Pubertal boy with the 3β-hydroxy steroid dehydrogenase defect

This is the first report of a child with the 3β-hydroxysteroid dehydrogenase (3β-HSD) defect to have reached a pubertal age. This 13-yr-old boy’s puberty was manifested by the development of male secondary sexual characteristics and marked gynecomastia. Clinical support for the diagnosis consisted of his marked salt-wasting, hypospadias and family history of 2 infants who died with congenital adrenal hyperplasia and ambiguous external genitalia. Laboratory support for the diagnosis consisted of greatly elevated plasma pregnenolone,⁶ 17-OH-pregnenolone and DHEA, as well as high urinary pregnenetriol and DHEA. The paradoxical presence of progesterone in blood and of pregnanetriol, androsterone and etiocholanolone in the urine of this and other patients probably results from peripheral conversion of pregnene compounds by liver 3β-HSD enzymes to pregnane compounds. In this patient there was a rise in plasma testosterone following human chorionic gonadotropin administration, suggesting that the pubertal testis does not lack 3β-HSD although there is ample laboratory evidence for adrenal deficiency of this enzyme. Intrauterine testosterone deficiency resulting from the impairment of 3β-HSD activity may have caused the hypospadias and the gynecomastia at puberty. The mechanism may be similar to the animal experiments in which male rats given 3β-HSD inhibitor in utero are born with ambiguous genitalia, fail to repress female breast anlage, and develop breasts at puberty.