Impaired Sensitivity to Thyroid Hormones Is Associated With Elevated Homocysteine Levels in the Euthyroid Population

Homocysteine (Hcy), a known risk factor for cardiovascular disease, has been reported to be linked with thyroid dysfunction. However, the association of thyroid hormones sensitivity with Hcy levels remains unknown.

We aimed to investigate the relationship between thyroid hormone sensitivity and elevated Hcy levels in the euthyroid population.

A total of 8957 euthyroid adults were included in this study. Free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), Hcy levels, and other clinical parameters were measured. Hyperhomocysteinemia (HHcy) was defined as serum Hcy level > 15 μmol/L. Thyroid hormone sensitivity indices were calculated by thyroid feedback quantile-based index (TFQI), Chinese-referenced parametric TFQI (PTFQI), TSH index (TSHI) and thyrotropin thyroxine resistance index (TT4RI).

Subjects with decreased sensitivity to thyroid hormones had higher Hcy levels (P for trend < 0.001). Logistic regression analysis revealed the higher quartiles of TFQI, PTFQI, TSHI, and TT4RI were significantly associated with elevated Hcy levels, and these associations remained significant even after adjustment for multiple risk factors. After adjusting for age, sex, body mass index, dyslipidemia, fatty liver, diabetes, and hypertension, the odds ratio (95% CI) for having HHcy of the TFQI in the highest quartile was 1.393 (1.210, 1.603), the PTFQI in the highest quartile was 1.409 (1.225, 1.621), the TSHI in the highest quartile was 1.372 (1.190, 1.583), and the TT4RI in the highest quartile was 1.315 (1.141, 1.515) (all P < 0.001).

In euthyroid subjects, impaired sensitivity to thyroid hormones was associated with elevated Hcy levels.