纳武利尤单抗相关孤立性促肾上腺皮质激素缺乏症29例文献分析

Literature analysis of 29 cases of nivolumab-related isolated adrenocorticotropin deficiency

目的分析纳武利尤单抗相关孤立性促肾上腺皮质激素缺乏症(IAD)的临床特点。方法以“纳武利尤单抗或纳武单抗、孤立性促肾上腺皮质激素缺乏症或促肾上腺皮质激素缺乏”和“nivolumab、isolated adrenocorticotropic hormone deficiency or adrenocorticotropic hormone deficiency”为检索词,检索1998年9月至2021年10月中国知网、万方、维普和PubMed、Web of Science数据库的纳武利尤单抗相关IAD的个案报道,提取相关信息进行描述性分析。结果共筛选出个案报道25篇,涉及纳武利尤抗相关IAD 29例,男性20例,女性9例,其中日本籍患者19例(66%);纳武利尤单抗单药治疗27例(93%)。26例(90%)患者在纳武利尤单抗治疗后300 d内发生IAD。临床症状以乏力、纳差多见,且易合并甲状腺疾病(14例,48%),早期实验室检查异常为血钠降低22例(76%)及嗜酸性粒细胞比率升高12例(41%)。28例(97%)患者长期服用氢化可的松替代治疗,除1例因原发病进展死亡外,其余均预后良好。结论纳武利尤单抗相关IAD可能存在地域或种族差异,治疗期间应密切关注患者甲状腺功能、血钠水平及嗜酸性粒细胞比率,氢化可的松替代治疗后预后良好。

AIM To analyze the clinical characteristics of nivolumab-related isolated adrenocorticotropic hormone deficiency(IAD).METHODS“Nivolumab,IAD or adrenocorticotropic hormone deficiency”were selected as the keywords.The case reports of nivolumab-related IAD were collected by CNKI,Wanfang,VIP,PubMed and Web of Science databases from September 1998 to October 2021,and extracted relevant data for descriptive analysis.RESULTS A total of 25 case reports were screened,involving 29 cases of nivolumab-related IAD,20 males and 9 females,including 19 Japanese patients(66%),and 27 cases(93%)were treated with nivolumab alone.The IAD occurred in 26 patients(90%)within 300 days after nivolumab treatment.The clinical symptoms of asthenia and anorexia were common,and thyroid diseases were easy to be combined(14 cases,48%).Early laboratory abnormalities included decreased serum sodium in 22 cases(76%)and increased eosinophil ratio in 12 cases(41%).Twenty-eight patients(97%)took hydrocortisone replacement therapy for a long time,and all patients had good prognosis except one patient who died due to the progression of the primary disease.CONCLUSION Nivolumab-related IAD may be regional or ethnic differences.The thyroid function,blood sodium level and eosinophil ratio should be monitored during the treatment,and the prognosis is good after hydrocortisone replacement therapy.