Background: Immune checkpoint inhibitors (ICIs) have shown promising anti-tumor activities and are widely used for the treatment of advanced cancers. However, they may lead to immune-related adverse events (irAEs) and some of them, such as hypophysitis, can be life-threatening. Here, early diagnosis is critical. Methods: We retrospectively analyzed 40 melanoma patients who developed hypophysitis during ICI treatment with either ipilimumab and/or anti-PD1 therapy and compared them to 40 control patients who did not develop hypophysitis during the ICI treatment, matched for age, gender, type of immunotherapy, and stage. Clinical data and blood values such as LDH, CRP, TSH, T3, T4, and absolute immune cell counts were retrieved from the medical records. Patient characteristics, laboratory values, progression-free survival, and overall survival were compared between the two groups. Results: Patients with ir-hypophysitis had a median age of 59 years, and most of them were male. Clinically, frequent symptoms were fatigue, headache, dizziness, and gastrointestinal symptoms such as nausea or abdominal pain. The onset of ir-hypophysitis differed much between ipilimumab- (median 8 weeks) and anti-PD1 (median 40 weeks)-induced hypophysitis (p< 0.001). At baseline, besides a slightly increased CRP level (p= 0.06), no differences were observed in patients who later developed hypophysitis compared to the control. After treatment started, hypophysitis patients showed a constant and significant decline in T4 levels from the start of therapy until diagnosis (p< 0.05), independent of the ICI treatment regime. However, a decline in T3 and TSH was only noted in patients with ipilimumab-induced ir-hypophysitis. Furthermore, serum sodium levels declined rapidly at the diagnosis of hypophysitis (p< 0.001). In addition, there was a constant increase in the absolute counts of eosinophils and lymphocytes from baseline in hypophysitis patients (p< 0.05). Conclusion: Ir-hypophysitis reveals different clinical pictures and onset times depending on the ICI regime used. Whereas a drop in T4 levels was indicative of developing hypophysitis independent of the ICI regime, TSH levels only declined in patients under ipilimumab-based ICI regimes. To best monitor our patients, it is important to recognize these differences.
背景：免疫检查点抑制剂（ICIs）已显示出良好的抗肿瘤活性，并广泛用于晚期癌症的治疗。然而，它们可能导致免疫相关不良事件（irAEs），其中一些如垂体炎可能危及生命。因此，早期诊断至关重要。方法：我们回顾性分析了40例在接受伊匹木单抗和/或抗PD1治疗的ICI治疗期间发生垂体炎的黑色素瘤患者，并将其与40例在ICI治疗期间未发生垂体炎的对照患者进行比较，两组患者在年龄、性别、免疫治疗类型和分期方面相匹配。从医疗记录中提取临床数据和血液指标，如LDH、CRP、TSH、T3、T4以及绝对免疫细胞计数。比较两组患者的临床特征、实验室指标、无进展生存期和总生存期。结果：发生ir-垂体炎的患者中位年龄为59岁，大多数为男性。临床上常见症状包括疲劳、头痛、头晕以及恶心或腹痛等胃肠道症状。伊匹木单抗诱导的垂体炎（中位8周）与抗PD1诱导的垂体炎（中位40周）的发病时间存在显著差异（p<0.001）。基线时，除CRP水平略有升高（p=0.06）外，后来发生垂体炎的患者与对照组相比未见其他差异。治疗开始后，垂体炎患者从治疗开始至诊断期间T4水平持续显著下降（p<0.05），且与ICI治疗方案无关。然而，T3和TSH水平下降仅见于伊匹木单抗诱导的ir-垂体炎患者。此外，垂体炎诊断时血清钠水平迅速下降（p<0.001）。同时，垂体炎患者的嗜酸性粒细胞和淋巴细胞绝对计数从基线水平持续增加（p<0.05）。结论：ir-垂体炎根据所用ICI方案的不同，呈现出不同的临床表现和发病时间。尽管T4水平下降提示垂体炎的发生与ICI方案无关，但TSH水平下降仅见于接受伊匹木单抗为基础的ICI治疗方案的患者。为更好地监测患者，认识这些差异至关重要。
Early Serum Markers for Immune Checkpoint Inhibitor Induced Hypophysitis in Melanoma Patients
肿瘤(癌症)患者之家