Побічна Дія Терапії Інгібіторами Имунних Контрольних Точок На Щитоподібну Залозу

Abstract

Introduction. Survival of patients with advanced-stage cancers remains poor despite significant successes in targeted and chemotherapy. Immunotherapy is a systemic method of treatment that has expanded the possibilities of drug therapy for malignant tumors. Immunotherapy's side effect significantly differs from chemotherapeutic drugs and targeted therapy.
 Research rationale. One of the most common side effects is a toxic effect on the endocrine system, particularly the thyroid gland.
 Aim of the research. Conduct a systematic analysis of scientific literature on the side effects of immune checkpoint inhibitors on the thyroid gland.
 Materials and methods. A scientific search was conducted in Pubmed, Scopus, and Web of Science databases. The following search terms were used: "immune checkpoint inhibitors," "immunotherapy," "thyroid gland," and "side effects."
 Research results and discussion. Both PD-1/PD-L1 inhibitors and CTLA-4 inhibitors can cause thyroid dysfunction (hyperthyroidism or hypothyroidism). One of the meta-analyses reported no difference in the incidence of thyrotoxicity between the two drug groups. However, other meta-analyses have shown that this phenomenon is more common in patients treated with PD-1/PD-L1 inhibitors than with CTLA-4 inhibitors. In addition, scientists proved that hypothyroidism occurred statistically more often (3.8% of patients) than hyperthyroidism (1.7%). Hypothyroidism was more common in PD-1 inhibitor users than hyperthyroidism (7.0% vs. 3.2%, respectively). Patients with a history of autoimmune thyroid disease have a high risk of disease exacerbation after initiating immune checkpoint inhibitor therapy. The side effect of immune checkpoint inhibitors is developed mainly in women. The first laboratory signs of hypothyroidism are observed after 2-4 courses of immunotherapy. In most cases, the disease is asymptomatic, but in rare cases, it turns into permanent hypothyroidism and even thyroid crisis. The leading causes of destruction of the thyroid gland due to immune checkpoint inhibitors are damaged by autoantibodies or the production of thyroid-stimulating antibodies.
 Levothyroxine is prescribed at 0.8–1.6 μg/kg/day for treating hypothyroidism with clinical symptoms. For elderly patients and patients with cardiac pathology, the initial dose of the drug should be no more than 25-50 μg. Treatment with immune checkpoint inhibitors is usually continued. Treatment of thyrotoxicosis depends on the pathological mechanism that caused it. Most often, beta-blockers (atenolol and propranolol) are used to eliminate the symptoms of thyrotoxicosis. A feature of thyroiditis is its ability to transition into hypothyroidism, which can become permanent.
 Conclusions. The development of thyroid dysfunction is the most common consequence of autoimmune damage. PD-1 inhibitors are the most common cause of this condition. Usually, the disorders are asymptomatic and have the first degree of severity. Timely appointment for hormone replacement therapy allows the effective continuation of immunotherapy. However, some conditions may be refractory to such treatment, requiring steroid therapy and discontinuation of immunotherapy.