Associations of Metal Mixtures with Thyroid Function and Potential Interactions with Iodine Status: Results from a Cross-sectional Study in MEWHC

Abstract

Abstract Few studies are available on associations between metal mixture exposures and disrupted thyroid hormone homeostasis. Here we aimed to explore the cross-sectional relationship of blood cells metals with thyroid homeostasis. Among 328 workers from the manganese exposed workers healthy cohort (MEWHC), we detected thyroid function parameters: thyroid stimulating hormone (TSH), total triiodothyronine (TT3), free triiodothyronine (FT3), total tetraiodothyronine (TT4), free tetraiodothyronine (FT4) as well as calculated sum activity of peripheral deiodinases (GD) and thyroid's secretory capacity (GT). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure 22 metal concentrations in blood cells. Based on the consistent results of least absolute shrinkage and selection operator (LASSO) and Bayesian kernel machine regression (BKMR) analyses, there were significant positive associations between Cu and TSH (beta = 2.016), Fe and FT4 (beta = 0.403), Ti and GD (beta = 0.142), Ni and GD (beta = 0.057) and negative associations between Cu and FT4 (beta = -0.226), Se and GD (beta = -0.332) among the participants. Interestingly, we observed an inverted-U shape relationship between Mg and FT4. Furthermore, we found a synergistic effect between As and Cu on TSH level, whilst antagonistic effects between Ni and Cu as well as Ni and Se on TSH level. We observed a modified effect of iodine status on association between Sr and GD (Pinteraction = 0.026). It suggests metal mixture exposures can alter thyroid homeostasis among the occupational population, possibly through an alteration of deiodinase activity. Validation of these associations and elucidation of underlying mechanisms require further researches in future.