THYROID DYSFUNCTION IN CHILDREN,DIAGNOSIS, AND TREATMENT

By ZINA E. MONCRIEFF, M.A., M.R.C.P.

Disease of the thyroid gland in childrendiffers sufficiently from thyroid dysfunction inadults to warrant some special study. It isnot common, and yet, with the exception ofadenomatous goitre with hyperthyroidism, allthe major diseases of the thyroid gland, whichaffect adults, have been seen in children. Theymay be divided for convenience into twogroups, non-endocrine, and endocrine dis-orders.

Nonr- Endocrine Conditions

Congestion. A temporary hyperaemia of thethyroid gland may occur at birth, puberty,menstruation, or during the course of an acuteillness. The gland becomes enlarged, firm andmay be tender. The swelling subsides with-out any treatment, though cold compressesmay hasten its disappearance.

Acute th,yroiditis. This is uncommon inchildren. It may result from the toxaemia ofan acute infection, or may be due to actualbacterial invasion of the gland. It may occurin a thyroid, which was previously normal, orbe superimposed on a goitrous gland(strumitis). The thyroid presents the featuresof an acute inflammation, and the generalsigns of any acute infection are present. Thegland becomes acutely swollen, and tender,and swallowing is usually painful. Theswelling may be large enough to producesymptoms of pressure, and then dyspnoea maybe severe, and distension of the neck vessels,with cyanosis of the face and neck may bepresent.

Treatment. It is that of any acute in-flammatory process with local applications ofheat to the gland, and general measures tocombat the infection. The patiept should be

kept at rest in bed, and fluids taken copiously.If dyspnoea is present, a tracheotomy setshould be kept ready at the bedside, for atracheotomy may become necessary. Sulpha-mezathine or penicillin should be given inadequate dosage.Acute thyroiditis generally subsides within

the course of a few days, but some cases maygo on to suppuration (suppurative thyroiditis).The treatment for this is surgical.

Chronic thyroiditis. This condition is vetyrare in children. The gland is enlarged andfirm and may be nodular There are no signsof endocrine disturbance, though in somerecorded cases a slightly lowered basalmetabolic rate has been noted. The diagnosismay be ascertained in some cases only afterstudying sections of the gland after subtotalthyroidectomy.

Carcinoma. This is- a rare occurrence in anormal thyroid gland. It is met with morefrequently as a secondary change in anadenomatous goitre. Cases occur at any age,and twice as commonly in females.The danger signals are:i. A change in consistency from a soft to a

hard, irregular, nodulated swelling, generallyin one portion of the gland.

2. An enlargement of cervical lymph nodes.3. The development of hoarseness,

dysphagia, or dyspnoea not due to obviouspressure from the size of the gland.

Treatment. This is surgical with subsequentirradiation therapy.

Endocrine Disorders

Simiple or endemic goitre (colloid, parenchy-matous, non-toxic). The simple hyperplasia

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POST-GRADUATE MEDICAL JOURNAL

which results from a low intake of iodine inthe diet is known as simple goitre. In thedistricts, chiefly mountainous, where thisdisease is endemic, there is an increased rate ofdeaf-mutism, cretinism and idiocy.The commonest age incidence is just before

or at the time of puberty, though cases haveoccurred in which a goitre has asphyxiated thefoetus in utero, and others in which the thyroidswelling produced a difficult delivery of theinfant (congenital goitre). Girls are moreaffected than boys.The thyroid presents a smooth, soft,

symmetrical enlargement. The swelling variesin size from one which is scarcely appreciableto an enlargement which may cause markedpressure symptoms. The latter is morefrequent in congenital goitre, and the criticalperiod is during the first 48 hours of birth.The swelling usually, though not always,diminishes in size after the first week of life.Some of these cases develop signs of hypo-

thyroidism, and in others carcinomatouschanges occur.

