Eveline Bruinstroop1,2, Rinkoo Dalan3,4, Yang Cao5, Yong Mong Bee6, Kurumbian Chandran7, Li Wei Cho8, Shui Boon Soh8, Eng Kiong Teo9, Sue-Anne Toh10, Melvin Khee Shing Leow1,3,11, Rohit A Sinha1, Suresh Anand Sadananthan11, Navin Michael11, Heather M Stapleton12, Christopher Leung13,14,15, Peter W Angus13,14, Sheila K Patel13, Louise M Burrell13,15, Su Chi Lim16,17, Chee Fang Sum16,18, S Sendhil Velan11,19, Paul M Yen1. 1. Cardiovascular & Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore. 2. Department of Endocrinology and Metabolism, Amsterdam, Netherlands. 3. Department of Endocrinology, Tan Tock Seng Hospital, Singapore. 4. NTU-Lee Kong Chian School of Medicine, Singapore. 5. Singapore Clinical Research Institute, Singapore. 6. Department of Endocrinology, Singapore General Hospital, Singapore. 7. Department of Medicine, Ng Teng Fong General Hospital, Singapore. 8. Department of Endocrinology, Changi General Hospital, Singapore. 9. Department of Gastroenterology, Changi General Hospital, Singapore. 10. Department of Endocrinology, National University Health System, Singapore. 11. Singapore Institute for Clinical Sciences, A*STAR, Singapore. 12. Duke University, Nicholas School of the Environment, A220 LSRC, Durham, North Carolina. 13. Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Melbourne, Victoria, Australia. 14. Department of Gastroenterology, Austin Health, Heidelberg, Victoria, Australia. 15. Department of General Medicine, Austin Health, Heidelberg, Victoria, Australia. 16. Department of Endocrinology, Khoo Teck Puat Hospital, Singapore. 17. Saw Swee Hock School of Public Health, National University Health System, Singapore. 18. Diabetes Centre, Admiralty Medical Centre, Singapore. 19. Singapore Bioimaging Consortium, Singapore.
Abstract
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.
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 intrahepaticlipid 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.
Authors: Paul Manka; Lars Bechmann; Jan Best; Svenja Sydor; Lee C Claridge; Jason D Coombes; Ali Canbay; Lars Moeller; Guido Gerken; Heiner Wedemeyer; Wing-Kin Syn Journal: Dig Dis Sci Date: 2019-06-03 Impact factor: 3.199
Authors: Jin Zhou; Lauren R Waskowicz; Andrea Lim; Xiao-Hui Liao; Brian Lian; Hiroko Masamune; Samuel Refetoff; Brian Tran; Dwight D Koeberl; Paul M Yen Journal: Thyroid Date: 2019-08 Impact factor: 6.568
Authors: Jacqueline Jonklaas; Antonio C Bianco; Anne R Cappola; Francesco S Celi; Eric Fliers; Heike Heuer; Elizabeth A McAninch; Lars C Moeller; Birte Nygaard; Anna M Sawka; Torquil Watt; Colin M Dayan Journal: Eur Thyroid J Date: 2021-02-16
Authors: Jacqueline Jonklaas; Antonio C Bianco; Anne R Cappola; Francesco S Celi; Eric Fliers; Heike Heuer; Elizabeth A McAninch; Lars C Moeller; Birte Nygaard; Anna M Sawka; Torquil Watt; Colin M Dayan Journal: Thyroid Date: 2021-02 Impact factor: 6.568