Mild adrenal and ovarian steroidogenic abnormalities in hirsute women without hyperandrogenemia: does idiopathic hirsutism exist?

To study ovarian and adrenal steroid profiles of women with idiopathic hirsutism, we compared sex steroid and basal and corticotropin (ACTH)-stimulated adrenal steroid levels before and after ovarian suppression induced by a long-acting gonadotropin-releasing hormone agonist analog (GnRH-a) in 24 hirsute women without hyperandrogenemia. Twelve healthy women served as controls for basal and ACTH-stimulated adrenal steroid levels. Serum levels of testosterone (T), sex hormone-binding globulin (SHBG), estradiol (E2), basal and ACTH-stimulated 17-hydroxyprogesterone (17OHP), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), delta 4-androstenedione (delta 4-A), 11-deoxycortisol (S) and cortisol (F), and basal and luteinizing hormone-releasing hormone (LHRH)-stimulated gonadotropin levels were measured before and 21 days after 3.75 mg intramuscular triptorelin in hirsute women. Basal T levels and basal and ACTH-stimulated delta 4-A, DHEA, and DHEAS levels were not different in hirsute women with respect to controls. Basal and ACTH-stimulated 17OHP was elevated, and decreased to normal after ovarian suppression with triptorelin. Although basal and ACTH-stimulated delta 4-A levels were normal, the delta delta 4-A/delta F and delta delta 4-A/delta 17OHP ratios were elevated and remained elevated after ovarian suppression, suggesting enhanced adrenal delta 4-17,20-lyase activity. T, F, S, and DHEAS levels were not affected by ovarian suppression. Basal and ACTH-stimulated 17OHP and delta 4-A, and stimulated DHEA concentrations were reduced with ovarian suppression, but their net increment and ratio to the increase of F in response to ACTH remained unchanged, reflecting the ovarian contribution to the secretion of these steroids. We conclude that idiopathic hirsute women with normoandrogenemia show an increase in ovarian secretion of 17OHP and a minimally increased adrenal delta 4-17, 20-lyase activity, suggesting that mild forms of ovarian and adrenal functional hyperandrogenism may be present in these patients with otherwise unexplained hirsutism.