Psychiatric Effects of Thyroid

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R ICHARD C . W . HALL, M .D .

ABSTRACT: Neuroendocrine disorders often present and/or are

assoc ia ted with psychiat ric s igns and symptoms .. The authorrev iews the l iterature on psychiat ric f ind ings in hypothyro id ismand hyperthy ro id ism and provide s recommenda tions fo rd iagnos tic and treatment procedures.

ma seems to be decreas ing, perhapsbecause of better and m ore availab le medical care , which interruptsthe d is ease a t an ear li er s tage . Earlyr ev iews o f the l it erature sugge st edth at p sy ch osis d id in de ed o ccu r inthe 50% range reported by theC lin ica l S ociety .6 '8 Mo re re cen ts tudie s, h owever , s ugge st th at th e

cu rren t in cid en ce o f p sy ch osis inmyxedematous pa ti en ts i s between5% and 15% . A s described in the

literature (there are severalhundred case reports on the psychiat ri c course and symptoms) ,9 -2 'the charact er is ti c course o f s low lyp rogr es siv e myxedema s eems t o b eone o f progre ss ive mental s low ing ,w ith a d ec lin e in memory func ti on ,sp eech , a nd lea rn in g a bility . P erc ep tual changes progres s, w ith d istor tionof hear ing, taste, v is ion , andsmel l. De lu sion s and f rank ha lluc inatio ns or p sychosis o ccur as thed is ease becomes more advanced.

The typical m anifestations ofmyxedema madness were described in 1949 by A scher,2Â °whoemphasized the prominence ofp sych ia tr ic symptoms in h is c la ss icreview of 14 cases in which the

Disturbances of endocrine functiona re among th e most common phy s

ical causes for the production ofwhat appears t o be primary psych ia tr ic d is ease .' 3 Th is paper rev iewspsychiatric, physical, and laboratory fin din gs a sso cia ted w ith h yp othyro id ism and hyper thyro id ism ,and pre sent s r ecommendat ions ford iagnos is and treatment.

HYPOTHYROIDISMHistory and symptomsIn 1874, Gull4 rep orted on a “ ¿cr etinoid state occurring in an adultfemale―who had psych ia tr ic symptoms. Four years later , Ord5coinedthe term “ ¿myxedema―nd commen ted th at m en ta l ch an ge s w ere

frequently assoc iated with this cond it ion . Ten years lat er , the C lini ca l

Soc ie ty o f London6pub li shed a detailed report that defined thesym ptoms of 109 patients withm yxedem a. T he m ajority of th eirf indings r emain val id . The Soc ie tyconcluded tha t “¿ delusionsnd halluc inat ions occurred in nearly ha lfo f th e c as es ,â €•and tha t “¿ n sani ty†•was seen in an equal number ofpatients. T he report defined thecharacterist ic “¿nsanity―f myxedem a as “ ¿acuter c hr on ic mani aor dem entia m elancholia with am arked prepond erance of suspicion and self-accusation.―

T he fre qu en cy o f a n in itia l p sychiat ri c pre sentat ion for myxede

Dr. Hall is chief of staff of the VA M edical Center, M emphis, associate dean for

v ete ra ns a ff air s, a nd p ro ft ss or o fp sy ch ia tr y a nd o f in te rn al m ed ic in e a t th e Uni ve rs it y

of Tennessee C ollege of M edicine. R eprint requests to him at V A M edical C enter,

1030 Jefferson A ye., M em phis, T N 38104.

JANUARY 1983 . VOL 24@ NO 1 7

Psychiatric effects ofthyroid hormone disturbancePsychosomatic illn ess review: No. 5 in a series

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T hyroid horm one disturbance

cold intolerance. H e noted thatchanges in fac ia l appearance, a lterations of voice, and snoring w ereoften complained of by the patient's rela tives. M ost of his ca seswere women . A lth ou gh n o ch ara cteristic psychosis occurred, in allcases he noted that the most frequent presentat ion was depressionoran agitated paranoid state . Otherpresentationsfor the conditiondes crib ed in th e lite ra tu re a re : c hro nici ns id ious p er sona lit y c hange w ithla bility o f moo d, a nx ie ty , a nd emotiona l w ithdr awal; g radually p ro

g re ssiv e d ep re ssiv e d iso rd er sim ulating psychogenic depression; apar anoid s ch iz ophr en ia -lik e s yndrom e; rapidly developing psy

