Hyperinsulinism (HI) is a disease characterized by inappropriate secretion of insulin. Insulin is a hormone secreted by a specialized type of cells in the pancreas called the beta cells. Insulin's role is to reduce the amount of sugar in the blood stream and is the one that is defective in children with type 1 diabetes. Children with HI have severe and frequent episodes of low blood sugar (hypoglycemia). 

An adequate supply of sugar to the brain is essential for brain function and development, particularly in infants and children. Therefore children with HI can suffer permanent brain damage and developmental delay if the diagnosis and treatment do not occur early enough in the child's life. 

The condition is also referred to as persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or congenital hyperinsulinism (CHI).

Patients can be seen by Texas Children's experts in Hyperinsulinism Program.

Causes & Risk Factors

HI is a congenital disease (present at birth), although the low glucose may not manifest itself until early infancy when babies' feedings are spaced out. The disease occurs due to mutations (change in genetic code) in one of several genes involved in the control of insulin secretion from the pancreatic beta cells. Each one of these genes normally plays an important role in causing insulin to be produced when the blood sugar is high and reducing insulin production when the blood sugar is normal or low. These mutations occur either spontaneously (not transmitted from parents) or are inherited (transmitted from one or both parents).

Symptoms & Types

Depending on the degree of involvement of the pancreas the disease has several forms: 

Diffuse Disease: All the beta cells of the pancreas are affected. 

Focal Disease: Only some beta cells are affected, usually in the form of a small non-cancerous tumor in a localized area of the pancreas.

Transient Disease: The low blood sugar resolves with age. This form can last a few weeks or up to several months. It is associated with prematurity, maternal diabetes during pregnancy (especially if not controlled), heart disease and severe infections in the pregnant mother.   

Symptoms of HI typically relate to low blood sugar and include:           

In Infants

  • Poor feeding
  • Pallor (lack of facial skin color)
  • Cyanosis in babies (blue discoloration of the face typically around the mouth)
  • Cyanosis (turning dusky or blue)
  • Breathing fast
  • Shaking
  • Seizures
  • Coma
  • Rarely death

In older children:

  • Hunger
  • Shaking
  • Sweating
  • Altered mental status or abnormal behavior in children (sudden aggressiveness or confusion or loss of consciousness)
  • Seizures
  • Coma
  • Rarely death

Diagnosis & Tests

The diagnosis of any form of HI relies on demonstrating inappropriate insulin secretion. Generally testing requires a hospital admission regardless of age to accurately assess the child's insulin secretion and blood sugar control. This involves a number of measurements of the child's blood hormone, sugar and substrates relating to fat metabolism and a glucagon (a hormone that raises the blood sugar) tolerance challenge. 

In children with an established diagnosis of HI additional genetic testing to identify the mutated gene as well as additional imaging tests are required. 

Genetic testing can be done on blood or saliva samples from the child. If the child is has one of these genetic disorders, the parents will be tested to identify whether one or both of them are carriers and should have genetic counseling to determine the risk of having a disease in future pregnancies. 

In addition, children with HI should undergo a special imaging study called a PET-MRI scan using a special tracer that allows doctors to see and evaluate the extent of involvement in the pancreas. It allows doctors to distinguish focal from diffuse disease. This technique is presently available in only 3 centers in the US and 1 in Canada. Texas Children Hospital is the only pediatric hospital to have PET-MRI imaging that can provide more details and better identification of focal lesions with less radiation exposure.

Treatment & Care

Treatment depends on the type of disease (diffuse vs. focal). 

Children with HI are treated with frequent intravenous sugar or feeding to avoid low blood glucose values during the process of diagnosing the underlying problem. Children with milder forms of these disorders can be managed on frequent oral feeding and medications. The majority of patients with HI require medications that reduce insulin production such as Diazoxide and Octreotide or increase blood sugar such as Glucagon. 

Children who fail to respond to medical therapy will require surgical removal of part or the entire pancreas to prevent severe low blood sugars and protect the brain. Because focal lesions affect a small area of the pancreas, it is important to have a PET scan of the pancreas. If the disease is focal then during surgery the planned approach would be to remove just the affected area. Such an approach prevents development of diabetes (high blood sugar) later on as frequently happens when a large part of the pancreas is removed. 

If the PET scan shows that the HI is diffuse and it does not respond to medical management, however, removal of almost the entire pancreas may be recommended. 

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