IODIDE GOITER IN THE NEWBORN

(1)

Abbreviations

LATS: long-acting thyroid stimulator TSH: thyrotropin

(Received May 11; revision accepted for publication October 29, 1970.)

ADDRESS FOR REPRINTS: (B.S.) New England Medical Center, Harrison Avenue, Boston,

Massachu-setts 02111.

PEDIATRICS, Vol. 47, No. 3, March 1971

510

IODIDE GOITER

IN THE

NEWBORN

Boris Senior, M.D., and Harvey L. Chernoff, M.D

From the Pediatric Endocrine-Metabolic and Pediatric Cardiolog11s Services of the Tufts-New England Medical Center Hospitals (Boston Floating Hospital for Infants and Children),

Boston, Massachusetts

ABSTRACT. A hyperthyroid mother, treated with potassium iodide, gave birth to a baby with an enormous goiter. The infant, although hrpothyroid, had massive cardiomegaly and high output failure due to a shunt across the vessels of the goiter. Ad-ministration of thyroid caused shrinkage of the

gland and concomitantly the heart became smaller. The infant then developed hyperthyroidi.sm which persisted for several months.

The late stage of onset of hyperthyroidism in the

infant, the inability to demonstrate LATS in mother

or child, and the resemblance to other reported

cases of iodide goiter in infancy together indicate

that the hyperthyroidism may have been a conse-quence of the iodide goiter rather than a result of

the transmission of LATS from the hyperthyroid mother.

Pediatrics, 47:510, 1971, NEWBORN INFANT,

10-DIDE-GOITER, CARDIOMEGALY, HYPOTHYROIDISM, HY-PERTHYROIDISM.

T

HE vulnerability of the fetus to

mater-nal illnesses or medications is particu-larly well exemplified by disorders of the thyroid in the newborn.

Temporary, but potentially

life-threat-ening hyperthyroidism in the newborn as a result of material hyperthyroidism has long

been recognized with over 30 cases

re-ported.’ The concept that long-acting thy-roid stimulator (LATS) plays a signfficant causative role derives from its presence in both mother and child.2

Antithyroid medication administered to

the hyperthyroid mother has produced goi-ter in the newborn.3 The precise functional status of the goiter presumably reflects the interplay between the dosage and duration of medication, the susceptibility of the fetal thyroid to its inhibitory action and the si-multaneous presence of LATS.

The subject of iodide goiter has recently been reviewed in depth.4 Chronic ingestion

of excessive amounts of iodide, ten times or

more the normal daily requirement,

usu-ally as a constituent of medication for the

treatment of asthma, may cause iodide

goi-ten, with or without hypothyroidism. If

io-dides are taken during pregnancy the new-born may be similarly affected.

This report is of the effects, particularly

on hemodynamics, of a massive iodide goi-ten in a newborn who later developed frank

hyperthyroidism.

CASE REPORT

D.M., a newborn male, was transferred to the

Boston Floating Hospital for Infants and Children

at the age of 3 hours because of a mass in the neck

and an episode of respiratory arrest. He was the

first-born child of a 20-year-old Caucasian female. Eighteen months previously she had consulted an internist because of increasing nervousness. She

had tachycardia, mild exophthalmos, and a goiter.

Tests confirmed the presence of hyperthvroidism and treatment with propylthiouracil was begun.

Her symptoms subsided, whereupon methiniazole

was substituted for the propylthiouracil as

mainte-nance therapy. Nine months later, early in her

pregnancy, she came under the care of an

obstetri-cian who stopped the methimazole and prescribed

10 drops of a saturated solution of potassium

io-dide, twice daily. This medication was taken

throughout pregnancy. She felt well and had few

symptoms of thyroid overactivity. At 37 weeks the membranes ruptured spontaneously; the patient

(2)

FIG. 1. Appearance on first day of life.

Fic. 2. Massive enlargement of heart on the first

ARTICLES 511

day of life.

Shortly after birth a respiratory arlest occurred.

