Associations Between Radioactive Iodine Treatment for Hyperthyroidism and Cancer Incidence and Mortality

Abstract Background Radioactive iodine (RAI) has been one of the main treatments for hyperthyroidism since the 1940s, but its long-term safety, particularly regarding cancer risk, remains controversial. This study evaluated associations between RAI treatment and cancer incidence and mortality, including overall and site-specific cancers. Methods We conducted a retrospective cohort study utilizing a University of Michigan de-identified electronic health record dataset. Adults (aged ≥18 years) newly diagnosed with hyperthyroidism between 2006-2019, without prior cancer, and treated with RAI, antithyroid medications, or thyroidectomy were included. Participants were followed until cancer diagnosis, death, or December 2022. Time-dependent Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) comparing RAI with other therapies using age-adjusted (age-adj) and multivariable (mv) models adjusting for demographics, lifestyle and clinical covariates. Sensitivity analysis stratified by cohort entry period, follow-up duration and restriction to ≥2 years of follow-up. Results The cohort included 6,435 participants contributing 52,909 person-years (mean follow up 8.2 years; range 0.5-17 years), with 487 incident cancers and 157 cancer deaths. RAI treatment was not associated with overall cancer incidence (mv HR= 1.02 0.76-1.47, p=0.734) or cancer mortality (mv HR = 0.81 0.45-1.44, p=0.471). However, RAI was significantly associated with increased breast cancer risk among women (mv HR = 2.24 1.21-4.17, p=0.011), and among postmenopausal women (mv HR = 2.65 1.24-5.66, p=0.011). An elevated pancreatic cancer mortality was observed in those with ≥ 2 years of follow-up (age-adj HR = 4.05 1.01-16.20, p=0.042). Conclusion RAI treatment was associated with increased breast cancer incidence but not overall cancer incidence or mortality. Findings for pancreatic cancer mortality were suggestive. These results support the importance of long-term safety monitoring among RAI-treated patients