SUN-073 Urine Steroid Profile of Girls with Premature Adrenarche

Background: Adrenarche describes the development of the human adrenal cortex when the zona reticularis increases the synthesis of C19 steroids (DHEA/-S). Girls with premature adrenarche have a higher risk to develop adverse outcomes including polycystic ovary syndrome and metabolic syndrome later in life. The role of novel biosynthetic pathways of androgen production in health and disease remains largely unsolved. Objective: This study aimed to compare the urinary steroid metabolome between girls with premature adrenarche and healthy girls with focus on metabolites originating of novel, alternate androgen pathways. Methods: In 23 girls with premature adrenarche (median age 7 years) and 22 healthy, age-matched girls, we measured 39 steroid metabolites comprising progesterones, corticosterones, aldosterone, androgens, estrogens and glucocorticoids in the urine collected over 24 h by gas chromatography mass spectrometry. We compared metabolites and metabolite ratios between both groups of girls using Mann-Whitney tests with Bonferroni correction to account for multiple testing. Results: Girls with premature adrenarche were heavier than healthy girls (median weight 26.2 kg vs. 21.5 kg, p=0.003) and had a higher BMI SDS (0.8 vs -0.3, p=0.013). Gestational age and birth weight was similar between groups. Overall androgen excretion was different between groups, in particular amounts of androsterone, etiocholanolone, androstanediol, dehydroepiandrosterone, androstenediol, androstenetriol and pregnenetriol were higher in girls with premature adrenarche than in healthy girls (p<0.05). Some of these metabolites originate from alternate androgen pathways, e.g. androsterone. We found no differences in progesterones, corticosterones, aldosterone, estrogens and glucocorticoids, except for 20β-dihydrocortisone, which was higher in girls with premature adrenarche. Activities of 17βHSD and of 17,20-lyase via the Δ4pathway were higher in girls with premature adrenarche than in healthy girls. Conclusions: Girls with premature adrenarche produce more androgens than healthy girls of similar age. The urinary steroid signature of adrenarche includes metabolites of alternate pathways. Androstanediol seems a marker of adrenarche. Future studies should assess whether the steroid signature of adrenarche is just appearing earlier in girls with premature adrenarche or earlier and different compared to adrenarche at normal timing.