Background: Adrenarche describes the developmental event of the human adrenal cortex when the zona reticularis increases the synthesis of C19 steroids (DHEA/-S) markedly at around 6-8 years of age. Early appearance of this event is called premature adrenarche (PA) and has been associated with adverse outcomes including polycystic ovary syndrome and metabolic syndrome. Recently novel biosynthetic pathways of androgen production have been revealed, but their role in health and disease remains largely unsolved.
Objective: This study aimed at characterizing the urinary steroid metabolome of girls with premature adrenarche in comparison to healthy controls with a special focus on metabolites originating of novel, alternate androgen pathways.
Methods: 39 steroid metabolites comprising progesterones, corticosterones, aldosterone, androgens, estrogens and glucocorticoids were measured in the urine by gas chromatography mass spectrometry in 23 girls with premature adrenarche (age range 3.9-8.4 years) and 22 healthy, age-matched controls (4.3-8.5 years). Groups were compared using Mann-Whitney test and Bonferroni correction applied to account for multiple testing.
Results: Girls with premature adrenarche were heavier (median weight 26.2±4.5 kg) than controls (21.5±3.4 kg) and had a higher BMI (17.2±2.0 vs 15.0±1.3kg/m2) (P<0.001). Gestational age and birth weight was comparable between groups. Steroid profiling revealed significant difference in overall androgen excretion, specifically the metabolites androsterone, etiocholanolone, dihydroandrosterone, dehydroepiandrosterone, androstenediol and androstenetriol were secreted in larger quantities in girls with premature adrenarche (P<0.001). Some of these metabolites originate from alternate androgen pathways, e.g. androsterone. No differences were found in progesterones, corticosterones, aldosterone, estrogens and glucocorticoids. Ratio calculations for steroid enzyme activities suggested lower HSD3B2 activity in girls with premature adrenarche than in controls, while no difference was found for CYP21A2 activity.
Conclusions: Girls with premature adrenarche produce more androgens than healthy girls of the same age. The urinary steroid signature of adrenarche includes steroid metabolites of alternate pathways, which shows differences in premature 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.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology