Cosyntropin-Stimulated Serum Free Cortisol in Healthy, Adrenally Insufficient, and Mildly Cirrhotic Populations

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CONTEXT: Serum free cortisol (SFF) responses to cosyntropin simulation test (CST) may more accurately assess adrenal function than total cortisol (TF). OBJECTIVE: The objective of the study was to evaluate the diagnostic utility of SFF responses during a 250-μg CST. DESIGN: We recruited healthy volunteers (HV; n = 27), patients with primary and secondary adrenal insufficiency (n = 19 and n = 24, respectively), and subjects with Child-Pugh class A cirrhosis (CH; n = 15). Each received 250 μg cosyntropin with measurement of ACTH and corticosteroid binding globulin (CBG) at time 0 and TF and SFF at 0, 30, and 60 minutes. Salivary cortisol was measured at all time points in CH subjects. RESULTS: Peak SFF and TF were significantly higher in HVs vs both AI groups (P < .05). Peak SFF and TF (6.8 μg/dL vs 2.2 μg/dL; [188 nmol/L vs 62 nmol/L]; P < .01) were significantly higher in the secondary adrenal insufficiency vs primary adrenal insufficiency patients. The optimal peak SFF criterion to identify adrenal insufficiency patients vs HV was 0.9 μg/dL (25 nmol/L) (sensitivity of 95%, specificity of 100%). Mean CBG and albumin levels were similar among all four groups. CH patients had a higher peak SFF than HV (2.4 vs 2.0 μg/dL; P = .02. In the CH patients, peak salivary cortisol levels correlated well with peak SFF (rs = 0.84, P = .005). CBG levels were similar among the groups. CONCLUSION: We provide normative data for SFF values in HV and AI during the CST. Normal CBG levels in mild cirrhosis did not affect the interpretation of the CST.