Endocrine Abstracts

JOINT317

Premature adrenarche (PA) is associated with increased adiposity and adverse metabolic profiles at presentation. Recent LC–MS/MS studies have demonstrated adrenal production of potent 11-oxygenated C19 androgens. However, evidence is conflicting about whether girls with PA are at higher risk of developing permanent metabolic dysfunction.

Objective: Does hyperandrogenism in childhood resulting from PA lead to metabolic dysfunction in young adulthood?

Methods: Girls from the prospective observational Growth and Obesity Chilean Cohort Study (GOCS, all with normal birth weight) who had DHEAS measured at age ~7 (n=504, 68%) were studied at 4 years after menarche (4yPM, age ~16 yr). Subjects were classified by DHEAS concentrations at age 7 into HD (>75^th percentile) or normal DHEAS (ND, ≤75^th percentile) subgroups. This definition of PA subgroups allowed identification of PA independently from factors influencing clinical manifestations (e.g., ethnicity or tissue sensitivity).

Results: At 4 YPM girls with HD at 7 years (n=96) exhibited higher BMI SDS (P<0.01), waist circumference (WC)/height (P<0.05), WC/hip ratio (P<0.05), and a 47% higher mean DHEAS concentration compared to ND girls. Nevertheless, glycemia, insulin, HOMA-IR, total cholesterol and its subfractions, triglycerides, testosterone, SHBG, FAI, LH, FSH, AMH, and all C19 11-oxo steroids (11-OHA4, 11-OHT, 11-KA4,1-KT) did not differ between the groups. Girls with HD 4YPM did not show greater frequency of metabolic syndrome score in the crude and adjusted models (covariates: birth weight SDS, age at menarche, and BMI at age ~7) but a higher blood pressure. Furthermore, there was no correlation between HD at age ~7 and C19 11-oxo concentrations at 4 YPM nor with concentrations of C19 11-oxo above the 75^th percentile. Linear regression analysis showed inverse correlations of 11-KA and 11-KT with metabolic score, WC, and triglycerides that were lost after adjustment for covariates. 11-KA4 showed an inverse correlation with glycemia in raw and adjusted models (β −0.02, 95%CI −0.04 to −0.006).

Discussion: Our observations indicate that girls with HD at the age of adrenarche continue to display higher levels of DHEAS after puberty completion but not of the more bioactive 11-oxygenated adrenal androgens. Apart from trends, the unfavorable metabolic signature at adrenarche appeared to diminish at 4 yr post menarche.