Abstract
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).
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Abbreviations
- 18F-DOPA:
-
18Fluoro-dihydroxyphenylalanine
- GCK:
-
Glucokinase
- GCK-HI:
-
Glucokinase hyperinsulinism
- HI:
-
Congenital hyperinsulinism
- HI:
-
Hyperinsulinism
- KATP :
-
ATP-sensitive potassium channel
- Kir6.2:
-
Inwardly rectifying potassium channel subunit (encoded by KCNJ11)
- LINE:
-
Localized islet cell nuclear enlargement
- PET:
-
Positron emission tomography
- SUR1:
-
Sulfonylurea receptor 1 (regulatory subunit encoded by ABCC8)
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Rayannavar, A., Christesen, H.T., De León-Crutchlow, D.D. (2019). Diazoxide-Unresponsive Forms of Congenital Hyperinsulinism. In: De León-Crutchlow, D., Stanley, C. (eds) Congenital Hyperinsulinism. Contemporary Endocrinology. Humana Press, Cham. https://doi.org/10.1007/978-3-030-02961-6_3
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