Daily urinary free cortisol and cortisone excretion is associated with urine volume in healthy children

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In experimental studies, a high fluid intake and a corresponding high urine volume have been shown to increase renal excretion rates of urinary free cortisol (UFF) and cortisone (UFE) in adults. We aimed to examine whether 24-h UFF and UFE excretion rates are also affected by urine volume in children.


In 24-h urine samples of 100 pre-pubertal and 100 pubertal healthy children UFF, UFE, tetrahydrocortisol (THF), 5α-tetrahydrocortisol (5α-THF), and tetrahydrocortisone (THE) were quantified by RIA. The sum of THF, 5α-THF, and THE, the 3 primarily glucuronidated tetrahydrometabolites (GC3), reflects daily cortisol secretion. Associations of urine volume with outcome variables UFF, UFE, and GC3 were examined in both developmental groups using multiple regression models adjusted for sex, body weight and height.


Significant positive associations were observed between 24-h urine volume and UFF and UFE in both groups with the highest explained variation for UFE [partial R2 = 0.11 in pre-pubertal group (P < 0.005); partial R2 = 0.15 in pubertal group (P < 0.0001)]. However, for outcome GC3, urine volume was not significant in either of the groups.


Urinary 24-h excretion rates of UFF and UFE but not of the marker of glucocorticoid secretion are affected by daily urine volume in healthy free-living children. For a specific assessment of associations of UFF and UFE with (patho)physiologically relevant factors, urine volume should be considered as a confounder.

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