Table_1_Differences in checkpoint-inhibitor-induced hypophysitis: mono- versus combination therapy induced hypophysitis.docx

ObjectiveImmune checkpoint inhibitors (ICIs) are revolutionary in oncology but may cause immune-related (IR) side effects, such as hypophysitis. Treatment with anti-PD-(L)1, anti-CTLA-4 or anti-CLTA-4/PD-1 may induce hypophysitis, but little is known about the differences in clinical presentation or need for different treatment. We analyzed the differences of anti-PD-(L)1, anti-CTLA-4 and anti-CTLA-4/PD-1 induced hypophysitisMethodsretrospective analysis of 67 patients (27 anti-PD-(L)1, 6 anti-CLTA-4 and 34 anti-CTLA-4/PD-1 induced hypophysitis).ResultsThe median time between starting ICIs and IR-hypophysitis was longer after anti-PD(L)-1) therapy (22 weeks versus 11 and 14 weeks after anti-CTLA-4 and anti-CTLA-4/PD-1 therapy, respectively). The majority of patients (>90%), presented with atypical complaints such as fatigue, nausea, and muscle complaints. Headache, TSH or LH/FSH deficiency were more common in anti-CTLA-4 and anti-CLTA-4/PD-1 versus anti-PD-(L)1 induced hypophysitis (83% and 58% versus 8%, 67% and 41% versus 11%, and 83% and 48% versus 7%, respectively). Pituitary abnormalities on MRI (hypophysitis or secondary empty sella syndrome) were only seen in patients receiving anti-CTLA-4 or anti-CTLA-4/PD-1 therapy. Recovery from TSH, LH/FSH and ACTH deficiency was described in 92%, 70% and 0% of patients after a mean period of 14 and 104 days, respectively, and did not differ between patients who did or did not receive high-dose steroids.ConclusionThe clinical presentation of IR-hypophysitis varies depending on the type of ICIs. MRI abnormalities were only seen in anti-CTLA-4 or anti-CTLA-4/PD-1 induced hypophysitis. Endocrine recovery is seen for LH/FSH and TSH deficiency but not for ACTH deficiency, irrespective of the corticosteroid dose.

免疫检查点抑制剂（ICIs）在肿瘤学领域具有革命性的意义，但其可能引发免疫相关（IR）副作用，例如垂体炎。抗PD-(L)1、抗CTLA-4或抗CTLA-4/PD-1治疗可能诱发垂体炎，然而关于其临床表现差异或不同治疗方案的需求知之甚少。本研究旨在分析抗PD-(L)1、抗CTLA-4及抗CTLA-4/PD-1诱导的垂体炎的差异，方法为对67名患者（27例抗PD-(L)1，6例抗CLTA-4和34例抗CTLA-4/PD-1诱导的垂体炎）进行回顾性分析。结果显示，相较于抗CTLA-4和抗CTLA-4/PD-1治疗，抗PD(L)-1治疗后ICIs启动与IR-垂体炎之间的中位时间更长（分别为22周、11周和14周）。超过90%的患者表现为非典型症状，如疲劳、恶心和肌肉疼痛。在抗CTLA-4和抗CTLA-4/PD-1诱导的垂体炎中，头痛、TSH或LH/FSH缺乏较为常见（分别为83%和58%，与抗PD-(L)1诱导的垂体炎的8%、67%和41%相比，以及11%、83%和48%相比）。在仅接受抗CTLA-4或抗CTLA-4/PD-1治疗的患者中，MRI检查发现垂体炎或继发性鞍区空腔。在92%、70%和0%的患者中描述了TSH、LH/FSH和ACTH缺乏的恢复情况，分别在平均14天、104天和0天后，且无论是否接受高剂量类固醇治疗，患者恢复情况无显著差异。结论表明，IR-垂体炎的临床表现因ICIs类型而异。MRI异常仅在抗CTLA-4或抗CTLA-4/PD-1诱导的垂体炎中观察到。内分泌功能恢复见于LH/FSH和TSH缺乏，但ACTH缺乏则不然，无论皮质类固醇剂量如何。