title: Three calculations of free cortisol versus measured values in the critically ill.
abstract: OBJECTIVE
  To investigate the agreement between the calculated free cortisol levels according to widely applied Coolens and adjusted Södergård equations with measured levels in the critically ill.
  
  
  METHODS
  A prospective study in a mixed intensive care unit. We consecutively included 103 patients with treatment-insensitive hypotension in whom an adrenocorticotropic hormone (ACTH) test (250μg) was performed. Serum total and free cortisol (equilibrium dialysis), corticosteroid-binding globulin and albumin were assessed. Free cortisol was estimated by the Coolens method (C) and two adjusted Södergård (S1 and S2) equations. Bland Altman plots were made.
  
  
  RESULTS
  The bias for absolute (t=0, 30 and 60min after ACTH injection) cortisol levels was 38, -24, 41nmol/L when the C, S1 and S2 equations were used, with 95% limits of agreement between -65-142, -182-135, and -57-139nmol/L and percentage errors of 66, 85, and 64%, respectively. Bias for delta (peak-baseline) cortisol was 14, -31 and 16nmol/L, with 95% limits of agreement between -80-108, -157-95, and -74-105nmol/L, and percentage errors of 107, 114, and 100% for C, S1 and S2 equations, respectively.
  
  
  CONCLUSIONS
  Calculated free cortisol levels have too high bias and imprecision to allow for acceptable use in the critically ill.
authors.affiliation: Department of Surgery, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
authors.forename: Nienke
authors.initials: N
authors.lastname: Molenaar
authors.affiliation: Department of Intensive Care, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
authors.forename: A B Johan
authors.initials: AB
authors.lastname: Groeneveld
authors.affiliation: Department of Nephrology, University Medical Center Groningen, 9700 RB Groningen, The Netherlands. Electronic address: m.f.c.de.jong@umcg.nl.
authors.forename: Margriet F C
authors.initials: MF
authors.lastname: de Jong
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000368:Aged; D000418:Albumins / Q000378:metabolism; D016638:Critical Illness; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007362:Intensive Care Units; D008297:Male; D011446:Prospective Studies; D014156:Transcortin / Q000378:metabolism
chemical_list: D000418:Albumins; D000324:Adrenocorticotropic Hormone; D014156:Transcortin; D006854:Hydrocortisone
keywords: Affinity constants; Coolens method; Cortisol-binding globulin; Critical illness related corticosteroid insufficiency; Equilibrium dialysis; Free cortisol; Relative adrenal insufficiency; Södergard equation