Psychia tr ic symp toms may

be the earlies to r most

prominentsignsor

symptomsreportedby the

hypothyroidpatient.

chot ic depress ion; and a mania-l ikep resen ta tio n w ith p ara no id id eation and agitation.8-'1-14.21.24

The most c ha ra cte ris tic p ic tu reo f rap id ly develop ing myxedema i sone o f g en er aliz ed agita tion, w ithprogre ss ive d isor ientat ion, per sec uto ry d elu sio ns, h allu cin atio ns,and in te rmit tent bou ts o f le thar gyand ext reme res tl es snes s. Pa ti en tsare often extremely irr itable, de lusio na l, p ara no id , a nd comp la in o faud ito ry and /o r v is ua l h allu cin a

t ions . Hyper sexual it y dur ing the sestates has also been reported)9Stol l2 'descr ibes the c lassic personality chang es as follow s: “ ¿Onesimpres sed by the marked per sona lity cha nges present in advancedcas es : i rr it ab il it y, un tr uthf ulness ,suspicion, delusions, retarded cereb ra tion, in ab ility to c on centr ate ,

in tro versio n a nd fa ilin g memoryare consp icuous .―Ruhberg22 belie ve d th at “¿everyase of uncomp li ca ted myxedema pre sent s w ith amental s ta te , the e ssen tial f ea ture sof w hich are fatiga bility an d p sychomotor retardation.―

E tiology o f mental symptomsA variety of theories have beendeveloped to explain the occurrence of m ental changes in hypoth yroid p atients. E arly th eories25s ug ge ste d th at m yx ed em ato us p sychos is was a direct resu lt of cerebral

hyp om etabolism or of the production of central nervous systemtoxins . Other theories26- '@7urmisedth at th e p sy ch osis w as d ue to cereb ra l ed ema, en zyma tic ch an ges inth e b ra in , o r d im in ish ed ce reb ra lb lo od flow. E as so n2 8p r op os ed th atm ental sym ptom s were related to“¿aap id change in int erna l s timul iand ext erna l percept ion wh ich maynot allow the physiological andemotiona l r ead justment necessaryto ma in ta in an in te gr ate d c on cept

of body stab il ity.―This th eo ry hadthe added advan tage o f exp la in ingthe fact that som e patients b ecam ewors e when tr ea tmen t was in itia ted : â €œ¿Furthernternal adjustment,alb eit tow ards no rm ality, oftencau sed a w orse ning of the m yxedematous pa ti en t' s emot iona l s ta te .†•Other authors29have noted that theseverity of mental symptoms isgreater in elderly pa tients and inpersons w ith rapidly changingle ve ls o f t hy ro id h ormone .

The cerebral effects of the hypothyroid s ta te were we ll d ep ic tedb y S cheinbe rg an d associates26 inthe ir s tudy o f e ight myxedematouspa ti en ts w i th sen sory impa irmen t.H e d oc umen ted a 3 8% d ecrea se inc er eb ra l b lo od flow , a 2 7% dec re as ein cerebral oxygen and glucoseconsumpt ion , and a 91%increase in

diagnosis of m yxedem a had notbeen previou sly e st ab li shed . A ll o fth es e p at ie nts p re se nte d w ith p sychotic changes, an d ten ha d b eenadm itted to a m ental w ard for observation under the L un acy A ct. Innine of the 14, “¿thereas a dram atic and com plete recovery ofsa nity w ith th yr oid trea tm en t.â €•Two patie nts p artia lly impro ve dwhen treated, one rem ained unchanged , and two d ie d.

I n d iscu ssin g th e ca ses, A sch ercalled attentio n to the very im portant fact that m yxedem a causes

psychosis:

If o ne observer can encounte r th isnumber i n fo ur yea rs , it must meanthat there are manyothers . Poss ib lythereare manycasesin mentalhospitalswhichhavenotbeendiagnosed.Ifthediagnosisis bornein mindby psychia trists a n umber of oth erw isehope lesspsychosesmay be cured,and the aw areness of an orga niccausefor one psychosismay lead tothe d iscoveryo f physica lcauses forotherswhichare at presentdismissed

as of psychologicalor id iopathicor igin.

Ascher suggested that the patien t's h isto ry was o f little h elp inini tial ly establ ish ing the d iagnos is ,although it w as of great utility inconfirming the diagnosis once ithad been suspected. T hat w as b ecause symptom s are “¿admittedr ath er th an c omp la in ed o f. - . . Thementa l s lown es s o f th e illn es s its elfsmo th ers s elf-c ritic ism . In fa ct, y ou

get n o histo ry of m yxedem a if youare not thinking of myxedemawhen you take tha t h is tory .†•

A scher d efined the follow ingsym ptom s as m ost common in hispatients: general t iredness , we ightga in , vague ach ing pains in the l egs,memory impairment, constipation,d ea fn ess, lo ss o f h air, d ry sk in , a nd

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c ere bro va scula r re sis ta nc e in th es epatients. He suggested that there

w as a specific correlation betw eendisturbed m etabolism and alteredmen ta l s ta te .

O fn ote to th e p ra ctic in g c lin ic ia nare the findings of B lum e and G rabow 3Â °nd C revasse an d L ogue,3'w ho established that unu sual neurologic symptoms may precedeother signs of myxedema. Theseauthors reported on the early occurrence of cerebellar ataxia andperipheral neuropathy as presentin g symp toms o f h yp oth yro id ism .

The EEG effects of myxedemahave been studied by a variety ofauthors, with mixed findings.B row ning and associates32 w ere unable to correlate the EEG patternand the clinical symptoms of hypothyroid patients. L ibow andDure ll 33demons tr at ed s low ing andflattening of the EEG in deliriousm yxedem atous patients. L ogothetis34also reported E EG slow ing andflattening, and suggested that thesechanges were associated with hy

perthyroid psychosis. He noted theresolution of these abnorm alitieswhen the patient was returned tothe euthyroid state. Using a carefully controlled research model inhypothyroid patients w ho had littlefunctional thyroid tissue, L ansingand T runnell35 deprived patients ofthyroid replacem ent and obtainedserial EEGs. T hese investigatorsfound slow ing of dominant alpharhythms, but were unable to docu

m ent significant changes in am plitude. When thyroid replacmentwas reinstituted, the EEG abnorma li ti es d is appea red .

New research by Whybrow andP rang e3 6-3 7o cu sin g o n th e th yro idaxis an d cate cho lam ine in teractio nsuggests that thyroid function playsa role in the expression of certainaf fec tive disorders:

A la ck o f th yro id hormones can lower

th e th re sh old fo r d ep re ss io n; a n e xcess can contr ibu te to a s ta te o f tense

d ysphoria . Thy ro id fu nc tio n in s omeper sonsa l so appea rs to inf luence theco urs e o f a ffe ctiv e d is ord ers . A dequate m obilization of thyroid hor

mones fa vo rs re co ve ry from dep re ss io n; e xc es s mobiliz atio n in cre asest he r is k o f mania in vulne rab le ind iv id

uals.37

These authors, in review ingava il ab le i nf ormat ion, p ropo se tha tthyroid hormones modulate the activity of central fl-adrenergic re

Dis continuati on o f therapy

by th e p atien t typ ica lly lea ds

to a return of sym ptom s

w ithin a short period of tim e.

ceptors in their response to thepresence of catecholam ines. Theysuggest that thyroid hormone increases the ability of these central/3-adrenergic receptors to receivestim ulatio n fro m n orep in eph rin e.Thyroid horm one, by m odulatingc ate ch olamin e n eu ro tra nsmiss io nin the CNS, would therefore serveas a mechanism for physiologic adjustment and “¿defense―uringtimes of adaptive demand. Thishypothesis is im portant, since it explains a wide variety of clinicalfindings and suggests im portantn ew areas of research .

D i ff er en ti al d iagnosi s

A s stated earlier, psychiatric sym ptoms may be the earliest or mostprominent signs or symptoms reported by the hypothyroid patient.The essential diagnostic featuresare shown in Table 1. Hypothyroidism should be considered in thedifferential diagnosis of patientswho appear neurasthenic and/or

have unexplained m enstrual diso rd ers, w eig ht g ain , o r m ac ro cy tic

a nem ia. T he condition should alsob e in clu de d in th e d iffe re ntia l d ia gnosis of unexplained ascites, refractory heart failure, and idiop ath ic h yp erlip em ia . V ario us e ffusions, all of which have high protein content, may occur inhypothyroid patients. The hypoth yro id p atie nt's th ic k to ng ue m ays ug ge st amy lo id osis. H yp oth yro idism should also be considered inpatients w ho presen t w ith w hat app ea r to b e mya sth en ic o r rh euma tic

syndrom es. T he clinician shouldrememb er th at c ere bro sp in al flu idpro tein levels are h igh in m yx edematous patien ts.

