Familial male pseudohermaphroditism due to 17-20-desmolase deficiency. I. In vivo endocrine studies.

In two siblings with male pseudohermaphroditism (ambiguous external genitalia, XY karyotype) and apparently normal glucocorticoid function, plasma concentrations of 10 progestagens or androgens measured by specific RIAs were found to be abnormal under either basal or dynamic conditions. Basal levels of delta 4-androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate were subnormal and failed to rise after ACTH stimulation both before and after castration. Meanwhile, levels of pregnenolone, pregnenolone sulfate, 17 alpha-hydroxyprogesterone, and 17 alpha-hydroxypregnenolone were extremely high under basal conditions and rose further after ACTH. All of the progestagens and cortisol were suppressed by dexamethasone. After hCG stimulation, either before treatment or during dexamethasone therapy, the rise in testosterone was less than 100 ng/dl, while the progestagens showed an abnormally high rise. The latter were markedly reduced after castration. These findings are consistent with steroid 17--20-desmolase deficiency in both the testes and adrenal glands. In the third brother, who had only slight abnormalities of his genitalia, a mild form of the same defect was suspected. Low androgens, high 17 alpha-hydroxypregnenolone, and 17 alpha-hydroxyprogesterone levels were found in the amniotic fluid and umbilical cord and peripheral blood at birth. The parents, who were not consanguine, had normal baseline levels of all hormones. The familial occurrence of the disease is suggestive of autosomal recessive inheritance.