BackgroundRadioiodine represents a cost-effective treatment option for Graves’ disease. In the UK, it is traditionally reserved for patients who relapse after initial thionamide therapy. In a change from current practice, the new guidelines of the National Institute for Health and Care Excellence (NICE) recommends that radioiodine should now be first line therapy for Graves’ disease. However, the safety of radioiodine with respect to long-term mortality risk has been the subject of recent debate. This analysis examines evidence from treatment related mortality studies in hyperthyroidism and discusses their implications for future Graves’ disease treatment strategies.Main bodySome studies have suggested an excess mortality in radioiodine treated cohorts compared to the background population. In particular, a recent observational study reported a modest increase in cancer-related mortality in hyperthyroid patients exposed to radioiodine. The interpretation of these studies is however constrained by study designs that lacked thionamide control groups or information on thyroid status and so could not distinguish the effect of treatment from disease. Two studies have shown survival advantages of radioiodine over thionamide therapy, but these benefits were only seen when radioiodine was successful in controlling hyperthyroidism. Notably, increased mortality was associated with uncontrolled hyperthyroidism irrespective of therapy modality.ConclusionsEarly radioiodine treatment will potentially reduce mortality and should be offered to patients with severe disease. However, thionamides are still suitable for patients with milder disease, contraindications to radioiodine, or individuals who choose to avoid permanent hypothyroidism. Ultimately, a patient individualised approach that prioritises early and sustained control of hyperthyroidism will improve long-term outcomes regardless of the therapy modality used.