Congenital Hyperinsulinism


Transient hypoglycemia at birth, particularly in premature neonates, is a very common event that occurs due to immaturity of the mechanisms that regulate glucose homeostasis. In sharp contrast, persistent hypoglycemia in newborns and infants is a very rare event which in almost all cases is caused by congenital hyperinsulinism (HI). HI is a rare and complex genetic disorder. There are 80 to 120 cases of HI per year in the United States. Due to their scarcity and the complexity of their management, patients with HI should be referred to a center with an expert multidisciplinary team.

The first successful pancreatectomy on a child with HI was performed in 1934 by Evarts Graham from St Louis [1]. The pancreas was explored searching for an adenoma in a patient with persistent hypoglycemia but since no adenoma was found a subtotal approximately 90% pancreatectomy was performed and the patient’s hypoglycemia resolved. This case was done 20 years before the first description of HI which was initially termed “syndrome of idiopathic hypoglycemia of infants” [2]. It was initially thought that HI was caused by excessive secretion of insulin secondary to an abnormally high number of pancreatic islets resulting from an anomalous phenomenon of postnatal budding of endocrine cells off the pancreatic ducts called nesidioblastosis (from nesidion meaning island). This theory was elaborated at the Children’s Hospital of Philadelphia and was based on the histologic analysis of pancreatic specimens from HI children stained with insulin specific techniques [3]. Later studies in the 1980’s showed that nesidioblastosis was actually a normal neonatal phenomenon [4]. Therefore the term was abandoned and is no longer used to describe the disease. Recent advances in molecular diagnosis have conclusively demonstrated that HI does not result from a developmental anatomical abnormality but from a variety of genetic derangements that alter the regulatory mechanisms of insulin secretion and glucose homeostasis .

Content in this topic is referenced in SCORE Endocrine Diseases overview

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Last updated: November 2, 2020