Hyperinsulinism

Congenital or monogenic hyperinsulinism (HI) is a group of rare genetic disorders characterized by dysregulated insulin secretion and is the most common cause of persistent hypoglycemia in children. Knowledge of normal glucose homeostasis allows for a better understanding of the underlying pathophysiology of hyperinsulinemic hypoglycemia, facilitating timely diagnosis and management. The goal of management is to prevent cerebral insults secondary to hypoglycemia, which can result in poor neurologic outcomes and intellectual disability. Responsiveness to diazoxide, the first-line pharmacologic therapy for persistent hypoglycemia, is also the first step to distinguishing the different genotypic causes of monogenic hyperinsulinism. Early genetic testing becomes necessary when monogenic HI is strongly considered. Knowledge of specific gene mutations allows the determination of a clinical prognosis and definite therapeutic options, such as identifying those with focal forms of hyperinsulinism, who may attain a complete cure through surgical removal of specific affected parts of the pancreas. However, the lack of identifiable cause in a considerable number of patients identified with HI suggests there may be other genetic loci that are yet to be discovered. Furthermore, continued research is needed to explore new forms of therapy, particularly in severe, diazoxide-nonresponsive cases.