Assessment of adrenal function in patients with acute hepatitis using serum free and total cortisol

{Background: Adrenal dysfunction is frequently reported in severe acute hepatitis using serum total cortisol. Aims: 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 (T-0) and cosyntropin-stimulated (T-60) serum total and free cortisol concentrations were measured. Results: T-0 and T-60 serum total cortisol did not differ significantly between severe, non-severe hepatitis and healthy controls. Conversely, serum free cortisol (T-0 p = 0.012; T-60 p < 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 T-0 serum free cortisol than others (103.1 [61.2-157] vs. 56.6 [43.6-81.9] nmol/L