An intratracheal tube was passed; lie was resusci-tated and transferred to this hospital. His weight

was 3.Z7 kg, length 49 cm, and head

circumfer-ence 35 cm. He as cyanotic and dyspneic. An

enormous mass filled the neck extending from the

chin to the sternum

(

Fig. 1). It was of

moder-ately firm consistency with a central swelling

and two larger attached symmetrical lateral

exten-sions. The surface felt coarsely granular. No bruit

was heard. Air entry into the lungs was extremely

poor. The heart rate was 90 per minute. With

ad-ministration of oxygen his color improved and the

heart rate increased to 140 per minute. A grade

Ill/VI pansystohc murmur was heard loudest in

the left subclavicular area and along the left upper

sternal border. It radiated over the entire

precor-dium and into the left axilla. The liver was felt 2.5 cm below the right midcostal margin. The genitalia

were normal. The anus was imperforate.

A roentgenogram of the chest revealed a

mas-sive density which filled almost the entire thorax

(Fig. 2). The concentration of thyroxine iodine

in the blood was 2.7 tg per 100 ml.

(

Normal is

2.5 to 7.5 tg per 100 ml. ) A scintigram

con-firmed that the mass in the neck was thyroid and

that the intrathoracic mass was completely

inde-pendent of it. The electrocardiogram revealed a

rate of 130 per minute. There was biatrial and

combined ventricular hypertrophy.

A diagnosis of iodide goiter was made and

treat-ment with dessicated thyroid was instituted in a

dose of 30 mg daily (Fig. 3). On the following

day the imperforate anus was repaired

unevent-fully.

Maintenance of an adequate airway was the

ma-jor problem. Through meticulous and unremitting

care by the house staff and anesthesia service the

intratracheal tube was kept patent and in place for

the first 6 days of life. His color improved during

this period and the tube was no longer needed.

However, the heart, although smaller, remained

massively enlarged and tachycardia persisted.

The history of maternal hyperthyroidism caused

concern that LATS might be present and that

hy-perthyroidism, of unpredictable onset, could

de-velop in the infant with potentially deleterious

con-sequences for the greatly enlarged heart. To

control any such drastic fluctuation in function of

the thyroid, propyithiouracil was administered on a

trial basis and thyroid was continued in a lower

dose. However the concentration of thyroxine

io-dine fell to an abnormally low level.

Propylthioura-cil was stopped after 6 days and the close of

thy-roid was restored to 30 mg daily (Fig. 3).

There had been some decrease in the size of the

heart but the liver had become larger, 4 cm below

the midcostal margin, and tachycardia continued.

Electrocardiograms and vectorcardiograms showed

persistent enlargement of both atria and both

yen-tricles. To elucidate the cause catheterization was

performed. There was dextro-rotation of the heart

with enlargement of all chambers and a small

(3)

4

0.8 1.0 5.0 92 .4

141 2.7

THYROID

42%

4

2

116 70 8.4 .9 Se 8.4

20

1:

6

WEEKS

RAI UPTAKE

CARDIAC

CATH.

PROPYL THIOURACIL

TOTAL I 2O 2O

9 10 12 lB 24

FIG. 3. Clinical course of D.M.

as shown by an oxygen saturation of 84% in the

superior vena cava as opposed to 70 in the

infe-nor vena cav:t and by cineangiography, was a

mas-sive shunting of blood across the grossly

hypervas-cular thyroid gland. Reduction of the flow of blood

timnigh the enlarged thyroid gland was considered

urgent. To hasten shrinkage of the goiter and of

the vessels supplying it, the dose of thyroid was

increased to 60 mg daily. The goiter did decrease

in size more rapidly with a concomitant decrease

III the size of the heart

(

Figs. 4 and 5

)

. Over the

next 4 weeks the thyroxine iodine concentrations

Successively rose to 5.0, 9.2, 10.4, and 11.6 tg per

100 ml. A raclioiodine uptake at 9 weeks of age

‘‘aS 42% at 24 hours, whereupon thyroid

adminis-tration was stopped. The thyroxine iodine

concen-tration showed a temporary modest reduction to

7.0 tg per 100 ml. It then remained elevated for

the next 4 months (Fig. 3). The clinical picture, in

keeping with the hormone assays, was now one of

hyperthyroidisni. The patient ate ravenously and

was hyperactive and alert with bright staring eyes.

