Late‐onset congenital adrenal hyperplasia in women with hirsutism

. Hirsutism in women is a clinical manifestation of excessive production of androgens. The source of the excess androgen may be either the ovaries or the adrenal glands, or increased peripheral conversion of weak androgenic hormones to more potent androgens. Late‐onset (non‐classic) congenital adrenal hyperplasia is a cause of hirsutism in adult women, but its frequency and the patterns of abnormalities in adrenal hormone secretion are not well understood. The frequency of non‐classical adrenal hyperplasia due to deficiencies of 3β‐hydroxy‐Δ 5 ‐steroid dehydrogenase, 21‐hydroxylase, and 11β‐hydroxylase among 65 women with hirsutism were determined. All enzyme defects were identified by comparing the patients' hormonal responses to 0.25 mg intravenous bolus of α 1–24 ‐ACTH with those of age‐matched normal women. The hormones measured in plasma during the ACTH stimulation tests were progesterone, 17‐hydroxypregnenolone, 17‐hydroxyprogesterone, DHEA‐sulfate, androstenedione, testosterone, 11‐deoxycortisol, and cortisol. Similarly these hormones were measured after overnight 1 mg oral dexamethasone. Twelve women (18.5%) had 3β‐hydroxy‐Δ 5 ‐steroid dehydrogenase deficiency, 24 (37%) 21‐hydroxylase deficiency, and 14 (21.5%) 1 lβ‐hydroxylase deficiency. Women with 21‐hydroxylase deficiency also had evidence of a partial deficiency in 11β‐hydroxylase activity (12 of the 24 patients). Similarly, most (11 of the 14) of the women with 11β‐hydroxylase deficiency also had evidence of a deficiency in 3β‐hydroxy‐δ 5 ‐steroid dehydrogenase activity. Among the 15 patients with no adrenal biosynthetic defect, eight had high plasma androgen concentrations, and seven had normal concentrations. Elevated basal levels of hormones were not predictive of the individual response to ACTH. Polycystic ovary syndrome was present in all four groups, with an incidence of 35% in the adrenal biosynthetic defect groups. Paternal consanguinity, whether first degree or second degree, was present in 50% of patients with adrenal biosynthetic defect groups as compared to 20% in patients with no adrenal biosynthetic defects ( P < 0.02). In conclusion, a substantial proportion (77%) of women with hirsutism had defects in adrenal steroidogenesis, revealed by ACTH stimulation test, that are indicative of non‐classical congenital adrenal hyperplasia. Measurements of basal steroid levels are not helpful in differentiating among the causes of increased androgen production in women with hirsutism. Secondary adrenal biosynthetic defects were frequent in these women and were probably caused by intraadrenal androgen excess rather than by dual inherited enzymatic deficiencies.