Bruinstroop E, Dalan R, Cao Y, et al. Low-Dose Levothyroxine Reduces Intrahepatic Lipid Content in Patients With Type 2 Diabetes Mellitus and NAFLD. J Clin Endocrinol Metab. 2018;103(7):2698‐2706. doi:10.1210/jc.2018-00475
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.
The animal research was supported by a National Health and Medical Research Council of Australia
Grant and scholarship [1029990 (to P.W.A. and C.L.) and 629025 (to C.L.)]. The human intervention study was sponsored by the Tanoto Initiative for Diabetes Research (to P.M.Y.). E.B. was funded by a Niels Stensen Fellowship, Ter Meulen Grant of the Royal Netherlands Academy of Arts and Sciences, and Catherine van Tussenbroekfonds (A3-2; www.cvtfonds.nl).
The full paper is available for download at the publisher's URL: https://doi.org/10.1210/jc.2018-00475