Growth Hormone Deficiency in Twins: Three Cases with Normal Co-twins

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486 PEDIATRICS Vol. 69 No. 4 April 1982

EXPERIENCE

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REASON-Briefly

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-In Medicine one must pay attention not to plausible theorizing but to experience and reason

together. . .- I agree that theorizing is to be approved, provided that it is based on facts, and

systematically makes its deductions from what is observed. - - - But conclusions drawn from unaided reason can hardly be serviceable; only those drawn from observed fact. ‘ ‘ Hippocrates:

Precepts. (Short communications of factual material are published here. Comments and criticisms appear as Letters to the Editor.)

Growth

Hormone

Deficiency

in Twins:

Three

Cases

with

Normal

Co-twins

Idiopathic growth hormone deficiency is unusual

in twin sibships. We report three twins with growth

hormone deficiency whose co-twins are growing

normally and have no evidence of

hypothalamic-pituitary dysfunction. It is likely that the affected

children sustained perinatal insult. The data

ifius-trate that idiopathic growth hormone deficiency

should be considered in the differential diagnosis

when there is a major discrepancy in height

be-tween twins.

CASE REPORTS

Ce1

Male twins I were born at 36 weeks’ gestation to a

27-year-old gravida 3, para 2. There was no history of

ab-normal vaginal bleeding, infection or, toxemia. Labor was spontaneous and lasted two hours. Both boys were deliv-ered from a vertex position, twin A 12 minutes before B.

Twin A weighed 2.2 kg, was 43.2 cm long, and had a

5-minute Apgar score of 10. Twin B weighed 2.38 kg and

had a 5-minute Apgar score of 9. His length was not

recorded. There were no neonatal complications. Twin A

was noted to grow slower than B from midinfancy onward.

When seen in Endocrine Clinic at 7/12 years, he was 20

cm shorter than his sibling. He had no measurable growth

hormone response to provocative testing with insulin and

arginine. Serum thyroxine and plasma cortisol

concentra-tions were normal. He grew well following treatment with

human growth hormone and reached an adult height of

166 cm. At comparable age, his twin was 181 cm tall (Fig

1). Both boys began puberty between ages 12#{189}and 13

years.

Case 2

Female twins II were born at term to a 19-year-old

gravida 1, para 0 after an unremarkable pregnancy. Labor

lasted 33/4 hours. The babies were delivered by low for-ceps, ten minutes apart, from a vertex position. There was no neonatal distress. Twin A weighed 2.4 kg, was 46

cm long, and had a 5-minute Apgar score of 9. Twin B

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EXPERIENCE

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weighed 2.4 kg, was 47 cm long, and had a 5-minute Apgar

score of 9. Both had congenitally dislocated hips. Twin A

began to fall below her sister in height at age 1 year and

was 18 cm shorter when first seen in Endocrine Clinic at

age 8#{176}/12 years (Fig 2). She had a maximum growth

hormone level of 1.8 ng/ml in response to insulin and

arginine stimulation. Serum thyroxine and plasma

corti-sol concentrations were normal. Following treatment with

human growth hormone, her growth rate has accelerated

(Fig 3). Spontaneous pubertal development of twin A

began at age 10 years, within six months of her twin

sister.

Case 3

Male twins III were born to a 23-year-old gravida 2,

para 1 at 38 weeks’ gestation. The pregnancy was

uncom-plicated and twins were not suspected until delivery.

Labor was spontaneous and lasted 56 minutes. The first

twin was delivered from a vertex position and the second

was delivered frank breech eight minutes later. Twin A

weighed 3 kg. Length and Apgar score could not be found

in the birth records. Twin B weighed 1.4 kg, was 46 cm

long, and had a 5-minute Apgar score of 9. When first

seen in Endocrine Clinic at age 11 years, twin B was 15

cm shorter than his brother and had a maximum growth

hormone concentration of 2.3 ng/ml in response to argi-nine and insulin stimulation. Serum thyroxine and plasma

Fig 2. Twins II at 8’#{176}/12years of age. Twin A has short

stature, rippling fat, and facial immaturity frequently seen in growth hormone-deficient children.

Age (years)

Fig 3. Linear growth data of twins II. Shaded area represents fifth to 95th percentiles; solid circles, healthy

twin; open circles, growth hormone-deficient twin; G.H., start of human growth hormone therapy.

cortisol levels were normal. He had a normal prepubertal

gonadotropin response to luteinizing hormone releasing factor infusion. Following treatment with human growth hormone, his growth rate accelerated from 2.4 to 6.8 cm/ yr (Fig 4).

