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

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 (T30) 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% (T0 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 T30 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 T30 SFC (≥ 78.9 nmol/L) (26.2%) and one patient with low T30 SFC (< 78.9 nmol/L) (3.4%) died (P = 0.027 for high vs low T30 SFC, log–rank test). Albeit not statistically significant, the risk of death for patients with T30 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 T30 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.