Hyperthyroidism in children under five years of age

HYPERTHYROIDISM IN CHILDREN UNDER FIVE YEARS OF AGE REPORT

OF FOUR

CASES

GEORGE CRILE, M.D. AND GEORGE CRILE, JR., Department

Resident

of Surgery

M.D.

in Surgery

CIeveIand Clinic Foundation CLEVELAND,

H

is not often YPERTHYROIDISM seen in childhood, and its occurrence A * in children under five years of age is so rare that it is aImost a medica curiosity. In a previous communication’ the Enghsh literature on hyperthyroidism in children has been reviewed and can be summarized by the statement that in children under five years of age, only seven cases of clearcut hyperthyroidism have been subjected

In a series of 26,682 cases of thyroid disease which have been seen at the Cleveland Clinic, the fohowing 4 occurred in chiIdren less than 5 years of age, an incidence of one in 6670 cases.

TABLE I CASESOFPROVEDHYPERTHYROIDISMINCHILDRENUNDER 5 YEARS OF AGE REPORTED IN THE ENGLISH LITERATURE

Author

Age

Sex

Treatment

HeImhoItz. Braid and NeaIe....

3

M

Thyroidectomy

Cure

2)s

F

Thyroidectomy

Lahey......

3

not

Thyroidectomy

Operative death Cure

Stephen .._

Beilby and Carlton., Kerley......

2

stated F Conservative

Outcome

Cure

!

234 35/z EIIiot....... 245

Thyroidectomy Conservative Thyroidectomy

Cure Cure Cure

to adequate diagnostic studies and fuIIy reported. These cases with the age and sex of the chiId and the name of the author who reported them are shown in Table I. ~CRILE, GEORGE, JR. and BLANTON, J. LEWIS. Exophthalmic goiter In a maIe child two and one-half years of age. Am. J. Dis. Cbild., 53: 1039-1046 (April) 1937.

OHIO

CASE I. The patient was a girl 4 years and 3 months of age (Fig. I). The parents stated that prominence of the eyes had been noted at the age of two and one-haIf years and had remained unchanged until eight months before entry at which time the tons& were removed. FoIIowing this procedure the eyes appeared to recede. FuIlness of the neck, excitabiIity and irritabiIity were also noted. During the year before entry LugoI’s soIution, in doses of one minim daily, was given and improvement was noted following this treatment. On several occasions when iodine was withdrawn for more than a week, it was noticed that the symptoms became worse. In the preceding eight months, aIthough the patient had grown one inch in height, she had Iost one pound of weight. It is interesting that the mother of the patient had a goiter, a maternal aunt had hyperthyroidism, and a materna1 uncIe had a goiter and had aIways been nervous. The mother took iodides for a time during her pregnancy. PhysicaI examination showed the p&e rate to be I~O. The systohc blood pressure in millimeters of mercury was IOO and the diastolic, 5. There was a diffuse, solid enlargement of both lobes of the thyroid gland but no thril1 or bruit couId be made out. The heart was slightIy enlarged to the left and there was a systolic murmur at the apex. A digital tremor was present and the skin was warm and moist.

389

390

American Journal al’ Surgery

CriIe

and

Crile,

Jr.-Hyperthyroidism

Inasmuch as the patient was improving she was advised to rest for two months and if sufficient progress had not been made at the

FIG. I. Case I. Photograph

of patient before operation.

end of this time, to have a thyroidectomy. From this point on, the patient was under the care of Dr. Dewitt Sherman of BuffaIo, New York, who states that her condition continued to improve with rest and smaI1 doses sf iodine but that the family moved away and he has had no further reports of her progress. CASE II. The patient was a girl 445 years of age. Two months before entry her mother had been toId that the chiId had a goiter and believed that the neck had enlarged a Iittle since this time. She had been taking smaI1 doses of iodine. The onIy symptoms were fatigue, nervousness and irritabiIity and the appetite was not very good. In addition, the parents had noticed that she had been masturbating. There had been no weight Ioss and no fever. The past history was entireIy negative except for a tonsiIIectomy at the age of one year. There was no family history of goiter. The weight was 39% pounds, the height forty-three inches. PhysicaI examination showed prominence of the eyes and a diffuse, smooth, firm enIargement of the thyroid gIand to about three times its normaI size. The puIse rate was 130, and the blood pressure in miIIimeters o diastoIic. of mercury was 123 systoIic, The heart was not enIarged but the apex

