Efficacy and safety of octreotide treatment for diazoxide-unresponsive congenital hyperinsulinism in China

Importance: Octreotide is an off-label medicine for congenital hyperinsulinism (CHI), but is currently widely used for treatment of patients with CHI. Thus far, variable efficacy and adverse effects have been reported for octreotide.Objective: The present study evaluated the efficacy and safety of a subcutaneous octreotide injection for treatment of diazoxide-unresponsive CHI in China.Methods: This study was a retrospective review of children with diazoxide-unresponsive CHI who were treated with a subcutaneous octreotide injection. The efficacy and side effects of the treatment were assessed.Results: Twenty-five Chinese children (15 boys) were involved in the study. Their median age at diagnosis was 8 weeks (range, 1-24 weeks) and median age at the final follow-up was 1.8 years (range, 0.3-3.3 years). Octreotide therapy effectively increased blood glucose levels in all patients. The intravenous glucose infusion rate was reduced in all patients. Twenty-one patients gradually discontinued the intravenous glucose infusion while receiving octreotide combined with frequent carbohydrate/glucose-rich feeding. Among patients with a monoallelic ATP-sensitive potassium (KATP) channel mutation, 50.0% showed gradual remission during follow up, indicating that the octreotide treatment may be a feasible alternative to surgery, especially for patients with monoallelic KATP-channel mutations. Transient elevation of liver enzymes occurred in 20.0% of patients, while asymptomatic gallbladder pathology occurred in one patient. The growth rates of these patients were normal (height standard deviation score was 0.3 ± 1.5 at the final follow-up).Interpretation: Octreotide was a well-tolerated, effective therapy for most children with diazoxide-unresponsive CHI.

Neonatal hyperinsulinism with an ABCC8 mutation:A case report

BACKGROUND Neonatal hyperinsulinism can result from perinatal stress,genetic disorders,or syndromes,which can lead to persistent or intractable hypoglycemia in newborns.Mutations in the ABCC8 gene result in abnormal functioning of potassium channel proteins in pancreaticβ-cells,leading to an overproduction of insulin and congenital hyperinsulinemia.CASE SUMMARY We report a case of a high-birth-weight infant with postnatal hypoglycemia and hyperinsulinemia,whose mother had pregestational diabetes mellitus with poor glycemic control and whose sister had a similar history at birth.Whole-exome sequencing revealed a new mutation in the ABCC8 gene in exon 8(c.1257T>G),which also occurred in his sister and mother;thus,the patient was diagnosed with neonatal hyperinsulinism with an ABCC8 mutation.With oral diazoxide treatment,the child’s blood glucose returned to normal,and the pediatrician gradually discontinued treatment because of the child’s good growth and development.CONCLUSION We report a new mutation locus in the ABCC8 gene.This mutation locus warrants attention for genetic disorders and long-term prognoses of hypoglycemic children.