The Link Between Acromegaly, Liver Morphology, and MASLD: A Large Cohort Analysis.

OBJECTIVE: To evaluate liver morphology and clinical determinants in acromegaly. DESIGN: Retrospective single-center cohort study. METHODS: We analyzed 394 acromegaly patients followed at a single tertiary center over four decades for hepatic morphology and metabolic dysfunction-associated steatotic liver disease (MASLD). Patients were compared by hepatic cyst and MASLD status; multivariable logistic regression identified independent predictors, using outcome-specific primary hormonal exposures-the peri-imaging IGF1×ULN for MASLD and time-weighted-average IGF1×ULN (TWAvg) for hepatic cysts. Standardized prevalence ratios (SPR) against age- and sex-stratified references were also examined. RESULTS: Of 282 imaged patients, MASLD, hepatic cyst, hemangioma, and cholelithiasis prevalence was 31.0%, 15.6%, 4.3%, and 36.8%. Cyst prevalence matched population estimates, whereas imaging-detected MASLD was significantly lower than expected (SPR 0.56-0.78). Hepatic cyst was independently associated with renal cyst (OR 2.769) and inversely with MASLD (0.231), with older age borderline significant. MASLD was inversely associated with the peri-imaging IGF1×ULN (OR 0.74 per doubling), hepatic cyst (0.109), and longitudinal exposure (log2 TWAvg IGF1×ULN 0.61), and positively with cholelithiasis (3.158). CONCLUSIONS: Hepatic cyst prevalence matched population estimates, whereas imaging-detected MASLD was significantly lower. Cysts associated with older age, renal cysts, and absence of MASLD; MASLD associated inversely with the peri-imaging and longitudinal IGF1 exposure and positively with cholelithiasis. The inverse cyst-MASLD relationship is hypothesis-generating: MASLD tracked GH/IGF1 activity whereas cysts did not, suggesting distinct hepatic phenotypes of a shared, as-yet-unmeasured determinant rather than opposite readouts of one hormonal signal.