SECONDARY BIOSYNTHETIC DEFECTS IN WOMEN WITH LATE-ONSET CONGENITAL ADRENAL-HYPERPLASIA

Late-onset (nonclassic) 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 3β-hydroxy△5-steroid dehydrogenase, 21-hydroxylase, or 11β-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 α1–24-ACTH with those of 26 age-matched normal women. Twenty women (12 percent) had 3β-hydroxy△5-steroid dehydrogenase deficiency, 18 (10 percent) 21-hydroxylase deficiency (14 homozygous), and 14 (8 percent) 11β-hydroxylase deficiency. All the homozygous women with 21-hydroxylase deficiency also had evidence of a partial deficiency in 11β-hydroxylase activity. Similarly, most of the women with 11β-hydroxylase deficiency also had evidence of a deficiency in 3β-hydroxy-△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 intraadrenal androgen excess rather than by dual inherited enzymatic deficiencies. NONCLASSIC (late-onset) congenital adrenal hyperplasia is a frequent and relatively mild disorder of cortisol biosynthesis, characterized by a spectrum of clinical manifestations of postnatal androgen excess. These characteristics distinguish it from the classic, severe forms of congenital adrenal hyperplasia.1 The nonclassic form is usually caused by a deficiency of steroid 21-hydroxylase (steroid 21-monooxygenase)1 or 3β-hydroxy-△5-steroid dehydrogenase,1,2 whereas steroid 11β-hydroxylase (steroid 11β-monooxygenase)1 deficiency is considered extremely rare.3 4 5 The clinical manifestations of these three deficiencies are similar, and the exact diagnosis can be established only by hormonal measurements. Steroid 21-hydroxylase deficiency is characterized by high plasma 17-hydroxyprogesterone concentrations after stimulation with… © 1990, Massachusetts Medical Society. All rights reserved.