Bilateral Adrenal Hyperplasia as a Possible Mechanism for Hyperandrogenism in Women With Polycystic Ovary Syndrome

Context: Androgen excess may be adrenal and/or ovarian in origin; we hypothesized that a subgroup of patients with polycystic ovarian syndrome (PCOS) may have some degree of abnormal adrenocortical function. Objective: The objective of the study was to evaluate the pituitary adrenal axis with an oral lowand high-dose dexamethasone-suppression test (Liddle's test) in women with PCOS. Design: This was a case-control study. Setting: The study was conducted at the National Institutes of Health Clinical Center. Participants: A total of 38 women with PCOS and 20 healthy volunteers (HV) aged 16-29 years participated in the study. Main Outcome Measures: Urinary free cortisol (UFC) and 17-hydroxysteroids (17OHS) before and after low-and high-dose dexamethasone and assessment of adrenal volume by computed tomography scan were measured. Results: Twenty-four-hour urinary 17OHS and UFC were measured during day 1 to day 6 of the Liddle's test. Baseline UFC levels were not different between PCOS and HVs; on the day after the completion of high-dose dexamethasone administration (d 6), UFC was higher in the PCOS group (2.0 +/- 0.7 mu g/m(2).d) than the HV group(1.5 +/- 0.5) (P = .038). On day 5,17OHS and UFC were negatively correlated with adrenal volumes(left side, r(p) = -0.47, P = .009, and r(p) = -0.61, P = .001, respectively). PCOS patients above the 75th percentile for UFC and/or 17OHS after high-dose dexamethasone (n = 15) had a significantly smaller total adrenal volume (6.9 +/- 1.9 cm(3) vs 9.2 +/- 1.8 cm(3), P = .003) when compared with the remaining PCOS patients (n = 22), but they did not have worse insulin resistance or hyperandrogenism. Conclusions: In a subset of young women with PCOS, we detected a pattern of glucocorticoid secretion that mimicked that of patients with micronodular adrenocortical hyperplasia: they had smaller adrenal volumes and higher steroid hormone secretion after dexamethasone compared with the group of PCOS with appropriate response to dexamethasone.