell J: Clinical studies on the relationship between psychosis and the regu lation of thyroid gland activity. II. Psychotic

HO (ed): Psychiatric ofNorth Clinics America: Symposiumon Brain Disorders: Clinical Diag
nosis and Management. Philadelphia, WB

genic hypothyroid psychosis. Br Med J

3:154, 1969.

Saunders, 1979, p 120. 50. Sachar E: Psychiatric disturbances associat ed with endocrine disorders, in Arieti 5,
Reiser M (eds): American Handbook of Psy chiatry. New York, Basic Books, 1975, vol 4, pp 299-31 3. 51. Rulison ET Jr. White JD, Stalker LK: Mental

68. Bessher PD, Gardiner AQ, Hedley AJ, et at: Psychosis after alteration of thyroid status. Psychol ed 1:260-262, M 1971. 69. Gold MS, PottashALC, Extein I: Hypothyroid ism and depression. Evidencefrom complete
thyroid function evaluation. JAMA 245:19191922, 1981. 70. Cohen KL, Swigar ME: Thyroid function screening in psychiatric patients. JAMA

symptomsand thyroid regulation in a case of post-thyroidectomy depressive psychosis. PsychosomMed 27:377-382, 1965. 34. Logethetis J: Psychotic behavior as the initial indicator of adult myxedema.J Nerv Ment Dis 136:561-568, 1963. 35. Lansing RW, Trunnell JB: Electroencephalo graph/c changes accompanying thyroid defi
ciency in man. J C/in Endocrino/ 23:470-480,

disorders associated with hyperthyroidism. Am J Surg54:499-501, 1941.

52. Greer 5, Parsons V: Schizophrenia-like psy chosis in thyroid crisis. Br J Psychiatry 114:1357-1362, 1968. 53. Jefferson JW, Marshall JR: Neuropsychiatric

Features f Medical o Disorders. York, New

Plenum Medical Book Co. 1981, p 145.

242:254-257, 1979. 71. KoIb ED, Camargo CA: Endocrine disorders, in Krupp MA, Chatton MJ (eds): Current Medicaliagnosis Treatment. D and LosAltos, Cal/f, Lange Medical Publications, 1980, pp
669-748.

1963. 36. Whybrow PC, Prange AJ: A hypothesis of

54. MacCrimmon Wallace Goldberg DJ, JE, W,et

al: Emotionaldisturbance and cognitive defi

18

PSYCHO5OMATIC5