Cosyntropin-stimulated serum free cortisol in healthy, adrenally insufficient, and mildly cirrhotic populations

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-=g CST. Design:Werecruited 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 =g 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 =g/dL vs 2.2 =g/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 =g/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 =g/dL; P =.02. In the CH patients, peak salivary cortisol levels correlated well with peak SFF (r_s=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.