Role of serum fasting glucagon in hypothyroidism-related nonalcoholic fatty liver disease

Abstract Background A bidirectional relationship between hypothyroidism and nonalcoholic fatty liver disease (NAFLD) has been proposed. Fasting hyperglucagonemia in patients with hypothyroidism induced NAFLD needs to be further clarified. The aim of the present study was to determine fasting serum glucagon levels in hypothyroid adults with and without NAFLD. The possible association between fasting glucagon and NAFLD in patients with hypothyroidism was also evaluated. Methods This study was comprised 60 patients with uncontrolled hypothyroidism and 30 healthy controls matched for age and sex. Patients with hypothyroidism were divided into 2 groups: 30 patients with NAFLD and 30 patients without NAFLD. Diagnosis of NAFLD was based on the combination of hepatic steatosis index (HSI) at a cutoff value of 36 and measurements of steatosis using fibroScan. Anthropometric measurements, lipids profile, homeostasis model assessment of insulin resistance (HOMA-IR), free thyroxine (FT4), triiodothyronine (FT3), thyroid stimulating hormone (TSH) and serum fasting glucagon were assessed. Results Serum fasting glucagon concentration was significantly higher in hypothyroid patients with and without NAFLD than in healthy controls; glucagon was also significantly higher in the hypothyroid patients with NAFLD than in those without NAFLD. Fasting glucagon was significantly correlated with waist circumference (WC), body mass index (BMI), TSH, HSI and fibroScan parameters in hypothyroid patients with NAFLD. Fasting glucagon predicts NAFLD in patients with hypothyroidism at a cutoff value 85 ng/L with 90% sensitivity, 100% specificity and p < 0.001. With multivariable analysis, age, BMI and TSH were significant positive predictors of NAFLD in patients with hypothyroidism. Conclusion Fasting glucagon concentration may play a role in the development of NAFLD in patients with hypothyroidism. However, the exact underlying mechanism needs further studies.