SEPTEMBER, ,937

imp&e was forcefu1; the sounds were reguIar and of good quality. A diagnosis of diffuse goiter with hyperthyroidism was made, and the patient was advised to take smaI1 doses of iodine (IO mg.) every second day and return in one month. In addition four minims of eIixir of sodium bromide three times daily were prescribed. One month Iater the pulse rate was stiI1 130 and the patient weighed forty pounds, a gain of one-half pound. The parents stated that she had improved strikingIy on iodine and bromides for the first two weeks, but that diarrhea deveIoped and the medicine was discontinued. The eyes were def?niteIy more prominent, and the thyroid gland seemed Iarger. The chiId was very nervous. The dosage of iodine was increased to two minims of Lugol’s soIution three times daiIy, and the patient was instructed to return in one month. At the end of this time she had gained two pounds, but was more nervous and active. A marked digita tremor and a definite staring expression and Iid Iag were present. At this time the eyes in the anteroposterior position measured Ig mm. and I 8 mm. respectiveIy and the paIpebra1 fissures measured 12 mm. each. There was definite weakness of the muscIes of accommodation and convergence. A determination of the basa1 metabolic rate, which was not satisfactory because of Iack of cooperation, showed pIus 32 per cent. Examination of the blood and urine reveaIed no abnormaIities. The blood sugar was norma and the Wassermann and Kahn reactions were negative. A roentgenogram of the chest showed a rather large heart, the Ieft auricIe being especiaIIy enIarged. In view of the steady progression of the disease, thyroidectomy was advised. The patient was admitted to the hospita1, was kept in bed, and was given five minims of Lugol’s soIution and ten grains of sodium bromide three times daiIy. The puIse rate which was 180 at entry faiIed to faI1 in response to this therapy and at the end of twelve days stiI1 120 and x50. A subtotal varied between performed under thyroidectomy was then IocaI anesthesia suppIemented with avertin in a dose of 80 mg. per kiIogram of body and gas oxygen analgesia. Fifteen weight, grams of thyroid tissue was removed and the pathoIogica1 diagnosis was “goiter, hypersIight and invoIuting.” A IittIe more pIa&,

~~~ sERIEs VOW.. XXXVII,

NO. 3

CriIe and CriIe, Jr.-Hyperthyroidism

than the usua1 amount of thyroid tissue was left in order to maintain the normaI thyroid baIance during the growth period. Operation was foIIowed by a minima1 reaction, the maximum temperature being 1or.3’~. and the puIse rate rising onIy to 160. The patient was discharged on the tenth postoperative day. Her puIse rate at that time was 120. Three months after operation, it was found that definite exophthaImos had occurred (Fig. 2). The right eye measured 20 mm. in the anteroposterior position and the Ieft eye 19 mm. The paIpebra1 fissures were widened 17 mm. The chiId had gained and measured four and three-fourths pounds since operation but was stiI1 very nervous and restIess. The had been puIse rate was 134. ConvaIescence retarded by the deveIopment of chicken pox and following this the chiId had not appeared to progress very well. A diagnosis of residua1 hyperthyroidism was made and smaI1 doses of Lugol’s solution were again prescribed. The chiId continued to masturbate a great dea1 of the time and this habit no doubt contributed to the nervousness. The teeth showed marked caries. In view of the rapidly progressive exophthalmos, it was decided to expIore the neck again, and IO grams of thyroid tissue were removed from the right Iobe. The pathologica report was again “goiter, hyperpIastic, moderate invoIuting.” The basa1 metaboIic rate at this time was only pIus 13 per cent, and in spite of the fact that a great dea1 of thyroid tissue had been removed at the first operation, symptoms of residual sympathetic nervous system instabiIity persisted; therefore it was decided to stabilize the sympathetic system further by performing a left adrenal denervation. A satisfactory denervation of the adrenal gIand was obtained five days after the thyroidectomy. FolIowing these procedures the puIse rate feI1 to 85 and remained at that IeveI. The exophthaImos, however, increased progressiveIy and six months Iater the Ieft eye measured 22 mm. in the anteroposterior position and the right 24 mm., the fissures measuring 17 and 18 mm. respectively. Twenty-one months after the chiId was first seen and fifteen months after the Iast operation, the eyes had receded to 22.5 mm. in the anteroposterior position. The puIse rate varied from 80 to 98 and the chiId weighed 47% pounds and was apparentIy deveIoping normaIIy in every respect.

A me&an Journal of Surgery 39 I

CASE III. The patient was a chiId 4 years of age. When she was about three years of age, the parents had noticed that the pulse was

FIG. 2. Case 11. Photograph of patient shortIq_ after operation.

Note persistent

exophthalmos.

abnormaIIy fast. Approximately seven months before entry it was noticed that the thyroid gIand was enIarged and about the same time the eyes became prominent. A diagnosis of hyperthyroidism was made at this time and roentgenotherapy was used twice over the thymus and six more times over the thyroid gIand. In the six months preceding this examination one minim of LugoI’s soIution had been taken twice daily. The parents stated that the chiId was nervous, irritabIe, cried easily, and had not gained in weight recentIy. It is interesting to note that the patient’s materna1 uncIe had had exophthaImic goiter. The chiId’s weight was 37 pounds and she was very nervous and excitabIe. The thyroid gIand was diffuseIy enIarged and rather soft; marked exophthaImos was present (Fig. 3). The p&e rate was 160, the apex impuIse was forcefu1, and there was a Ioud systolic murmur over the entire precordium.

