Familial Male Pseudohermaphroditism due to 17–20- Desmolase Deficiency. I.In VivoEndocrine Studies*

Abstract

In 2 siblings with male pseudohermaphroditism (ambiguous external genitalia, XY karyotype) and apparently normal glucocorticoid function, plasma concentrations of 10 progestagens or androgens measured by specific radioimmunoassays were 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. 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 [human chorionic gonadotropin] stimulation, either before treatment or during dexamethasone therapy, the testosterone rise was < 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 3rd 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.