Male pseudohermaphroditism due to multiple defects in steroid-biosynthetic microsomal mixed-function oxidases — a new variant of congenital adrenal hyperplasia

Abstract

A six-month-old 46,XY infant with a female phenotype and ambiguous genitalia was evaluated for male pseudohermaphroditism. The principal findings were (1) low basal plasma levels of all measured C19 steroids and their sulfates, which were unchanged or only minimally increased after stimulation with human chorionic gonadotropin or ACTH, (2) no urinary metabolites of C19 11-deoxy steroids, and decreased amounts of C19 11-oxo steroids, (3) normal basal plasma cortisol levels and normal urinary excretion of cortisol metabolites, (4) high plasma corticosterone and deoxycorticosterone levels and elevated urinary excretion of their metabolites, (5) high plasma progesterone and pregnenolone levels and increased urinary excretion of pregnanediol and pregnenediol, (6) high plasma 17α-hydroxyprogesterone and 21-deoxycortisol levels and increased urinary excretion of pregnanetriol, 17α-hydroxypregnanolone, and pregnenetriolone, (7) high plasma and urinary levels of 5-pregnene-3β,20α-diol sulfate, (8) low plasma levels of 21-hydroxypregnenolone and 5-pregnene-3β,17α,20α-triol sulfate, (9) high plasma ACTH levels, and (10) suppression of the high plasma steroid levels by dexamethasone.

The unusual pattern of plasma and urinary steroids indicated that this child had multiple abnormalities of steroid-biosynthetic microsomal mixed-function oxidases — 21-hydroxylase, 17α-hydroxylase, and 17,20 desmolase. The deficit in the activities of the first two enzymes resulted in decreased cortisol synthesis with subsequent increased ACTH secretion and adrenocortical hyperplasia. The male pseudohermaphroditism resulted from deficient testosterone synthesis due to deficiency of 17α-hydroxylase and 17,20 desmolase. The mother and two sisters of the affected child had evidence of mild 17α-hydroxylase deficiency.