Endocrine Abstracts

Introduction: Congenital hyperinsulinism (CHI) is a rare disease with an incidence of 1 in 30,000. It is the most common cause of persistent neonatal hypoglycemia, primarily due to inhibitory mutations in genes encoding the ATP-sensitive potassium channel in pancreatic beta cells, with ABCC8 (SUR1) and KCNJ11 (Kir6.2) mutations being the most frequent. In this context, we report a highly unusual case in terms of phenotypic and evolutionary aspects.

Clinical Case: A 17-year-old female presented with severe organic hypoglycemia related to endogenous CHI diagnosed since neonatal age. She had been treated with Diazoxide since childhood, but experienced recurrent hypoglycemia and therapeutic escape. The diagnosis of focal CHI was established based on pancreatic MRI and endoscopic ultrasound findings revealing hyperplasia in the pancreatic tail. A caudal pancreatectomy was performed, paradoxically leading to severe and persistent hyperglycemia reaching 8 g/l for 20 hours, accompanied by a significant decrease in insulin levels during its kinetic evaluation, dropping from 400 µIU/ml to 25 µIU/ml (concurrent blood glucose at 3 g/l). Subsequent postoperative evolution showed a gradual spontaneous normalization of blood glucose to 1 g/l, followed by the recurrence of hypoglycemia with a rise in insulin levels. Histopathological data confirmed the diffuse nature of pancreatic hyperplasia, indicating the need for total pancreatectomy. Molecular analysis of candidate genes involved in CHI was negative for ABCC8 and KCNJ11 genes. However, involvement of a molecular anomaly in the enzymatic chain of insulin secretion process was considered.

Conclusion: CHI, seemingly a straightforward entity, exhibits a highly complex etiopathogenesis, making the correlation between phenotypic and genotypic expression challenging. High-throughput sequencing techniques have provided insights into insulin secretion signaling pathways, but the involvement of environmental factors opens up a new research avenue, highlighting the Gene-Environment interrelation.