Thyroid Storm in an 11-Year-Old Boy Managed by Propranolol

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920 PEDIATRICS

Vol.

53 No. 6

June

1974

Thyroid

Storm in an 1 1-Year-Old

Boy

Managed

by Propranolol

Margaret

Galaburda,

M.D.,

N. Paul Rosman,

M.D.,

and

James

E. Haddow,

M.D.

From the Departments of Pediatrics and Neurology, Boston University School of Medicine, Boston City Hospital, Boston

ABSTRACT. An 11-year-old boy with an 18-month history

of incompletely treated thyrotoxicosis was hospitalized

be-cause of progressive weakness. During his first hospital day he suddenly decompensated, with signs of acute thyroid

storm. He responded dramatically to intravenously and then

orally administered propranolol which controlled his

hyper-thyroid symptomatology until propylthiouracil could take

effect. This is the first reported description of the use of propranolol in the treatment of thyroid storm in childhood

thyrotoxicosis. Pediatrics, 53:920, 1974, THYROID STORM,

THYROTOXICOSIS, HYPERTHYROIDISM, PROPRANOLOL.

Thyroid storm is a serious complication of

thy-rotoxicosis

with

a mortality

rate of 20% to 50%. In

recent years it has been appreciated that many

features of

the

thyrotoxic state are due to increased

adrenergic stimulation of peripheral tissues.24

Ef-forts

directed at beta-adrenergic blockade

with

such

drugs as reserpine, guanethidine and propranolol

have successfully controlled thyrotoxic symptoms in

acutely ill

adults.5

Only

a

few cases of thyroid storm have been

re-ported

in

children,2’68

one of whom was managed

with

guanethidine.2 There thus has been little

op-portunity

to study the treatment of thyroid storm

in children, and previously no child

with

that

dis-order has been managed

with

propranolol. This

report describes a

case

of childhood thyrotoxicosis

with

storm that was treated successfully

with

pro-pranolol.

There was little clinical improvement, although the PBI came down to high-normal levels. Four months later he began to have frequent episodes of headache, sweating, weakness, and lethargy. His speech became “thicker,” and

he developed proptosis. Chest x-ray demonstrated an

en-larged heart; electroencephalogram showed high-voltage

synchronous slow-wave activity; and radioactive

iodine

up-take at 24 hours was 78% (normal, 15% to 40%). Dilantin, 100 mg/day, was begun because of suspected seizures or

seizure equivalents. His thyrotoxic symptoms continued. Six

months later, at age 11 years 4 months, his PBI

was

10.7

g/100 ml and serum thyroxine (T4) was 15g/10O ml

(normal, 4 to 11 ). During the few weeks prior to hospital-ization, the boy had become listless and was unable to open

doors or climb stairs. He slept poorly, awakening several times each night for large meals. Weight loss continued. He was referred to the Pediatric Neurological Service at

Boston City Hospital for evaluation of progressive

weak-ness.

On admission at age 11 years 8 months, the patient

was

found to be tall (65th percentile), thin (25th percentile),

markedly hyperactive and clumsy. Blood pressure was 120/

65 mm Hg, pulse rate was 110 per minute and he was

afebrile. There was a mild proptosis, with an alternating

esotropia and poor convergence. The thyroid gland was firm,

diffusely enlarged (6 cm X 7 cm), and had a systolic bruit.

The cardiac impulse was forceful, and a grade 2/6 harsh

systolic ejection murmur was present at the apex. Muscle

bulk, tone, and power were diffusely decreased with

wast-ing over the shoulders, arms, legs and paravertebral muscles.

An electrocardiogram showed left ventricular hypertrophy

and chest x-ray showed cardiomegaly with prominence of the left ventricle. An electroencephalogram showed exces-sive slowing and frequent bilateral bursts of high-voltage

sharp- and slow-wave activity. Serum Ti-iodine was 7.5g/

CASE REPORT

An 11 8/12-year-old boy with developmental retardation was first evaluated at age 10% years for a four-month history of hyperactivity, irritability, clumsiness, deteriorating school

performance, hyperphagia, dysphagia, weight loss, and

goiter. Serum protein bound iodine (PB!

)

was greater than

2Og/100 ml

(

normal, 4 to 8). Propylthiouracil (PTU), 75 mg/day, was begun and later increased to 125 mg/day.

(Received August 24; revision accepted for publication

De-cember 19, 1973.)

Supported in part by grants awarded by the Charles H.