392

American hurd

of Surgery

CriIe and CriIe, Jr.-Hyperthyroidism

The patient was admitted to the hospita1 where she was kept in bed for ten days and was given three-fourths of a grain of Iuminal

FIG.

3.

Case

III.

Photograph operation.

of patient

before

daiIy and two minims of Lugol’s soIution three times daiIy. At the end of this time, her pulse rate was stiI1 consistently between 140 and 160. BiIateraI Iigations of the superior thyroid arteries were performed under gas oxygen anesthesia. The improvement foIIowing this procedure was striking, the puIse rate faIiing to 135 by the eighth postoperative day. A Ieft Iobectomy was then performed and aIthough the puIse rate rose to 190 beats per minute on the second night after operation, the maximum postoperative temperature was I o I .6’~., and the condition was never critical. She was discharged from the hospital on the seventh postoperative day, the puIse rate still averaging 140. The pathoIogica1 report of the tissue excised was moderate hyperplasia of the thyroid gland. Four months Iater the patient returned and she was much improved in every way. The pulse rate was 130 at that time. The fina Iobectomy was performed with a minimum postoperative reaction and the patient was discharged on the twentieth postoperative day with a puIse rate of 90 to I 00. ConvaIescence was compIicated by the deveIopment of a transitory tetany which soon cIeared. Eighteen months after the fina Iobectomy, the patient was readmitted to the hospital for

SEPTEMBER, 1937

tonsiIIectomy. At that time her pulse rate varied between 85 to IOO and the basa1 metaboIic rate was pIus 4 per cent. Her deveIopment appeared to be norma in every respect. CASE IV.* The patient, a boy 235 years of age, was referred to the CIinic by Dr. J. Lewis BIanton who had made a diagnosis of diffuse goiter with hyperthyroidism. The onset of the hyperthyroidism had been rapid and at the time of entry to the hospital the chiId was crying continuousIy and appeared to be on the verge of a thyroid crisis (Fig. 4). ExophthaImos was present. There was a diffuse enIargement of the thyroid gIand, a persistent, forcefur tachycardia, a puIse rate of 160, muscuIar weakness, and a Iow bIood choIestero1. After tweIve days of bed rest during which four minims of LugoI’s soIution and five grains of sodium bromide were given three times daiIy, subtota1 thyroidectomy was performed under IocaI anesthesia suppIemented with IOO mg. of avertin per kiIogram of body weight. Operation was folIowed by a moderateIy severe reaction during which the puIse rate rose to 170 and the temperature to 105’~. An acute foIIicuIar tonsiIIitis complicated the convalescence, but the child made an uneventfu1 recovery. SeveraI months after operation, Dr. BIanton reported that the patient was gaining weight, was Iess nervous, and was improving in every way. DISCUSSION

As a ruIe the hyperthyroidism of chiIdren is typica exophthaImic goiter in which a11 the cIassica1 signs are present. EnIargement of the thyroid gIand and exophthaImos are quite constant findings and the diagnosis can usuaIIy be made at a gIance. TabIe II taken from Dinsmore and HeImhoItz’s studies shows the reIative incidence of the classical symptoms in chiIdren. It is apparent that exophthaImos is much more common in the hyperthyroidism of chiIdren than in that of aduIts. For this reason, the eyes shouId be one of our chief concerns in the management of the chiId * DetaiIed study of this case report appeared in Am. 1937. J. Dis. Child., 53: 1039-1046, in chiI2 DINSMORE, ROBERT, S. Hyperthyroidism dren; a review of fifty-seven cases. J. A. M. A., 99: 636-638, 1932.

NEW SERIES

VOL. XXXVII,

No.

3

CriIe and CriIe, Jr.-Hyperthyroidism

with hyperthyroidism. In al1 four cases reported here, exophthalmos was present and in the second case severe exophthaImos developed during the time the child was under treatment. This exophthaImos, as is so often the case, has not as yet receded to normaI and wiII doubtless be a cause of considerabIe diffrcuIty in Iater Iife if the patient’s occupation requires much close work with the eyes. TABLE COMPARISON HOLZ’S

OF

FREQUENCY

CASES

CLEVELAND

AND

CLINIC

AS

IN

SYMPTOMS CASES

REPORTED

BY

40 Cases,

Per Cent

100 93

IN

FROM

of Surgery

393

can safeIy be given a tria1. If conservative therapy is seIected, foca1 infection shouId be eIiminated, bed rest should be pre-

HELMTHE

DINSMORE

HeImhoIz,

Tachycardia. Nervousness. Thyroid enlargement, ExophthaImos. Bruit. Hyperhidrosis Tremor Loss of weight. Polyphagia. Weakness in quadriceps. Genera1 weakness.. Gastrointestinal symptoms Dyspnea.

Journal

II OF

THOSE

Ame&an

Cleveland Clinic, 57 Cases

(Dinsmore), Per Cent

100 91 93

:;

76 49

i; 57

ii

53

50

50

40

47 58 47

43

40

55

Since exophthaImos occurs so frequently in chiIdren, since its deveIopment may represent an irreversibIe change, and since earIy and adequate operation usuaIIy prevents the deveIopment of marked exophthaImos, it is extremeIy important to make accurate measurements of the position of the eyes if conservative management of hyperthyroidism in a chiId is to be tried. At the first definite indication of the deveIopment of progressive exophthaImos, subtota1 thyroidectomy shouId be performed. AIthough our experience with conservative therapy has not been satisfactory and we have rareIy been abIe to controI the disease without operation, in miId or early cases when the patient can be kept under cIose observation, conservative measures

