ESPE Abstracts

Introduction: Congenital Hyperinsulism (CHI) is a common cause of recurrent and persistent hypoglycemia in the neonatal period. Diazoxide is the first line medication used for the management of CHI. We report the clinical profile and the management outcome of a large cohort of patients with diazoxide responsive CHI.

Methodology: A retrospective data collection including antenatal, perinatal and postnatal clinical parameters, laboratory diagnostic data, genetic tests and treatment duration was undertaken on 103 CHI patients managed in a quaternary referral center over a 10 year period.

Results: 90 patients with diazoxide responsive CHI were included in the final analysis. Among these, 78 patients were diagnosed in the neonatal period (mean age of diagnosis 1.36 days [SEM ±0.4]). Majority of them were boys (69.4%). Nearly 1/3^rd of the patients were premature and 1/3^rd were born small for gestational age (SGA). Twelve patients presented in the post-neonatal period (after 1 month of life) with CHI and none had history of prematurity, SGA or gestational diabetes mellitus. The mean dose of diazoxide was 4mg/kg/day (±0.22). Baseline echocardiogram was undertaken in all patients prior to diazoxide initiation. The average duration of the diazoxide therapy was 8.5±6 months and 81.9% needed treatment for less than 2 years. Children needing treatment for >2 years were found to have high C-peptide (P = 0.02) at the time of diagnosis. Genetic mutation was found in 11.1% among the overall study group [11p15.5 methylation defect (1), HNF4A (2), HNF1A (1), INSR (1), GLUD1 (1), ABCC8 (4)]. Patients with genetically proven CHI were on diazoxide treatment for more than 2 years. Adverse effects of diazoxide therapy (fluid retention, hyponatremia, hyperkalemia, pulmonary hypertension and hirsuitism) were observed in 15.8% of the cohort.

Conclusion: Majority of patients with diazoxide responsive CHI were diagnosed in the neonatal period and were associated with risk factors like prematurity and SGA and tend to require diazoxide treatment for less than one year. Hence, a periodic evaluation of these patients to assess the discontinuation of diazoxide therapy should be undertaken. Patients with genetically proven CHI tend to require longer duration of treatment.