This clinical state persisted for as long as the

con-centration of thyroxine iodine remained elevat2d.

The gland further reduced in size but remained

easily palpable.

Recatheterization at 10 weeks of age revealed

dextro-rotation of the heart and no evidence of

ei-ther the small ventricular septal defect or of shunt

across the thyroid.

Samples of blood were drawn on the first day of

life, at 1 month of age, and at 6 weeks for assay of

LATS and of thyrotropin (TSH). The first was

un-satisfactory for assay purposes but no activity,

LATS or TSH, was detected in the remaining

sam-ples, nor in blood taken from the mother 2 days

after delivery. Antibodies to thyroglobulin were not

detected in either mother or child.

Two days post partum the mother showed only

minimal clinical evidence of thyroid overactivity.

She had slight enlargement of the thyroid; the

con-centration of thyroxine iodine was 9.0 .tg per 100

ml. She stopped taking the solution of potassium

iodide. Within 2 weeks she again complained of

nervousness, her thyroid enlarged, and tachvcardia

was present. Laboratory tests confirmed the

pres-ence of hyperthyroidism. Treatment with

methima-zole was reinstituted, with good effect.

DISCUSSION

An excess of iodide affects function of the thyroid through two or more independent mechanisms. In acute studies in animals, the increased formation of organic iodine, produced

by

the administration of iodide, is

paradoxically decreased when still greater quantities of iodide are given; the so-called

Wolif-Chaikoff effect. A similar process is presumed to occur in man.4 This inhibitory effect of an excess of iodide on organifica-tion is, however, relatively brief in dura-tion.4 Escape from the inhibition occurs,

possibly by an adaptive decrease in

the ability of the gland to concentrate io-dide.’

(4)

FIG. 4. Appearance at 2 months of age.

ARTICLES

513 by

a mechanisn which is different from the Wolif-Chaikoff effect, and which results in

a decrease in the release of hormone from the gland.7

However brought about, iodide goiter

formation appears dependent on TSH

se-cretion since administration of thyroxine

causes shrinkage of the gland, even if io-dides are continued.8

The maternal ingestion of iodide often

appears to produce a relatively greater

en-largement of the fetal thyroid than of the gland of the mother. Possibly the increased

secretion of TSH by the newborn9 enhances

the goitrogenic effect of the iodide.

The quantity of iodide taken by the

mother of the patient was large-equivalent

to approximately 1 gm of iodine daily and some 5,000 times the normal requirement.

It controlled her hyperthyroidism in that

she felt well throughout pregnancy. The

effect on the child was less felicitous. A massive suffocative goiter was present at

birth. Surgical intervention was only

avoided by dint of intubation and unreniit-ting care to ensure patency of the airway.

This critical period lasted for a week. An interpretation of the sequence in the baby is that the inhibitory effects on the thyroid of an excess of maternally derived

iodide caused an increased secretion of fe-tal TSH. An enormous goiter with hypothy-roidism resulted. Administration of thyroid on the first day of life suppressed the se-cretion of TSH with reduction in size of the

goiter. Later, as the concentration of iodide fell below the inhibitory level, hyperthy-roidism supervened. As judged by the

thy-roxine iodine concentrations and the

rela-tively high uptake of radioiodine in the

presence of administered thyroid, this state

of thyroid hyperactivity occurred at about 2 months of age. The clinical picture was in keeping with a state of hyperthyroidisni

which persisted for approximately 4

months. Thc usefulness of the thyroxine io-dine assay was borne out in this patient since unlike the PBI it is unaffected by in-organic iodide or organic iodine.’#{176}

The pathogenesis of the hyperthyroidism

is by no means clear. \Ve first

consid-ered that maternally transmitted LATS, the

effects of which were initially blocked by the iodide, produced the hypertlwroidism

as the inhibitory concentration of iodide

fell. However, LATS was undetectable in

(5)

the sera of either mother or child and the onset of hyperactivity occurred later than

one might reasonably attribute to LATS. With a reported half-life of 6 days,11 a mi-flute residual fraction would have been pres-ent at 8 weeks. Furthermore, there are re-ports of two other infants with iodide goiter

and hyperthyroidism whose mothers had

ingested iodide preparations for the treat-ment of asthma.12’1’

Although secretion of TSH may have

caused the goiter to develop, it appeared to

play no part in producing the hyperthyroid

state. Not only was TSH undetectable but

the marked decrease in the size of the goi-ten with thyroid administration offered functional confirmation of suppression of

TSH secretion.

