Biochemical remission of Cushing's syndrome reduces hepatic steatosis and fibrosis indices in adult patients.

BackgroundMetabolic dysfunction–associated steatotic liver disease (MASLD) is increasingly recognized as a systemic manifestation of endocrine disorders. Cushing’s syndrome (CS), characterized by chronic endogenous hypercortisolism, is associated with profound metabolic disturbances that may predispose to MASLD; however, data on its prevalence, determinants, and reversibility after remission remain limited and inconsistent.ObjectiveTo evaluate the prevalence of MASLD in patients with CS, assess changes in hepatic steatosis and fibrosis-related indices following biochemical remission, and identify independent clinical, metabolic, and etiological predictors of MASLD.MethodsIn this retrospective study, 126 adult patients with endogenous CS diagnosed between 2014 and 2025 were included. MASLD was defined according to contemporary consensus criteria. Imaging-based hepatic steatosis was evaluated by abdominal ultrasonography. Hepatic steatosis and fibrosis risk were assessed using the hepatic steatosis index (HSI) and Fibrosis-4 index (FIB-4), respectively, during the active disease phase and six months after biochemical remission. Comparisons were performed between adrenal and pituitary CS. Logistic regression analyses were used to identify factors independently associated with MASLD.ResultsMASLD was present in 62.7% of patients with CS. At baseline, MASLD prevalence did not differ significantly between adrenal and pituitary CS. HSI decreased from the active phase to six months after remission in both adrenal and pituitary CS (p < 0.01 for both), indicating partial reversibility of hepatosteatosis following cortisol normalization. Overall, FIB-4 values did not change; however, patients with elevated baseline fibrosis risk (FIB-4 ≥1.3) demonstrated a significant reduction after remission (p = 0.010). In multivariate analysis, higher body mass index (adjusted OR 1.30), longer duration of symptoms before diagnosis (adjusted OR 1.06), and adrenal CS (adjusted OR 2.90) were independently associated with MASLD, whereas increasing age was inversely associated. Biochemical measures of cortisol excess were not independently related to MASLD.ConclusionsMASLD is highly prevalent in CS and is primarily driven by metabolic burden, disease chronicity, and etiology rather than by biochemical severity of hypercortisolism. Hepatic steatosis shows partial improvement after remission, whereas the risk of fibrosis declines primarily among patients with elevated baseline risk. These findings support routine hepatic assessment in CS, particularly those with prolonged disease duration and increased metabolic risk.