An evaluation of measured and calculated serum free cortisol in a group of patients with known adrenal suppression

Background: Since more than 90% of cortisol is bound to protein, serum free cortisol (SFC) may be a more appropriate marker of adrenal status than total cortisol. However, measurement of SFC is technically difficult and calculated SFC may offer a more practical alternative. Methods: SFC, measured by equilibrium dialysis coupled with immunoassay, and calculated using Coo lens' equation from total cortisol and corticosteroid binding globulin (CBG) concentrations, was compared in short Synacthen test (SST) serum from 42 patients, of whom 20 demonstrated a suppressed adrenal response. Results: Considering the patient group as a whole, calculated SFC was found to be significantly lower than measured SFC, pre- and post-Synacthen (P < 0.05 and <0.001, respectively). Upon classifying the patients as pass or fail based on total cortisol response to Synacthen, the difference in calculated and measured SFC only reached statistical significance for post-Synacthen concentrations in the pass group (P < 0.01), suggesting a greater discrepancy at higher cortisol concentrations. There was no difference in CBG levels between the pass and fail groups and both measured and calculated SFC gave a diminished 30 min response in subjects deemed to have failed the SST. Conclusion: Coo lens' equation was found to underestimate measured SFC in this cohort of outpatients, as has been previously demonstrated, particularly in patients with a pronounced acute phase response. Although calculated SFC gave a diminished response in individuals deemed to have failed the SST, the concentration-dependent nature of the discrepancy may limit the usefulness of this method for assessing adrenal status.