TreatmentProphylactic. Endemic goitre ranks as one

of the most striking examples of a preventabledisease. By the addition of iodine to the dietin goitrous areas the disease can be prevented.To this measure should be added the im-provement of bad hygiene and poor living con-ditions, for McCarrison showed that in someareas the drinking water is bacterially con-taminated, and that boiling and filtering of thewater may prevent the disease.The thyroid gland has the power to take up

iodine from any of the known compounds ofthe substance, irrespective of the method ofadministration. The method of choice, there-fore, should provide a compound which ispalatable, cheap, harmless and easy to ad-minister. The most satisfactory method ofadministration of iodine is in iodized tablesalt. It is used in place of ordinary table salt,and the recommended proportion is i part ofsodium iodide to Io,ooO parts of salt. Anychild consuming an average amount of thistable salt per day will be protected against thedisease.

Other methods of administration are avail-able. Sodium iodide 0.I3 gm. (2 gr.) may be

given daily for two consecutive weeks everyspring and autumn, or Lugol's solution onedrop weekly throughout the year. Chocolate-coated' tablets of iodostarine, a combination oforganic iodine and a vegetable fatty acid com-pound are available, the dose being ! to one5 mgm .tablet once a week.

It is important that the foetus should beprotected against this disease, and it is recom'mended that an extra intake of iodine be in-gested by the pregnant woman in endemicareas.

Curative. Once the colloid stage hasdeveloped, iodine is of limited value. It isworthy of a trial, however, for, in some cases,a diminution in the size of the gland occurs.In Great Britain Lugol's solution 9-I5 dropsare given daily, but in some parts of the world,particularly in Switzerland, and in certainparts of America, much smaller doses ofiodine are given. Workers in these partsclaim that there is a real danger of provokingsymptoms of hyperthyroidism, if excessivequantities of iodine are administered (Iodine-Basedow). Other American workers, in areasof high goitre endemicity, do not record thiscomplication.When symptoms of hypothyroidism are

present adequate dessicated thyroid substanceshould be given. The size of the gland willnot be reduced by this treatment.

Surgery is indicated if the swelling isobjected to on aesthetic grounds, or if pressuresymptoms appear; also if a nodular swellingdevelops in the goitre (this is potentiallymalignant), or if there arises the suspicion ofcarcinomatous change.

Irradiation therapy is contraindicated, for itmay result in hypothyroidism.Adenoma of the ThyroidAdenomatous goitre occurs most commonly

in goitrous areas. It has been recorded in allage groups, with the greatest number occurringin older children. As with other varieties ofgoitre, females are more affected than males.The adenomata vary in size and number, andmay cause symptoms of pressure. No case ofhyperthyroidism in an adenomatous goitre hasbeen redorded in childhood.

Treatment. Some of these cases have showna diminution in the size of the goitre after the

t (Continued on page 42.)

.7anuary, 194740

January, I947 THYROID DYSFUNCTION IN CHILDREN 41

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FIG. I.-Cretin aged six months.

42 POST-GRADUATE MEDICAL JOURNAL Jranuary, 1947

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FIG. 2.-Electrocardiogram of cretin in Fig. i, showing low voltage.

(Continued from page 40.)administration of iodine, or of dessicatedthyroid, or of both given at the same time.Others have shown no improvement. If adefinite nodular swelling persists, then surgicalremoval should be advised, for adenomata ofthe thyroid show a high rate of malignancy.Enucleation of the adenoma, lobectomy, orsubtotal thyroidectomy may be carried out.

CretinismCretinism occurs in Great Britain in sporadic

form, and in goitrous areas it appears en-demically. Endemic cretins may have thesigns of the disease at birth. In cases ofsporadic cretinism, however, the symptomsrarely appear before the twelfth week of life.

