帕博利珠单抗致原发性肾上腺功能减退1例及文献分析

目的探讨帕博利珠单抗致原发性肾上腺功能减退的发病机制及管理措施。方法分析1例帕博利珠单抗致原发性肾上腺功能减退的诊疗经过,结合文献分析,阐述帕博利珠单抗与原发性肾上腺功能减退不良反应的因果关系、发生率、发病机制和处理措施。结果患者静脉使用帕博利珠单抗6个月后出现明显乏力、体力差、食欲差、皮肤变黑症状。入院行实验室检查8AM血清促肾上腺皮质激素(ACTH)16.7 pmol·L^-1,8AM血清皮质醇<25.7 nmol·L^-1,考虑为帕博利珠单抗致原发性肾上腺功能减退。建议暂停帕博利珠单抗治疗,口服醋酸泼尼松片每日2次,每次5 mg用于类固醇激素替代治疗,1周后患者症状好转出院。院外逐渐减少醋酸泼尼松片至5 mg·d^-1维持剂量。结论对帕博利珠单抗致原发性肾上腺功能减退,应根据不良反应分级标准采取相应的分级处理措施。

One case of primary adrenal insufficiency induced by pembrolizumab

Objective To investigate the pathogenesis and management of primary adrenal insufficiency caused by pembrolizumab.Methods The diagnosis and treatment process of one case with primary adrenal insufficiency caused by pembrolizumab was analyzed.Based on literature analysis,the causal relationships between pembrolizumab and primary adrenal insufficiency,incidence,pathogenesis and treatments were explored.Results After 6 months of intravenous administration of pembrolizumab,the patient showed obvious symptoms of fatigue,poor physical strength,poor appetite and blackened skin.The patient was hospitalized for laboratory examination of 8AM serum ACTH 16.7 pmol·L^-1 and 8AM serum cortisol<25.7 nmol·L-1.Primary adrenal insufficiency caused by pembrolizumab was suspected.It was recommended that pembrolizumab be suspended,and that oral prednisone(5 mg·time^-1,bid)was used as an alternative therapy with steroid hormone.The patient’s symptoms improved after one week and he was discharged.The dosage of prednisone was gradually reduced to 5 mg·d^-1.Conclusion Primary adrenal insufficiency caused by pembrolizumab should be treated according to the classification standards for adverse reactions.