Mortality Risks Associated with Antithyroid Drugs, Radioactive Iodine, and Surgery for Hyperthyroidism: A Systematic...

Introduction: Hyperthyroidism can be treated with antithyroid drugs (ATD), radioactive iodine (RAI), or surgery. We aimed to evaluate the long-term outcomes of these treatments through a systematic review and network meta-analysis (NMA). Methods: A systematic literature search of PubMed, EMBASE, Web of Science, and the Cochrane Library (from inception to March 7, 2025) was conducted to identify studies comparing the risks of all-cause mortality, cardiovascular mortality, major adverse cardiovascular events (MACE), and cancer mortality among patients with hyperthyroidism treated with ATD, RAI, or surgery. Pooled effect estimates were expressed as hazard ratios (HR) with confidence intervals (CI) using a random-effects model. The study was registered with PROSPERO (CRD420250543380) and adhered to the PRISMA-NMA guidelines. Results: Of the 8163 studies screened, 12 observational studies with an overall moderate risk of bias, comprising 192,208 patients were included in this NMA. Most patients received ATD (n = 142,622), followed by RAI (n = 19,303) and surgery (n = 10,360). Surgery was associated with decreased risks of all-cause mortality and cardiovascular mortality compared with both ATD and RAI. For all-cause mortality, the pooled HRs (CI, p-values) were 0.58 (0.45-0.75, p < 0.0001) for surgery versus ATD and 0.68 (0.56-0.84, p = 0.0004) for surgery versus RAI. For cardiovascular mortality, the pooled HR (CI, p-values) were 0.43 (0.19-0.98, p = 0.0445) for surgery versus ATD and 0.55 (0.33-0.93, p = 0.0269) for surgery versus RAI. No significant differences were observed in MACE or cancer mortality across the treatment groups. Conclusions: In patients with hyperthyroidism, surgery was associated with significantly decreased risks of all-cause mortality and cardiovascular mortality compared with ATD and RAI. Risks of MACE and cancer mortality did not differ by type of hyperthyroidism treatment. However, these findings should be interpreted with caution due to inherent methodological limitations of observational studies, including, but not limited to heterogeneity and potential selection bias.