Premature adrenarche in girls is characterized by enhanced 17,20-lyase and 17β-hydroxysteroid dehydrogenase activities

CONTEXT Girls with premature adrenarche (PA) may have a higher risk to develop polycystic ovary syndrome (PCOS) and metabolic syndrome. The biological purpose of adrenarche is unknown and the role of novel biosynthetic pathways remains unclear. OBJECTIVE To compare the urinary steroid metabolome and enzyme activities of girls with PA to age-matched control girls and to published steroid values of girls with normal adrenarche and of women with PCOS and their newborn daughters. DESIGN Prospective observational study from 2009-2014. SETTING Academic pediatric endocrinology referral center. PARTICIPANTS Twenty-three (23) girls with PA and 22 healthy, age-matched girls. MAIN OUTCOME MEASURES Steroid metabolites in 24h urine samples, including 4 progesterones, 5 corticosterones, aldosterone, 13 androgens, 2 estrogens and 14 glucocorticoids, and enzyme activities represented by metabolite ratios. RESULTS Girls with PA had a higher BMI (mean SDS 0.9 vs -0.3, p=0.013). Androgen excretion was higher in PA girls than in control girls (median 3257 nmol/24h vs 1627 nmol/24h, p<0.001), in particular metabolites from alternate androgen pathways. Amounts of progesterone, corticosterone, aldosterone, estrogen and cortisol metabolites were similar between groups. Activities of 17β-hydroxysteroid-dehydrogenase and of 17,20-lyase were higher in girls with PA. Activities of 3β-hydroxysteroid-dehydrogenase, 21-hydroxylase and 5α-reductase activity were not different between groups, in contrast to published results on girls with normal adrenarche or PCOS females. CONCLUSIONS Metabolites and enzymes involved in alternate androgen pathways appear to be markers of PA. Prospective studies should assess whether steroid production in PA also differs from adrenarche at normal timing and persists into adulthood.