The child is afforded the protection of themother's secretion in utero, and it takes fourto eight weeks after birth for the store ofthyroxin, obtained from the mother, to bedepleted. Instances have been recorded,however, of women with goitre giving birth toinfants recognizable as cretins from birth.The earliest sign of the disease is a failure

to grow. It'soon becomes apparent that thereis a failure in mental development as well.Constipation, however, may be the firstsymptom which comes to the mother's notice,and which causes her to seek medical advice.The hoarse, rough cry of a cretinous infant isvery characteristic, and may lead one to lookelsewhere for the other symptoms or signs of

(Continued on page 45.)

January, 1947 THYROID DYSFUNCTION IN CHILDREN 43

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FIG. 3.-Toxic goitre in a girl of io years of age.

44 POST-GRADUATE MEDICAL JOURNAL January, 1947

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FIG. 4.-Same child, showing the exophthalmos.

I am indebted to Dr. Chas. Donald and to the Hospitalfor SickChildren, Great Ormond Street, for permission to publish these photo-graphs.

THYROID DYSFUNCTION IN CHILDREN'

(Continuedfrom page 42.)the disease. Even in very young cretins thethickening of subcutaneous tissues is usuallyalready present when the child is first seen. Itproduces the typical facies which makes thediagnosis unmistakeable in the fully developedcase. The face is puffy, and the eyelidsthickened, and the tongue is enlarged and pro-trudes from the half open mouth. There isoften broadening at the root of the nose withnarrow palpebral fissures. In addition to this,the hair may be coarse and dry, and the skin isthickened and may show eczematous patches.The abdomen is usually protuberant and anumbilical hernia is present. The extremitiesmay be blue and cold, as the result of the poorcirculation, and there may be markedhypotonicity of muscles. In older cretinsfatty tumours are frequently present. Theyare about the size of a hen's egg, and areplaced symmetrically in certain positions.Above the clavicles, behind the stero-mastoid muscles, in the axillae and between thescapulae are the common sites. There maybe evidence of an anaemia.

Later ManifestationsIn older cretins there may be clinical

evidence of a delay in ossification. Theanterior fontanelle which normally closes bythe end of the eighteenth month may remainpatent into adult life. Infantile proportions ofthe skeleton may persist. (That is, the midpoint of the total height is about the level ofthe umbilicus). Dwarfism, is always marked,and an untreated cretin rarely grows higherthan 3 to 4 ft., and is often much shorter. Theteeth erupt late in the case of both dentitions,and are of poor quality. Secondary sexcharacteristics may never appear.The energy exchange in cretinism is small

and these children are very susceptible to cold.The temperature tends to be subnormal andthe pulse slow. The blood pressure is low.Other aids to diagnosis

It is difficult to record an accurate estimationof the basal metabolic rate in cretins. Othermethods are available, however, for confirmingthe diagnosis.

i. Radiograms of the carpal bones will showdelayed ossification. (Normally one centre ofossification appears in the wrist per year for

the first seven years of life, excepting in thefourth year.)

2. The blood cholesterol is raised (N =I50-230 mgms. per cent.) It is inverselyproportional to the B.M.R. Its return tonormal forms a good criterion of the responseto thyroid therapy.

3. The total blood lipoids are increased.4. There is an absence or diminution of

creatinin in the urine.5. There is a therapeutic response to the

administration of thyroid substance and, indifficult cases, this may be the most helpfulconfirmatory measure. It produces a briskreticulocytosis after ten days administration,and this fact may be used as an early diagnosticfactor. The improvement in the general con-dition may be seen after one week's therapy.Differential diagnosis

I. Mongolism is often discussed as present-ing a possible difficulty in the differentialdiagnosis from cretinism. The two conditionsare quite dissimilar. Once a mongol childwith its slanting eyes and brachycephalic skullhas been recognized, there can be no difficultyabout the diagnosis in future cases.

2. Gargoylism at first sight is usually mis-taken for cretinism. In this condition, how-ever, as well as mental deficiency and dwarfism,there are various eye defects, and enlargementof the liver and spleen and an osteodystrophy.There is no evidence of a delay in ossification.Radiograms of the lumbar spine and the headsof long bones show characteristic changes.

