Urinary Markers of Adrenarche: Reference Values in Healthy Subjects, Aged 3–18 Years

Abstract

Information on the urinary excretion of dehydroepiandrosterone (DHEA) and its direct metabolites is scarce for healthy subjects during growth. We used gas chromatography-mass spectrometry urinary steroid profiling to noninvasively study adrenarchal metabolome in 400 healthy subjects, aged 3-18 yr. Urinary 24-h excretion rates of DHEA did not increase significantly before age 7-8 yr. However, DHEA together with its 16alpha-hydroxylated downstream metabolites, 16alpha-hydroxy-DHEA and 3beta,16alpha,17beta-androstenetriol (DHEA&M), as well as the DHEA metabolite, 5-androstene-3beta,17beta-diol (ADIOL), and the sum of major urinary androgen metabolites (C19) rose consistently from the youngest to the oldest age group. The significant increases (P < 0.01) observed for 24-h excretion rates of C19, ADIOL, and DHEA&M were 2- to 4-fold in boys and girls between age 3 and 8 yr. DHEA&M, for example, rose from about 20 to 80 microg/d (P < 0.0001) during this period. Until the age of 16 yr, DHEA&M excretion also increased to nearly 1000 microg/d. Patterns of steroidogenic enzyme activities were assessed (from definite ratios of urinary steroid metabolites) for 21-hydroxylase, 3beta-hydroxysteroid dehydrogenase, 17beta-hydroxysteroid dehydrogenase, and 5alpha-reductase. Our results indicate for healthy boys and girls that adrenarche is a gradual process starting much earlier than hitherto believed. Efficient metabolism of DHEA, especially to 16-hydroxylated steroids, may explain the almost constant levels seen for this steroid until age 7-8 yr. The established reference values for DHEA, DHEA&M, ADIOL, C19 (including androsterone and etiocholanolone), and urinary parameters of steroidogenic enzyme activities could be useful to identify nutritional, environmental, and pathophysiological interrelations with the progressive maturational process of adrenarche. Our data may also be used as reference data for the diagnosis of steroid-related disorders.

Morphological adrenarche in rhesus macaques: development of the zona reticularis is concurrent with fetal zone regression in the early neonatal period

“…This does not indicate any fundamental difference exists between human and rhesus adrenal with respect to ZR development. In fact, it is entirely consistent with the physiological independence of ZR development from gonadal function, as evidenced in normal children and those with precocious puberty (Sklar et al 1980, Palmert et al 2001, Remer et al 2005. Although the decline in DS (adrenopause) is readily detectable in the rhesus, adrenarche is certainly not.…”

Reduced 11β-hydroxysteroid dehydrogenase type 1 activity in obese boys

“…Reference values from healthy controls were chosen from 400 healthy children and adolescents of the DONALD study (11), specifically calculated for mean ages of 15 years for boys and 15.5 years for girls. Selection criteria for matching the healthy controls (15 boys and 6 girls) to the obese cohort were: 1) pubertal Tanner stages (boys, 2-5; girls, 3-5), 2) minimum and maximum ages of 12 and 18 years respectively, and 3) a BMI-SDS of 0.0G0.3.…”

Gender and gonadal status differences in zona reticularis expression in marmoset monkey adrenals: Cytochrome b5 localization with respect to cytochrome P450 17,20-lyase activity

“…At around 5-7 years of age in the human, DHEAS levels begin to rise (~50 μg/dL) in a process known as adrenarche, which marks the development of a functional ZR (Havelock et al 2004). Recent evidence suggests that adrenarche is a continuous process beginning in utero or at birth (Remer et al 2005). Once again, ZR development of DHEA production by CYP17 in the adrenal cortex is associated with both a reticularis-specific increase in cyt b5 expression while 3β-HSD expression decreases (Endoh et al 1996, Gell et al 1996, Suzuki et al 2000.…”