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 (T0) and cosyntropin-stimulated (T60) serum total and free cortisol concentrations were measured.
Results: T0 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 (<28mg/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).
Conclusions: In severe hepatitis, the decrease in cortisol-binding proteins impairs correct diagnosis of adrenal dysfunction. This could be corrected by measuring or estimating free cortisol.
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