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Objective Our study aimed to identify and characterize thyroid dysfunctions associated with immune checkpoint inhibitors (ICIs). Design Data were obtained from VigiBase, between January 1, 2011 to March 6, 2019. Methods All thyroid drug-adverse events are classified by group queries according to the Medical Dictionary for Regulatory Activities. Information component (IC) and reporting odds ratio (ROR) were considered as measures of disproportionality for the assessment of association between ICIs and thyroid dysfunctions. We used IC to identify meaningful drug-adverse events while using ROR to compare differences in the reporting of drug-adverse events caused by different ICI subgroups. Positive IC values are deemed significant. Results Compared with the full database, the following ICI-associated thyroid dysfunctions were over-reported: hypothyroidism (1125 reports for ICIs vs 12495 for all drugs; Information Component 4.28 (95% CI: 4.18–4.35)), hyperthyroidism (926 vs 7538; 4.66 (95% CI: 4.55–4.74)), thyroiditis (294 vs 1237; 5.40 (95% CI: 5.21–5.54)), thyrotoxic crisis (11 vs 288; 3.55 (95% CI: 2.61–4.20)). Hypothyroidism was over-reported for patients treated with ICI combination therapy versus those treated with ICI monotherapy (ROR 1.3 (95% CI: 1.1–1.7)), and the same was observed for hyperthyroidism (ROR: 1.9 (95% CI: 1.5–2.4)), thyroiditis (ROR: 3.3 (95% CI: 2.3–4.8)), thyrotoxic crisis (ROR: 11.5 (95% CI: 2.4–53.8)). All 11 thyrotoxic crisis cases were malignant melanoma patients, of which seven occurred under ICI combination therapy. Conclusions Thyroid dysfunction may occur after ICI therapies, and severe thyrotoxic crisis may even occur. Raising awareness of ICI-associated thyroid dysfunction can improve the detection and treatment of these diseases.

ObjectiveAn increase in the expression of autoantigens and their presenting molecules human leukocyte antigen (HLA) class I has been demonstrated to be responsible for autoimmune diseases. Thyroid transcription factor-1 (TTF-1 or NKX2-1) synchronously upregulates both HLA class I and thyroid-specific autoantigen, which may be involved in the pathological process of autoimmune thyroiditis. In this study, the expressions and potential role of TTF-1 and HLA class I in Hashimoto's disease (HT) were examined.PatientsIn this study, 22 resection specimens clinically and histopathologically confirmed to have Hashimoto's disease and 30 normal thyroid specimens from adjacent tissues of thyroid adenoma were used.MeasurementWestern blot, real-time PCR, and immunohistochemistry were performed to assay TTF-1 and HLA class I in the thyrocytes of Hashimoto's disease as well as in the normal thyroid from adjacent tissues of thyroid adenoma.ResultsThe TTF-1 and HLA class I in Hashimoto's disease were significantly higher than those in the controls.ConclusionUpregulation of TTF-1 and HLA class I in Hashimoto's disease provide a clinical evidence for possible triggering of autoimmune reaction.