Diazoxide-Unresponsive Forms of Congenital Hyperinsulinism

  • Arpana Rayannavar
  • Henrik Thybo Christesen
  • Diva D. De León-Crutchlow
Part of the Contemporary Endocrinology book series (COE)


Congenital hyperinsulinism (HI) is defined as being “diazoxide-unresponsive” if the hypoglycemia persists despite maximum doses of diazoxide for at least five days . Inactivating mutations in the genes encoding the two subunits of the beta-cell ATP-sensitive potassium (KATP) channel are the most frequent cause of diazoxide-unresponsive hyperinsulinism. Children with KATPHI typically present at birth with severe hypoglycemia. Genetic testing can be used to identify children with focal KATPHI and 18F-DOPA-PET imaging aids with focal lesion localization for curative surgery. A less common form of diazoxide-unresponsive HI is caused by activating mutations in glucokinase (GCK). Clinical phenotypes in children with GCK HI vary, but may be diazoxide-unresponsive and medically uncontrollable, requiring pancreatectomy. Approximately ten percent of diazoxide-unresponsive HI cases are of unknown genetic etiology. The overall goal in the management of infants with diazoxide-unresponsive HI is to identify those with focal HI and to find an effective treatment regimen for those that cannot be cured by surgery (diffuse HI).







Glucokinase hyperinsulinism


Congenital hyperinsulinism




ATP-sensitive potassium channel


Inwardly rectifying potassium channel subunit (encoded by KCNJ11)


Localized islet cell nuclear enlargement


Positron emission tomography


Sulfonylurea receptor 1 (regulatory subunit encoded by ABCC8)


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Arpana Rayannavar
    • 1
  • Henrik Thybo Christesen
    • 2
  • Diva D. De León-Crutchlow
    • 3
  1. 1.Division of Endocrinology and Diabetes, The Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  2. 2.Hans Christian Andersen Children’s HospitalOdense University HospitalOdenseDenmark
  3. 3.Division of Endocrinology and Diabetes, Department of PediatricsPerelman School of Medicine at the University of Pennsylvania and The Children’s Hospital of PhiladelphiaPhiladelphiaUSA

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