Hyperinsulinism
Hyperinsulinism is a rare and serious disorder where the pancreas produces too much insulin, causing dangerously low blood sugar levels that can permanently harm the brain, especially in newborns and infants.
Table of contents
- What is Hyperinsulinism?
- Forms and Types of Hyperinsulinism
- How Common is Hyperinsulinism?
- Causes and Genetic Factors
- Signs and Symptoms
- Diagnosis and Testing
- Treatment Options
- Monitoring and Long-Term Care
What is Hyperinsulinism?
Hyperinsulinism is a condition where the pancreas produces too much of a hormone called insulin (a substance that helps control blood sugar levels). This excessive insulin causes blood sugar to drop to dangerously low levels, a condition known as hypoglycemia (abnormally low blood sugar).[1]
The pancreas is an organ located below the stomach that contains special cells called beta cells. These cells normally produce just enough insulin to keep blood sugar in a healthy range. In people with hyperinsulinism, the insulin-producing cells don’t work properly and release too much insulin even when blood sugar is already low.[4]
This matters greatly because the brain needs a constant supply of sugar to function. Without enough sugar, the brain can be damaged. During the newborn and infant period, hyperinsulinism is the most common and severe cause of persistent low blood sugar.[1] If not quickly diagnosed and treated, severe and prolonged low blood sugar episodes can lead to seizures, developmental delays, learning disabilities, and in rare cases, death.[1]
- Pancreas
- Beta cells
Forms and Types of Hyperinsulinism
Hyperinsulinism comes in several different forms, depending on what part of the pancreas is affected and what causes the condition.[4]
Diffuse hyperinsulinism affects all the beta cells throughout the entire pancreas. In this form, the whole organ is involved in producing too much insulin.[8]
Focal hyperinsulinism involves only a small, isolated area of abnormal cells in the pancreas. The rest of the pancreas works normally. This form can often be cured by surgically removing only the affected area.[9]
Transient hyperinsulinism is temporary and usually affects newborns. It can be caused by stress during birth, problems with the placenta, or the baby not getting enough oxygen. This form is associated with premature babies and mothers who had poorly controlled diabetes during pregnancy. The condition typically resolves on its own within weeks to several months.[8]
Several specific genetic types have been identified based on which genes are affected. These include KATP hyperinsulinism (where potassium channels in beta cells don’t work properly), GDH-HI (where blood sugar drops after fasting or eating protein), glucokinase HI (where beta cells can’t turn off insulin production when blood sugar is low), and several other rare forms.[4] The genetic types don’t go away on their own, but they may become easier to manage as the child grows.[4]
How Common is Hyperinsulinism?
Congenital hyperinsulinism is a rare disorder. It affects approximately 1 in every 25,000 to 50,000 newborn babies, affecting both males and females equally.[4] In the United States, there are about 80 to 120 new cases each year.[2]
Because the condition is so rare and complex to manage, children with hyperinsulinism should be cared for at specialized medical centers with teams experienced in treating this disorder.[2] Most children’s hospitals see only one or two cases per year, which is why referral to expert centers is important.[9]
Causes and Genetic Factors
Congenital hyperinsulinism is often inherited, meaning it can be passed down from parents to children through genes. The condition results from changes or mutations (alterations in genetic code) in any of several genes that control how insulin is released from beta cells.[4]
Scientists have identified mutations in 12 different key genes that can cause hyperinsulinism. These genes are normally involved in regulating insulin secretion from pancreatic beta cells.[7] The mutations can occur either spontaneously (not inherited from parents) or can be transmitted from one or both parents.[8]
It’s important to understand that hyperinsulinism does not result from a developmental problem with how the pancreas formed. Instead, it results from genetic changes that alter the mechanisms that normally regulate insulin secretion and control blood sugar levels.[2]
Less commonly, hyperinsulinism can be caused by rare tumors of the insulin-producing cells called insulinomas, or by other medical conditions and syndromes such as Beckwith-Wiedemann syndrome, Kabuki syndrome, Sotos syndrome, and Turner syndrome.[4]
Signs and Symptoms
The symptoms of hyperinsulinism are caused by low blood sugar and can be difficult to recognize, especially in newborns and infants. Many symptoms can easily be confused with normal baby behavior.[4]
