467 MARSHALL-SMITH SYNDROME: ANDROGEN ABNORMALITIES

Abstract

In 1971 Marshall et al described a syndrome consisting of markedly accelerated skeletal maturation, relative failure to thrive and dysmorphism. Since then 11 cases have been reported. With the exception of an elevated testosterone in a neonatal female, hormonal evaluations have been normal. We present a male with Marshall-Smith Syndrome with abnormal adrenal androgen production. A.S. was noted at birth to have a bone age of 2 yrs. At age 8 mos. the bone age was 6 yrs. Noted were generalized hirsutism, prominent forehead, low set ears, shallow orbits with prominent eyes, small triangular upturned nose, hypoplasia of facial bones, long, tapered fingers, inguinal testes, small scrotum and a penile length of 5¼ cm. The following were normal for age: T4, FSH, LH, somatomedin-C, testosterone, testicular response to HCG, and androgen receptors in cultured skin fibroblasts. Seventeen hydroxyprogesterone (17-OHP) was elevated (840 ng/dl; nl 30-100) as was androstenedione (67 ng/dl; nl<50). An ACTH stimulation test was done. A 30 min. increase in 17-OHP of 23.4 ng/dl/min. suggested an adrenal enzymatic defect and hydrocortisone 20 mg/m2/day was begun. The androstenedione decreased to 13/ng/dl and on therapy has remained normal. ACTH stimulation tests were performed on both parents. The 30 min. increase in 17-OHP was elevated in both (father-13.8 ng/dl/min; mother-8.9 ng/dl/min; nl<6.5 ng/dl/min) suggesting a heterozygous state for congenital adrenal hyperplasia. It is speculated that an inherited abnormality in androgen production may be contributory to the osseous maturation seen in the Marshall-Smith Syndrome.