Clinical factors and prognostic outcomes of hyperthyroidism induced by immune checkpoint inhibitor therapy.

Abstract

2620 Background: Hyperthyroidism is a recognized but less frequent immune-related adverse event (iRAE) associated with Immune Checkpoint Inhibitor (ICI) use. While its occurrence has been documented, gaps remain in understanding the underlying risk factors, and its impact on patient outcomes. This study seeks to provide clarity on these aspects and guide improved management strategies. Methods: Data were obtained from the TriNetX research network for patients with cancers where ICI is used. Inclusion criteria encompassed patients aged 18 years or older treated with ICIs (e.g., pembrolizumab, nivolumab, atezolizumab, cemiplimab) between January 1, 2013, and December 31, 2024. Patients with a history of thyroid disorders or Levothyroxine use were excluded. Competing risk analyses evaluated the likelihood of hyperthyroidism versus death up to 12 months after ICI use and the likelihood of beta-blocker usage after diagnosis. Cox proportional hazards modeling was used to identify significant covariates associated with hyperthyroidism, including age, sex, cancer type, comorbidities, and ICI type. Backwards batchwise elimination was employed to retain only significant variables. Results: Among 39,749 patients receiving ICIs, 2.3% developed hyperthyroidism within 12 months after treatment. In patients with hyperthyroidism, 31.3% initiated metoprolol, 9.5% initiated propranolol, and 6.0% initiated atenolol for symptom management. The mortality rate in the group was 32.1% based on the cumulative incidence. An increased risk of hyperthyroidism was associated with endometrial cancer (HR: 1.44; 95CI: 1.23-1.69; p < 0.0001), non-Hodgkin lymphoma (HR: 1.42; 95CI: 1.09-1.84; p = 0.010), and kidney cancer (HR: 1.34; 95CI: 1.25-1.63; p = 0.001). Conversely, patients with colon cancer (HR: 0.74; 95CI: 0.55-0.98; p = 0.038) had a lower chance of developing hyperthyroidism. Among all ICIs, atezolizumab (OR: 1.32; 95% CI: 0.82–2.13; p = 0.25) showed the strongest trend toward hyperthyroidism, followed by durvalumab (OR: 1.24; 95% CI: 0.75–2.05; p = 0.39), pembrolizumab (OR: 1.23; 95% CI: 0.81–1.87; p = 0.34), and nivolumab (OR: 1.22; 95% CI: 0.80–1.86; p = 0.37). In contrast, cemiplimab (OR: 0.61; 95% CI: 0.17–2.16; p = 0.44) showed a lower likelihood of causing hyperthyroidism. Conclusions: ICI-induced hyperthyroidism, while less common, has a significant impact on patient outcomes, including mortality. Identifying high-risk cancer subtypes and implementing proactive management, including beta-blocker therapy for symptom control, are critical steps to mitigate adverse effects and improve patient care. Personalized management and early intervention, particularly for high-risk groups, are essential to improving patient outcomes.