TY - CHAP
T1 - Diazoxide-unresponsive forms of congenital hyperinsulinism
AU - Rayannavar, Arpana
AU - Christesen, Henrik Thybo
AU - De León-Crutchlow, Diva D.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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).
AB - 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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U2 - 10.1007/978-3-030-02961-6_3
DO - 10.1007/978-3-030-02961-6_3
M3 - Chapter
AN - SCOPUS:85060526201
T3 - Contemporary Endocrinology
SP - 33
EP - 47
BT - Contemporary Endocrinology
PB - Humana Press Inc.
ER -