Prevalence of Thyroid Cancer in Multinodular Goiter Versus Single Nodule: A Systematic Review and Meta-Analysis

Background: Whether the prevalence of thyroid cancer is different in thyroid glands with a single nodule (SN) versus multinodular goiter (MNG) remains uncertain. Therefore, a meta-analysis was performed to evaluate the extant literature on the comparative prevalence of thyroid cancer in SN compared with MNG. Methods: We searched MEDLINE, EMBASE, Scopus, Cochrane Central, and reference list for selected observational, cross-sectional, and longitudinal studies evaluating thyroid cancer in SN and MNG. Toxic nodules were not included in the analysis. Two reviewers working independently extracted descriptive, methodological and outcome data from each study with consensus resolution of discrepancies. Meta-analytic estimates of treatment effects were generated using a random-effect model. Results: Fourteen studies encompassing 23565 patients with MNG and 20723 patients with SN were eligible for inclusion. Most eligible studies were at a moderate risk of bias. MNGs were associated with a lower risk of thyroid cancer than SN (pooled odds ratio 0.8 [95% confidence interval 0.67-0.96]; I-2 = 35%). Subgroup analysis suggested that this difference depends on the inclusion of studies conducted outside the United States (odds ratio 0.71 [95% confidence interval 0.60-0.83]; I-2 = 11%). Conclusions: Thyroid cancer may be less frequent in MNG compared to SN, particularly outside the United States and perhaps in iodine-deficient areas.