Is mild adrenal hyperplasia a mechanism for hyperandrogenism in women with Polycystic Ovarian Syndrome (PCOS)?

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 548-560-Hyperandrogenic Disorders
Basic/Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-557
Evgenia Gourgari*1, Maya Beth Lodish2, Chris Crutchfield3, Margaret Keil4, Ninet Sinai5, Charalampos Lyssikatos6, Maria V Nesterova1, Maria De La Luz Sierra1, Divya Khurana7, Paraskevi Xekouki8, Mary Fedewa9, Svetlana B Ten10, Al Yergey11, Adrian Sandra Dobs12 and Constantine A Stratakis1
1National Institutes of Health (NIH), Bethesda, MD, 2NIH, 3NIH/NICHD, 4NICHD/NIH, Bethesda, MD, 5NICHD, 6National Institutes of Health, Bethesda, MD, 7MMC, Brooklyn, NY, 8National Institute of Health, Bethesda, MD, 9NICHD, Bethesda, 10Maimonides Med Ctr, Brooklyn, NY, 11NICHD/NIH, 12Johns Hopkins Univ Schl of Med, Baltimore, MD
Introduction:We hypothesized that a subgroup of patients with PCOS has abnormal adrenocortical function or bilateral adrenal hyperplasia (BAH). We examined adrenocortical and other steroid secretion in young women with PCOS and healthy controls; the function of their hypothalamic pituitary adrenal axis (HPAA) was examined by a number of tests including an oral low- and high-dose dexamethasone (DEX)-suppression test (Liddle’s test). Methods: 30 women with PCOS (Androgen excess criteria) and 8 healthy volunteers (HV) aged 16-29 yrs were studied. All medications were discontinued one month prior to participation.Patients with non-classic adrenal hyperplasia, severe insulin resistance-acanthosis nigricans syndrome, thyroid dysfunction, and hyperprolactinemia were excluded.We obtained BMI, Ferriman Gallaway scores (FGS), OGTT, and measured urinary cortisol and 17OH steroids (17OHS), and several steroid hormones in the blood. Data were analyzed by mixed modeling for repeated measures, multiple regression analysis, and two-sample t-tests or its non-parametric parallel.Results: 24hr urinary 17OHS (mg/gr creatinine clearance/day) and urinary free cortisol (mcg/m2/day) were measured during day 1 to day 8 of the Liddle’s test. Overall, the PCOS group had consistently higher levels of 17OHS compared to HVs (p=0.019). In the PCOS group, 17OHS increased after day 5 (end of low dose) to day 7 (end of high dose) (p<0.001) while a significant increase was not observed in the HV group. Moreover, on day 7, urinary free cortisol was higher in the PCOS group than the HV group (p=0.0007). FGS (rp=0.65, p=0.041), blood total testosterone (rp=0.69, p=0.004), age (rp=0.63, p=0.039) and androstenedione levels (rp=0.63, p=0.036) were related to urinary cortisol percent change from baseline to day 7. When corrected for age, only testosterone remained statistically significant (rp=0.69, p=0.024). FGS was lower in those that suppressed the 17OHS more than 67%(p=0.014). The glucuronidated form of etiocholanolone (EG) was higher in PCOS than HVs (p=0.017).Conclusion:These preliminary data indicate that, indeed, a subset of young women with PCOS has abnormal adrenocortical function: their glucocorticoid secretion pattern in response to dexamethasone is similar to that in patients with BAH, albeit at overall lower levels of cortisol and 17OHS. Thus, these women do not have an abnormal HPAA function but they do have abnormal adrenocortical function that appears to be ACTH-independent.

Nothing to Disclose: EG, MBL, CC, MK, NS, CL, MVN, MDLLS, DK, PX, MF, SBT, AY, ASD, CAS

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