V.I. Starikov
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引用次数: 0

摘要

介绍。尽管靶向和化疗取得了重大成功,但晚期癌症患者的生存率仍然很低。免疫疗法是一种系统性的治疗方法,它扩大了恶性肿瘤药物治疗的可能性。免疫治疗的副作用与化疗药物和靶向治疗明显不同。研究的基本原理。最常见的副作用之一是对内分泌系统,特别是甲状腺的毒性作用。研究的目的。系统分析免疫检查点抑制剂对甲状腺的副作用的科学文献。材料和方法。在Pubmed, Scopus和Web of Science数据库中进行了科学搜索。使用了以下搜索词:“免疫检查点抑制剂”、“免疫疗法”、“甲状腺”和“副作用”。研究结果与讨论。PD-1/PD-L1抑制剂和CTLA-4抑制剂均可引起甲状腺功能障碍(甲状腺功能亢进或甲状腺功能减退)。其中一项荟萃分析报告两种药物组间甲状腺毒性发生率无差异。然而,其他荟萃分析表明,这种现象在PD-1/PD-L1抑制剂治疗的患者中比CTLA-4抑制剂治疗的患者更常见。此外,科学家证实,甲状腺功能减退(3.8%)比甲状腺功能亢进(1.7%)发生的频率更高。PD-1抑制剂使用者中甲状腺功能减退比甲状腺功能亢进更常见(分别为7.0%和3.2%)。有自身免疫性甲状腺疾病史的患者在开始免疫检查点抑制剂治疗后疾病恶化的风险很高。免疫检查点抑制剂的副作用主要发生在女性身上。在免疫治疗2-4个疗程后观察到甲减的第一个实验室体征。在大多数情况下,这种疾病是无症状的,但在极少数情况下,它会变成永久性甲状腺功能减退,甚至甲状腺危象。由于免疫检查点抑制剂导致甲状腺破坏的主要原因是自身抗体或促甲状腺抗体的产生。左甲状腺素0.8 ~ 1.6 μg/kg/天用于治疗有临床症状的甲状腺功能减退。对于老年患者和有心脏病变的患者,初始给药剂量不应超过25-50 μg。通常继续使用免疫检查点抑制剂治疗。甲状腺毒症的治疗取决于引起它的病理机制。通常,受体阻滞剂(阿替洛尔和普萘洛尔)用于消除甲状腺毒症的症状。甲状腺炎的一个特点是它能够转变为甲状腺功能减退,这可能成为永久性的。结论。甲状腺功能障碍的发展是自身免疫损伤最常见的后果。PD-1抑制剂是这种情况最常见的原因。通常,这些疾病是无症状的,有一级的严重程度。及时预约激素替代疗法可以有效地继续免疫治疗。然而,有些情况可能难以治疗,需要类固醇治疗和停止免疫治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ПОБІЧНА ДІЯ ТЕРАПІЇ ІНГІБІТОРАМИ ИМУННИХ КОНТРОЛЬНИХ ТОЧОК НА ЩИТОПОДІБНУ ЗАЛОЗУ
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.  
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