Adult-onset familial adrenal 21-hydroxylase deficiency

Abstract

Two sisters (28 and 30 years) were investigated for primary infertility and mild hirsutism. Both had normal puberty, were having regular menses and had normal female sexual characteristics. Studies revealed elevated urinary 17-ketosteroid levels (15.8, 18.8 mg/24 hours) and increased serum levels of 17-OH-progesterone (2,756, 1,121 ng/dl), 21-desoxycortisol (1,882, 1,090 ng/dl), progesterone (300, 346 ng/dl), dehydroepiandrosterone (DHA) (1,600, 1,700 ng/dl), androstenedione (402, 366 ng/dl) and testosterone (100, 104 ng/dl), together with a slight increase in serum 11-desoxycortisol (1,180, 1,560 ng/dl). Blood pressure, serum sodium/potassium, plasma renin and serum aldosterone, corticosterone, 11-desoxycorticosterone and cortisol levels were normal. The administration of ACTH caused a further increase in 21-hydroxylase precursors; the administration of dexamethasone normalized hormone levels and produced ovulatory cycles. Similar studies in two siblings were normal. The affected sisters were HLA identical and did not share any HLA antigens with their healthy siblings. The data suggest that these patients have a mild form of 21-hydroxylase deficiency which was insufficient to cause prenatal virilization. The gene for this disorder may be allelic with that for typical congenital adrenal hyperplasia.