The m ajor com plications of thedisease are cardiac in nature, ando cc as io na lly a p atie nt may d ev elo pre fra cto ry h ypon atrem ia re su lt in gfrom inappropriate secretion of antidiuretic horm on e. T he clinicianshould also remember that myxedem ato us patients are u nusuallysensitive to opiates and that thea dm in istra tio n o f a ve ra ge d ose s o fth ese d ru gs m ay p ro ve fa ta l.3 8

TreatmentFollowin g a pp ro pria te d ia gn osis,thyroid replacem ent treatm entshould be initiated cautiously. Ifthe myxedema is severe, if myxedemato us h ea rt d is ea se exis ts , o r ifth e p atie nt is e ld erly , th e c lin ic ia nshould begin treatment w ith extre me cau tio n, as rap id p hy sio lo gic

changes in thyroid levels may beassociated w ith w orsening of cardiac symptoms or the development ofa m ania-like or organic psychosis.If replacement therapy is used,doses in the range of 8 to 15 mg/dfor a week, then increased by 15mg/d up to a total of 100 to 200mg /d , a re u su ally e ffe ct iv e.

Levothyroxine sodium given in

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Table 1—Diagnosticeaturesof Hypothyroidism5

,SymptomsWeaknessHoarsenessFatiguePathological

f at igue ( ie ,adeMental

slowingworse byleep)Cold

intoleranceLethargyConstipationHeadacheConfusionJoint

painDepressionNervousnessAgitated

paranoiaWeightainMenorrhagia

or amenorrheaDecreased taste and smellSch izophren iform or man ia -l ike

psychosesSignsSkin—dry,

co ld , pu ff y,aleBradycardiayellowishDelayedretu rn o f deependonScant

eyebrowsref lexesCoarse,br it tle hairi iWater bottle―eartThick

tongueThin, brittleailsLaboratory

f indings

Thyroid horm one disturbance

the range of 0.15 to 0.3 mg/d isprobably the medication of choicefor the majority of hypothyroid patients because of its predictable action. Dosage should be adjustedupward until the T4 rises to highnormal levels. When a rapid response is necessary, the clinicianm ay w ish to consider liothyroninesodium (T3). Lower doses, beginning in the 5-@ sgrange, should beused because of this agent's rapidity of action. The level should bei nc reas ed s low ly . New med icat ion s

that represent a mixture of T4 andT3 in 4-to- 1 ratio (liotrix) arethought by some to represent amore “¿c omp le te a nd bala nc ed †•p roduct f or r ep la cemen t. 38

Cour se f ol low ing t re atmen t

If treatm ent is initiated slowly andthe patient is followed carefully,most mental and physical symptoms abate over a period of days tomonths. Some physicians have them istaken belief that if psychological symptoms have not abated

within five days following treatment, an underlying thought disorder must be present. In fact,many behavioral and mentalsymptoms may persist for considerable periods after resolution ofthe physical complaints. It is notunusual for patients to report thatfrom two to six months elapsedbefore they felt that their mentalfunction had fully returned to normal. Sleep and consequentlyhuman-growth-hormone releaseduring sleep m ay rem ain disturbedfor several w eeks to m onths follow

ing replacement of thyroid hormone.Patients who have been psychot

ic usually experience the disappearance of delusions and hallucinations w ithin the first w eek. T his isp articu larly tru e if a ntipsy ch oticsare added when thyroid hormonereplacem ent is begun. Gradually,over the next week to ten days, thepatient becomes more alert and thephysical signs of myxedema beginto resolve.3 9 K ales a nd asso ciates4 °

have shown that improvement inclinical condition tends to parallelresto ratio n o fn orm al sleep pattern sand, in fact, suggested that the return of normal sleep may be anexcellent predictor of treatm entoutcome.

Discontinuation of therapy bythe patient typically leads to a return of symptoms within a shortperiod.33 If the patient is taking T4or a m ixed T3 plus T 4 preparation,psychotic sym ptom s usually reap

pear over four to seven days. Psychosis may reappear w ithin 12 to 18ho urs w hen T 3 is d isco ntin ued .

