摘要
目的探讨西罗莫司治疗二氮嗪治疗无效型先天性高胰岛素血症(congenital hyperinsulinism,CHI)的有效性及安全性,总结单中心诊治经验。方法回顾性分析2017年1月至2022年12月郑州大学附属儿童医院收治的5例二氮嗪治疗无效后应用西罗莫司治疗的CHI患儿临床资料,对西罗莫司治疗CHI的疗效及安全性进行评估。结果研究共纳入5例患儿,其中男性3例、女性2例。患儿发病年龄1~90 d,起病表现为精神差(2/5)、抽搐(3/5),血糖1.1~2.3 mmol/L,同期胰岛素13.52~70.53μIU/mL,组织学分型2例为弥漫型,3例未知。经基因检测确诊,全外显子基因检测发现1例未经报道新变异(ABCC8 exon 2528 del)。5例患儿中,3例应用二氮嗪及奥曲肽治疗无效后应用西罗莫司,1例患儿二氮嗪治疗无效后应用西罗莫司,1例应用二氮嗪及奥曲肽治疗无效,接受胰腺大部分切除术后仍反复低血糖,应用西罗莫司。5例患儿开始应用西罗莫司的年龄为1~20个月,西罗莫司最大剂量1.2~3.2 mg·m^(-2)·d^(-1),用药时间2~12个月,1例应用西罗莫司完全有效,4例部分有效,出院后单用西罗莫司或联合CHI常规治疗,血糖平稳。患儿随访中存在非感染性腹泻、癌胚抗原升高、三酰甘油升高、肝酶升高。结论西罗莫司在二氮嗪治疗无效的CHI患者中应用有一定疗效,短期应用安全性较好,但远期疗效及安全性尚不明确,尚需多中心研究进一步明确疗效及安全性。
Objective To explore the efficacy and safety of sirolimus in the treatment of diazoxide unresponsive congenital hyperinsulinism(CHI)and summarize the single-center experience.Methods A retrospective analysis was conducted on the clinical data of 5 cases of CHI treated with sirolimus after ineffective treatment with diazoxide,admitted to the Children′s Hospital Affiliated to Zhengzhou University from January 2017 to December 2022.The efficacy and safety of sirolimus in the treatment of CHI were evaluated.Results The study included 5 patients,3 males and 2 females.The age of onset ranged from 1 to 90 days.Initial symptoms included poor mental state(2/5)and convulsions(3/5).Blood glucose levels were 1.1 to 2.3 mmol/L,and insulin levels ranged from 13.52 to 70.53μIU/mL.Two cases were classified as diffuse type,and the histological type of 3 cases was unknown.Genetic testing confirmed the diagnosis,with whole-exome sequencing revealing an unreported novel mutation in 1 case(ABCC8 exon 25_28del).Of the five patients,three patients were treated with sirolimus after diazoxide and octreotide failed,one patient was treated after unresponsive diazoxide,and the other one was treated after diazoxide,octreotide,and even near-total pancreatectomy failed.The onset age of sirolimus therapy ranged from 1 to 20 months.The maximum dosage of sirolimus was 1.2-3.2 mg·m^(-2)·d^(-1),and the duration of medication ranged from 2 to 12 months.One patient was fully responsive to sirolimus,and the other four patients were partially responsive.All patients achieved euglycemia with sirolimus alone or in combination with standard CHI treatment.During follow-up,non-infectious diarrhea,elevated carcinoembryonic antigen,elevated triglycerides,and elevated liver enzymes were observed.Conclusion This study indicates that sirolimus has a certain degree of efficacy in CHI patients for whom diazoxide treatment is ineffective.However,the long-term efficacy and safety warrant further multicenter trials.
作者
陈琼
吴雪
王小红
陈永兴
张英娴
李杨世玉
杨海花
毋盛楠
卫海燕
Chen Qiong;Wu Xue;Wang Xiaohong;Chen Yongxing;Zhang Yingxian;Li-Yang Shiyu;Yang Haihua;Wu Shengnan;Wei Haiyan(Department of Endocrinology,Genetics and Metabolism,Children′s Hospital Affiliated to Zhengzhou University,Henan Children′s Hospital,Zhengzhou Children′s Hospital,Zhengzhou 450053,China)
出处
《中华内分泌代谢杂志》
CAS
CSCD
北大核心
2024年第9期740-745,共6页
Chinese Journal of Endocrinology and Metabolism
基金
河南省科技攻关项目(222102310508)。
