Abstract
Introduction
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.
Methods
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.
Results
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: 2.237–6.056, P
Discussion
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.