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

作者：Bruinstroop Eveline; Dalan Rinkoo; Cao Yang; Bee Yong Mong; Chandran Kurumbian; Cho Li Wei; Soh Shui Boon; Teo Eng Kiong; Toh Sue Anne; Leow Melvin Khee Shing; Sinha Rohit A; Sadananthan Suresh Anand; Michael Navin; Stapleton Heather M; Leung Christopher; Angus Peter W; Patel Sheila K; Burrell Louise M; Lim Su Chi; Sum Chee Fang; Velan S Sendhil; Yen Paul M^*

来源：Journal of Clinical Endocrinology & Metabolism, 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 beta-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 6 SD: age, 47.8 6 7.8 years; body mass index (BMI), 30.964.4 kg/m(2); baseline IHLC, 13% 64%]. After treatment, IHLC was decreased 12% (6SEM, 26%) relative to baseline (absolute change, 22%; 95% CI, 23 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.

• 出版日期2018-7