Metabolic Dysfunction-Associated Steatotic Liver Disease in Klinefelter Syndrome: High Prevalence Uncovers an Unmet Need

Context: Klinefelter Syndrome (KS) has a higher propensity for metabolic disorders and increased cardiovascular risk. The prevalence and the characteristics of metabolic dysfunction-associated steatotic liver disease (MASLD) have not been described yet in KS. Objective: We aim to study the relationship between hypogonadism, liver diseases and cardiovascular risk using the unique KS model. Methods: This cross-sectional study included 82 KS patients. Data collected included anthropometric measurements, hormonal and liver function parameters, abdominal ultrasound findings. In a subgroup of 46 patients, hepatic steatosis was evaluated using the control attenuation parameter (CAP) via Fibroscan®. Cardiovascular risk was assessed using Score2 and Score2-Diabetes. Results: The prevalence of MASLD in KS patients was 45.1%. Patients with MASLD were significantly older(p < 0.001), had higher body mass index (BMI) (p < 0.001), waist circumference (WC)(p < 0.001) and a greater prevalence of diabetes(p = 0.004). In multivariable logistic regression analysis, Metabolic Syndrome (MetS) was the only independent predictor of MASLD. For FibroScan®/CAP evaluation, the median liver stiffness (KPa) was 4.7. The median CAP value was 244.0 ± 59.4 dB/m. Correlation analysis revealed a significant negative relationship between CAP and IGF-1(p ≤ 0.001). In contrast, CAP was positively correlated with triglycerides (p = 0.020), Insulin resistance index (HOMA-IR)(p = 0.017), WC (p < 0.001), BMI (p ≤ 0.001). Cardiovascular risk showed no significant differences between the MASLD and non-MASLD groups. Conclusion: This first study highlights substantial MASLD prevalence in KS patients (45.1%). MetS is the major independent predictor of MASLD with a negative correlation between CAP and IGF-1. Early identification of MASLD is crucial to address the elevated risk of metabolic complications in this vulnerable population.