Managing persistent neonatal hyperinsulinemic hypoglycemia: Insights from nesidioblastosis research

Background: Persistent neonatal hyperinsulinemic hypoglycemia (PNHH), frequently associated with nesidioblastosis, poses significant diagnostic and therapeutic challenges due to dysregulated insulin secretion. Congenital hyperinsulinism (CHI), the primary cause of PNHH, exhibits diverse genetic and phenotypic presentations, necessitating tailored management strategies. This review integrates insights from 20 studies, examining genetic, therapeutic, and psychosocial dimensions of CHI.

Objectives: To evaluate genotype-phenotype correlations and their implications for therapeutic outcomes in CHI, compare long-term medical and surgical outcomes, and identify risk factors affecting growth, metabolism, and neurodevelopment. Additionally, the study explores effective strategies to address the psychosocial and dietary challenges associated with CHI.

Methods: A systematic review of 20 studies, encompassing over 2,000 patients, was conducted. Diagnostic criteria included genetic analyses of mutations in KATP channel genes (ABCC8, KCNJ11), GLUD1, and HNF4A, along with imaging and histopathological assessments. Treatment efficacy, long-term outcomes, and the impact of caregiver burden were analyzed. Data were synthesized into thematic categories, supported by statistical and qualitative assessments.

Results: Dominant KATP mutations exhibited high responsiveness to diazoxide (70%), whereas recessive mutations necessitated surgical interventions, particularly near-total pancreatectomy. Focal CHI resolved hypoglycemia effectively with lesionectomy, whereas diffuse CHI presented ongoing risks, including diabetes and neurodevelopmental impairments. Personalized dietary strategies, such as high-protein diets and gastrostomy feeding, were effective in stabilizing glucose levels. Psychological stress in caregivers emerged as a significant concern, emphasizing the need for supportive interventions. Emerging therapies like lanreotide showed promise in refractory CHI cases.

Discussion: The findings align with prior research, confirming the role of genetic mutations in determining treatment responsiveness. Surgical interventions, though effective in resolving hypoglycemia, carry long-term metabolic risks. Recent advances in genetic diagnostics and personalized medical therapies highlight opportunities for optimizing outcomes. However, caregiver burden and psychosocial challenges remain underexplored areas that require structured support systems.

Conclusion: Managing CHI necessitates a multidisciplinary approach, integrating genetic insights, advanced therapies, and psychosocial support. Continued research is essential to develop innovative solutions for refractory CHI cases and to improve long-term outcomes for patients and families.