24 h urinary free cortisol in large-scale epidemiological studies: Short-term and long-term stability and sources of variability

Rosmalen, J. G. M., Kema, I. P., Wüst, S., van der Ley, C., Visser, S. T., Snieder, H. & Bakker, S. J. L., Sep-2014, In : Psychoneuroendocrinology. 47, p. 10-16 7 p.

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Background: Function of the hypothalamus-pituitary-adrenal (HPA) axis has been associated with several somatic and psychiatric health problems. The amount of free cortisol excreted in the urine during 24 h (24-h UFC) has often been used as a proxy for HPA-axis function. Reference values for 24-h UFC and their stability in the short and long term, as well as sources of variability, are largely lacking.

Methods: This study was performed in a general population cohort. Participants collected 24-h UFC on two consecutive days (T1), and repeated this collection approximately 2 years later (T2). Cortisol in urine was measured using LC-MS/MS. Height and weight were measured at the research facilities; glomerular filtration rate was estimated using creatinine clearance. Psychological distress (General Health Questionnaire), smoking, alcohol use and exercise were measured by means of questionnaires.

Results: 24-h UFC stability on a day-to-day basis was 0.69 (T1, N = 1192) and 0.72 (T2, N = 963) (both p <0.001). Long-term stability as indicated by correlation between 2-day averages of T1 and T2 was 0.60 (N = 972, p <0.001). Multivariable linear regression analysis revealed that 24-h UFC was predicted by urine volume (standardized beta 0.282 (T1, N = 1556) and 0.276 (T2, N = 1244); both p <0.001) and glomerular filtration rate (standardized beta 0.137 (T1) and 0.179 (T2); both p <0.001), while also sex explained a small part (standardized beta for female sex -0.057 (T1) and -0.080 (T2); both p <0.05).

Conclusion: 24-h UFC is moderately stable both in the short and the long term. The effects of urine volume and glomerular filtration rate on 24-h UFC are much stronger than those of sex. (C) 2014 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)10-16
Number of pages7
Publication statusPublished - Sep-2014


  • Urinary cortisol, 24-h UFC, Epidemiology, General population, Stability, Variability, Urine volume, Glomerular filtration rate, PITUITARY-ADRENAL AXIS, HEALTHY-INDIVIDUALS, EXCRETION, POPULATION, SPECIFICITY, COLLECTION, CREATININE, RESPONSES, SYMPTOMS, STRESS

ID: 13792743