Thyroid dysfunction related to immune checkpoint inhibitors

ABSTRACT Introduction-Aim: Immune checkpoint inhibitors are used in the treatment of various types of cancer. Although these drugs have a lower side effect profile compared to cytotoxic chemotherapies, they can cause various immunity-related side effects by making immune system cells overly active. One of these side ef-fects is thyroid dysfunction. Thyroid dysfunction usually occurs weeks or months after treatment. The fact that most clinical symptoms are insidious and non-specific in the early stages of thyroid dysfunction, and the uncertain timing of thyroid dysfunction development, make diagnosis challenging. If thyroid dys-function is not recognized, it can lead to the discontinuation of the immune checkpoint inhibitor and, in some cases, even mortality. This study aims to investi-gate the frequency of thyroid dysfunction, the types of thyroid dysfunction that develop, the timing of thyroid dysfunction development, and the effects on mor-tality in patients using nivolumab, pembrolizumab, and atezolizumab. Materials and Methods: Patients with a pathological cancer diagnosis and no prior thyroid disease who received at least one course of immune checkpoint inhi-bitors at Akdeniz University Medical Faculty Hospital between January 2018 and December 2023 were included in the study. The data of the patients included in the study were reviewed retrospectively. In addition to the characteristics of the patients such as age, height, and weight, the presence of diabetes and hyperten-sion before treatment, whether they received chemotherapy or radiotherapy before immunotherapy, and whether they had undergone surgery for the primary cancer site before immunotherapy were retrospectively examined. In patients receiving immunotherapy, TSH and ST4 levels at the 3rd, 6th, 9th, and 12th months after treatment were evaluated to determine whether thyroid dysfunction developed and whether this thyroid dysfunction affected survival. Results: In our study, it was found that 71 out of 199 patients (35.6%) who used immune checkpoint inhibitors for cancer treatment developed thyroid dysfunction. When looking at the treatment specifics, thyroid dysfunction developed in 54 out of 150 patients (36%) using nivolumab, 9 out of 25 patients (36%) using pembroli-zumab, and 9 out of 25 patients (33.33%) using atezolizumab. Regarding the dist-ribution of thyroid dysfunction based on survival status, it was observed that 35.71% of the survivors and 35.65% of the deceased had thyroid dysfunction. There was no statistically significant relationship between the distribution of thy-roid dysfunction and survival status. (p=0,992) Conclusion: Patients using immune checkpoint inhibitors should be closely moni-tored for thyroid dysfunction. In patients who develop thyroid dysfunction, tre-atment should be initiated or monitored as necessary. Depending on the severity of the thyroid dysfunction, options such as temporarily discontinuing the use of immune checkpoint inhibitors or requesting an endocrinology consultation should be considered. Keywords: Immune checkpoint inhibitör, nivolumab, atezolizumab, pembrolizu-mab, thyroid dysfunction