Immune checkpoint inhibitor–induced hyperthyroidism: Incidence, risk factors, and clinical outcomes in a real-world cohort study

BackgroundHyperthyroidism is an immune-related adverse event associated with ICI use. Its underlying risk factors, progression to thyroiditis, and impact on patient outcomes remain less understood.MethodsData were obtained from the TriNetX network for patients aged ≥ 18 yr with cancers indicated for ICI therapy between January 1, 2013, and December 31, 2024. Patients with pre-existing thyroid disorders were excluded. Competing risk analyses evaluated hyperthyroidism or thyroiditis versus death within 12 months of ICI initiation. Cox proportional hazards modeling identified significant predictors, and backward elimination retained variables that met significance threshold.ResultsAmong 41,629 patients receiving ICIs, 2.2% developed hyperthyroidism and 1.6% developed thyroiditis within 12 months. In those with hyperthyroidism, 17% initiated metoprolol, 8.9% initiated propranolol, and 5.2% initiated atenolol. Mortality rate was 2.9%. Patients who developed hyperthyroidism were more likely to have RCC (p < 0.0001, SMD = 0.27) or endometrial cancer (p < 0.0001, SMD = 0.24) and less likely to have liver (p < 0.0001, SMD = 0.24) or bladder cancer (p < 0.0001, SMD = 0.1575). While Nivolumab and ipilimumab usage was more common in patients who developed hyperthyroidism, ipilimumab showed a higher hazard in CPH (HR: 1.39, p = 0.0001). Patients with type 1 diabetes also showed significantly higher risk (HR 1.70, p = 0.0362), while black or African American patients showed lower hazard (HR: 0.798, p = 0.0305).ConclusionICI-induced hyperthyroidism is associated with significant mortality. Identifying high-risk cancer subtypes and using beta-blockers for symptom control are essential to mitigating adverse effects.