Comparison of Total Cortisol, Free Cortisol, and Surrogate Markers of Free Cortisol in Diagnosis of Adrenal Insufficiency in Patients with Stable Cirrhosis.

AbstractBACKGROUND AND AIMS:Measurements of serum levels of total cortisol can overestimate the prevalence of adrenal dysfunction in patients with cirrhosis, because they have low concentrations of cortisol-binding globulin (CBG) and albumin. We used measurements of serum total cortisol and serum free cortisol after the low-dose short Synacthen test (LDSST) to assess adrenal dysfunction.METHODS:We studied 79 patients with stable cirrhosis; adrenal dysfunction was defined by a peak concentrations of total cortisol ≤494 mmol/L and/or peak concentrations of free cortisol ≤33 nmol/L after the LDSST. We determined free cortisol index (FCI) scores and calculated free cortisol (cFC) levels using Coolens' equation. The Cox regression model was used to assess the relationship between adrenal dysfunction and outcomes (death or liver transplant).RESULTS:Based on measurement of total cortisol, 34% of patients had adrenal dysfunction, and based on measurement of free cortisol, 29% had adrenal dysfunction. There was agreement between total cortisol and free cortisol levels in 22% of patients; in 13%, adrenal dysfunction was diagnosed only based on total cortisol, and in 6% only based on free cortisol (κ-coefficient 0.56, P<.01). Low concentrations of CBG (21 vs 54 ug/ml, P<.01) led to an overestimation of adrenal dysfunction based on measurement of total cortisol. Measurements of cFC constantly overestimated free cortisol concentrations, with variations as large as 87% for baseline values and up to 84% after stimulation. Adrenal insufficiency, defined by FCI scores<12, was detected in 30% of patients; among them 23% had also a subnormal peak levels of free cortisol (κ-coefficient, 0.70; P<.001). Adrenal dysfunction was not significantly associated with patient outcomes, based on Cox model analysis.CONCLUSIONS:Adrenal insufficiency, defined by LDSST, is frequent in patients with stable cirrhosis, based on measurements of total and free cortisol. FCI scores are better than measurement of total cortisol in assessing adrenal function in patients with cirrhosis. We did not associate adrenal dysfunction with outcome, but further studies are needed.