Introduction

Cancer therapy has greatly progressed in the past few years, due to development of immune checkpoint proteins. These immunotherapies, when applied to eligible patients, have significantly reduced mortality but are prone to induce immune side-effects, including pituitary disorder and low adreno-corticotropic hormone (ACTH) and cortisol levels. We aimed to assess the prevalence and etiology of corticotropic insufficiency through a systematic screening of cortisol and ACTH levels in patients with lung cancer treated with nivolumab perfusion.

Material and methods

All patients from our Center with indications for nivolumab treatment for pulmonary squamous cell carcinoma or adenocarcinoma resistant to chemotherapy were successively included and underwent cortisol and ACTH assay before each nivolumab perfusion. When cortisol was below normal without ACTH elevation, we screened for pituitary metastasis, hypophysitis or corticosteroid treatment that could explain the corticotropic insufficiency.

Results

Data from 75 patients (80.0% men, 20.0% women) showed 10.7% asymptomatic corticotropic insufficiency, with a mean cortisol level of 2.76 ± 1.27 μg/dl. Diagnosis was made during the first 2 months of nivolumab treatment in 88% of cases. Corticosteroid treatment explained the low cortisol level in 25.0% of cases. No pituitary metastases were found. Hypophysitis was suspected in 75.0% of cases.

Conclusion

In a 75-patient cohort with non-small cell lung cancer treated with the PD1 antibody nivolumab and systematically screened for cortisol abnormalities, 10.7% of patients showed asymptomatic corticotropic insufficiency. Excluding corticotropic insufficiency secondary to corticosteroid treatment, 8.0% of patients presented cortisol level < 5 μg/dl attributed to hypophysitis. Cortisol screening enables hydrocortisone replacement treatment to be prescribed if necessary, preventing risk of adrenal crisis.

中文翻译：

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接受纳武单抗治疗的单中心前瞻性肺癌患者队列中促肾上腺皮质功能不全：患病率和病因

介绍

由于免疫检查点蛋白的发展，癌症治疗在过去几年取得了很大进展。这些免疫疗法应用于符合条件的患者时，死亡率显着降低，但容易诱发免疫副作用，包括垂体疾病和低促肾上腺皮质激素 (ACTH) 和皮质醇水平。我们旨在通过系统筛查接受纳武单抗灌注治疗的肺癌患者的皮质醇和 ACTH 水平来评估促肾上腺皮质功能不全的患病率和病因。

材料与方法

我们中心的所有具有纳武单抗治疗肺鳞状细胞癌或对化疗耐药的腺癌适应症的患者都被依次纳入，并在每次纳武单抗灌注前接受皮质醇和促肾上腺皮质激素测定。当皮质醇低于正常但没有 ACTH 升高时，我们筛选了可以解释促肾上腺皮质功能不全的垂体转移、垂体炎或皮质类固醇治疗。

结果

来自 75 名患者（80.0% 男性，20.0% 女性）的数据显示 10.7% 的无症状性促肾上腺皮质激素功能不全，平均皮质醇水平为 2.76  ±  1.27  μg/dl。88% 的病例在纳武单抗治疗的前 2 个月内做出诊断。皮质类固醇治疗解释了 25.0% 病例的低皮质醇水平。未发现垂体转移。75.0% 的病例怀疑垂体炎。

结论

在 75 名非小细胞肺癌患者接受 PD1 抗体纳武单抗治疗并系统筛查皮质醇异常后，10.7% 的患者表现出无症状的促肾上腺皮质功能不全。排除继发于皮质类固醇治疗的促​​皮质功能不全，8.0% 的患者因垂体炎而表现出皮质醇水平 <  5  μg/dl。皮质醇筛查可以在必要时开具氢化可的松替代治疗，从而预防肾上腺危象的风险。