Some patients become worse follow ing initiation of treatment.Mason4' suggests that smallchanges in thyroid levels produced ram atic effects' o n b rain fu nc tio n.If mental symptoms are worsened;

T4le ss th an 3 .5 @g /1 00mL

Radio io din e upta ke below 10% in 24 hou rs

T3uptake usua lly lowPlasmacho les te rol e leva ted in pr imary hypothy ro id ismMacrocyt ic anemia poss ib ly present17-ke tos te ro ids may be low

Thyro id -s timulat ing hormone (TSH) radioassay e levated in primaryhypothyroidism

Adap led w it h pe rm is si on f rom Cu rr en t Medi ca l D iagnos is and T rea tmen t, 1978 , pp 67O@672Ko lbFO@).

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by treatment, the reinstitution oftherapy at lower dosages is recommended . Phenothi az in e s ( ch lo rp rom azine or thioridazin e) are usefulin moderate dosages (100 to 300mg/d) for the treatment of myxedematous p sy chos is .

HYPERTHYROIDISMHistory

In 1 91 8, W oo db ury °2 de scrib ed th em anifestations of G raves' diseaseas inv olv in g fatigu e, irritab ility , intolerance to cold, fine trem or, restlessness, in som nia, ex citability , la

bile emotional disposition, nerv ou sn es s, w eig ht lo ss, p alp ita tio ns ,doubts, and fears. Amburg andLunde43 later depicted the hyperthyroid patient as “¿characterizedby hyperexcitability, irritability,restlessness, increased sexual m otivation, exaggerated response toenvironm ental stim uli, em otionalinstability and ultim ately psychosis.―There seem s to be a consensusin the literature concerning the occ urren ce o f fatig ue, irritab ility , an d

instability of personality, but psychosis associated with hyperthyroidism remains a much less common f inding.

The prevalence of psychosis insevere hyperthyroid states has beenreported to range between 1% and2 0% . In 1928, Johnson 44 studied2 ,2 86 patien ts w ith o perativ e g oiterand found only 24 cases of psychosis. However, many clinicians believ e that th e in cid en ce of p sy ch osisin hyperthyroid states is consider

a bly h ig her. L id z an d W hiteho rn ,2 4K lein sc hm id t a nd asso ciates,4 5 a ndDeutsch46 stated that the rate ofpsychosis in hyperthyroid patientsapproximated 20% . Bursten47 reported an 18.5% rate of psychosisam ong hospitalized hyperthyroidpatients, but noted that this was aselected population. In another

s tu dy 'Â °7 f8 ,0 00 p sy ch otic a nd 2 ,5 00schizophrenic patients, he found ano verall in cid en ce o f h yp erth yroidism of less than 1% ; these figuresare in fundam ental agreem ent withf in dings by B lu es tone .48

It is interesting to note that them ajority of the existing literatureconcerning the mental effects ofh yperthy ro id ism ex plo res p ossib lepsychogenic etiologies for this syndrome, rather than defining clearcut mental changes of the type thatoccur w ith hypothyroidism . In reviewing the literature, one is left

The pre va lenc e o f psy chos is

in severe h yp erth yro id ism is

between 1% and 20% .

w ith the im pression that psychoticm en tal ch an ges in the hy perth yro idstate are not only less common butless ex trem e in th eir m an ifestationthan those occurring w ith hypothyroidism.

Ettigi and Brown49 note that hy

perthyroidisms“¿lmostnevitablyassociated w ith m ental changes.―The most common presentingsymptoms includenervousness,

manifested as apprehension, restlessness, and inability to concentrate; m arked em otional lability;and hyperkines ia .5°

PsychosisThe “¿ yp ic al †•sychosis of hyperthyroidism is reported by most authors42-44 to sim ulate a m anic-de

p re ssiv e p sy ch osis. O th er p re se ntations reported in the literature2 4-'1'4 749 i nclu de sim ple, catato nic , a nd p ara no id s ch iz op hre nia ;p sy cho tic d epression ; “ ¿ un ction alpsychosis―; organic brain syndrome; and psychoses of undeterm in ed ty pe.

Reports are available of psycho

sis o ccu rrin g in h yp erth yro id states,w hich w ere subsequently reversedb y s urg ery . R uliso n a nd a sso cia te s5 'describe a case characterized bypsychosis with hallucinations anddelusions that cleared follow ingth yro id ec tomy . B lu esto ne 48 re po rted on three cases “¿eachf whichresponded to thyroidectomy withabrupt cessation of psychoticsym ptom s.― G reer and Parsons52described a hyperthyroid patientwho presented as a paranoidschizophrenic. Consistent agreem ent can be found in the literature

th at fatigu e, irritab ility , em otio nalinstability, and excitability are allcommon features of the hyperthyroid state, as are episodes of severeand often disabling anxiety. Noclear picture, how ever, exists concerning any fixed psychotic constellation of sym ptom s or progression of psychiatric disease. Someind iv id uals b eco me d elirio us, w hileothers experience periods of hyperexcitability sim ulating m aniathat alternate with periods of ex

h au stio n a nd d ep re ss io n.

