内分泌失调是癌症治疗的代价

Jalila Ahmed, Hanan Abdlhay
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摘要

许多药物用于治疗癌症。包括化疗,激素治疗和免疫治疗。免疫疗法的投资改善了治疗癌症的程序,利用免疫系统通过免疫检查点抑制剂识别和攻击癌细胞。这是通过两种主要机制完成的,第一种是CTLA-4抑制剂,如伊匹单抗,第二种途径是PD-1/PD- L1抑制剂,如纳武单抗。然而,由于使用免疫疗法,引起了许多不良反应。包括非内分泌的副作用,如结肠炎和皮炎,以及主要涉及垂体和甲状腺以及内分泌胰腺的内分泌副作用。垂体受累性可能危及生命,主要是由于CTLA-4抑制剂,导致多种垂体激素缺乏。主要表现为头痛,MRI显示垂体肿大。用高剂量糖皮质激素治疗以防止交叉受压。根据激素缺乏情况,需要激素替代治疗。甲状腺是最常见的受累腺体之一。主要是PD-1和CTLA-4抑制剂的联合作用。主要表现为一过性甲状腺功能亢进继发甲状腺功能减退,用左旋甲状腺素替代疗法治疗。免疫治疗将导致内分泌和外分泌功能紊乱。ICIs相关的糖尿病根据病理分为四种不同类型。它包括所有急性自身免疫性胰岛素依赖型糖尿病、2型糖尿病样表型、自身免疫性胰腺炎诱导的糖尿病和自身免疫性脂肪萎缩后的糖尿病。出现酮症酸中毒的患者采用标准治疗方法,病情稳定的患者采用常规胰岛素治疗方案。
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Endocrinopathies as a price of cancer treatment
Many drugs are used in treatment of cancer. Including chemotherapy, hormonal therapy and immunotherapy. The investment of immunotherapy has improve the procedure for treating cancer by utilizing the immune system to identify and attack cancer cells through immune checkpoint inhibitors. This is done by two major mechanisms, the first is CTLA-4 inhibitors like ipilimumab, and the second pathways is PD-1/PD- L1 inhibitors like nivolumab. However many adverse effects have aroused as a consequence of immunotherapy usage. Including non-endocrinal adverse effects like colitis and dermatitis, and endocrinal side effects predominantly involving pituitary and thyroid gland plus the endocrine pancreas. Pituitary gland involvement is potentially life threatening and is mainly due to CTLA-4 inhibitors, leading to multiple pituitary hormone deficiencies. It mainly present with headache, and pituitary enlargement is reported in MRI. Which is treated by high dose glucocorticoids to prevent chiasmal compression. Hormone replacement therapy is required according to the deficient hormone. Thyroid gland is one of the most commonly involved glands. Predominately by a combination of both PD-1 and CTLA-4 inhibitors. It mainly present with transient hyperthyroidism followed by hypothyroidism, which is treated by levothyroxine replacement therapy. Immunotherapy will result in both endocrine and exocrine dysfunction. ICIs associated DM is classified into four different types according to the pathology. It includes all of Acute autoimmune insulin-dependent diabetes, type 2 diabetes-like phenotype, autoimmune pancreatitis-induced diabetes, and diabetes after autoimmune lipoatrophy. Patients presented with d ketoacidosis are treated with standard approach while stable patient will be subjected to a regular insulin regimen.
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