A systematic examination of the placenta was not

performed in any of the cases and none of the twins have had blood grouping of HLA typing. Thus, zygosity cannot be determined.

DISCUSSION

Idiopathic growth hormone deficiency appears to

be a rare disorder in twins. We could find only three

case reports in the literature of single members of

monozygotic”2 and dizygotic3 twins with isolated

growth hormone deficiency. This low frequency is

surprising inasmuch as twinning occurs in 1 of 80

pregnancies in the United States,4 and growth

hor-mone deficiency is estimated to occur once in every

4,000 children.5 It is also surprising that there have

been no cases in which both twins were growth

hormone deficient inasmuch as they usually

expe-rience similar intrauterine environments and, in

monozygous pairs, an identical genetic makeup. At

the time of delivery, however, the amount of stress

may be very different for the firstborn compared

with the second-born twin. Potential problems that

can be encountered by only one twin include poor

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ACKNOWLEDGMENT

Human growth hormone used for treatment of the

patients was provided by the National Pituitary Agency.

REFERENCES

1. Rosenbloom AL, Smith DW: Idiopathic anterior hypopitui-tarism in one of identical twins. J Pediatr 67:84, 1965

2. Rosenfield RL, Root AW, Bongiovanni AM, et al: Idiopathic

anterior hypopituitarism in one of monozygous twins. J Pediatr 70:114, 1967

3. Rona 1W, Tanner JM: Aetiology of idiopathic growth

hor-mone deficiency in England and Wales. Arch Die Child 52: 197, 1977

4. Benirschke K, Kim CK: Multiple pregnancy. N Engi JMed

288:1276, 1973

5. Vimpani GU, Vimpani AF, Lidgard GP, et al: Prevalence of

severe growth hormone deficiency. Br Med J 2:427, 1977

6. Craft WH, Underwood LE, van Wyk JJ: High incidence of

perinatal insult in children with idiopathic hypopituitarism. J Pediatr 96:397, 1980

488 PEDIATRICS Vol. 69 No. 4 April 1982

Age

(years)

Fig 4. Linear growth data of twins III. Shaded area

represents fifth to 95th percentiles; solid circles healthy

twin; open circles, growth hormone-deficient twin; G.H.,

start of human growth hormone therapy.

progress through the birth canal or a breech

pres-entation, or a difficult forceps delivery. In a recent report, Craft et al6 hypothesized that many children

with idiopathic hypopituitarism sustain a perinatal

injury that causes hypothalamic dysfunction. They

observed a higher incidence of significant

gesta-tional bleeding, prematurity, prolonged or

unusu-ally short labors, breech presentation, difficult

for-ceps deliveries, and intrapartum distress among

their patients.

Labor was short for twins I (two hours) and III

(56 minutes) and was only 33/4 hours for twins II

whose mother was a primigravida. Twins I-A and

Il-A developed growth hormone deficiency,

sug-gesting that the short labor placed the firstborn at

risk even though there was no apparent neonatal

distress. By history, twins I-A and Il-A were

notice-ably smaller than their co-twins by age 2 years and

fell progressively further from normal values

whereas twins I-B and Il-B continued to grow at a

constant rate. Figs 1 and 2 demonstrate the marked

discrepancy in height at time of diagnosis.

Twin Ill-B experienced two perinatal insults:

pre-cipitous labor and frank breech delivery. There was

also discordant size of unknown cause between

twins Ill-A and Ill-B at birth. This difference

per-sisted during infancy and childhood and was

pre-sumed to be the result of intrauterine factors alone

until testing at age 11 years revealed growth

hor-mone deficiency.

Our studies document the presence of idiopathic

growth hormone deficiency in one member of three

twin pairs, each of whom experienced at least one

perinatal insult. The results indicate the need to

test for hormone deficiency whenever there is a

subnormal growth rate and an increasing height

discrepancy between twins.

ALAN N. LINDSAY, MD

MARGARET H. MACGILLIVRAY, MD MARY L. VOORHESS, MD

Department of Pediatrics

State University of New York at Buffalo

School of Medicine and

The Children’s Hospital of Buffalo

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1982;69;486

Pediatrics

Alan N. Lindsay, Margaret H. MacGillivray and Mary L. Voorhess