Sexual dimorphism in cortisol secretion starts after age 10 in healthy children: urinary cortisol metabolite excretion rates during growth

Abstract

Wudy SA, Hartmann MF, Remer T. Sexual dimorphism in cortisol secretion starts after age 10 in healthy children: urinary cortisol metabolite excretion rates during growth. Am J Physiol Endocrinol Metab 293: E970-E976, 2007. First published July 17, 2007; doi:10.1152/ajpendo.00495.2006.-Detailed data on the physiological pattern of adrenocortical activity during normal growth are lacking. An established method to determine adrenocortical glucocorticoid secretion is the measurement of 24-h excretion rates of major urinary cortisol metabolites (C21). To test the hypothesis that the frequently reported higher cortisol secretion in men than in women develops during puberty, we examined C21 together with excretions of combined urinary free and conjugated cortisol (F comb) in 400 healthy boys and girls aged 3-18 yr using GC-MS. Daily excretion rates of C21, F comb, and body surface area (BSA)-corrected Fcomb significantly increased with age in both sexes. In contrast, C21/BSA (g ⅐ m Ϫ2 ⅐ day Ϫ1 ) declined from the age of 3-4 yr to 7-8 yr in boys and girls (P Ͻ 0.01; e.g., in boys: from 3,991 Ϯ 1,167 to 3,193 Ϯ 804), then increased in both sexes, and finally became discordant after the age of 11-12 yr with a further rise in males only (17-to 18-yr-olds: boys, 5,275 Ϯ 1,414; girls 3,939 Ϯ 1,586, P Ͻ 0.01). This pattern was associated with the occurrence of a lower index for 5␣-reductase activity (allotetrahydrocortisol/tetrahydrocortisol) in females compared with males. Our results demonstrate dynamic changes in adrenocortical activity in healthy children resulting in an emerging sexual dimorphism in cortisol secretion after age 11. The latter can be explained, at least partly, by diverging 5␣-reductase activities in boys and girls. F comb , a frequently analyzed GC-MS parameter, proved not to reflect dynamic changes in cortisol secretion. In conclusion, the varying metabolic need for cortisol during normal growth may have implications for future improvements in glucocorticoid replacement therapy. steroid; glucocorticoid; gas chromatography; mass spectrometry IT HAS SO FAR BEEN ASSUMED that cortisol secretion corrected for body surface area is constant throughout childhood and adolescence. This assumption has been based on studies investigating urinary excretion rates of selected glucocorticoid metabolites in mostly small samples of children (2,15,17). However, detailed data on the physiological pattern of daily cortisol secretion, i.e., of adrenocortical activity during normal growth, are lacking.Assessment of cortisol secretion in a huge sample of healthy children and adolescents requires not only a nonstressful and noninvasive protocol but also a practical approach to permit successful realization. The application of invasive techniques based on isotope dilution requires venipuncture and infusions of either stable or radioactively labeled cortisol in specialized hospitals or research units with subsequent sampling of blood and/or urine to recover labeled metabolites (19,22,50). Additionally, administration of isotope...

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