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

Abstract

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 low- and 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 μg/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, rp = -0.47, P = .009, and rp = -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.

Trial registration: ClinicalTrials.gov NCT01313455.

Figures

Figure 1.

End of Liddle's test of UFC, 17OH, and 17-ketosteroids. The UFC at the end of the Liddle's test was higher in the PCOS group than in the HV group, which is indicative of a lack of adequate suppression of glucocorticoid secretion after high-dose dexamethasone in the PCOS group. No differences were found in the suppression of the 17OHS and 17-ketosteroids. We report UFC in micrograms per day per square meter and 17OHS and 17-ketosteroids in micrograms per gram creatinine 24-hour urine.

Figure 2.

Correlation of 17OHS and UFC on day 5 (at the end of the high dose dexamethasone) with adrenal volumes.

Figure 3.

Correlation of adrenal volume with BMI in lean (BMI ≤ 25 kg/m2) vs overweight/obese (BMI > 25 kg/m2) PCOS subjects. L, left; R, right.