ESPE Abstracts

Background: Congenital hyperinsulinism (CHI) is the most common cause of neonatal persistent hypoglycaemia. Current treatment lacks efficiency, and so are methods for differential diagnosis of diffuse and focal histological forms. Novel diagnostic and treatment approaches with the use of another hormone – glucagon-like-peptide-1 (GLP-1) – have been developed. GLP-1 is one of the key factors for maintaining euglycaemia. It stimulates insulin secretion and inhibits glucagon production. PET scan with GLP-1 agonist (exendine-4) has been proposed for differential diagnosis of diffuse and focal CHI. Infusion with GLP-1 antagonist is promising for patients who are unresponsive to standard treatment (diazoxide, octreotide). However, there is insufficient information regarding GLP-1 receptor expression in pancreatic tissue in patients with CHI. Thus, we conducted a study to evaluate GLP-1 receptor expression in patients with diffuse and focal CHI.

Methods: Informed consent and tissue samples were obtained from 5 paediatric patients with diffuse CHI and 9 children with focal CHI. All patients required surgical treatment due to persistent hypoglycaemia and poor or absent response to diazoxide and octreotide treatment. Histological form in each case was established using immunohistochemistry with insulin and p57 antibodies. The tissue samples were fixed in 10% formaldehyde solution and embedded in paraffin wax. Immunohistochemistry with GLP-1 receptor antigen (3F52, Developmental Studies Hybridoma Bank, USA) was performed on 3-µm-thick sections.

Results: All patients carry pathogenic variants in ABCC8/KCNJ11 genes. The median age at surgery was 4 months in patients with diffuse CHI, 6 months – in focal CHI cases. Based upon immunohistochemistry with GLP-1 receptor antigen, a focal lesion and diffuse CHI tissue differ significantly. A focus has a form of endocrine islets confluence with apparent staining. There are no evident discrepancies in diffuse CHI and non-focal region of focal CHI. Pancreatic islets and single endocrine cells express GLP-1 receptor in both groups. Surprisingly, acinar cells show mild but positive staining with GLP-1 receptor antigen.

Conclusion: To the best of our knowledge, it is the first study on GLP-1 receptor expression in CHI. Immunohistochemistry with GLP-1 receptor antigen is able to reveal a focal lesion. While our data are promising for using PET with GLP-1 agonist (exendin-4) for differentiating CHI forms, expression of GLP-1 receptors in acinar cells could interfere with PET scan results. However, not all of the previous studies on pancreatic tissue show presence of GLP-1 receptor in acinar cells. Our results also indicate GLP-1 antagonist treatment might be helpful in both histological forms.