Endocrine Abstracts

JOINT1012

Introduction: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in neonates and encompasses a heterogeneous group of genetic, syndromic, and reversible causes. Timely and targeted diagnostics and therapy are crucial to prevent developmental damage and fatal outcomes. Genetic diagnostics are of particular importance, especially in Diazoxide-resistant cases, as they provide insight into further treatment steps and prognosis.

Methods: We present the cases of two neonates and one infant with different genetic causes of CHI (1-HFN4A, 2-, 3-ABCC8). The clinical course during the neonatal period, diagnosis, acute therapy, further diagnostic and therapeutic steps, and follow-up are described. Differences between medication-sensitive, diffuse, and focal forms are discussed.

Results: 1. A female full-term infant who was large for gestational age (39 weeks gestation, 4670g) with postnatal hypoglycemia. Despite a carbohydrate-enriched diet, euglycemia could not be achieved. Diagnosis of CHI was confirmed through blood sampling during hypoglycemia, successful therapy with Diazoxide. HFN4A variant was identified. 2. A female pre-term infant who was large for gestational age (35 weeks gestation, 3330g) with postnatal and persistent hypoglycemia under carbohydrate diet. CHI was confirmed. Diazoxide therapy was ineffective, Octreotide provided insufficient response. A heterozygous compound ABCC8 mutation was found. Surgical intervention revealed a diffuse form histologically and 50% pancreas resection. Post-surgery, hyperinsulinism persisted. A therapy trial with lanreotide is planned. 3. A male full-term infant who was large for gestational age (40 weeks gestation, 4280g) with postnatal euglycemia, developing generalized seizures at 7 months due to hypoglycemia. Fewer hypoglycemic events under Diazoxide and carbohydrate diet. Paternal ABCC8 mutation was detected. PET-CT showed no focal abnormality, and a Diazoxide withdrawal trial has not yet resulted in severe hypoglycemia.

Conclusion: Persistent hypoglycemia in the neonatal period and infancy requires prompt and sequential diagnostics and therapy. Rapid genetic testing can help narrow down differential diagnoses. Until genetic results are available, a Diazoxide trial is recommended. In focal forms of CHI, PET-CT and surgery are often beneficial, whereas in diffuse forms, partial pancreatectomy rarely achieves euglycemia. Effective collaboration between neonatology, pediatric endocrinology, and human genetics is crucial for timely diagnosis and treatment.