Since the development of

hyperthyroid-ism in our patient appeared to be unrelated

to an excess of either LATS or TSH, one

must look elsewhere for an explanation.

Hyperthyroidism consequent on iodide goi-ten is

by

no means peculiar to infants; adult

cases have been reported.1#{176} However,

only few of the many adults who ingest

io-dides develop a goiter. It has therefore been postulated that both the goiter and the sub-sequent occurrence of hyperthyroidism re-flect an intrinsic abnormality of the gland. The nature of this abnormality, if present at all, is quite unknown.

In subjects with an iodide goiter an in-creased uptake of radioiodine, so-called “re-bound” hyperactivity, is a fairly consistent finding after cessation of iodides. The

hy-peractivity may persist for weeks and in

some cases at least is not suppressed by ad-ministration of thyroid.1618 This functional state of nonsuppressible rebound

hyperac-tivity would be difficult to distinguish from

“true” hyperthyroidism other than in terms

of duration. Possibly in our patient the hy-perthyroidism resulted from a failure of in-hibition of this virtually universal process

of rebound hyperactivity. Whether such

failure bore any genetic relationship to the

maternal disease is conjectural.

The unusual cardiac disorder merits

com-ment. The heart shadow was enormous at

birth, so large that an intrathoracic exten-sion of the thyroid was suspected. The

scm-tigram showed otherwise.

Hypoxia and hypercapnea due to airway

obstruction can cause cardiomegaly and

failure. Our patient however was in high output failure because of a massive shunt across the vascular bed of the goiter. This occurred at a time when the patient, both clinically and by hormone assay, was

Iiypo-thyroid. Whether cardiac myxedema could

have contributed to the cardiomegaly is un-certain; the functional picture indicated that the shunt was the major disorder. The heart diminished in size with reduction in the size of the goiter despite the

develop-ment of hyperthyroidism. The presence of a

shunt in our patient may have bearing on

other cases in which cardiac enlargement is found in association with a massive goiter.

REFERENCES

1. Johnson, C. A., and Senior, B. : Neonatal

Hy-perthyroidism in Clinical Endocrinology II.

New York: Crune and Stratton, p. 2:32,

1968.

2. McKenzie, J. M.: Humoral factors in the

pathogenesis of Craves’ disease. Physiol.

Rev., 48:252, 1968.

3. Burrow, C. N.: Neonatal goiter after maternal

propylthiouracil therapy. J. Gun. Endocr.

Metab., 25:403, 1965.

4. Wolff, J.: Iodide goiter and the pharmacologic

effects of excess iodide. Amer. J. Med., 47:

101, 1969.

5. Wolff,

J.,

and Chaikoff, I. L.: The inhibitory

action of iodide upon organic binding of

io-(line by the normal thyroid gland. j. Biol.

Chem., 172:855, 1948.

6. Braverman, L. E., and Ingbar, S. H.: Changes

in thyroidal function during adaptation to

large doses of iodide. J. Clin. Invest., 42:

1216, 1963.

7. Wartofskv, L., Ransil, B. J., and Ingbar, S. H.:

Inhibition by iodine of the release of

thyrox-ine from the thyroid glands of patients with

thyrotoxicosis. J. Clin. Invest., 49:78, 1970.

8. Caplin, I., Parker, C. F., Hall, J. H., and

Kha-jezadeh, H.: Coiter and mvxedema from

io-dine. j. Allergy, 32:402, 1961.

9. Fisher, D. A., Odell, W. D., Hobel, C.

J.,

and

Carza, R.: Thyroid function in the term

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ARTICLES 515

10. Cassidy, C. E., Benotti,

J.,

and Peno, S.:

Clini-cal evaluation of the determination of thy-roxine iodine.

