Risk factors for immune checkpoint inhibitor-related thyroid dysfunction: a retrospective cohort study

Immune checkpoint inhibitors (ICIs) are widely used to treat various malignancies; however, the high incidence of immune-related adverse events, including thyroid dysfunction, is a major clinical concern. Thyroid dysfunction occurs frequently, affects patient health and quality of life, and can be life-threatening when severe, necessitating prompt identification and management. Herein, we aimed to identify pretreatment risk factors associated with ICI-induced thyroid dysfunction.

Medical records of patients administered ICIs were retrospectively reviewed. Data on patient age, sex, and body weight; primary tumor type; ICI agent; programmed death-ligand 1 status; disease stage; line(s) of treatment; and laboratory parameters measured before treatment initiation were extracted. These characteristics were compared between patients who developed thyroid dysfunction and those who did not.

An elevated pretreatment eosinophil count was significantly associated with thyroid dysfunction following ICI therapy. In the multivariable logistic regression analysis, eosinophil count remained significantly associated with thyroid dysfunction after adjustment for lactate dehydrogenase (LDH; adjusted odds ratio per 0.1 × 10³/µL increase, 2.18; 95% confidence interval [CI], 1.56-3.04; P < 0.001). Receiver operating characteristic analysis yielded an area under the curve of 0.812 (95% CI, 0.722-0.902). The optimal cutoff value was 0.2 × 10³/µL, with a sensitivity of 81.0% and a specificity of 68.2%.

An elevated pretreatment eosinophil count was associated with subsequent thyroid dysfunction following ICI therapy after adjustment for LDH. Further prospective studies incorporating thyroid autoantibody status are required to determine its clinical utility as a candidate marker.