title: Higher free serum cortisol is associated with worse survival in acute variceal bleeding because of cirrhosis: a prospective study.
abstract: OBJECTIVE
  Critical illness-related corticosteroid insufficiency has been reported in acute variceal bleeding (AVB). In cirrhosis, free serum cortisol (FC) is considered optimal to assess adrenal function. Salivary cortisol (SC) is considered a surrogate for FC. We evaluated FC and its prognostic role in AVB.
  
  
  METHODS
  Total serum cortisol, SC, cortisol-binding globulin, and FC (Coolens' formula) were evaluated in AVB (n=38) and in stable cirrhosis (CC) (n=31). A Cox proportional hazards model was evaluated for 6-week survival.
  
  
  RESULTS
  In AVB, the median FC and SC levels were higher with worse liver dysfunction [Child-Pugh (CP) A/B/C: 1.59/2.62/3.26 μg/dl, P=0.019; CPA/B/C: 0.48/0.897/1.81 μg/ml, P<0.001, respectively]. In AVB compared with CC, median total serum cortisol: 24.3 versus 11.6 μg/dl (P<0.001), SC: 0.86 versus 0.407 μg/ml (P<0.001); FC 2.4 versus 0.57 μg/dl (P<0.001). In AVB, 5-day rebleeding was 10.5%, and 6-week and total mortality were 21.1 and 23.7%, respectively. Independent associations with 6-week mortality in AVB were FC at least 3.2 μg/dl (P<0.001), hepatocellular carcinoma (P<0.001), CPC (P<0.001), and early rebleeding (P<0.001). Among patients with normal cortisol-binding globulin (n=14) and albumin (n=31), the factors were hepatocellular carcinoma (P=0.003), CP (P=0.003), and FC (P=0.036). SC was also found to be an independent predictor of 6-week mortality (P<0.001). Area under the curve of FC for predicting 6-week mortality was 0.79.
  
  
  CONCLUSIONS
  Higher FC is present in cirrhosis with AVB compared with CC and is associated independently with bleeding-related mortality. However, whether high FC solely indicates the severity of illness or whether there is significant adrenal insufficiency cannot be discerned.
authors.affiliation: Departments of aGastroenterology bEndocrinology cInternal Medicine, University Hospital of Patras dDepartment of Public Health, Medical School, University of Patras, Patras eDepartment of Gastroenterology, University Hospital of Heraklion, Heraklion, Greece fThe Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, London, UK.
authors.forename: Christos K
authors.initials: CK
authors.lastname: Triantos
authors.forename: Maria
authors.initials: M
authors.lastname: Kalafateli
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Samonakis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Zisimopoulos
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Papiamonis
authors.forename: Apostolos
authors.initials: A
authors.lastname: Sapountzis
authors.forename: Marina
authors.initials: M
authors.lastname: Michalaki
authors.forename: Georgios
authors.initials: G
authors.lastname: Theocharis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Thomopoulos
authors.forename: Chryssoula
authors.initials: C
authors.lastname: Labropoulou-Karatza
authors.forename: Venetsanea
authors.initials: V
authors.lastname: Kyriazopoulou
authors.forename: Eleni
authors.initials: E
authors.lastname: Jelastopulu
authors.forename: Elias A
authors.initials: EA
authors.lastname: Kouroumalis
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Nikolopoulou
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Burroughs
mesh_terms: D000208:Acute Disease; D000302:Adrenal Cortex / Q000378:metabolism* / Q000503:physiopathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000209:etiology / Q000401:mortality; D002352:Carrier Proteins / Q000097:blood; D016009:Chi-Square Distribution; D004932:Esophageal and Gastric Varices / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D006115:Greece; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000401:mortality; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000097:blood / Q000209:etiology / Q000401:mortality; D016015:Logistic Models; D008131:London; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism; D000075462:Serum Albumin, Human; D012720:Severity of Illness Index; D013997:Time Factors; D015854:Up-Regulation
chemical_list: C422455:ALB protein, human; D015415:Biomarkers; D002352:Carrier Proteins; D012709:Serum Albumin; C027091:cortisol binding globulin; D006854:Hydrocortisone; D000075462:Serum Albumin, Human