Association of free triiodothyronine and total triiodothyronine with nonalcoholic fatty liver disease: from National Health and Nutrition Examination Survey and Mendelian randomization study.

Background: Nonalcoholic fatty liver disease (NAFLD) is associated with multiple factors, yet the relationship between NAFLD and thyroid-related biomarkers remains unclear. This study aims to elucidate this potential linkage.

Methods: Utilizing data from the US National Health and Nutrition Examination Survey (NHANES), we explored the possible associations between thyroid-related biomarkers and NAFLD through multivariable logistic regression, subgroup analysis, and interaction tests. A bidirectional Mendelian randomization (MR) approach complemented by various sensitivity analyses was then employed to ascertain these relationships' causality.

Results: Our NHANES analysis indicated significant associations between elevated levels of free triiodothyronine (FT3) [odds ratio (OR): 2.59, 95% confidence interval (CI): 1.50-4.49] and total triiodothyronine (TT3) (OR: 2.01, 95% CI: 1.27-3.18) with the prevalence of NAFLD. MR findings reinforced the causal relationship, demonstrating that NAFLD may elevate FT3 ( β : 0.05, 95% CI: 0.01-0.09) and TT3 ( β : 0.08, 95% CI: 0.02-0.14) levels. Additionally, thyroid-stimulating hormone (TSH) was confirmed as an independent risk factor for NAFLD (OR: 1.10, 95% CI: 1.04-1.18), with specific MR sensitivity analyses supporting the robustness of these results.

Conclusion: This study indicates potential elevations in FT3, TT3, and thyroglobulin levels associated with NAFLD, while also identifying TSH as a risk factor for NAFLD. These findings underscore the importance of routine thyroid function monitoring both in the general population and particularly in individuals with NAFLD.