EVIDENCE FOR HETEROGENEOUS ETIOLOGIES OF ADRENAL DYSFUNCTION IN POLYCYSTIC-OVARY-SYNDROME

Objective: To examine the hypothesis that, in polycystic ovary syndrom e (PCOS), ovarian steroids induce adrenal enzyme dysfunction or adrena l androgen hyperresponsiveness to ACTH. Design: Prospective controlled clinical study. Setting: Reproductive endocrinology unit of an academ ic medical center. Patients: Twelve women with PCOS who, had adrenal a ndrogen excess were compared with five weight-matched ovulatory women. In half of the women with PCOS, prestudy screening was suggestive of mild 3 beta-hydroxysteroid dehydrogenase (HSD) deficiency. Interventio ns: Basal and adrenal dynamic blood sampling before and after GnRH ago nist (GnRH-a) administration for 6 months. Main Outcome Measures: Basa l E(2) and androgen levels as well as dexamethasone-suppressed. ACTH-s timulated 17 alpha-hydroxyprogesterone, 17 alpha-hydroxypregnenolane, and androgen levels before and after ovarian suppression. Results: Alt hough none of the subjects with PCOS proved to have mild 3 beta-HSD de ficiency, the majority of them (58%) met the criteria for 17,20 lyase hyperactivity before and after GnRH-a therapy. As a group, the remaini ng subjects with PCOS exhibited an elevated DHEAS response to ACTH bef ore GnRH-a treatment, which may have normalized after GnRH-a treatment . Conclusion: Adrenal androgen excess in PCOS may be heterogeneous in etiology, whereas 17,20 lyase hyperactivity appears to be an intrinsic adrenal disorder, adrenal androgen hyperresponsiveness to ACTH mag be ovarian induced. Reliance on historical controls may lead to overdiag nosis of mild 3 beta-HSD deficiency.