Sirolimus therapy for diazoxide resistant congenital hyperinsulinism: A retrospective analysis
10.3760/cma.j.cn311282-20230414-00172
- VernacularTitle:西罗莫司治疗二氮嗪无效型先天性高胰岛素血症回顾性分析
- Author:
Qiong CHEN
1
;
Xue WU
;
Xiaohong WANG
;
Yongxing CHEN
;
Yingxian ZHANG
;
Shiyu LI-YANG
;
Haihua YANG
;
Shengnan WU
;
Haiyan WEI
Author Information
1. 郑州大学附属儿童医院，河南省儿童医院，郑州儿童医院内分泌遗传代谢科，郑州 450053
- Keywords:
Sirolimus;
Congenital hyperinsulinism;
ABCC8 gene
- From:
Chinese Journal of Endocrinology and Metabolism
2024;40(9):740-745
- CountryChina
- Language:Chinese
-
Abstract:
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 70.53 μIU/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.
