Jang Hyuna, Calder Luke, Choi Jeong Weon, Kwon Ba Reum, Pearce Elizabeth N, Shin Hyeong-Moo
Department of Environmental Science, Baylor University, Waco, TX, USA.
Section of Endocrinology, Diabetes, and Nutrition, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Chemosphere. 2025 Mar;372:144098. doi: 10.1016/j.chemosphere.2025.144098. Epub 2025 Jan 11.
Perchlorate, nitrate, and thiocyanate are well-known sodium/iodide symporter (NIS) inhibitors that disturb iodide uptake at the thyroid, affecting thyroid function. However, the associations between NIS inhibitor exposure and thyroid function are not well summarized in humans.
We aimed to summarize associations between NIS inhibitor exposure and thyroid function markers and to identify key information gaps for future studies.
From four databases (Embase, Web of Science, PubMed, CINAHL plus) up to May 31, 2024, we systematically searched studies that examined associations between levels of the three NIS inhibitors and thyroid hormones, including free thyroxine (FT4), total thyroxine (TT4), free triiodothyronine (FT3), and total triiodothyronine (TT3) as well as thyroid-stimulating hormone (TSH). We also conducted a random-effects meta-analysis to estimate the pooled effect size of the associations between NIS inhibitor levels and thyroid function marker levels.
Of 2,588 identified studies, we selected 9 studies for full-text review and 4 studies for a meta-analysis. The association between perchlorate and TSH was primarily studied and only three studies considered iodine concentrations. As a result of a meta-analysis, TSH levels were positively associated with levels of combined NIS inhibitors [β: 0.105; 95% confidence interval (CI): 0.046, 0.160] and perchlorate [β = 0.133; 95% CI: 0.056, 0.211]. We found negative trends between NIS inhibitors and FT3 and TT4 and positive but nonsignificant trends between FT3 and perchlorate and between TT4 and thiocyanate.
Our study provided comprehensive evidence on the association between exposure to NIS inhibitors and thyroid function markers in humans, aligning with the mechanisms observed in in vivo studies.
高氯酸盐、硝酸盐和硫氰酸盐是众所周知的钠/碘同向转运体（NIS）抑制剂，它们会干扰甲状腺对碘的摄取，影响甲状腺功能。然而，在人类中，NIS抑制剂暴露与甲状腺功能之间的关联尚未得到很好的总结。
我们旨在总结NIS抑制剂暴露与甲状腺功能标志物之间的关联，并确定未来研究的关键信息空白。
截至2024年5月31日，我们从四个数据库（Embase、科学网、PubMed、CINAHL plus）中系统检索了研究三种NIS抑制剂水平与甲状腺激素之间关联的研究，这些甲状腺激素包括游离甲状腺素（FT4）、总甲状腺素（TT4）、游离三碘甲状腺原氨酸（FT3）、总三碘甲状腺原氨酸（TT3）以及促甲状腺激素（TSH）。我们还进行了随机效应荟萃分析，以估计NIS抑制剂水平与甲状腺功能标志物水平之间关联的合并效应大小。
在2588项已识别的研究中，我们选择了9项进行全文审查，4项进行荟萃分析。主要研究了高氯酸盐与TSH之间的关联，只有三项研究考虑了碘浓度。荟萃分析的结果显示，TSH水平与NIS抑制剂组合水平呈正相关[β：0.105；95%置信区间（CI）：0.046，0.160]，与高氯酸盐也呈正相关[β = 0.133；95%CI：0.056，0.211]。我们发现NIS抑制剂与FT3和TT4之间呈负趋势，而FT3与高氯酸盐之间以及TT4与硫氰酸盐之间呈正但不显著的趋势。
我们的研究为人类暴露于NIS抑制剂与甲状腺功能标志物之间的关联提供了全面证据，这与体内研究中观察到的机制一致。
