Low-dose levothyroxine can lower intrahepatic lipid in patients with NAFLD + T2D
Treatment with the synthetic thyroid hormone (TH) levothyroxine can decrease intrahepatic lipid content (IHLC) in patients with nonalchoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), especially in older patients, a recent study found.
“Although the long-term effects of moderate reduction of IHLC on morbidity and mortality are currently not known, improvement of insulin resistance and possible prevention of fibrosis by TH as recently shown in the lung will have important clinical significance,” according to the researchers led by Professor Paul Yen from Duke-NUS Medical School, Singapore.
In the phase IIb, multicentre, single-arm study, 20 male patients (mean age 47.8 years) with T2D (HbA1c ≤10 percent) and steatosis were titrated with low-dose oral levothyroxine to a target thyroid stimulating hormone (TSH) level of 0.34–1.70 mIU/L in six hospitals in Singapore. Upon reaching the target range, the patients started a 16-week maintenance phase with the last titrated levothyroxine dose. [J Clin Endocrinol Metab 2018;doi:10.1210/jc.2018-00475]
After 16 weeks, there was a 12-percent decrease in IHLC relative to baseline (absolute change, -2 percent; p=0.046). In particular, the drop in IHLC was significantly greater in patients ≥50 years compared with younger patients aged <50 years (p=0.024).
“The moderate effect shown in our study of euthyroid patients could be improved by better selection of patients for treatment, setting a lower TSH target, and increasing treatment duration,” suggested Yen and co-authors. “Furthermore, selecting patients with higher baseline TSH values such as those occurring in subclinical hypothyroidism … and older patients [may] benefit more from treatment with levothyroxine.”
Levothyroxine also led to decreased body weight (-1 kg), BMI (-0.4 kg/m2), visceral adipose tissue volume (-139 mL), and abdominal subcutaneous adipose tissue volume (-131 mL) ─ which were small changes but nonetheless significant (p<0.05 for all).
There was no change in glycaemic control in terms of HbA1c or fasting serum glucose and insulin levels with levothyroxine treatment. Nor was insulin resistance significantly altered after levothyroxine treatment, as indicated by changes in HOMA-IR* levels.
Although levothyroxine did not improve glycaemic control, the researchers observed that a greater reduction in IHLC was associated with improved HbA1c and less insulin resistance.
Lipid profile, including serum total cholesterol, LDL-C, HDL-C, and triglycerides, also did not change significantly after levothyroxine treatment.
No serious adverse events occurred during the study, with most of the adverse events reported being mild or moderate. Heart rate also did not increase significantly with levothyroxine. These observations, according to researchers, indicate that the treatment is safe for T2D patients with NAFLD.
“Diet and exercise are the cornerstones for the treatment of NAFLD since no drug treatment currently is registered for the treatment of NAFLD,” explained Yen and co-authors. “The moderate beneficial effect on IHLC by levothyroxine that we observed in our study (-12 percent) was comparable to the effect observed in patients undergoing the currently advised exercise regimen of 30–60 minutes 5 times per week for 16 weeks (-10 percent). Therefore levothyroxine alone, or in combination with diet and exercise, could reduce IHLC even in patients resistant to lifestyle modifications.” [Hepatology 2012;55:1738-1745; Hepatology 2018;67:328-357]
“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,” they added, while noting that they were unable to exclude any placebo effect and suggested that placebo-controlled randomized trials involving a larger number of patients be conducted to confirm the findings.