Association between Sensitivity to Thyroid Hormones and Metabolic Dysfunction-Associated Fatty Liver Disease: A...

To investigate the association between thyroid hormone sensitivity indices and metabolic dysfunction-associated fatty liver disease (MAFLD) in euthyroid Chinese adults.

This cohort study included 5,356 euthyroid patients. The peripheral and central thyroid hormone sensitivity indices were calculated. Cox regression models were used to evaluate associations with MAFLD risk, and restricted cubic splines were used to assess potential nonlinearity. Mediation analyses based on an accelerated failure-time model were used to examine the role of the triglyceride-glucose (TyG) index.

MAFLD incidence in euthyroid participants was 18.26%. After adjustment, higher free thyroxine (FT4) levels were inversely associated with MAFLD ( HR = 0.973, 95% CI: 0.948 to 0.999, P = 0.043), whereas higher free triiodothyronine (FT3) levels increased MAFLD risk ( HR = 1.118, 95% CI: 1.000 to 1.250, P = 0.050). Enhanced thyroid hormone sensitivity, as reflected by elevated FT3/FT4 levels and lower total thyroxine resistance index (TT4RI), thyroid stimulating hormone index (TSHI), and thyroid feedback quantile-based index (TFQI _FT4), was also associated with a higher incidence (all P < 0.05). Mediation analyses indicated that TyG partially mediated the FT3/FT4-MAFLD and TFQI _FT4-MAFLD associations, with indirect effects of -96.27 (95% CI: -124.67 to -70.42) and -4.95 (95% CI: -8.29 to -2.10), respectively.

Increased FT3/FT4 and decreased TFQI _FT4 levels were significantly associated with a higher MAFLD risk in euthyroid adults, with TyG acting as a partial mediator.