3. The individual features of cretinism maybe simulated as in macroglossia, and ichthyosis,but other features of the disease are notpresent.

Treatment. When thyroid substitutiontherapy is begun and maintained from theearly months of the disease, the results oftreatment may be satisfactory. The prospectsof relief of symptoms, however, steadilydiminish with the increase in age of the un-treated patient, and this is most marked in thealleviation of mental retardation. Treatmentbegun after the child has reached the age of oneyear will produce a marked physical improve-ment, but the mental condition will never benormal. If left untreated, cretins becomedwarfs 2 to 3 ft. high with a gross amount of

.7anuary, 11947

POST-GRADUATE MEDICAL JOURNALmental defect. Treatment begun in olderchildren may rouse a placid cretin into a stateof peevish irritability, and, in others, symp-toms of hyperthyroidism may be induced.The correct dose of thyroid extract is that

amount which will produce normal growth anddevelopment, without any symptoms of hyper-thyroidism. The substance must be ad-ministered only under medical supervision.Parents must be instructed that the treatmentmust continue throughout the child's life-time, for an interval of some months withouttreatment may produce mental impairment,which is never correctable.Thyroid substance begins to act within

three to seven days of ingestion and, whencontinuous daily doses are taken, the maximaleffect may be delayed until the end of thethird week. Signs of toxic reaction to thedrug in cretins are not unusual, and thismay appear after the exhibition of a singledose or during the course of thyroid therapy,which has continued for several yeals. Bearingthese facts in mind, a useful scheme of dosageis the following:

Extract thyroid sicc. gr. I/IO t.d.s. for oneweek.

Extract thyroid sicc. gr. I/8 t.d.s. for afurther week.

Extract thyroid sicc. gr. I/4 t.d.s. for onemore week, and so on.The correct maintenance dose of thyroid

extract is obtained by producing signs ofhyperthyroidism, it is then reduced and it isthat amount at which these signs disappear.The signs of hyperthyroidism may bediarrhoea a rise in the body temperature anincrease in the pulse rate, sweating, irritability,disturbed sleep, or a marked loss of weight.An initial loss of weight is common, but thisshould never be allowed to become drastic. Ifany of these signs become severe, the drugshould be withdrawn completely until theydisappear, and a start then made again with areduced amount. If, however, any of thesesigns appear and are not sufficiently severe toaffect the child's general condition, the drugshould be persevered with.

Care should be taken to ensure that thethyroid substance which is being administeredis potent.As growth is likely to be rapid, it is important

that big doses of vitamins, particularly ofvitamin D, should be given with regularity.

If there is any anaemia present, it is likelyto be of a simple nutritional type. Iron may begiven as iron and ammonium citrate, or asferrous sulphate, in a mixture starting withsmall doses and working up to relatively largeamounts by daily increases.

Hypothyroidism-Infantile MyxoedemaThyroid deficiency may become apparent at

some time after birth, generally not before thesecond year. The history is frequently thatthe child has been developing normally, andthen, often after some acute illness, a delay ingrowth and signs of mental retardation appear.He shows an inability to learn and may losethe ability to do the things he had formerlyacquired. He becomes dull, lethargic, andunclean in his habits. He often complainsreadily of cold.The signs of the disease are essentially those

of cretinism. In severe cases it is hardlypossible to err in the diagnosis, but when thedisease is mild, or of short duration, thediagnosis may be made only by the therapeuticresponse to the giving of thyroid.The rules for treatment are similar to those

already indicated foi cretinism. Prompttreatment produces a striking relief ofsymptoms, and physical growth and in-tellectual attainment may become normal.Delayed, or inadequate therapy will bringabout mental retardation, which can never becorrected.As in cretinism, a generous allowance of

vitamins must be provided, and iron should begiven to correct any anaemia.

