Real-world insights into incidence and risk factors of thyroid dysfunction following immune checkpoint inhibitor therapy.

BACKGROUND: Real-world findings regarding the risk factors for immune checkpoint inhibitor (ICI) -related conditions remain scarce and show a lack of consistency. RESEARCH DESIGN AND METHODS: We conducted a retrospective study of patients who treated with ICIs between October 2014 and June 2023. Patient follow-up was extended until death or July 4, 2025. Logistic regression was used to investigate the associations between clinical characteristics and thyroid dysfunction after ICI initiation. RESULTS: After excluding 411 patients with missing key data and 1,342 with pre-existing thyroid dysfunction, 6,857 patients were included in the final cohort. ICI-related thyroid dysfunction was identified in 1,342 cases (19.57% overall), with 582 subclinical hypothyroidism, 155 overt hypothyroidism, 521 central hypothyroidis, and 84 thyrotoxicosis. Logistic regression identified subtype-specific risk factors. For subclinical hypothyroidism, smoking (OR 0.766, 95% CI: 0.589-0.996, P = 0.047), lung cancer (OR 0.708, 95% CI: 0.567-0.884, P = 0.002), and esophageal cancer (OR 0.544, 95% CI: 0.360-0.821, P = 0.004) were protective, while hepatocellular carcinoma (OR 1.871, 95% CI: 1.438-2.433, P < 0.001) was a risk factor. For overt hypothyroidism, increasing age (OR 0.978, 95% CI: 0.965-0.990, P = 0.001) and gastric cancer (OR 0.279, 95% CI: 0.101-0.771, P = 0.014) were protective, whereas PD-L1 inhibitor use (OR 1.695, 95% CI: 1.017-2.825, P = 0.043) increased risk. For central hypothyroidism, hepatocellular carcinoma (OR 0.473, 95% CI: 0.310-0.723, P = 0.001) and esophageal cancer (OR 0.552, 95% CI: 0.360-0.846, P = 0.006) were protective, and gastric cancer (OR 1.374, 95% CI: 1.005-1.878, P = 0.047) was a risk factor. For thyrotoxicosis, male sex (OR 0.578, 95% CI: 0.358-0.934, P = 0.025) was protective, while esophageal cancer (OR 2.639, 95% CI: 1.306-5.334, P = 0.007) was a risk factor. CONCLUSIONS: This large real-world cohort reveals a high incidence of ICI-related thyroid dysfunction and identifies subtype-specific risk factors, underscoring the importance of routine thyroid function monitoring in high-risk patients receiving ICI therapy. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn, identifier ChiCTR2300075974.