MON-376 Deciphering the Relationship Between Immune Checkpoint Inhibitor-Related Thyroiditis and Spontaneous Thyroid Autoimmunity

Abstract Disclosure: R. Crespo Trevino: None. K. Okazaki: None. B. Kuo: None. E. Martinez Jaime: None. M. Rengarajan: None. Immune checkpoint inhibitors (ICIs) have revolutionized cancer care, but their use is accompanied by highly morbid immune-related adverse events (irAEs), often affecting endocrine organs. Our group has previously shown that ICI-related diabetes shares genetic architecture with spontaneous type 1 diabetes1, suggesting that subclinical autoimmunity predisposes to endocrine irAEs. To test this hypothesis, we focused on ICI-induced thyroiditis, a common irAE affecting up to 20% of patients treated with ICI2. We examined the relationship between ICI thyroiditis and Hashimoto’s thyroiditis, to understand how ICI targets influence progression of thyroid autoimmunity and to identify risk factors that may better predict patients at risk of ICI-related thyroiditis.Using our institution’s Research Patient Data Registry (RPDR), we analyzed data from 19434 patients treated with ICI in our institution’s system between January 2010 and September 2023. We excluded patients with a prior history of thyroid dysfunction. Exclusion criteria included: abnormal thyroid function tests within 1 year prior to ICI initiation, positive thyroid stimulating immunoglobulin or thyrotropin-binding inhibitory immunoglobulin, history of thyroid cancer, and history of prescriptions for methimazole, propylthiouracil, or levothyroxine. We first examined the relationship between ICI-related thyroiditis and Hashimoto’s thyroiditis in these patients, leveraging measurements of TPO antibodies, which are diagnostic of lymphocytic infiltration in the thyroid. In total, 224 patients have TPO antibody levels checked prior to ICI initiation, with 19 elevated (TPOpos) and 205 negative (TPOneg). ICI-induced thyroiditis was defined as the development of hyperthyroidism or hypothyroidism, occurring between 7 days after receiving ICI and up to 6 months thereafter. The incidence of ICI thyroiditis was markedly higher in the TPO-positive group (36.8% versus 9.7%, OR = 5.4; 95% CI = [1.91, 15.27]). Based on our exclusion criteria TPOpos patients had normal thyroid function (euthyroid Hashimoto’s), enabling us to examine whether ICI accelerated the incidence of hypothyroidism; strikingly, the same 36% of TPOpos patients developed hypothyroidism within 6 months of ICI initiation. In comparison, published literature suggests that the spontaneous rate of progression is 4% per year. Strikingly, anti-thyroglobulin (Tg) antibodies were an even stronger predictor of development of ICI thyroiditis, with 66% of Tgpos patients developing ICI-related thyroiditis compared to 11.6% of Tgneg (n=164, OR = 15.2; 95% CI = [5.04, 45.72]). Collectively, our results suggest a potential shared immunologic architecture underlying spontaneous and ICI-related thyroid autoimmunity.1 PMID:392077732 PMID: 39792969 Presentation: Monday, July 14, 2025