Othe r symp toms

T he m ost frequent office presentation of hyperthyroidism is a hyperactive individual com plainingof anxiety and nervousness. Often afine generalized trem or is present,and the patient w ill report feelingshakyorjittery.amilymembers

often remark about personalitychanges and marked increases inboth irritability and emotional lability. Jefferson and M arshall53point out that this “ ¿nervousness―sd is sim il ar to th at s ee n in th e p atie ntwith anxiety neurosis, in that it is“¿c ha ra cte riz ed b y re stle ss ne ss ,shortnessf attentionpan,and a

need to m ove about.―Popkin and M ackenzie2 state

that the behavioral changes of hy

(continued)

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Thyroid hormone dis turbance

perthyroidism are numerous andfrequently suggest a diagnosis of

either anxiety neurosis orn eu rasthe nia. H yp erth yroidismcan be differentiated from theselatter conditions by the follow ingfin din gs: â €œ ¿ nhyr oid dys func tio n,sleeping pulse w ill rem ain accelerated; sedated pulse will exceed 80;palms will be dry and warm, notcool and clammy; fatigue will beaccompanied by a desire to be active; and cognitive dysfunction ismore prominent than in neurasthenia.―

R estlessness, increased w ork activ ity , a nd emo tio na l e xp lo siv en essoccur fairly frequently, as doesm arked em otional lability w ith unexpected tearfulness and crying,which often produce a sense ofshame and bewilderment in thep atien t. W hen q uestion ed , p atien tsreport that they are unaware of whyth ey are cryin g. O ften th ey d escrib edim inished frustration tolerance,and although their work energyseem s in creased, th eir actu al ab ility

to complete tasks is diminishedowing to shortened attention spanand heighte ned d is tra ctib ilit y.

Subtle cognitive changes areclearly dem onstrable in the hyperthyroid patient.54 Cognitive diso rd ers p resen t o n testin g d isapp earas thyroid levels return to norm al.W ilson and associates55 were ableto show that the experimental adm inistration of T3 to 11 norm al volunteers, sim ulating an acute hyperthyroid state, produced markedchanges in interpersonal functioning and caused dysphoria, depression, jitteriness, and decreasedfriendliness.

Several invest igators45-56have reported depression to be associatedwith the hyperthyroid state. W hendepression does occur in the hyperthyroid patient, it is qualitatively

and quantitatively less severe thand ep ressio n in hy po th yro id p atien ts.

M ost patients w ith hyperthyroidism do not report significant depression. When it does occur, it ismore likely to be of the agitatedtype rather than the retarded type,and to be associated with markedvariability of mood rather thanc on siste ntly d ep ressed m oo d.

Apathetic hyperthyroidism , described by Lackey57 in 1931 (andalso referred to as “¿silentorm ask ed†• thy ro to xico sis bec ausethese patients do not appear to be

The b eh avio ra l ch an ges o f

h yp erth yro id ism a re many

an d o ften sim ula te an xiety

neuros is or neuras thenia.

in a hypermetabolic state), maypresent as retarded or stuporousdepression or apathetic dem entia.This presentation is m ost frequentin the elderly. Initially the patient

may complain of confusion, fatigue, weakness, profound weightlo ss, and cardiov ascu lar co mp lications. L ater, depressive features becom e m ore m arked. T he depressionderiving from apathetic hyperthyroidism sim ulates that seen in som ecases of hypothyroidism . Oftenthese patients appear to have advanced psychom otor retardationand to be totally detached and disinterested in any attempt to reachthem 58