Hood Dairy Foundation to Dr. Rosman (4829-5) and Dr.

Haddow (3132-5).

ADDRESS FOR REPRINTS: (N.P.R.) Department of

Pediatrics, Boston City Hospital, Boston, Massachusetts

02118.

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(‘1 PULSE RATE beo/s/mu (.1 8L000 PRESSURE mm/Ic

(_‘)

02 RECTAL 00 TEMPERATURE .P

HOURS AFTER AOM/SS/ON

DISCUSSION

ARTICLES

921

100 ml (normal, 2.6 to 7.2), total T4 was 11.5g/100 ml, free T4 was 2.5i.g/100 ml

(

normal, 0.8 to 2.4), total quantitative T8 was 355 ng/100 ml

(

normal, 140 to 250). Dilantin therapy was discontinued.

Sixteen hours after admission, the patient suddenly be-came lethargic and vomited several times. His temperature

was 98.0 F, pulse rate was 1 15 per minute, and blood pres-sure was 150/60 mm Hg. These and other representative subsequent vital signs are shown in Figure 1. He was

flushed, perspiring, and drowsy. When awake he was apathetic, and unable to lift his head from the bed. PTU was increased to 100 mg every eight hours, and guanethi-dine, 10 mg, was given orally. Acute symptoms of prostra-tion progressed and vital signs became increasingly abnor-mal. His rectal temperature increased to 102 F, pulse rate was 154 per minute, blood pressure was 160/80 mm Hg, and he was difficult to arouse. A trial dose of 3 mg of propranolol was given intravenously over ten minutes. The

pulse rate fell immediately to 100 per minute, but soon

re-turned to pretreatment values. Two hours later a second

dose of 3 mg of propranolol was given intravenously. This time his pulse rate immediately slowed and remained

slowed, his temperature returned to normal, and his systolic

blood pressure fell. Within two hours the patient became alert, spoke spontaneously, and stood unassisted. Propranolol,

30 mg, was given orally at this time. Thereafter, 20 mg of propranolol were given orally every six hours and PTU was continued at 300 mg/day for the remainder of the hos-pitalization. His vital signs stabilized. He remained alert, gained weight steadily, and his muscle strength gradually improved. Two attempts to discontinue propranolol during the first three weeks were unsuccessful, with recurrence of tachycardia, nervousness and weight loss. He was dis-charged from the hospital on 40 mg of propranolol per day, which was discontinued successfully during the fifth treat-ment week. He subsequently has remained euthyroid, both

clinically and biochemically, and has continued to gain

weight and muscle strength. His school performance has improved, headaches and flushing have disappeared, and his electroencephalogram is improved with some persistence of slow- and sharp-wave activity.

This patient presented a number of unusual features and problems relating to juvenile

hyper-thyroidism. He had symptoms of hyperthyroidism

for 18 months before effective treatment was begun,

and this delay in recognition and treatment may

have predisposed to the development of storm. The

addition

of Dilantin

to his

treatment

program

5ev-eral months before hospitalization complicated

in-terpretation of his thyroid function studies, since

Dilantin

is known

to suppress

protein

bound

iodine

values and thyroxine values without altering the state of thyroid function.9’1#{176}

The serum T3 measurement was particularly valu-able in this case of obvious clinical hyperthyroidism

with

high-normal

serum

T4 determinations. Recent

work has stressed the importance of T3 as a

param-eter of thyroid function. Syndromes of

hyperthy-roidism

with

normal T4 values and elevated T3 levels have been called “T3 toxicosis.” Ability to

measure

T3

has

permitted

recognition

of a

group

Fic. 1. Alteration of vital signs during treatment of thyroid

storm.

of patients with hyperthyroidism in whom the

diag-nosis might not otherwise have been made.11

It is fortuitous that

this

patient was hospitalized

shortly before showing signs of acute deterioration.

It is unclear what precipitated his acute illness.

Guanethidine was begun early and might have

been effective if it had been used more aggressively. Waldstein reported successful control of symptoms

of hyperthyroidism

within

four days in three

thyro-toxic children treated

with

guanethidine in a

dos-age of 1 mg/kg/day. Postural hypotension occurred

in all these cases.2 In our case, propranolol had the advantage of acting rapidly, and the patient’s re-sponse was dramatic. The

drug

was continued after

the storm had subsided

with

the hope that his

con-valescence could be shortened by controlling the thyrotoxic symptomatology. Propylthiouracil, even in adequate dosage, may require weeks to reach

full effectiveness in suppressing thyroid activity di-recfly.12 It was not until the

fifth

week of treatment

that propranolol could be discontinued without the recurrence of nervousness and tachycardia.