Hyperthyroidism (Toxic, exophthalmicGoitre)

This is an uncommon disease in children.It has been recorded in the infant of a mothersuffering from toxic goitre, but it is unusualbefore the age of eight years. The commonestage incidence is before puberty. It is com-moner in girls in the proportion of 5 : I.The clinical picture is essentially the same

as that seen in adults, but the disease appearsmore suddenly and disappears with much

46 ya2nuary,. I947

THYROID DYSFUNCTION IN CHILDREN

greater rapidity. The late results of un-treated, or improperly t;eated cases, are seenfar less frequently than in adults. Permanentdamage to the heart has not been recorded.Crises are less frequent and less severe.Nervousness is the most frequent complaint,followed by tachycardia, goitre, and exophthal-mos in that order. Nervousness associatedwith an enlargement of the thyroid gland inchildren is very suggestive of this disease.The child usually becomes irritable, emotion-ally unstable, and unmanageable. She is oftenconstantly in motion with chorea-like move-ments and can be kept quiet only withdifficulty. Vivacity is usually a markedfeature. Augmentation of the height iscommon, yet there is usually a loss of weight,associated with an excellent appetite. Someof these patients gain weight. Diarrhoea iscommon.On examination, four-fifths of the cases

show exophthalmos, and Stellwag's and vonGraefe's signs are usually present. The skinmay be warm and moist. The fine tremor ofthe hands seen in adults is usually missing. Itis a coarse tremor and may be accompanied bycoarse involuntary movements. The goitre isa diffuse enlargement of one or both lobes, anda bruit can be heard on auscultation. Almostevery case of this disease, though not all,shows an enlargement of the gland. It maybe sufficiently enlarged to come to the notice ofthe parents, or may be discovered only afterclose scrutiny. Tachycardia is likewise almostalways present, and the child may complain ofthe violent action of the heart. There may besome evidence of cardiac dilatation. Thesystolic blood pressure is raised, with aresultant high pulse pressure. A disturbancein carbohydrate metabolism may be apparentby occasional glycosuria.Investigations

I. The basal metabolic rate is raised, and itis often higher than the clinical picture wouldwarrant one to expect. It can be estimatedwithout difficulty as a rule, and it forms anexcellent measure of severity and progress.

2. Radiograms may show an advanced boneage.

3. The blood cholesterol is diminished.4. Some workers have shown that there is a

lack of sensitivity to the action of quinine.They claim that quinine sulphate, 5 gr. giventhree times a day for some days, will notproduce the signs of cinchonism.

Medical TreatmentTreatment. In mild cases, and in those of

short duration medical treatment is justified.If a prompt subsidence of symptoms and signsoccurs then it may be continued. Attentionshould be directed towards securing mentaland physical rest. It may be sufficient to keepthe child at home with extra rest and with anadequate intake of a sedative. In less mildexamples of hyperthyroidism, it may benecessary to keep the child in bed completelyat rest. It may be wise to remove the childfrom its home, away from family discussions,quarrels and extraneous noists. If the diseaseis of any severity, contact with other childrenmust be avoided. Anything calculated toirritate ol excite the patient must be eliminated.She must be piotected from intercurrent in-fection. Attention must b;- directed towardsthe eradication of any septic focus, but anyoperative procedures must be permitted onlyduring a quiescent period of the hyper-thyroidism.

Sedatives. Phenobarbitone is still one of themost effective drugs for producing a quietstate in this condition. Children tolerate itwell and there is no cumulative action. Thedose varies from 1 gr. in small children to1 gr. at the age of twelve years given threetimes a day. Older children may be givenlarge doses with impunity. It may be givenwith a potassium bromide and chloral hydratemixture. Other drugs which may be tried arenembutal and amytal. Whatever drug ischosen, enough of it must be given to keep thepatient quiet, without producing any toxicmanifestations.

Diet. It should provide a high caloric intakeand, in most cases, be unrestricted in variety.Protein is necessary to make good the tissuewaste inevitable with a high metabolic rate,but should not be given in excess, because ofits specific dynamic action.

