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免疫检查点抑制剂相关垂体不良反应临床特征分析

Clinical characteristic analysis of immune checkpoint inhibitor-related pituitary adverse events

    摘要
  • 摘要:
    目的 探讨恶性肿瘤患者使用免疫检查点抑制剂（immune checkpoint inhibitor, ICI）后发生垂体免疫相关不良反应（immune-related adverse events，irAEs）的临床特征，并与原发性垂体炎对比。
    方法 回顾性分析于2019年1月至2022年11月在浙江大学医学院附属邵逸夫医院住院并接受ICI治疗的753例恶性肿瘤患者的临床资料，分析内分泌irAEs发生率；分析垂体irAEs患者的临床特征，并与原发性垂体炎患者（n＝18）的临床特征比较。
    结果 ICI以PD-1/PD-L1单抗为主（742例，98.5%）。内分泌irAEs发生率为32.0%（241/753），以原发性甲状腺功能障碍最常见（212例，28.2%），其次是垂体irAEs（35例，4.6%）。发生垂体irAEs的中位用药时间为5.8个月，33例（94.3%）表现为继发性肾上腺皮质功能减退。联合手术是预防垂体irAEs发生的保护因素（P＝0.002），而较大的体质量指数（body mass index, BMI）和使用免疫双抗是垂体irAEs发生危险因素（P＜0.05）。与原发性垂体炎患者相比，垂体irAEs患者男性比例高、BMI小，视野缺损及尿崩症发生率低，继发性肾上腺皮质功能减退比例高，垂体MRI阳性率低（P＜0.05）。
    结论 恶性肿瘤患者接受ICI治疗后内分泌irAEs发生率较高，以甲状腺受累最多见，其次为垂体。垂体irAEs主要表现为继发性肾上腺皮质功能减退，缺乏特异性临床症状，MRI阳性率低，易被误诊、漏诊，应提高警惕。

     

    Abstract:
    Objective To explore the clinical characteristics of immune-related adverse events (irAEs) involving the pituitary gland in malignant tumor patients following the administration of immune checkpoint inhibitors (ICIs), and to compare characteristics of pituitary irAEs with primary hypophysitis.
    Methods A total of 753 malignant tumor patients who were hospitalized at Sir Run Run Shaw Hospital School of Medicine, Zhejiang University from January 2019 to November 2022 and received ICIs treatment were retrospectively included. The incidence of endocrine irAEs were statistically analyzed. The clinical characteristics of patients with pituitary irAEs were analyzed and compared with those of patients with primary hypophysitis (n＝18).
    Results Among the 753 patients treated with ICIs, the majority (742, 98.5%) received PD-1/PD-L1 inhibitors. The incidence of endocrine irAEs was 32.0% (241/753), with primary thyroid dysfunction being most common (212, 28.2%), followed by pituitary dysfunction (35, 4.6%). The median time to onset of pituitary irAEs was 5.8 months, with the majority presenting as secondary hypoadrenocorticism (33, 94.3%). Surgery was a protective factor for preventing pituitary irAEs (P＝0.002), whereas higher body mass index (BMI) and dual ICIs combination therapy were recognized as risk factors (P＜0.05). Compared to patients with primary hypophysitis, patients with pituitary irAEs had a higher proportion of males, lower BMI, lower rates of visual field defects and diabetes insipidus, higher rate of secondary hypoadrenocorticism and lower positive rate on MRI (P＜0.05).
    Conclusions Malignant tumor patients treated with ICIs exhibit a relatively high incidence of endocrine irAEs, with thyroid involvement being most common, followed by the pituitary gland. Pituitary irAEs primarily manifest as secondary hypoadrenocorticism, lacking specific clinical symptoms and exhibiting a low positive rate on MRI. These factors contribute to a high risk of misdiagnosis or missed diagnosis, necessitating heightened clinical vigilance.

     

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