FIG. 4. Case LV.Photograph of patient before operation. Patient was crying and the exophthaImos therefore, is not apparent in the photograph.

scribed, and smaI1 doses of iodine and bromides given. But since hyperthyroidism in a chiId differs in no way from exophthaImic goiter in an aduIt, and the risk of operation is no greater than in hyperthyroidism of equa1 severity in an aduIt, and since protracted conservative therapy entaiIs Ioss of opportunities in both educationa1 and physica deveIopment at a period in the chiId’s Iife when these opportunities are most needed, we can see no reason for proIonged delay of an operation which in a11 probabiIity wiI1 eventuaIIy be necessary. The mortaIity rate from operations on chiIdren with exophthaImic goiter has not been high. In the CIeveIand CIinic series onIy 2 deaths occurred in a series of 54 cases of hyperthyroidism in chiIdren under fourteen years of age. Since 1924 iodine has been used routineIy in preparing patients with hyperthyroidism for operation and since this time there have been no fataIities in a series of forty thyroidectomies for hyperthyroidism in chiIdren.

394

American Journal of surgery

C ri‘Ie and CriIe, Jr.-Hyperthyroidism

If the patient is adequateIy prepared for operation and if the postoperative course is carefuhy managed, there is no reason why thyroidectomy should entai1 any greater risk in chiIdren than in aduIts. The same principIes of management shouId appIy in deaIing with chiIdren as in aduIts. The procedure shouId be carried out as much as possibIe under Iocal anesthesia with enough basal anesthesia and gas oxygen analgesia to render the patient cooperative and quiet. After the operation, an adequate carbohydrate intake shouId be assured and glucose should be given if necessary. In severe cases, it is advisabIe to administer a soIution of IO per cent gIucose by means of a continuous intravenous drip. In norma chiIdren the metaboIism per unit of body weight is high as compared with adults, and in chiIdren with exophthalmic goiter it is extremeIy high. ChiIdren, therefore, toIerate Iarge doses of sedative drugs without much depression. In Case IV, that of a 2% year oId boy, there was no depression of respiration after hypodermic injections of one-eighth grain of morphine sulphate. CaIcuIated according to weight, this dose would be the equivaIent of five-eighths of a grain of morphia in an aduIt. It is important to remember that children with high metaboIic rates oxidize and detoxify drugs with great rapidity and that the usua1 dosages must be increased if the fuI1 therapeutic effect is to be obtained. Morphia is the most vaIuabIe sedative in the postoperative management of patients with hyperthyroidism. ChiIdren cannot rationahze or cooperate enough to remain quiet voIuntariIy, and it is here that morphia is of vaIue in giving the rest and sedation which are so essentia1 if the postoperative reaction is to be minimized. Any hesitancy in the administration of reIativeIy large doses of morphia to children should be overcome and the morphia shouId be given not in doses calcuIated on body weight, but in accordance with the physioIogica1 reaction obtained.

SEPEMBER. 1937

Avertin, in doses of 60 to IOO mg. per kilogram of body weight, has given satisfactory basaI anesthesia in operations for exophthalmic goiter in chiIdren. Before the introduction of this drug, operations were performed under gas oxygen anesthesia (as in Case III) and induction was rendered quiet and easy by the anesthetist making daiIy visits to the chiId’s room and giving her oxygen inhalations to accustom her to the gas machine. Ligations and thyroidectomy were performed in this way without arousing the suspicion of the patient or having her associate the presence of the gas machine with the postoperative discomfort. ChiIdren with hyperthyroidism require reIativeIy Iarger doses of avertin in order to obtain a given sedative effect. The 2% oId boy (Case IV) dozed for forty-five minutes after a dose of IOO mg. avertin per kilogram of body weight and at the end of this time was asking for candy. The three most common causes of death foIIowing operations for hyperthyroidism are (I) pneumonia, (2) cardiac failure, and (3) thyroid crisis. In chiIdren there is Iittle danger of postoperative pneumonia; the myocardium is not affected as is so frequentIy the case in eIderIy patients, and auricuIar fibriIIation and cardiac faiIure are rare compIications. In none of the three cases of severe hyperthyroidism reported here did any cardiac arrhythmia occur after operation. The chief danger foIIowing operation in chiIdren is the development of a thyroid crisis with its attendant vicious cIrcIe of hyperthermia and hypermetaboIism. This compIication did not occur in this series, but in Case IV the temperature rose to 105’~. and the puIse rate to I 70. AIthough the development of acute foIIicuIar tonsihitis increased the severity of the postoperative reaction, the patient’s condition was never critica1. Five grains of aspirin aIways resuhed in defervescence to a IeveI two or three degrees F. Iower than before the medication was given, and the oxygen tent afforded comfort and rest. Since the susceptibihty to postoperative pneumonia is not as marked in chiIdren as

