Immune-related endocrine disorders in novel Immune checkpoint inhibition therapy.
Immune-related endocrine disorders in novel Immune checkpoint inhibition therapy.
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DOI：
10.1016/j.gendis.2016.10.002
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发表时间：
2016-12
期刊：
影响因子：
6.8
通讯作者：
Min L
中科院分区：
文献类型：
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作者：
Min L
针对晚期癌症的免疫检查点抑制被《科学》杂志评为2013年的突破性发现。在大量的临床研究中，针对免疫检查点CTLA4、PD1和PD1配体PDL1的单抗在不同类型的转移恶性肿瘤中显示出良好的肿瘤反应。不良反应与自身免疫有关。内分泌紊乱、脑垂体炎和甲状腺炎是免疫检查点抑制治疗最常见的副作用之一。脑垂体炎是一种非常罕见的内分泌疾病，在接受抗CTLA4治疗的患者中约有十分之一会发生。另一方面，甲状腺炎更常见于接受抗PD1治疗的患者。此外，在接受抗CTLA4和抗PD1联合治疗的患者中，甲状腺炎和垂体炎都很常见。垂体炎和甲状腺炎发病时间短。大多数内分泌疾病发生在免疫检查点抑制治疗开始后12周内。垂体炎可表现为完全的垂体前叶激素缺乏或单独的垂体激素缺乏。尿崩症是罕见的。促甲状腺激素和促性腺激素缺乏可能是可逆的，但促肾上腺皮质激素缺乏似乎是永久性的。甲状腺炎可表现为甲状腺功能减退或甲状腺机能亢进，继之为甲状腺功能减退。甲状腺功能减退症似乎不可逆转。早期识别垂体炎和甲状腺炎的发病，并正确处理这些内分泌疾病，将改善这种新型免疫疗法的生活质量和结果。
Immune checkpoint inhibition against advance malignancies was named breakthrough discovery by the science magazine in 2013. In numerous clinical studies, monoclonal antibodies against the immune checkpoints, CTLA4, PD1 and PD1 ligand PDL1 have shown promising tumor response in different type of metastatic malignancies. The adverse events are autoimmune-related. The endocrine disorders, hypophysitis and thyroiditis are among the most common side effects associated with immune checkpoint inhibition treatment. Hypophysitis, a very rare endocrine disorder occurs in about one tenth of the patients receiving anti-CTLA4 treatment. Thyroiditis, on the other hand, is more commonly seen in patients receiving anti-PD1 treatment. In addition, both thyroiditis and hypophysitis are common in patients receiving combination treatment with anti-CTLA4 and anti-PD1 treatment. The time to onset of hypophysitis and thyroiditis is short. Most of the endocrine disorders occur within 12 weeks after initiation of the immune checkpoint inhibition therapy. Hypophysitis can manifest as total anterior pituitary hormone deficiency or isolated pituitary hormone deficiency. Diabetes insipidus is rare. TSH and gonadotropin deficiencies may be reversible but ACTH deficiency appears permanent. Thyroiditis can present as hypothyroidism or thyrotoxicosis followed by hypothyroidism. Hypothyroidism appears irreversible. Early identifying the onset of hypophysitis and thyroiditis and proper management of these endocrine disorders will improve the quality of the life and the outcome of this novel immunotherapy.