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Diazoxide-Unresponsive Forms of Congenital Hyperinsulinism

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Book cover Congenital Hyperinsulinism

Part of the book series: Contemporary Endocrinology ((COE))

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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Author information

Authors and Affiliations

  1. Division of Endocrinology and Diabetes, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Arpana Rayannavar

  2. Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, Denmark

    Henrik Thybo Christesen

  3. Division of Endocrinology and Diabetes, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania and The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Diva D. De León-Crutchlow

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  1. Arpana Rayannavar
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  2. Henrik Thybo Christesen
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  3. Diva D. De León-Crutchlow
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Editors and Affiliations

  1. Division of Endocrinology and Diabetes, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania and The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Diva D. De León-Crutchlow

  2. Division of Endocrinology and Diabetes, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania and The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Charles A. Stanley

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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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  • DOI: https://doi.org/10.1007/978-3-030-02961-6_3

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