Metabolic Dysfunction-associated Steatotic Liver Disease in Klinefelter Syndrome: High Prevalence Uncovers an Unmet...

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.

We aim to study the relationship between hypogonadism, liver diseases, and cardiovascular risk using a unique KS model.

This cross-sectional study included 82 patients with KS. Data collected included anthropometric measurements, hormonal and liver function parameters, and 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.

The prevalence of MASLD in patients with KS was 45.1%. Patients with MASLD were significantly older (P < .001), had higher body mass index (P < .001), waist circumference (P < .001), and a greater prevalence of diabetes (P = .004). In multivariable logistic regression analysis, metabolic syndrome 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 ≤ .001). In contrast, CAP was positively correlated with triglycerides (P = .020), insulin resistance index (P = .017), waist circumference (P < .001), and body mass index (P ≤ .001). Cardiovascular risk showed no significant differences between the MASLD and non-MASLD groups.

This first study highlights substantial MASLD prevalence in patients with KS (45.1%). Metabolic syndrome 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.