Secondary Biosynthetic Defects in Women with Late-Onset Congenital Adrenal Hyperplasia

Abstract

Late-onset (non-classic) congenital adrenal hyperplasia is a cause of hirsutism, menstrual disorders, and infertility, but its frequency and the patterns of abnormalities in adrenal hormone secretion are not well understood. We investigated the frequency and ethnic distribution of nonclassic congenital adrenal hyperplasia due to deficiencies of 3 beta-hydroxy-delta 5-steroid dehydrogenase, 21-hydroxylase, or 11 beta-hydroxylase among 170 Israeli Jewish women with these clinical problems. All enzyme defects were identified by comparing the patients' hormonal responses to a 0.25-mg intravenous bolus dose of alpha 1-24-ACTH with those of 26 age-matched normal women. Twenty women (12 percent) had 3 beta-hydroxy-delta 5-steroid dehydrogenase deficiency, 18 (10 percent) 21-hydroxylase deficiency (14 homozygous), and 14 (8 percent) 11 beta-hydroxylase deficiency. All the homozygous women with 21-hydroxylase deficiency also had evidence of a partial deficiency in 11 beta-hydroxylase activity. Similarly, most of the women with 11 beta-hydroxylase deficiency also had evidence of a deficiency in 3 beta-hydroxy-delta 5-steroid dehydrogenase. Among the 118 women with no adrenal biosynthetic defect, 38 had high plasma androgen concentrations, and 80 had normal concentrations. About one third of Israeli Jewish women with hirsutism, menstrual disorders, or unexplained infertility had nonclassic congenital adrenal hyperplasia. Secondary adrenal biosynthetic defects were frequent in these women and were probably caused by intra-adrenal androgen excess rather than by dual inherited enzymatic deficiencies.