{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:05:12Z","timestamp":1789707912325,"version":"4.0.1"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICIs), particularly programmed cell death-1 (PD-1) inhibitors, have revolutionized cancer treatment but frequently induce thyroid dysfunction as the most common endocrine immune-related adverse event (irAE). Baseline thyroid autoantibodies have been implicated as potential risk factors, yet the dose-response relationship between antibody titers and hypothyroidism risk, and the differential predictive value of thyroperoxidase antibody (TPOAb) versus thyroglobulin antibody (TGAb) titers, remain incompletely characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective analysis of 627 patients with various malignancies who received PD-1 inhibitor therapy between 2015 and 2025. Thyroid function and autoantibodies (TPOAb, TGAb) were monitored every 3 weeks. Antibody titers were analyzed both as continuous variables and as ordinal strata. Univariate and multivariate logistic regression analyses were performed; receiver operating characteristic (ROC) curve analysis was used to determine optimal titer cutoffs, and a predictive model was constructed and evaluated. Kaplan-Meier survival analysis assessed prognostic implications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Hypothyroidism occurred in 247 patients (39.4%), with onset at a median of 12.0 weeks. In multivariate analysis, baseline TPOAb positivity (OR = 3.681, 95% CI: 2.237\u20136.056, P &amp;lt; 0.001) and TGAb positivity (OR = 4.635, 95% CI: 2.335\u20139.200, P &amp;lt; 0.001) were independently associated with hypothyroidism risk. When analyzed as continuous variables, each 100 IU\/mL increase in TPOAb conferred an OR of 2.699 (P &amp;lt; 0.001), and each 100 IU\/mL increase in TGAb conferred an OR of 1.516 (P = 0.007). Dose-response analysis revealed progressive escalation of hypothyroidism rates with increasing antibody titers: for TPOAb, 30.7% (normal), 34.9% (mild, 10\u201349 IU\/mL), 52.2% (moderate, 50\u201399 IU\/mL), 69.6% (high, 100\u2013499 IU\/mL), and 77.5% (very high, \u2265500 IU\/mL); for TGAb, 34.1% (normal), 89.3% (mild, 80\u2013199 IU\/mL), 64.3% (moderate, 200\u2013499 IU\/mL), and 72.5% (high, \u2265500 IU\/mL). ROC analysis identified optimal titer cutoffs of 14.5 IU\/mL for TPOAb (AUC = 0.647) and 11.5 IU\/mL for TGAb (AUC = 0.588); the combined predictive model achieved an AUC of 0.718.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Baseline thyroid autoantibody titers demonstrate a clear dose-response relationship with hypothyroidism risk following PD-1 inhibitor therapy. TGAb positivity, even at mildly elevated titers, confers exceptionally high risk. The optimal TGAb cutoff of 11.5 IU\/mL, substantially below conventional thresholds, suggests that even low-level TGAb may indicate clinically relevant subclinical autoimmunity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1905074","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:33:41Z","timestamp":1789706021000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Predictive value of pre-existing thyroid autoantibodies for PD-1 inhibitor-induced hypothyroidism: a retrospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Peiying","family":"Huang","sequence":"first","affiliation":[{"name":"Xiamen First Clinical Medical College of Fujian Medical University","place":["Xiamen, China"]},{"name":"Department of Endocrinology and Diabetes, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University","place":["Xiamen, China"]},{"name":"Xiamen Diabetes Institute","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huangdao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology Surgery, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanling","family":"Zheng","sequence":"additional","affiliation":[{"name":"Xiamen First Clinical Medical College of Fujian Medical University","place":["Xiamen, China"]},{"name":"Department of Endocrinology and Diabetes, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University","place":["Xiamen, China"]},{"name":"Xiamen Diabetes Institute","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhu","family":"Lin","sequence":"additional","affiliation":[{"name":"Xiamen First Clinical Medical College of Fujian Medical University","place":["Xiamen, China"]},{"name":"Department of Endocrinology and Diabetes, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University","place":["Xiamen, China"]},{"name":"Xiamen Diabetes Institute","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangsen","family":"Xiao","sequence":"additional","affiliation":[{"name":"Xiamen First Clinical Medical College of Fujian Medical University","place":["Xiamen, China"]},{"name":"Department of Endocrinology and Diabetes, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University","place":["Xiamen, China"]},{"name":"Xiamen Diabetes Institute","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Li","sequence":"additional","affiliation":[{"name":"Xiamen First Clinical Medical College of Fujian Medical University","place":["Xiamen, China"]},{"name":"Department of Endocrinology and Diabetes, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University","place":["Xiamen, China"]},{"name":"Xiamen Diabetes Institute","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyang","family":"Zeng","sequence":"additional","affiliation":[{"name":"Xiamen First Clinical Medical College of Fujian Medical University","place":["Xiamen, China"]},{"name":"Department of Endocrinology and Diabetes, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University","place":["Xiamen, China"]},{"name":"Xiamen Diabetes Institute","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Yan","sequence":"additional","affiliation":[{"name":"Xiamen First Clinical Medical College of Fujian Medical University","place":["Xiamen, China"]},{"name":"Department of Endocrinology and Diabetes, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University","place":["Xiamen, China"]},{"name":"Xiamen Diabetes Institute","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.11818","article-title":"Evaluation of Programmed Death Ligand 1 (PD-L1) Gene Amplification and Response to Nivolumab Monotherapy in Non-small Cell Lung Cancer","volume":"3","author":"Inoue","year":"2020","journal-title":"JAMA Netw 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