Nesidioblastosis

Description

• Nesidioblastosis (NB) is a disease characterized by hyperfunctioning pancreatic β cells, usually associated with hypoglycemia in the presence of high endogenous insulin levels. It is necessary to exclude insulinoma or exogenous insulin of sulfonylurea administration when making the diagnosis.
• Most commonly described in neonates and children, but recent studies have shown an increased number of cases in adults
  • Focal NB: confined to one discrete area of the pancreas
  • Diffuse NB: All or most islet cells are affected.
• Most common cause of persistent hyperinsulinemic hypoglycemia in neonates
• Synonym(s): noninsulinoma pancreatogenous hypoglycemia (NIPHS); persistent hyperinsulinemic hypoglycemia of infancy (PHHI); congenital hyperinsulinism; islet cell hyperplasia

Epidemiology

Few data available on the incidence of disease

Incidence

• Infants/children
  • Sporadic: 1/30,000 to 1/50,000 live births
  • Familial: 1/2,500 births have been seen.
• Adults: 0.5–15% of organic hyperinsulinemias
  • Annual incidence is 0.09/100,000.
  • Peaks in 5th decade of life

Etiology and Pathophysiology

NB involves hyperplastic pancreatic β cells that hyperfunction and cause excessive insulin secretion. K_ATP channel activity results with a constant insulin release:

• Focal NB: accounts for up to 40% of cases and consists of a discrete area of the pancreas with adenomatous hyperplasia of the islet cells
• Diffuse NB: Most or all β cells in the pancreas show hyperplasia.
• Most cases have a genetic predisposition; in adults, may involve dysregulation
• Increase in expression of IGF-2, IGF-1 receptor-α, and TGF-β in islet cells from NB patients compared with controls
• Associated with gastric bypass surgery; has been associated with other upper gastrointestinal surgeries; elevated levels of GLP-1 in response to rapid presentation of nutrients to the distal jejunum (1)

Genetics

• Complex AR/AD mutations on ABCC8 and KCJN11 genes on chromosome 11 have been found in focal and diffuse NB (2).
• More recent discoveries:
  • HADH1: Studies have shown good response with diazoxide (AR).
  • GK: poor response with diazoxide (AD)
  • GLUD1: associated with high ammonia levels, also called HI/HA syndrome (AD)
  • SLC16A1
  • HNF4A: has shown spontaneous resolution in a few cases (3)

Risk Factors

• Infants/children: likely a genetic predisposition to this disorder
• Adults: NB may also be genetically linked. However, there has been an association with gastric bypass surgery (1).

General Prevention

• Genetic counseling may be of benefit to families affected by this disease. No clear guidelines exist for preconception genetic counseling.
• Adults who are considering gastric bypass surgery should be cautioned.

Commonly Associated Conditions

• Insulinoma (most common)
• Teratomas
• MEN1 syndrome
• Glucagonoma
• VIPoma
• Neuroblastoma