J.

Clin. Endocrinol. Metab.,

28:420, 1968.

11. Sunshine, P., Kusumoto, H., and Kriss,J. P.:

Survival time of circulating long-acting thy-roid stimulator in neonatal thy rotoxicosis.

PEDIATRICS, 36:869, 1965.

12. Thomson, J. A., and Riley, I. D.: Neonatal

thy-rotoxicosis associated with maternal

hypo-thyroidism. Lancet, 1:635, 1966.

13. Louw,

J.

H.: Congenital goitre. South African

Med.

J.,

37:976, 1963.

14. Vanderlaan, W. P.: Myxedema and goiter

at-tributed to iodine ingestion in a patient

sub-sequently developing hyperthyroidism. Me-tabolism, 5:640, 1956.

15. Harrison, M. T., Alexander, W. D., and

Harden, R. M.: Thyroid function and iodine

metabolism in iodine-induced

hypothyroid-ism. Lancet, 1:1238, 1963.

16. Hall, R., Turner-Warwick, M., and Doniach,

D.: Autoantibodies in iodide goitre and

asthma. Clin. Exper. Immunol., 1:285, 1966.

17. Falliers, C. J.: Coiter and thyroid dysfunction

following the use of iodides in asthmatic children. Am.

J.

Dis. Child., 99:428, 1960.

18. Helgason, T.: lodides, goitre and myxoedema

in chronic respiratory disorders. Brit. J. Dis.

Chest, 58:73, 1964.

ON CATS AND CRIB DEATH

Crib death or the Sudden Infant Death

syndrome

(

SIDS

)

continues to be a major cause of death of young babies and yet there

is no known common pathogenic mechanism

for this syndrome. Of all the proposed hy. potheses to explain the syndrome’s etiology, that of mechanical suffocation by a cat is not even mentioned.1 But almost all grandmothers

-whether they be ailurophiles or ailurophobes

-are convinced that cats may mechanically suffocate an infant while he sleeps in his crib. The annotation below written in 1905 for a leading pediatric journal supports the widely held belief that cats should be banished from the nursery.2

The fondness many children display in taking

cherished toys to bed with them is proverbial, and

frequently these favourite bedfellows take the form

of animal representations in the shape of rabbits,

monkeys, and so on, the fur of which is usually much

the worse for wear, and requires frequent stitching

to prevent the shedding of the interior and for the

preservation of the original outline. The more

dis-reputable the appearance of the toy the better it is liked. Some children show a partiality for live

ani-mals, and of these cats are not unpopular. Cats,

un-like dogs, evince a partiality for lying on the

chil-dren’s chests in close proximity to their faces, and

when that is the case there is a real danger of a

fatal termination by suffocation. An inquiry was

recently held at Battersea into the circumstances of

the death of a 1-month-old infant. A relative of the

deceased stated that the infant was put to bed at

mid-day, and half an hour later, when she went into

the room, she found the cat curled up on the child’s

face. She took the cat away but found the child was

dead. The medical evidence showed that the infant

died of suffocation, and the opinion was expressed

that this occurred by gradual deprivation of fresh air. It was not supposed that the cat lay on the

child’s face, but that it was too close to the child,

and its fur prevented the child breathing. The

weight of the cat on the infant’s chest probably

materially assisted in bringing about a fatal

termi-nation. It is, therefore, not wise, apart from obvious hygienic reasons, to encourage children to make

bedfellows of the feline race, which should be

ban-ished from the night nursery.

NOTED B T. E. C., JR., M.D.

REFERENCES

1. Vald#{233}s-Dapena, M.: Progress in sudden infant

death research, 1963-1969. In Bergman, A. B.,

Beckwith,

J.

B., and Ray, C. C., ed.: Sudden

Infant Death Syndrome. Seattle: University

of Washington Press, pp. 10, 11, 12, 1970.

2. Excerpta Pueriia: Suffocated by a cat. Brit. J.

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1971;47;510

Pediatrics

Boris Senior and Harvey L. Chernoff