Congenital hyperinsulinism (CHI) is a cause of severe and persistent hypoglycaemia due to unregulated insulin secretion from pancreatic β-cells. Mutations in the ABCC8 and KCNJ11 genes are the most common cause of medically unresponsive CHI. Histologically there are three major subgroups, focal, diffuse and atypical. The pathophysiology of focal CHI is complex and involves a two hit process with the patient firstly inheriting a paternal ABCC8/KCNJ11 mutation and then with the somatic paternal uniparental isodisomy for the chromosome 11p15 region only within the focal domain. Focal CHI is typically unresponsive to diazoxide and can be cured with complete surgical removal of the focal lesion. We report on three patients with focal CHI to illustrate the marked clinical, genetic, radiological and histological heterogeneity. The first two patients had focal CHI due to a paternal (c.3992-9G>A) ABCC8 mutation. However one of these patients was fully responsive to a small dose (5 mg/kg per day) of diazoxide and was initially discharged home whereas the other patient was medically unresponsive. In both patients the focal lesions were accurately localised pre-operatively by 18F-DOPAPET and surgically resected. The third patient had a paternally inherited ABCC8 (A1493T) mutation and the initial 18F-DOPA-PET scan indicated extensive uptake of DOPA in the body and tail of the pancreas. However despite surgical resection of the body and tail this patient continued to have severe CHI. A subsequent 18F-DOPA-PET scan four weeks later now showed markedly increased DOPA uptake in the remaining body and head of the pancreas. This focal lesion occupied virtually the whole of the pancreas and the patient required a second surgical procedure. These three cases illustrate the complex nature of focal CHI. The clinical observations suggest that focal lesions even with the same genotype (c.3992-9G>A) may have a very different clinical presentation and that 18F-DOPA-PET scans in very large focal lesions may be difficult to interpret. The radiological interpretation of the 18F-DOPA-PET scan in large focal lesion may be difficult.
09 - 11 Nov 2011
British Society for Paediatric Endocrinology and Diabetes