Iodine. Much difference of opinion existsover the advisability of administering iodine topatients suffering from hyperthyroidism.

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POST-GRADUATE MEDICAL JOURNAL

Many mild cases will be cured by employingthe treatment which has been outlined. Itmust be remembered that others achieve aspontaneous cure at puberty. When thesymptoms of the disease are not checked bya short course of rest and sedatives. then it isjustifiable to administer iodine. In childrenits maximal effect may not become apparentfor two to three weeks. As little as 2 m.Lugol's solution three times a day will producethe optimum effect, and larger doses of themixture do not enhance its beneficial action.It may be given in courses of from one tothree weeks, the drug being withdrawn be-tween courses when it becomes apparent thatthe optimum effect has been obtained. Theresponse to iodine is never so dramatic as it isafter the first course. In some cases sufficientimprovement in the nervOus and toxic symp-toms and in the B.M.R. is maintained aftereach course to warrant the continued adminis-tration of iodine. In others it becomes evidentthat the disease has become refractory tofurther dosage and the drug should bewithdrawn.No one will challenge the undoubted value of

iodine *in pre-operative and post-operativetreatment. Lugol's solution, 2 m. t.d.s.,should be given for the three weeks immedi-ately pre-ceding operation.

Thiouracil. This drug may be used in thetreatment of thyrotoxicosis per se in mild cases,or as a pre-operative measure. The prepara-tion of patients for surgery can usually beaccomplished with this drug in eight weeks orless. Its employment in children has not yetbeen fully evaluated. Three results, howevermay be looked for.

i. The drug may produce no effect. Dosesemployed have varied, but average about o.ior 0.2 gMn. per day. If there has been noprevious iodine therapy, medication should becontinued for at least 30 days or, if iodine hasbeen administered, for 6o to IOO days, beforeconcluding that no response to thiouracil willoccur.

2. The disease may be controlled and thebasal metabolic rate may be reduced or evenfall to within normal limits. The amount ofthiouracil is then reduced by at least half andthis may be continued as a maintenance dose.

Information is still lacking as to the pet -manence of improveVient in the disease.

3. Toxic manifestations may appear. Thedanger period is within the first I2 weeks oftreatment, and from four to eight weeks mostcomplications have been recorded. In patientswho have received previous treatment withthiouracil these may appear as early as thesecond week. The incidence of toxic re-actions up to nine months make continuedsupervision essential during administration.The reactioris to be looked for are granu-

locytopenia, leucopenia, fever, skin lesions,lymph node enlargement, jaundice, purpuraand anaemia. Parents must be instructed toreport at once the occurtence of sore throat,fever, cold in the head or malaise, and anyother untoward symptom which may occur.Toxic reactions appearing early call for awithdrawal of the drug. Blood changes arealways of serious significance and they indicatean instant cessation of the treatment. It isimportant to note the fact that toxic manifesta-tions may appear during a second course ofthiouracil, although the first course was givenwithout incident.

Surgical TreatmentIn any but the mild cases of this disease

surgical intervention is advisable. Childrentend to react severely to surgical operation butthe pre-operative treatment with iodine and,more recently, thiouracil, has materiallyaffected the mortality rate. The operation issubtotal thyroidectomy. At the Mayo Clinic157 children suffering from hyperthy.,oidismhave been treated. Of these 136 were tieatedsurgically, and surgical intervention wasrecommended, but did not take place, in someof the remaining 2I cases. Before the intro-duction of iodine the surgical mortality rateat the Clinic was estimated at 9 per cent., and,since iodine has been used pre-, and post-operatively, this figure has been reduced to2.5 per cent.These patients should be observed at fre-

quent intervals for one to two years afteroperation. Some of them develop signs ofhypothyroidism; others show a recurrence ofthyrotoxicosis. A watch should be kept, there-fore, and if symptoms appear, the appropriatetreatment should be cai ried out.

)Ianuary, 1947