title: Assessment of adrenal function in patients with acute hepatitis using serum free and total cortisol.
abstract: BACKGROUND
  Adrenal dysfunction is frequently reported in severe acute hepatitis using serum total cortisol.
  
  
  OBJECTIVE
  Because 90% of serum cortisol is bound to proteins that are altered during stress, we investigated the effect of decreased cortisol-binding proteins on serum total and free cortisol in severe acute hepatitis.
  
  
  METHODS
  43 severe and 31 non-severe acute hepatitis and 29 healthy controls were enrolled consecutively and studied prospectively. Baseline (T0) and cosyntropin-stimulated (T60) serum total and free cortisol concentrations were measured.
  
  
  RESULTS
  T0 and T60 serum total cortisol did not differ significantly between severe, non-severe hepatitis and healthy controls. Conversely, serum free cortisol (T0p=0.012; T60p<0.001) concentrations increased from healthy controls to severe hepatitis, accompanied by a decrease in corticosteroid-binding globulin and albumin (all p<0.001). In acute hepatitis (n=74), patients with "low" corticosteroid-binding globulin (<28mg/L) had higher T0 serum free cortisol than others (103.1 [61.2-157] vs. 56.6 [43.6-81.9]nmol/L, p=0.0024). Analysis of covariance showed that at equal concentration of total cortisol, the free cortisol concentration was significantly higher in severe than in non-severe hepatitis (p<0.001) or healthy controls (p<0.001).
  
  
  CONCLUSIONS
  In severe hepatitis, the decrease in cortisol-binding proteins impairs correct diagnosis of adrenal dysfunction. This could be corrected by measuring or estimating free cortisol.
authors.affiliation: Hepatology and Digestive Intensive Care Unit, University Hospital of Besançon, France; EA UPRES 3186 « Agents Pathogènes et Inflammation » of Franche-Comté University, France.
authors.forename: Thibault
authors.initials: T
authors.lastname: Degand
authors.affiliation: Hepatology and Digestive Intensive Care Unit, University Hospital of Besançon, France; EA UPRES 3186 « Agents Pathogènes et Inflammation » of Franche-Comté University, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Monnet
authors.affiliation: Hepatology Unit, Beaujon Hospital, Clichy cedex, France.
authors.forename: François
authors.initials: F
authors.lastname: Durand
authors.affiliation: Laboratory for Endocrinology and Metabolism, University Hospital of Besançon, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Grandclement
authors.affiliation: Hepatobiliary Unit and Liver Intensive Care, Paul Brousse University Hospital AP-HP, Villejuif cedex, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ichai
authors.affiliation: Department of Endocrinology, University Hospital of Besançon, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Borot
authors.affiliation: Clinical Translational Science Center, University of New Mexico Health Science Center, USA.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Qualls
authors.affiliation: ICube, UMR 7357, University of Strasbourg and CNRS, FMTS, Strasbourg, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Agin
authors.affiliation: Department of Hepatogastroenterology, University Hospital of Lille, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Louvet
authors.affiliation: Department of Hepatogastroenterology, University Hospital Edouard Herriot of Lyon, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Dumortier
authors.affiliation: Hepatology Unit, Beaujon Hospital, Clichy cedex, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Francoz
authors.affiliation: Laboratory for Endocrinology and Metabolism, University Hospital of Besançon, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Dumoulin
authors.affiliation: Hepatology and Digestive Intensive Care Unit, University Hospital of Besançon, France; EA UPRES 3186 « Agents Pathogènes et Inflammation » of Franche-Comté University, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Di Martino
authors.affiliation: Department of Medicine, New Mexico VA Medical Center and University of New Mexico Health Science Center, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Dorin
authors.affiliation: Hepatology and Digestive Intensive Care Unit, University Hospital of Besançon, France; EA UPRES 3186 « Agents Pathogènes et Inflammation » of Franche-Comté University, France. Electronic address: tthevenot@chu-besancon.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Thevenot
mesh_terms: D000208:Acute Disease; D000309:Adrenal Insufficiency / Q000453:epidemiology*; D000328:Adult; D000418:Albumins / Q000032:analysis*; D002352:Carrier Proteins / Q000032:analysis*; D016022:Case-Control Studies; D005260:Female; D005602:France; D006505:Hepatitis / Q000150:complications*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000418:Albumins; D002352:Carrier Proteins; D006854:Hydrocortisone
keywords: Acute liver failure; Hypothalamic–pituitary–adrenal axis