The myth of iodine: A systematic review and meta-analysis on the relationship between iodine and thyroid nodule

Iodine is an essential trace element for thyroid hormone synthesis, and its role in thyroid health has been widely studied. While iodine deficiency is recognized as a risk factor for goiter, its association with thyroid nodules remains controversial. The aim of this systematic review and meta-analysis was to evaluate the relationship between iodine intake and the development of thyroid nodules.

A systematic literature search was conducted in Medline (via PubMed), the Cochrane Library, and guideline registries (AWMF, GIN) for studies published between 2012 and 2023. Inclusion criteria focused on studies examining the association between iodine intake and thyroid nodule. Systematic review has been conducted whereas study quality was assessed using the checklists of Critical Appraisal Skills Programme (CASP). A meta-analysis was performed for studies reporting odds ratios based on WHO-defined iodine categories.

A total of 31 studies were included. Most studies (n = 23) were cross-sectional, limiting causal conclusions. The most used method for assessing iodine intake was urinary iodine concentration (UIC), though measurement approaches varied. N = 10 studies compared median UIC between groups with and without thyroid nodules, with n = 8 reporting significant differences. However, the iodine levels in both groups often remained within the WHO-defined adequate iodine range. N = 8 studies examined odds ratios for iodine intake and thyroid nodule risk, with n = 5 identifying iodine deficiency (< 100 μg/L) as a significant risk factor. However, results for more than adequate (> 200 μg/L) and excessive iodine intake (> 300 μg/L) were inconsistent. N = 3 studies suggested a U-shaped relationship between iodine and thyroid nodule prevalence, but meta-analysis findings did not confirm this hypothesis. The pooled odds ratio for iodine deficiency was 1.24 (95% CI [1.16-1.33], I² = 0.00), while more than adequate and excessive iodine intake showed no significant association.

This systematic review and meta-analysis indicate that iodine deficiency increases moderately the risk of developing thyroid nodules, while more than adequate and excessive iodine intake does not show a consistent effect. However, the heterogeneity of study results and the predominance of cross-sectional designs limit definitive conclusions. Further prospective studies are needed to clarify the causal relationship between iodine intake and thyroid nodules.