Endocrine Abstracts

Non-alcoholic fatty liver disease (NAFLD) is becoming more common over the world. Its predisposition for evolving to cirrhosis and hepatocellular cancer, as well as its link to extrahepatic symptoms, puts patients and clinicians under a double burden. Several studies have found a link between NAFLD and many endocrinopathies, demonstrating a substantial bi-directional link between NAFLD and hypogonadism, in both men and women. In man with T2DM, NAFLD is linked to reduced total testosterone, however this is owing to a common soil of insulin resistance/obesity rather than the degree of liver necroinflammation or fibrosis. No data are available regarding Klinefelter syndrome (KS), the most common chromosomal condition associated with hypogonadism and NAFLD.

Methods: Thirty-five KS on Testosterone (T) replacement treatment were recruited. All patients underwent physical examination, full liver function tests, fasting glucose, triglycerides, cholesterol, blood cell counts, viral markers (HBV, HCV, HIV) and liver ultrasonography. The presence of autoimmune liver disease was assessed. The body mass index (BMI: kg/m2) was recorded for all patients. Insulin resistance index (HOMA-IR), and renal function were calculated. Conventional ultrasonography was performed to assess liver dimension, hyper echogenicity as compared to the right kidney parenchyma, distal attenuation, and the presence of areas of focal sparing. Prevalence of steatosis, using non-invasive methods in relation to anthropometric, biochemical, virological and ultrasound was estimated.

Results: Prevalence of steatosis in KS was 51%. BMI was 28.4±1.3 and HOMA-IR 3.8±1.0(Mean±SEM). T, 393.3±22 ng/dl, and SHBG, 31±2 nmol/l, serum levels were in the normal range. AMA, ANA and ASMA were negative. AST, ALT, and gamma GT were slightly increased in 11.1%, 44.4% and 31.1%, respectively. No patient shows signs of advanced liver disease. Total and LDL cholesterol were normal (174±9 and 112±7, Mean±SEM, respectively). Serologic markers for HBV, HCV, HAV infection were negative.

Conclusions: The prevalence of NAFLD increases by up to 80-90% in cohorts of individuals with dysmetabolic conditions such as overweight/obesity, T2DM, and metabolic syndrome, underscoring the primary role of metabolic factors in its development. These data are consistent with our preliminary findings in KS patients in whom the prevalence of steatosis was relevant in 51% of cases. The presence of autoimmune liver disease was excluded, and viral markers were negative, while KS were overweight and exhibited insulin resistance, despite normal T levels. However, the main pathophysiological mechanisms linking hypogonadism to NAFLD are complex and still under investigation, and more data are needed to better understand this condition.