High serum levels of free cortisol indicate severity of cirrhosis in hemodynamically stable patients

J Gastroenterol Hepatol. 2012 Oct;27(10):1596-601. doi: 10.1111/j.1440-1746.2012.07188.x.


Background and aim: We investigated: (i) the association between severity of cirrhosis and serum levels of free cortisol (SFC) and total cortisol (STC), measured before and 30 min after (T(30)) the low-dose 1-µg short synacthen test (LD-SST); and (ii) the prognostic value of SFC and STC.

Methods: Consecutive, hemodynamically stable, cirrhotic patients (34 Child-Pugh class A, 29B, and 32C) underwent the LD-SST. Patients were followed for at least 12 months to assess non-transplant-related mortality.

Results: Child-Pugh class C patients had significantly higher basal levels of SFC than Child-Pugh class A or B patients. Prevalence of suspected adrenal dysfunction ranged between 7.4% (T(0) STC < 138 nmol/L) and 49.4% (change in STC < 250 nmol/L) according to the threshold used. In receiver-operator curve analysis, the area-under-the-curve values were 0.67 for T(30) SFC (0.51-0.79), 0.81 for Child-Pugh score (0.70-0.88), and 0.79 for albumin level (0.63-0.88). During the follow-up period, 16 patients with high T(30) SFC (≥ 78.9 nmol/L) (26.2%) and one patient with low T(30) SFC (< 78.9 nmol/L) (3.4%) died (P = 0.027 for high vs low T(30) SFC, log-rank test). Albeit not statistically significant, the risk of death for patients with T(30) SFC ≥ 78.9 nmol/L was fivefold higher than for patients with lower levels after adjusting for cirrhosis severity and level of albumin.

Conclusions: One-year, non-transplant-related mortality is high among patients with T(30) levels of SFC ≥ 78.9 nmol/L (26.2%). These findings might result from latent inflammatory stress in hemodynamically stable cirrhotic patients, detected by adrenal testing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Function Tests*
  • Adrenal Gland Diseases / blood
  • Adrenal Gland Diseases / diagnosis*
  • Adrenal Gland Diseases / mortality
  • Adrenal Gland Diseases / physiopathology
  • Adult
  • Aged
  • Biomarkers / blood
  • Cosyntropin
  • Female
  • Hemodynamics*
  • Humans
  • Hydrocortisone / blood*
  • Kaplan-Meier Estimate
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / diagnosis*
  • Liver Cirrhosis / mortality
  • Liver Cirrhosis / physiopathology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prevalence
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Time Factors
  • Up-Regulation


  • Biomarkers
  • Cosyntropin
  • adrenocorticotropin zinc
  • Hydrocortisone