ESPE Abstracts

Premature adrenarche (PremA), is associated to increased adiposity and in girls to earlier puberty and adverse metabolic profiles. Recently, the use LC-MS/MS studies demonstrated adrenal production of more potent androgens:11-oxygenatedC19 steroids. Defining the mechanisms that regulate adrenal C19 steroid production has been elusive. We recently showed that genetic determinants of DHEAS during adrenarche differed from those identified during adulthood. One top variant was at the Prolactin receptor which is strongly expressed in human adrenal tissue. The aim of this study was to test whether there is an association between DHEAS and 11-oxyandrogen with prolactin concentrations in pre-pubertal girls.

Methods: 244 prepubertal girls recruited within the “the Food and Environment Chilean longitudinal Cohort-FECHIC”, with normal birth weight (3.37±0.02 Kg) examined at 6.7±0.6 years, anthropometry, and blood sampling. Steroids measured by use LC-MS/MS. Girls were categorized according to the DHEAS concentrations in normal DHEAS (ND, < 75th) or high DHEAS (HD, ≥75th percentile for the population). This definition of adrenarche subgroups allows identification of biochemical PremA from other independent factors influencing clinical manifestations (i.e: ethnicity, tissue sensitivity).

Results: None of the girls presented clinical evidence of pubarche. At this age mean DHEAS concentration was 16.4 (9.6 -25) μg/dL and the 75th percentile set at 25.0 μg/dL. Girls with HD had higher weight (1.3 ±1.2 vs 0.7± 1.1, P <0.001), height (0.6 ±1.0 vs 0.0± 0.9, P <0.001) and BMI (1.3 ±1.2 vs 0.9± 1.1, P <0.01) SDS compared to ND. All the concentrations of 11 oxy-androgens (ng/ml) were higher in girls with HD compared to girls with ND: 11KA4 by 16% [0.14 (0.12,0.16) vs 0.12 (0.10,0.14)], 11OHA4 by 43 % [0.07(0.05, 0.08) vs 0.04(0.03,0.05)],11KT by 35% [0.19(0.15,0.25) vs 0.14(0.11,0.19)] and by 30% 11OHT [0.03(0.02.0.05) vs 0.03(0.01,0.04)]. DHEAS correlated with each of the 11-oxyandrogens in the raw and fully adjusted models. Prolactin [6.5(4.4,10.7) vs 5.7(4.1,9.3)] ng/ml and insulin [7.2(5.7-8.7) vs 6.8(5.3-9.4)] uUI/ml did not differ in HD compared to ND girls. Prolactin did not associate to DHEAS concentrations but significantly associated to 11 KA4 (P <0.001) even after adjustment by covariates and was in the limit of significance in the fully adjusted model for 11 OHA4 (P = 0.051).

Conclusion: Our observations confirm that 11 KT is the dominant bioactive androgen in children during adrenarche and PremA. Second that prolactin associates to the concentrations of the adrenal bioactive androgens. Conditions or medications that increase prolactin concentrations during childhood could have a role in modulating PremA.