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

• Published in: The journal of clinical endocrinology and metabolism Vol. 90; no. 4; pp. 2015 - 2021
• Main Authors: Remer, Thomas, Boye, Kai R., Hartmann, Michaela F., Wudy, Stefan A.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.04.2005; Endocrine Society
• Subjects: 3-Hydroxysteroid Dehydrogenases - urine; Adolescent; Age; Age Factors; Biological and medical sciences; Biomarkers; Child; Child Development - physiology; Child, Preschool; Cross-Sectional Studies; Dehydroepiandrosterone; Dehydroepiandrosterone - urine; Dehydrogenases; Endocrinopathies; Enzymatic activity; Enzymes; Excretion; Female; Fundamental and applied biological sciences. Psychology; Gas chromatography; Gas Chromatography-Mass Spectrometry; Humans; Male; Mass spectroscopy; Medical sciences; Metabolites; Reference Values; Sex Factors; Steroid 5α-reductase; Steroid hormones; Steroids; Vertebrates: endocrinology; Urine; Reference value; Healthy subject; Biological marker; Adrenarche; Age; Endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2004-1571

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 16α-hydroxylated downstream metabolites, 16α-hydroxy-DHEA and 3β,16α,17β-androstenetriol (DHEA&M), as well as the DHEA metabolite, 5-androstene-3β,17β-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 μg/d (P < 0.0001) during this period. Until the age of 16 yr, DHEA&M excretion also increased to nearly 1000 μg/d. Patterns of steroidogenic enzyme activities were assessed (from definite ratios of urinary steroid metabolites) for 21-hydroxylase, 3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, and 5α-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.