Low-Dose Levothyroxine Reduces Intrahepatic Lipid Content in Patients With Type 2 Diabetes Mellitus and NAFLD

Context: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes mellitus (T2DM) and associated with significant morbidity and mortality. Thyroid hormone (TH) increases β-oxidation of fatty acids and decreases intrahepatic lipid content (IHLC) in rodents with NAFLD. Objective: We investigated the possibility of low intrahepatic TH concentration in NAFLD and studied the effect of TH treatment in humans. Design/Setting: This was a phase 2b single-arm study in six hospitals in Singapore. Intrahepatic thyroid hormone concentrations were measured in rats with induced NAFLD. Patients: Euthyroid patients with T2DM and steatosis measured by ultrasonography. Intervention: Levothyroxine was titrated to reach a thyroid-stimulating hormone level of 0.34 to 1.70 mIU/L before a 16-week maintenance phase. Main Outcome Measures: The primary outcome measure was change in IHLC measured by proton magnetic resonance spectroscopy after treatment. Results: Twenty male patients were included in the per-protocol analysis [mean ± SD: age, 47.8 ± 7.8 years; body mass index (BMI), 30.9 ± 4.4 kg/m2; baseline IHLC, 13% ± 4%]. After treatment, IHLC was decreased 12% (±SEM, 26%) relative to baseline (absolute change, -2%; 95% CI, -3 to 0; P = 0.046). Small decreases in BMI (P = 0.044), visceral adipose tissue volume (P = 0.047), and subcutaneous adipose tissue volume (P = 0.045) were observed. No significant changes in glucose regulation or lipid profile occurred. Conclusion: This study demonstrated the efficacy and safety of low-dose TH therapy for NAFLD in men. TH or TH analogs may be beneficial for this condition.