title: 24 h urinary free cortisol in large-scale epidemiological studies: short-term and long-term stability and sources of variability.
abstract: 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 24h (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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Groningen, University Medical Center Groningen, Interdisciplinary Center Psychopathology and Emotion regulation, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. Electronic address: j.g.m.rosmalen@umcg.nl.
authors.forename: Judith G M
authors.initials: JG
authors.lastname: Rosmalen
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Laboratory Medicine, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Ido P
authors.initials: IP
authors.lastname: Kema
authors.affiliation: Institute of Experimental Psychology, University of Regensburg, 93040 Regensburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wüst
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Laboratory Medicine, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Claude
authors.initials: C
authors.lastname: van der Ley
authors.affiliation: University of Groningen, University Medical Center Groningen, Unit of PharmacoEpidemiology & PharmacoEconomics, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Sipke T
authors.initials: ST
authors.lastname: Visser
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Epidemiology, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Harold
authors.initials: H
authors.lastname: Snieder
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Internal Medicine, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
mesh_terms: D000328:Adult; D002940:Circadian Rhythm; D015331:Cohort Studies; D004355:Drug Stability; D015340:Epidemiologic Research Design; D016021:Epidemiologic Studies; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000652:urine*; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D011309:Preservation, Biological / Q000592:standards; D012107:Research Design; D018401:Sample Size; D059349:Urine Specimen Collection / Q000379:methods* / Q000592:standards
chemical_list: D006854:Hydrocortisone
keywords: 24-h UFC; Epidemiology; General population; Glomerular filtration rate; Stability; Urinary cortisol; Urine volume; Variability