The Heterogeneity of Focal Forms of Congenital Hyperinsulinism

J Clin Endocrinol Metab. 2012 Jan;97(1):E94-9. doi: 10.1210/jc.2011-1628. Epub 2011 Oct 26.


Background: Congenital hyperinsulinism (CHI) is a cause of persistent hypoglycemia due to unregulated insulin secretion from pancreatic β-cells. Histologically, there are two major subgroups, focal and diffuse. Focal CHI is typically unresponsive to diazoxide and can be cured with surgical removal of the focal lesion.

Aims: We report on three patients with focal CHI to illustrate the marked clinical, genetic, radiological, and histological heterogeneity.

Methods and results: The first two patients had focal CHI due to a paternal (c.3992-9G→A) ABCC8 mutation. One of these patients was fully responsive to a small dose (5 mg/kg · d) of diazoxide, whereas the other patient was medically unresponsive. In both patients, the focal lesions were accurately localized preoperatively by [(18)F]dihydroxyphenylalanine (DOPA) positron emission tomography (PET) and surgically resected. The third patient had a paternally inherited ABCC8 (A1493T) mutation, and the initial [(18)F]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 [(18)F]DOPA PET scan 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. conclusions: These three cases illustrate that focal lesions even with the same genotype (c.3992-9G→A) may have a different clinical presentation and that [(18)F]DOPA PET scans in very large focal lesions may be difficult to interpret.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Congenital Hyperinsulinism / diagnosis*
  • Congenital Hyperinsulinism / diagnostic imaging
  • Congenital Hyperinsulinism / genetics*
  • Congenital Hyperinsulinism / pathology*
  • DNA Mutational Analysis
  • Dihydroxyphenylalanine
  • Fluorine Radioisotopes
  • Genetic Heterogeneity*
  • Humans
  • Infant, Newborn
  • Loss of Heterozygosity
  • Models, Biological
  • Pancreas / diagnostic imaging
  • Pancreas / pathology
  • Phenotype
  • Positron-Emission Tomography / methods
  • Potassium Channels, Inwardly Rectifying / genetics
  • Receptors, Drug / genetics
  • Sulfonylurea Receptors


  • ATP-Binding Cassette Transporters
  • Fluorine Radioisotopes
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Receptors
  • Dihydroxyphenylalanine