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

Authors

Lingyan Zhou, Qinran Long, Ying Zhang, Mei Zhan

Published in

Frontiers in immunology. Volume 17. Pages 1882182. Epub Aug 07, 2026.

Abstract

Real-world findings regarding the risk factors for immune checkpoint inhibitor (ICI) -related conditions remain scarce and show a lack of consistency.
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.
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.
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.
https://www.chictr.org.cn, identifier ChiCTR2300075974.

PMID:
42630547
Bibliographic data and abstract were imported from PubMed on 23 Aug 2026.

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