~~~ sERlrsvoL.XXXVII,

No. 3

CriIe and CriIe, Jr.-Hyperthyroidism

in oIder peopIe, since the myocardium is stronger in chiIdren, and since a thyroid crisis can usuaIIy be modified or averted by the parentera administration of gIucose soIution, by adequate sedation with morphia, and by use of the oxygen tent, there is IittIe reason to fee1 that thyroidectomy for hyperthyroidism is more dangerous in a child than in an adult. In the early days before iodine was used in the preoperative preparation of patients with hyperthyroidism, it was often necessary to remove the gIand in stages or to perform preliminary Iigations of the superior thyroid arteries. In recent years however, we have been performing more and more one stage operations on chiIdren and have not as yet seen any reason to change our beIief that the chiId is an exceIIent surgica1 risk. SUMMARY I. Four cases of exophthaImic goiter in chiIdren under five years of age are reported.

A m&can Journal of Surgery 395

AI1 patients recovered, three after thyroidectomy and one after conservative therapy. 2. Hyperthyroidism in chiIdren is no different from exophthaImic goiter in the aduIt and thyroidectomy is the treatment of choice. 3. If it is decided to treat a miId or earIy case of hyperthyroidism conservatively, it is important to have accurate measurements of the extent of exophthaImos and to advise prompt thyroidectomy if the exophthaImos progresses. 4. Thyroidectomy presents no greater hazard in a chiId than in an aduIt. No fataIities have occurred in the Iast forty which have been perthyroidectomies formed for hyperthyroidism in chiIdren under fourteen years of age. 3. Since chiIdren are exceIIent operative risks, one-stage thyroidectomy can usuaIIy be performed without danger.