W hile h yp oth yroid ism freq uen tly coexists w ith m ajor psychiatricsymptoms in hospitalized mentalpatients, hyperthyroidism does notseem to be particularly prevalent inth is p op ula tio n. B urs te n4 7 re po rte donly ten cases of thyrotoxicosis in8,000 overtly psychotic patients,while Bluestone48 was able to find

only one hyperthyroid patient in agroup of 1,000 patients at a large

pub li c menta l in sti tu tio n.A ltho ug h the re is n o ch aracte ristic, sin gle psy cho sis asso ciated w ithhyperthyroidism , paranoid sym ptoms, suspiciousness, and maniclike states are most frequently reported. W hybrow and associates59report that both the schizophreniaand paranoia scales of the MMPIare consistently elevated in hyperthyroid patients w ith psychosis.These authors stress that the mental changes encountered clear

quickly following treatment, suggesting that the behavioral manifestations of hyperthyroidism aretoxic pheno mena rather than som eform of liberated “ ¿atentsychos is.â €•T he se fin din gs a re s up po rte dby the work of MacCrimmon anda sso cia te s,6° who d emon stra te dM MPI scale deviations in hyperth yro id p atie nts su gg estiv e o f h yste ric al s om atiz atio n. T he se p atte rn sreturned rapidly to norm al following treatm ent. T his study indicates

that the behavioral, neurotic, andpsychotic m anifestations of hyperthyroidism are related more to thebiochemical abnormalities associated with the disease than theyare to the patient's previous persona li ty pa tt ern.

Physi ca l d iagnosi s

P hysical sig ns and sy mptom s tha toccur in 70% or more of hyperthyroid patients include tachycardia,go iter, nerv ou sn ess, so ft m oist skin,fine trem or, hyperhidrosis, heat hyp ers en sitiv ity , e xo ph th alm os , sta re ,dyspnea, weight loss, bruit over thethyroid, palpitations, fatigue, m uscular weakness, and loose stools.The disease has its highest incidence in women between the agesof 20 and 40. W hen hyperthyroidism is associated with a diffuse

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WeaknessHeatntoleranceIrritabilityRestlessnessNervousnessEasy

fatigabilityPersonality

changeIncreasedppetiteAnxiety

statesSpeechuickenedLoose

stoolsSignsSweatingPretibial

myxedemaWeight

lossPeriorbitaldemaTachycardiaLidlagSkin—soft,

mo is t, warm, thinLack of pupil laryccommodationTremorHair

fine andilkyStareSpider

angiomasExophthalmosGynecomastiaGoiterMeans'

murmurBruit

overhyroidSplenomegalyClubbingofingersLymphadenopathyInfiltrativedermopathyMuscleast ingDyspneaOsteoporosisPalpitat ionsLaboratory

findings

Thy ro id hormone d istu rb an ce

goiter and ocular signs, the condition is term ed Graves' disease. Clinicians should remember thats pid er a ng ioma s a nd g yn ec omastia ,w hich m ight otherw ise sugg est h epatic disease or alcoholism , occurcommonly in hyperthyroid patients. O ther physical signs that theclinician may not routinely associate with the condition, but whichin fact are com mon, include a harshpulmonary systolic (M eans') murmur, lymp ha de no pa th y, a nd s ple nom egaly. O steoporosis also occurscommonly in patients w ith long

standing disease. Additional skinsigns include pretibial m yxedem a(a localized, nonpitting, hard, bilateral sw elling over the tibia), andan infiltrative derm opathy withsimilar infiltrations over the dorsum of the feet. Clubbing andswelling of the fingers may alsoo cc ur (se e T ab le 2 ).

Labor ato ry d ia gnos is

L ab ora to ry fin din gs c ha ra cte risticof the disease include elevated

rad io -T 3 resin u ptak e, an d elev atedT4 and radioiodine uptake. The radio iod ine up take charac teri st ica llycannot be suppressed by T3 adm inistration. A n unusual conditioncalled T3 toxicosis evidences normal T4 levels with elevated serumT3. Serum cholesterol may be lowand postprandial glucosuria maybe present. Urinary creatininelevels are usually increased. Lymphocytosis is generally present. H ypokalemia may also occur. Thy

roid-stimulating hormone (TSH)levels are usually low, while longacting thyroid stimulator (LATS)and thyroid stimulating immunog lo bu lin (T SI) a re e le va te d.3 8

Differential diagnosis

T he m ajo r p syc hiatric differen tia lsinclude m anic-depressive psycho

sis, manic phase; anxiety neurosis,

particularly in menopausalw om en; schizoaffective disorders:

and drug abuse (stimulants, amphetam ines. cocaine, phencyclidine). O ther m edical problem s thatshould be included in the differential diagnosis are acute and subacute thyroiditis, pituitary tum or,and other conditions associated

Symptoms

with a hyperm etabolic state such asleukemia, polycythemia vera, andsevere anem ias. Pheochrom ocyto

ma and acromegaly may be associated with hypermetabolism andan enla rg ed th yro id g la nd !@

Treatment

Controversy still exists as to themost efficacious treatment for a

Elevated 14

Elevated radio-T3resin uptakeRadioiod ine up take e leva ted (Fa ilu re o f supp ress ion by T3

administration).