Canary

was

the

first

to

show

that

thyroid

hor-mone’s peripheral effects were counteracted by

re-serpine.4

Since that time, reserpine, guanethidine, and propranolol

all

have been used successfully to counteract thyrotoxic symptoms. The interaction of

thyroxine and epinephrine is not

fully

understood,

but it is thought that thyroxine enchances adren-ergic stimulation and has a direct effect of its own

on cardiac and peripheral tissues.1315

The very favorable response of our patient to

propranolol leads us to recommend

its

use in other

similar circumstances. A unique role can be played by beta-adrenergic blocking agents, such as prop-ranolol, in the acute management of symptomatic

hyperthyroid patients. Before the overall benefits

and shortcomings of propranolol can be

appreci-ated, however,

more cases

must be treated similarly.

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922 THYROID

STORM

SUMMARY

A case

of

longstanding childhood thyrotoxicosis

with

complicating thyroid storm is described. This

acute exacerbation of thyrotoxicosis responded in a

dramatic

and

sustained fashion to propranolol

ther-apy.

REFERENCES

1. Ingbar, W. H. : Management of emergencies: IX. Thyro-toxic storm. New Eng. J. Med.,

274:1252,

1966. 2. Waldstein, S. S., West, G. H., Jr., Lee, W. Y., and

Bronsky, D. : Guanethidine in hyperthyroidism.

JAMA, 189:609, 1964.

3. Levey, G. S. : Catecholamine sensitivity, thyroid hor-mone and the heart. Amer. J. Med., 50:413, 1971.

4. Canary, J. J., Schaef, H., Duffy, B. J., Jr., and Kyle,

L. H.

:

Effects of oral and intramuscular adminis-tration of reserpine in thyrotoxicosis. New Eng. J.

Med., 257:435, 1957.

5. Das, G., and Krieger, M. : Treatment of thyrotoxic

storm with intravenous administration of

proprano-lol. Ann. Intern. Med., 70:985, 1969.

6. Hedge, K. K. : Monoclonal gammopathy, thyroid crisis

and congenital heart disease in a patient with tri-somy syndrome

(

Down’s syndrome or mongolism).

Rhode Island Med. J., 53:102, 1970.

7. Grossman, A., and Waldstein, S. S. : Apathetic thyroid

storm in a 10-year-old child. Pedkztrics, 28:447, 1961.

8. Darby, C. P. : Three episodes of spontaneous thyroid storm occurring in a nine-year-old child. Pediatrics,

30:927,

1962.

9. Oppenheimer, J. H., Fisher, L. V., Nelson, K. M., and

Jailer, J. W. : Depression of serum protein bound iodine by diphenyihydantoin. J. Clin. Endoer., 21:

252, 1961.

10. Larsen, P. R., Atkinson, A. J., Jr., Weliman, H. N., and Goldsmith, R. E. : The effect of diphenyihydantoin on thyroxin metabolism in man. J. Clin. Invest.,

49:1266, 1970.

11. Hollander, C. S.: Newer aspects of hyperthyroidism.

Hosp. Practice, 7:87, 1972.

12. Goodman, L. S., and Gilman, A.: The Pharmacological

Basis of Therapeutics, ed. 4. New York:

Macmil-lan Co., 1970, p. 1482.

13. Weiner, L., Stat, B. D., and Cox, J. W. :

Influence

of

beta

sympathetic blockade (propranolol) on the

remodynamics of hyperthyroidism. Amer. J.

Med.,

46:227, 1967.

14. Gaffney, T. E., Braunwald, E., and Kabler, R. L.:

Effects of guanethidine on induced

hyperthyroid-inn in man. New Eng. J. Med., 265:16, 1961. 15. Levey, C. S., and Epstein, S. E.

:

Myocardial adenyl

cyclase: Activation by thyroid hormone and

evi-dence for two adenyl cyclase systems. J. Cliii.

Invest., 48:1663, 1969.

16. Rosenberg, I. N.: Thyroid storm. New Eng. J. Med.,

283:1052, 1970.

ACKNOWLEDGMENT

We wish to thank Mr. Norbert Benotti of the Boston

Medical Laboratory for his determinations of total

quanti-tative T.

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1974;53;920

Pediatrics

Margaret Galaburda, N. Paul Rosman and James E. Haddow