High-normal thyroid function predicts incident non-alcoholic fatty liver disease among middle-aged and elderly euthyroid subjects

BACKGROUND Thyroid hormones (THs) influence hepatic lipid homeostasis through multiple pathways, suggesting that THs may predict the risk of non-alcoholic fatty liver disease (NAFLD). However, prospective studies on the association between THs levels and incident NAFLD in euthyroid subjects are limited. This prospective cohort study aimed to explore whether THs were associated with the development of NAFLD in middle-aged and elderly euthyroid subjects. METHODS A total of 6,462 subjects without baseline NAFLD were included in the cohort study (~6-year follow-up period, median: 4.2 years). Chemiluminescence immunoassay was used to measure serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH), and NAFLD was diagnosed by abdominal ultrasonography. Multivariable Cox proportional hazards regression models were used to assess the association between baseline THs, TSH, and the risk of NAFLD. RESULTS During the follow-up period, 1,675 subjects developed NAFLD. The incidence rate of NAFLD was 85.0 per 1000 person-years. Compared with the lowest FT3, FT4, and TSH quartiles, the multivariable-adjusted hazard ratios (95% confidence interval) of incident NAFLD for highest quartiles were 1.30 (1.12, 1.51), 1.07 (0.93, 1.23), 0.82 (0.71, 0.95) (P <0.001, =0.56, =0.01, respectively), respectively. CONCLUSIONS In middle-aged and elderly euthyroid subjects, high-normal FT3 and low-normal TSH are independently associated with a higher incidence of NAFLD.