Serum cho les te ro l usual ly lowUr inary creatine increased

Pos tprand ia l g lycosuria may occurLymphocytosis

Ur ina ry and serum ca lc ium may be e leva tedTSH c a n b e low w hile L ATSa n d TSI a re e le va te d

Adaptedwithpermissionfrom CurrentMedicalDiagnosisand Treatment.1980,pp687-694(KoIbFO,CamargocA7t).

16 PSYCHOSOMATICS

Table2—D iagnosticeaturesof Hype rthyroidism5

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particular patient. The literaturetoday suggests an increased tendency toward long-term medical

treatm ent, fo llow ed b y rad io io dinetherapy, rather than surgicalth yro id ectom y. M edical treatm en tis performed with drugs of thethiouracil type, often combinedwith iodine. In addition, particularly for patients being preparedfor surgery, the use of propranololin doses of 80 to 240 mg/d seems aneffectiv e and rap id w ay o f rev ersin gthe toxic m anifestations of the disease. Because propranolol m erely

controls the symptoms rather thanrev ersin g th e hy perm etab olic state,escape and thyroid storm mayoccur. Radioactive iodine has provided excellent results in the treatment of diffuse or toxic nodulargoiter.

T he clinician needs to rem em berthat lithium , which acts as a colloidtrap, is effective in reducing theseverity of hyperthyroidism . T his isparticularly im portant in psychiatry, since one of the most frequent

psychiatric m isdiagnoses is that ofm anic-depressive disorder. If thisdiagnosis is accepted in a hyperthyroid patient without appropriate study, lithium adm inistration often produces dram atic shortterm results and thereby erroneously confirms in the clinician'smind the diagnosis of mania. Thedilemma with lithium therapy is

that it is only an adjunctive treatment for hyperthyroidism , andmisdiagnosis may predispose the

patient to the subsequent developm ent of thyroid storm .

If a hyperthy roid patient de velops psychotic sym ptom s, these canoften be controlled with either res erp in e o r c hlo rp romaz in e.6 ' H a loperidol has also been reported62 tobe effective in treating psychosisassociated w ith thyrotoxicosis thatis u nre sp on siv e to c hlo rp roma zin e.H ow ever, several case reports63'66indicate that there may be in

creased neurotoxicity associatedwith haloperidol in hyperthyroidpatients.

F in ally , se ve ra l re po rts 67 '6 8 e xistof nonpsychotic hyperthyroid patients developing what appears tobe either a schizophreniform psychosis or an agitated organic psychosis following the initiation oftreatm ent w ith antithyroid drugs.Consequently, vigilance is neededduring the treatm ent phase.

Thyroid screeningin psychiatric patientsGold and associates69 recentlydemonstrated the value of endocrine screening in psychiatric patients. In their study of 250 consecutive patients adm itted to a psychiatric hospital with the diagnosis ofdepression and anergia, endocrinediseases were a frequent finding.

Twenty of these patients w ere determined to be hypothyroid. Thethyrotropin-releasing horm one test

w as the m ost useful in establishingth e p ro pe r d ia gn osis .

In a study of 480 newly adm ittedpsychiatric patients, conducted atthe Y ale-N ew H aven P sychiatricEvaluation Unit, Cohen and Swigar7°dem onstrated elevations ineffective free thyroxin (EFT) in 43patients (9%). Twenty-seven ofthese patients were thought to besu ffering fro m †œ¿acutet ress hyperth yroidism .― T he E FT lev els o f th is

group spontaneously reverted tonorm al w ithin tw o w eeks follow ingadmission.

In addition, the EFT level wasdim inished in 42 patients adm ittedto the unit (9%). In 16 of thesep atie nts th e E FT le ve l su bse qu en tly had returned to norm al, A presumptive diagnosis of secondaryhypothyroidism was made in eightpatients. A n additional nine patients w it h known thyroid d is ea sewere fo un d to b e ta kin g in ad eq ua te

or excessive replacem ent therapy.Cohen and Sw igar 7°onc luded tha tthyroid function tests are of valuein psychiatric patients, but theycaution that diagnosis and treatment should not be based on asingle laboratory value. Rather,careful physical and laboratory examination is necessary to ensureproper diagnosis a nd treatm ent. 0

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18 PSYCHO5OMATIC5

T hyroid horm one disturbance