PMID- 29718334 OWN - NLM STAT- MEDLINE DCOM- 20190104 LR - 20190104 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 103 IP - 7 DP - 2018 Jul 1 TI - Low-Dose Levothyroxine Reduces Intrahepatic Lipid Content in Patients With Type 2 Diabetes Mellitus and NAFLD. PG - 2698-2706 LID - 10.1210/jc.2018-00475 [doi] AB - 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 +/- 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. FAU - Bruinstroop, Eveline AU - Bruinstroop E AD - Cardiovascular & Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore. AD - Department of Endocrinology and Metabolism, Amsterdam, Netherlands. FAU - Dalan, Rinkoo AU - Dalan R AD - Department of Endocrinology, Tan Tock Seng Hospital, Singapore. AD - NTU-Lee Kong Chian School of Medicine, Singapore. FAU - Cao, Yang AU - Cao Y AD - Singapore Clinical Research Institute, Singapore. FAU - Bee, Yong Mong AU - Bee YM AD - Department of Endocrinology, Singapore General Hospital, Singapore. FAU - Chandran, Kurumbian AU - Chandran K AD - Department of Medicine, Ng Teng Fong General Hospital, Singapore. FAU - Cho, Li Wei AU - Cho LW AD - Department of Endocrinology, Changi General Hospital, Singapore. FAU - Soh, Shui Boon AU - Soh SB AD - Department of Endocrinology, Changi General Hospital, Singapore. FAU - Teo, Eng Kiong AU - Teo EK AD - Department of Gastroenterology, Changi General Hospital, Singapore. FAU - Toh, Sue-Anne AU - Toh SA AD - Department of Endocrinology, National University Health System, Singapore. FAU - Leow, Melvin Khee Shing AU - Leow MKS AD - Cardiovascular & Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore. AD - Department of Endocrinology, Tan Tock Seng Hospital, Singapore. AD - Singapore Institute for Clinical Sciences, A*STAR, Singapore. FAU - Sinha, Rohit A AU - Sinha RA AD - Cardiovascular & Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore. FAU - Sadananthan, Suresh Anand AU - Sadananthan SA AD - Singapore Institute for Clinical Sciences, A*STAR, Singapore. FAU - Michael, Navin AU - Michael N AD - Singapore Institute for Clinical Sciences, A*STAR, Singapore. FAU - Stapleton, Heather M AU - Stapleton HM AD - Duke University, Nicholas School of the Environment, A220 LSRC, Durham, North Carolina. FAU - Leung, Christopher AU - Leung C AD - Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Melbourne, Victoria, Australia. AD - Department of Gastroenterology, Austin Health, Heidelberg, Victoria, Australia. AD - Department of General Medicine, Austin Health, Heidelberg, Victoria, Australia. FAU - Angus, Peter W AU - Angus PW AD - Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Melbourne, Victoria, Australia. AD - Department of Gastroenterology, Austin Health, Heidelberg, Victoria, Australia. FAU - Patel, Sheila K AU - Patel SK AD - Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Melbourne, Victoria, Australia. FAU - Burrell, Louise M AU - Burrell LM AD - Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Melbourne, Victoria, Australia. AD - Department of General Medicine, Austin Health, Heidelberg, Victoria, Australia. FAU - Lim, Su Chi AU - Lim SC AD - Department of Endocrinology, Khoo Teck Puat Hospital, Singapore. AD - Saw Swee Hock School of Public Health, National University Health System, Singapore. FAU - Sum, Chee Fang AU - Sum CF AD - Department of Endocrinology, Khoo Teck Puat Hospital, Singapore. AD - Diabetes Centre, Admiralty Medical Centre, Singapore. FAU - Velan, S Sendhil AU - Velan SS AD - Singapore Institute for Clinical Sciences, A*STAR, Singapore. AD - Singapore Bioimaging Consortium, Singapore. FAU - Yen, Paul M AU - Yen PM AD - Cardiovascular & Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore. LA - eng SI - ClinicalTrials.gov/NCT03281083 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Lipids) RN - Q51BO43MG4 (Thyroxine) SB - IM MH - Adult MH - Diabetes Mellitus, Type 2/*complications MH - Humans MH - Lipids/*analysis MH - Liver/*chemistry/metabolism MH - Male MH - Middle Aged MH - Non-alcoholic Fatty Liver Disease/*drug therapy/etiology/metabolism MH - Thyroxine/*administration & dosage MH - Treatment Outcome MH - Young Adult EDAT- 2018/05/03 06:00 MHDA- 2019/01/05 06:00 CRDT- 2018/05/03 06:00 PHST- 2018/02/27 00:00 [received] PHST- 2018/04/24 00:00 [accepted] PHST- 2018/05/03 06:00 [pubmed] PHST- 2019/01/05 06:00 [medline] PHST- 2018/05/03 06:00 [entrez] AID - 4987160 [pii] AID - 10.1210/jc.2018-00475 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2018 Jul 1;103(7):2698-2706. doi: 10.1210/jc.2018-00475.