Introduction: Adrenarche refers to the increase in adrenal androgen synthesis. However, process of adrenal androgen production in early childhood remains to be elucidated. The aim of this study was to evaluate changes in adrenal androgen levels and steroidogenic enzyme activities associated with adrenarche using a prospective cohort.
Methods: A total of 229 children (124 boys, 52.4%), who had participated in the Environment and Development of Children (EDC) cohort at age 2, 4, and 6 years old were enrolled. Anthropometric data at each visit and birth data were collected. Steroid profiles were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 10 adrenal hormones were measured including dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), 17-hydroxyprogesterone, androstenedione, testosterone, pregnenolone sulfate, cholesterol sulfate, testosterone, progesterone, 17-hydroxypregnenolone, and pregnenolone. Steroidogenic enzyme activities were calculated using precursor/product ratios, such as 17α-hydroxylase, 17,20-lyase, 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, and DHEA sulfotransferase. Steroid levels and enzyme activities were compared according to age and sex. Biochemical adrenarche was defined as a DHEA-S concentration of 188.1 ng/mL using LC-MS/MS. Factors affecting increasing levels of DHEA-S were analyzed.
Results: Data for 200 subjects (114 boys, 57.0%) with all steroid profiling results at 2, 4, and 6 years were analyzed. DHEA, DHEA-S, and androstenedione increased between 2 and 4 years in both sexes. DHEA and androstenedione were higher in girls than in boys at the age of 6 years. DHEA sulfotransferase activity increased between 2 and 4 years in both sexes. Between 4 and 6 years, activities of 17α-hydroxylase and 17,20-lyase increased, although 3β-HSD and 17β-HSD activities decreased. In girls, 17,20-lyase activity was higher and 3β-HSD and 17β-HSD activities were lower than in boys. Factors associated with increasing DHEA-S concentration over visits were age and body mass index. DHEA-S levels at the age of 6 years were significantly associated with being born small for gestational age and bone age on the third visit. Biochemical adrenarche was observed in 27 children (13.5%) with no sex difference.
Conclusions: Adrenal androgens began to increase between the ages 2 to 4 years. Increased activity of DHEA sulfotransferase began between 2 and 4 years. Changes in steroidogenic enzyme activity to increase DHEA-S concentrations started between 4 and 6 years with increased 17,20-lyase and decreased 3β-HSD activity. A longitudinal study with samples at the age of 8 years would be needed.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology