Thyroid UK
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Low Dose Levothyroxine Reduces Intrahepatic Lipid Content in Patients with Type 2 Diabetes Mellitus and NAFLD

I just don't know where to begin with this paper!

Maybe by noting that there are more authors than there were subjects!

Then by highlighting that they targetted a TSH range of 0.34 to 1.70. But in the abstract no consideration that the subjects might not actually have been euthyroid. And that all too many formally diagnosed hypothyroid patients are left with a TSH higher than 1.70 - sometimes much higher.

Also, no mention of what is meant by "low dose"?

J Clin Endocrinol Metab. 2018 Apr 27. doi: 10.1210/jc.2018-00475. [Epub ahead of print]

Low Dose Levothyroxine Reduces Intrahepatic Lipid Content in Patients with Type 2 Diabetes Mellitus and NAFLD.

Bruinstroop E1,2, Dalan R3, Yang C4, Bee YM5, Chandran K6, Cho LW7, Soh SB7, Teo EK8, Toh SA9, Leow MKS1,3,10, Sinha RA1, Sadananthan SA10, Michael N10, Stapleton H11, Leung C12,13,14, Angus PW12,13, Patel SK12, Burrell LM12,14, Chi LS15,16, Fang SC15,17, Velan SS10,18, Yen PM1.

Author information

1 Cardiovascular & Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore.

2 Department of Endocrinology and Metabolism, Amsterdam, The Netherlands.

3 Department of Endocrinology, Tan Tock Seng Hospital, Singapore.

4 Singapore Clinical Research Institute, Singapore.

5 Department of Endocrinology, Singapore General Hospital, Singapore.

6 Department of Medicine, Ng Teng Fong General Hospital, Singapore.

7 Department of Endocrinology, Changi General Hospital, Singapore.

8 Department of Gastroenterology, Changi General Hospital, Singapore.

9 Department of Endocrinology, National University Health System, Singapore.

10 Singapore Institute for Clinical Sciences, A*STAR, Singapore.

11 Duke University, Nicholas School of the Environment, A220 LSRC, Durham, North Carolina, USA.

12 Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Melbourne, Australia.

13 Department of Gastroenterology, Austin Health, Heidelberg, Victoria.

14 Department of General Medicine, Austin Health, Heidelberg, Victoria.

15 Department of Endocrinology, Khoo Teck Puat Hospital, Singapore.

16 Saw Swee Hock School of Public Health, National University Health System, Singapore.

17 Diabetes Centre, Admiralty Medical Centre, Singapore.

18 Singapore Bioimaging Consortium, Singapore.



Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes mellitus 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. In this study we investigated the possibility of low intrahepatic TH concentration in NAFLD and studied the effect of TH treatment in humans.


We performed a phase 2b single arm study in six hospitals in Singapore to study whether TH reduced IHLC. Rats fed a MCD diet to induce NAFLD were used to show intrahepatic thyroid hormone concentrations.


Euthyroid patients with type 2 diabetes mellitus and steatosis measured by ultrasonograpy.


Levothyroxine was titrated at TSH 0.34-1.70 mIU/L before a 16-week maintenance phase.

Main outcome measures:

The primary outcome measure was change in IHLC measured by 1H-MRS after treatment.


20 male patients were included in the per protocol analysis (mean age 47.8±7.8 years, BMI 30.9±4.4 kg/m2, baseline IHLC 13±4 %). After treatment IHLC was decreased by 12 % ± 26 % relative to baseline (absolute change -2 %; 95% CI -3 to 0, p=0.046). Small decreases in BMI (p=0.044), VAT volume (p=0.047), and SAT volume (p=0.045) were observed. No significant changes in glucose regulation or lipid profile occurred.


This is the first study demonstrating the efficacy and safety of low dose TH therapy for NAFLD in man, and suggests that TH or TH analogs may be beneficial for this condition.

PMID: 29718334

DOI: 10.1210/jc.2018-00475

1 Reply

Weird that the second sentence in the design is about rats! I like the idea of a study where human participants are paired with matched rats at the start ;D


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