ESPE Abstracts

Background: Compound heterozygous or homozygous recessive variants within the ABCC8 and KCNJ11 genes represent common genetic aetiologies for Congenital Hyperinsulinism (CHI). These variants are associated with a severe diffuse form of the disease, often refractory to medical management, necessitating near-total pancreatectomy. Post-surgery, patients may develop diabetes mellitus (DM) and pancreatic exocrine insufficiency (PEI), necessitating lifelong pancreatic enzyme replacement therapy (PERT). Interestingly, our patient cohort showed gradual exocrine function improvement, evidenced by normalised faecal elastase levels and resolution of PEI symptoms, allowing PERT discontinuation.

Aim: Our study aims to assess the dynamic changes in exocrine pancreatic enzyme production in patients with diffuse CHI due to compound heterozygous or homozygous ABCC8 and KCNJ11 variants following near-total pancreatectomy at a specialized referral center.

Method: We analyzed 13 patients (6 male, 7 female) with medically unresponsive diffuse CHI, caused by recessive variants 5 homozygous for ABCC8, 1 homozygous for KCNJ11, 7 compound heterozygous for ABCC8. They underwent a near-total pancreatectomy (>95%) and developed PEI post-surgery. Retrospective data spanning 23 years (2000-2024) included genotype, pancreatectomy timing, PERT, PEI symptoms, and CHI/DM treatment.

Results: All patients initiated PERT at an average of 46 months (2 weeks - 204 months) after surgery. Reasons for starting PERT varied: four patients due to PEI symptoms, five due to low faecal elastase levels, and two with both PEI symptoms and low faecal elastase levels. Six patients (46%) eventually discontinued PERT after demonstrating normal faecal elastase levels and being asymptomatic for PEI, at a mean of 78 months (3-160 months) from starting treatment and 101 months (6-164 months) post-pancreatectomy. At discontinuation, three patients were still on CHI treatment, while three had DM. Five patients (38%) remained off PERT without PEI symptoms, and one resumed PERT due to recurrence of PEI symptoms within six weeks.

Conclusion: In our cohort, 38% of patients demonstrated improved pancreatic exocrine function at a variable time after near-total pancreatectomy. This suggests that PEI may ameliorate over time in patients with diffuse CHI caused by compound heterozygous or homozygous recessive variants in the ABCC8 and KCNJ11 genes. To guide clinical practice, we recommend regular monitoring of PEI symptoms and faecal elastase levels after initiating PERT. This monitoring can inform decisions about PERT discontinuation. Additionally, ongoing follow-up is crucial for developing post-pancreatectomy guidelines to manage PEI and PERT, potentially reducing medication burden and healthcare costs.