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

• Published in: Clinical gastroenterology and hepatology Vol. 12; no. 3; pp. 504 - 512.e8
• Main Authors: Fede, Giuseppe, Spadaro, Luisa, Tomaselli, Tania, Privitera, Graziella, Scicali, Roberto, Vasianopoulou, Panayota, Thalassinos, Evangelos, Martin, Nicholas, Thomas, Michael, Purrello, Francesco, Burroughs, Andrew Kenneth
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2014
• Subjects: Adrenal Function; Adrenal Insufficiency - diagnosis; Adrenal Insufficiency - pathology; Adult; Biomarkers - blood; Diagnosis; Diagnostic Assay; Female; Gastroenterology and Hepatology; Humans; Hydrocortisone - blood; Liver Cirrhosis - complications; Liver Disease; Male; Middle Aged; Prospective Studies; Serum - chemistry; Test; Diagnostic Assay; low-dose short Synacthen test; ACTH; CBG; coefficient of variability; total serum cortisol; adrenocorticotropic hormone; Model for End-stage Liver Disease; Test; hypothalamus-pituitary-adrenal; Diagnosis; receiver operating characteristic; short Synacthen test; cFC; serum free cortisol; calculated free cortisol; ROC; AI; corticosteroid-binding globulin; FCI; TC; Adrenal Function; adrenal insufficiency; CV; LDSST; MELD; SST; HPA; free cortisol index; Liver Disease; FC
• ISSN: 1542-3565; 1542-7714
• DOI: 10.1016/j.cgh.2013.08.028

Background & 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 corticosteroid-binding globulin 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 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 levels by using Coolens’ equation. The Cox regression model was used to assess the relationship between adrenal dysfunction and outcomes (death or liver transplant). Results On the basis of measurement of total cortisol, 34% of patients had adrenal dysfunction, and on the basis of 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 on the basis of total cortisol and in 6% only on the basis of free cortisol (κ coefficient, 0.56; P < .01). Low concentrations of corticosteroid-binding globulin (21 vs 54 μg/mL, P < .01) led to an overestimation of adrenal dysfunction that was based on measurement of total cortisol. Measurements of calculated free cortisol 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% also had subnormal peak levels of free cortisol (κ coefficient, 0.70; P < .001). Adrenal dysfunction was not significantly associated with patient outcomes, on the basis of Cox model analysis. Conclusions Adrenal insufficiency, defined by LDSST, is frequent in patients with stable cirrhosis, on the basis of 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.