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.