SAT380 Clinical, Metabolic And Hormonal Profile In Women Carrying Cyp21a2 Mutations

Abstract

Abstract Disclosure: S. Livadas: None. D.G. Goulis: None. E. Belardinelli: None. E. Armeni: None. B. Solmi: None. S. veneti: None. I. Lambrinoudaki: None. C. Cecchetti: None. D.P. Macut: None. A. Gambineri: None. Background: Heterozygote (HET) CYP21A2 gene mutations are present in 5-10% of the general Mediterranean population. Despite that homozygotes suffer from classical or non-classical congenital adrenal hyperplasia (NC-CAH), a survival advantage has been suggested for heterozygote carriers. The aim of this study was to describe the clinical, metabolic and hormonal profile in reproductive age women with CYP21A2 HET. Methods: Data from 56 HET women were compared with 105 controls, 64 untreated women with NC-CAH and 63 women with polycystic ovary syndrome (PCOS) of similar age and body mass index. Results: The prevalence of hirsutism (54 vs. 8%) and acne (44 vs. 4%) was higher in HET than controls. The degree of menstrual irregularities was similar between HET and NC-CAH and worse than controls. The lipid profile was better in HET than PCOS (Cholesterol 170.2±37.1 vs. 187. 7±39.3 mg/dl, HDL 61.4±26.1 vs. 46.8±8.6 mg/dl), but similar to NC-CAH. Testosterone (0.78±0.45 vs. 0.50±0.25 ng/dl), SHBG (38.2±20.1 vs. 56.2±31.4 nmol/l), FAI (9.56±3.45 vs. 5.37±1.24) and DHEAS concentrations (2.62±1.31 vs. 1.27±0.94 nmol/l) were similar to HET, NC-CAH and PCOS and significantly higher than controls as well as insulin (13.88±7.96 vs. 7.51±2.82 IU/l) and HOMA-IR (2.95±1.60 vs. 1.65±0.67). Δ4- androstenedione (5.97±2.88 vs. 8.80±3.45 ng/ml) and 17(OH)-progesterone (4.32±2.02 vs. 13.75±8.34 ng/ml) concentrations were lower in HET than in NC-CAH, but higher than PCOS and controls. Finally, ovarian PCO morphology prevalence was similar in HET than NC-CAH and PCOS. Conclusions: HET display a favorable lipidemic profile, but a similar degree of hyperandrogenic signs, menstrual disturbances, insulin resistance, hyperandrogenemia and ovarian morphology than women with PCOS or NC-CAH. Therefore, these women, when identified, should be followed-up. Presentation Date: Saturday, June 17, 2023