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High Fluid Intake Increases Urine Free Cortisol Excretion in Normal Subjects

Developmental Endocrinology Branch, National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 10892-1862

Address all correspondence and requests for reprints to: M. Veronica Mericq, National Institutes of Child Health and Human Development, Developmental Endocrinology Branch, SDE, Building 10, Room 10N262, 10 Center Drive, MSC 1862, Bethesda, Maryland 20892-1862. E-mail: mericqV{at}cc1.NICHD.NIH.gov

To test the hypothesis that increased fluid intake increases the urine free cortisol, we prescribed 5 liters of fluid intake per day or a normal fluid intake according to a randomized cross-over design in six normal volunteers. Each period lasted 5 days, with a 2-day washout period of normal fluid intake between the two periods. Urine free cortisol, 17-hydroxycorticosteroids, and creatinine were measured daily during each study period, and the average value over each 5-day period was calculated for each subject. High fluid intake caused a significant increase in the mean urine free cortisol [126 ± 33 (SD) vs. 77 ± 18 µg/day, P < 0.005]. The frequency of urine free cortisol results that exceeded the upper normal limit of 95 µg/day was also much higher during high fluid intake (23/30 vs. 6/30, P < 0.005). By contrast, urine 17-hydroxycorticosteroids (high fluid vs. normal fluid: 5.3 ± 1.5 vs. 5.0 ± 1.7 mg/day, respectively, P = not significant) and urine creatinine (1.51 ± 0.48 vs. 1.45 ± 0.37 g/day, P = not significant) did not differ between the two study periods. We conclude that high fluid intake (5 liters/day) increases free cortisol excretion without an increase in urine 17-hydroxycorticosteroids. Thus, mild to moderate increases in urine cortisol excretion may not indicate hypercortisolism in individuals who have a high fluid intake and urine volume.

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