Rai Maitreyee, Go Mylene
Internal Medicine, Crozer Chester Medical Center, Upland, USA.
Hematology Oncology, Crozer Chester Medical Center, Upland, USA.
Cureus. 2020 Apr 10;12(4):e7625. doi: 10.7759/cureus.7625.
Immune-checkpoint inhibitors are immuno-modulatory antibodies used in patients with advanced cancers like melanoma, renal cell carcinoma, non-small cell lung cancer, etc. They are associated with a wide array of side effects, commonly known as immune-related adverse events (irAEs), affecting dermatological, gastrointestinal, hepatic, endocrine, and other systems. We present a case of nivolumab-induced adrenal insufficiency in a patient presenting with refractory hypotension. The patient is a 77-year-old caucasian male with metastatic renal cell carcinoma (RCC) on nivolumab therapy, presented to his primary doctor for symptoms of fatigue, weakness, loss of appetite, and dizziness. His initial blood pressure (BP) was noted to be 78/44 mmHg, so he was referred to the emergency department. He received several liters of intravenous (IV) fluid boluses; however, BP consistently stayed in 90s systolic and 40-50 diastolic. The lab investigations showed a low sodium level at 128 mmol/L, blood urea nitrogen (BUN) elevated at 37 mg/dL, creatinine elevated at 2.7 mg/dL. A morning cortisol level was checked; it came back low at 1.3 mcg/dL. Further testing with the cosyntropin stimulation test revealed low basal cortisol of 1 mcg/dL and only a mild increase to 10.20 mcg/dL after the cosyntropin administration. Adrenocorticotrophic hormone (ACTH) was checked that came out to be low <5pg/mL, favoring a diagnosis of secondary adrenal insufficiency likely due to hypophysitis. In the meantime, the patient was started on hydrocortisone, which improved his blood pressure significantly. He was eventually weaned from IV hydrocortisone to p.o. hydrocortisone. The nivolumab was discontinued, and oncology decided on giving a nivolumab re-challenge once the patient was stabilized. Our patient presented with common manifestations of adrenal insufficiency like fatigue, hypotension, and hyponatremia, which is one of the rare irAEs occurring in <1% of the patients. These are non-specific manifestations and can be easily overlooked if adverse events of immunotherapy are not suspected. Even though rare, adrenal insufficiency is a life-threatening side-effect of immune checkpoint inhibitor drugs that need to be recognized immediately and managed with intravenous glucocorticoids.
免疫检查点抑制剂是用于治疗晚期癌症患者（如黑色素瘤、肾细胞癌、非小细胞肺癌等）的免疫调节抗体。它们与一系列副作用相关，通常称为免疫相关不良事件（irAEs），会影响皮肤、胃肠道、肝脏、内分泌和其他系统。我们报告一例因使用纳武单抗导致肾上腺功能不全的患者，该患者出现难治性低血压。患者为一名77岁的白种男性，患有转移性肾细胞癌（RCC），正在接受纳武单抗治疗，因疲劳、虚弱、食欲不振和头晕症状就诊于他的初级医生。他的初始血压（BP）为78/44 mmHg，因此被转诊至急诊科。他接受了几升静脉（IV）液体冲击治疗；然而，血压收缩压始终维持在90多，舒张压在40 - 50。实验室检查显示血钠水平低至128 mmol/L，血尿素氮（BUN）升高至37 mg/dL，肌酐升高至2.7 mg/dL。检测了早晨的皮质醇水平；结果显示较低，为1.3 mcg/dL。进一步用促肾上腺皮质激素刺激试验检测发现基础皮质醇低至1 mcg/dL，给予促肾上腺皮质激素后仅轻度升高至10.20 mcg/dL。检测促肾上腺皮质激素（ACTH）结果显示低至<5pg/mL，支持可能因垂体炎导致继发性肾上腺功能不全的诊断。与此同时，患者开始使用氢化可的松治疗，其血压显著改善。他最终从静脉注射氢化可的松逐渐减量至口服氢化可的松。纳武单抗停药，肿瘤学专家决定在患者病情稳定后再次给予纳武单抗治疗。我们的患者出现了肾上腺功能不全的常见表现，如疲劳、低血压和低钠血症，这是在不到1%的患者中发生的罕见irAEs之一。这些是非特异性表现，如果不怀疑免疫治疗的不良事件，很容易被忽视。尽管罕见，但肾上腺功能不全是免疫检查点抑制剂药物的一种危及生命的副作用，需要立即识别并用静脉糖皮质激素进行治疗。
