Abstract
Background: Relative adrenal insufficiency is a negative prognostic marker for patients with septic shock. Cortisol is highly protein-bound so the hypoproteinaemic state in these patients complicates the diagnosis of adrenal insufficiency using total cortisol measurement. Direct free cortisol measurement, however, is not suitable for routine use. Surrogate markers of free cortisol were evaluated for relative adrenal insufficiency diagnosis. Objectives: We aimed to compare the diagnostic value of stimulated, free and total cortisol to assess adrenal function and to determine the accuracy and diagnostic value of surrogate markers (total cortisol:CBG ratio, total cortisol:albumin ratio, Coolen’s equation, and an adapted Vermeulen’s equation) as indices of adrenal insufficiency. Methods: The standard 250 μg SST was conducted on fifteen control subjects and five samples from patients with septic shock. Baseline samples were analysed for ACTH (Immulite) and albumin (BCG) concentrations. Serum total cortisol (Elecsys), free cortisol (steady state gel filtration) and cortisol binding globulin (CBG, Biosource RIA) concentrations were determined in samples taken 0, 30 and 60 minutes after synacthen administration. Results: Albumin and CBG concentrations were significantly lower and baseline total and free cortisol concentrations were significantly higher in patients than control subjects (p<0.002). All surrogate markers correlated well with free cortisol across the duration of the SST. Free cortisol values determined by an adapted Vermeulen’s equation showed the greatest association (r2=0.959, p=0.01). Coolen’s equation was clinically most significant identifying the same patients to have adrenal insufficiency as direct free cortisol. Conclusions: Serum free cortisol concentrations are likely to provide a more accurate reflection of adrenal status than total cortisol concentrations in hypoproteinaemic pateints. Surrogate markers would appear to be applicable for the indirect estimation of free cortisol. We found the Coolen’s equation to be clinically the most significant marker.