Deligiorgi Maria V, Liapi Charis, Trafalis Dimitrios T
Department of Pharmacology-Clinical Pharmacology Unit, National and Kapodistrian University of Athens, Faculty of Medicine, Athens, Greece.
Expert Opin Biol Ther. 2021 Aug;21(8):1097-1120. doi: 10.1080/14712598.2021.1869211. Epub 2021 Apr 1.
The incorporation of immune checkpoint inhibitors in the oncologists' arsenal is a milestone in cancer therapeutics, though not being devoid of toxicities.Areas covered: The present review provides a comprehensive and up-to-date overview of the immune-related hypophysitis with focus on the elusive biological background, the wide spectrum of the epidemiological profile, the varying clinical aspects, and the diagnostic and therapeutic challenges.Expert opinion: Historically considered distinctive of anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibodies (mAbs), the immune-related hypophysitis is increasingly correlated with the anti-programmed cell-death (PD) protein 1 (PD-1)/anti-PD ligand 1 (PD-L1) mAbs. The distinct phenotype of hypophysitis related to anti-PD1/anti-PD-L1 mAbs is highlighted with focus on the immune-related isolated adrenocorticotropic (ACTH) deficiency. The immune-related central diabetes insipidus is discussed as a rare aspect of anti-CTL-A4 mAbs-induced hypophysitis, recently related to anti-PD1/anti-PD-L1 mAbs as well. The present review builds on existing literature concerning immune-related hypophysitis underscoring the pending issues still to be addressed, including (i) pathogenesis; (ii) correlation with preexisting autoimmunity; (iii) predictive value; (iv) utility of high-dose glucocorticoids; and (v) establishment of evidence-based diagnostic and therapeutic protocols. Increased awareness and constant vigilance are advocated as cornerstone of a multidisciplinary approach to ensure optimal patients' care.
免疫检查点抑制剂纳入肿瘤学家的治疗手段是癌症治疗领域的一个里程碑，尽管并非没有毒性。
本综述全面且最新地概述了免疫相关性垂体炎，重点关注难以捉摸的生物学背景、广泛的流行病学特征、多样的临床方面以及诊断和治疗挑战。
免疫相关性垂体炎在历史上被认为是抗细胞毒性T淋巴细胞抗原4（CTLA-4）单克隆抗体（mAb）所特有的，但现在越来越多地与抗程序性细胞死亡（PD）蛋白1（PD-1）/抗PD配体1（PD-L1）mAb相关。重点强调了与抗PD1/抗PD-L1 mAb相关的垂体炎的独特表型，尤其关注免疫相关性孤立性促肾上腺皮质激素（ACTH）缺乏。免疫相关性中枢性尿崩症作为抗CTLA-4 mAb诱导的垂体炎的罕见方面进行了讨论，最近也发现其与抗PD1/抗PD-L1 mAb有关。本综述基于有关免疫相关性垂体炎的现有文献，强调了仍有待解决的悬而未决的问题，包括（i）发病机制；（ii）与既往自身免疫的相关性；（iii）预测价值；（iv）高剂量糖皮质激素的效用；以及（v）循证诊断和治疗方案的建立。提倡提高认识和持续警惕，将其作为多学科方法的基石，以确保为患者提供最佳护理。
