Liver, Pancreas and Biliary TractAssessment of adrenal function in patients with acute hepatitis using serum free and total cortisol

BackgroundAdrenal dysfunction is frequently reported in severe acute hepatitis using serum total cortisol.AimsBecause 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.Methods43 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.ResultsT0 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 (<28 mg/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).ConclusionsIn severe hepatitis, the decrease in cortisol-binding proteins impairs correct diagnosis of adrenal dysfunction. This could be corrected by measuring or estimating free cortisol.