Congenital Adrenal Hyperplasia Due to a Deficiency of One of the Enzymes Involved in the Biosynthesis of Pregnenolone

Abstract

A normotensive male pseudohermaphrodite (buccal smear chromatin negative, and karyotype XY) with cryptorchidism and minimal masculinization of the external genitalia manifested, at the age of 8 months, symptoms of salt loss with hyponatremia, hypochloremia and hyperkalemia. Intramuscular administration of desoxycorticosterone acetate corrected the electrolyte imbalance. Twentyfour hr urinary excretions of 17-ketosteroids, 17-hydroxycorticosteroids, Δ5 -3β-hydroxysteroids, pregnanetriol, pregnanediol, dehydroepiandrosterone, tetrahydro S, tetrahydrodesoxycorticosterone and tetrahydrocorticosterone were not elevated. The cortisol and aldosterone secretion rates were low. The patient died unexpectedly, probably of hypoadrenocorticism. Post-mortem examination revealed adrenal cortical hyperplasia. A testis and epididymis were present in the inguinal canal bilaterally and there were no uterus, fallopian tubes or ovaries. The data collected in this case of the adrenogenital syndrome due to congenital adrenal hyperplasia exclude the presence of the recognized enzymatic deficiencies of this disorder (deficiency of 21-hydroxylase, 11β-hydroxylase, 17α-hydroxylase and 3β-hydroxysteroid dehydrogenase) and represent the basis for a new biochemical defect in this disorder, namely, a deficiency of one of the enzymes involved in the formation of pregnenolone. A similar deficiency was probably present in the gonads, resulting in the minimal masculinization of the external genitalia.