Associations between exposure to sodium/iodide symporter inhibitors and markers of thyroid function: A systematic review and meta-analysis.

Background: 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.

Objective: We aimed to summarize associations between NIS inhibitor exposure and thyroid function markers and to identify key information gaps for future studies.

Methods: 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.

Results: 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.

Conclusions: 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.