Glucocorticoid Replacement for Adrenal Insufficiency and the Development of Non-Alcoholic Fatty Liver Disease

Glucocorticoid excess is a known risk factor for non-alcoholic fatty liver disease (NAFLD). Our objective was to analyse the impact of glucocorticoid replacement therapy on the development of NAFLD and NAFLD-related fibrosis and, therefore, on cardiovascular as well as hepatic morbidity in patients with adrenal insufficiency. Two hundred and fifteen individuals with primary (n = 111) or secondary (n = 104) adrenal insufficiency were investigated for hepatic steatosis and fibrosis using the fatty liver index (FLI), NAFLD fibrosis score (NAFLD-FS), Fibrosis-4 Index (FiB-4) plus sonographic transient elastography. Results were correlated with glucocorticoid doses and cardiometabolic risk parameters. The median dose of hydrocortisone equivalent was 20 mg daily, with a median therapy duration of 15 years. The presence and grade of hepatic steatosis and fibrosis were significantly correlated with cardiometabolic risk factors. We could not find any significant correlations between single, daily or cumulative doses of glucocorticoids and the grade of liver steatosis, nor with fibrosis measured via validated sonographic techniques. In patients with adrenal insufficiency, glucocorticoid replacement within a physiological range of 15–25 mg hydrocortisone equivalent per day does not appear to pose an additional risk for the development of NAFLD, subsequent liver fibrosis, or the cardiovascular morbidity associated with these conditions.