ABSTRACT

Introduction: 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.

摘要

简介：在肿瘤学家的武器库中加入免疫检查点抑制剂是癌症治疗的一个里程碑，尽管并非没有毒性。

涵盖的领域：本综述提供了免疫相关垂体炎的全面和最新概述，重点关注难以捉摸的生物学背景、广泛的流行病学特征、不同的临床方面以及诊断和治疗挑战。

专家意见：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) 的独特之处，免疫相关垂体炎与抗程序性细胞死亡 (PD) 蛋白 1 (PD- 1)/抗 PD 配体 1 (PD-L1) mAb。突出显示与抗 PD1/抗 PD-L1 mAb 相关的垂体炎的独特表型，重点是免疫相关的孤立性促肾上腺皮质激素 (ACTH) 缺乏症。免疫相关的中枢性尿崩症被讨论为抗 CTL-A4 单克隆抗体诱导的垂体炎的罕见方面，最近也与抗 PD1/抗 PD-L1 单克隆抗体有关。本综述建立在有关免疫相关垂体炎的现有文献的基础上，强调仍有待解决的未决问题，包括 (i) 发病机制；(ii) 与先前存在的自身免疫相关；(iii) 预测值；(iv) 大剂量糖皮质激素的效用；(v) 建立循证诊断和治疗方案。提倡提高认识和持续警惕作为多学科方法的基石，以确保最佳患者护理。