In infants and newborns, common signs include excessive hunger, poor feeding, irritability, lethargy (extreme tiredness or lack of energy), and sleeping more than usual. Babies may also have a rapid heart rate, appear pale, or have a blue discoloration around the mouth.[4][8]
In older children, symptoms may include shaking, weakness, confusion, anxiety, excessive hunger, and difficulty concentrating.[4]
When blood sugar becomes very low or stays low for a long time, more serious symptoms can occur. These include seizures (sudden, uncontrolled electrical disturbances in the brain) and coma (a state of unconsciousness from which the person cannot be awakened). These severe symptoms can lead to permanent brain damage.[4][8]
Doctors generally consider blood sugar levels above 70 milligrams per deciliter (mg/dL) to be normal. Anything below 60 mg/dL is considered low, and levels below 50 mg/dL can cause serious symptoms.[4]
Diagnosis and Testing
Diagnosing hyperinsulinism can be challenging because blood sugar levels can change several times throughout the day. About 60% of babies with congenital hyperinsulinism are diagnosed before they’re a month old. About 30% are diagnosed later in their first year, and the rest are diagnosed sometime after that.[4]
When doctors suspect hyperinsulinism, they take a detailed medical history and ask questions about when symptoms started and how often they occur. Blood tests are performed when the child has low blood sugar to check insulin levels and other substances. The diagnosis is made when insulin levels are inappropriately high despite low blood sugar levels.[4]
To help plan treatment, additional tests may be needed. Genetic testing can identify which gene mutation is causing the condition, which helps predict how the disease will progress and what treatments might work best.[7]
A special imaging test called an 18F-DOPA PET scan (also called a PET scan) can help doctors determine whether a child has the focal or diffuse form of hyperinsulinism. This test is like a special x-ray that can show which parts of the pancreas are producing too much insulin.[7] Finding a focal lesion is important because it can be surgically removed, potentially curing the child.[7]
In some cases, a short fasting study (where the child goes without food for 6-8 hours while being carefully monitored) may be performed to ensure the child can safely tolerate a missed feeding.[6]
Treatment Options
The main goal of treatment is to maintain normal blood sugar levels at all times to prevent brain damage. Blood sugar should be kept above 60 mg/dL at all times.[6]
Medical treatment is usually the first approach. The most commonly used medication is diazoxide, which helps reduce insulin secretion. This is the only medication approved by the U.S. Food and Drug Administration specifically for treating hyperinsulinism and is considered an essential medicine by the World Health Organization.[11] About 84% of patients are treated with diazoxide, with an average dose of 12.5 mg per kilogram of body weight per day. Many children take this medication for an average of 57 months before the condition resolves.[12]
When diazoxide doesn’t work or can’t be used, other medications may be tried. These include somatostatin analogues (such as octreotide or lanreotide), which work by suppressing insulin secretion. About 16% of patients use these medications. Other options include calcium channel blockers like nifedipine, or glucagon.[12][6]
Infants with severe hyperinsulinism often need very high rates of glucose infusion through an intravenous line (a tube inserted into a vein) to keep blood sugar levels safe. They may require 20-30 mg of glucose per kilogram of body weight per minute, which is much higher than normal needs.[6]
Surgical treatment may be necessary when medications cannot control blood sugar levels. For children with focal hyperinsulinism, surgery to remove only the abnormal part of the pancreas can cure the condition.[14] For diffuse hyperinsulinism that doesn’t respond to medication, removing most of the pancreas (called a near-total pancreatectomy) may be needed. However, this surgery carries the risk of developing diabetes later in life because not enough insulin-producing cells remain.[2]
Some children need feeding tubes and continuous feeds to prevent blood sugar from dropping too low, especially if medications aren’t fully effective.[18]
Monitoring and Long-Term Care
Children with hyperinsulinism need careful, ongoing monitoring. Blood sugar should be checked before each feeding and whenever any symptoms appear. While bedside glucose meters can provide quick results, they may not be accurate when blood sugar is very low, so results below 60 mg/dL should be confirmed with laboratory testing.[6]
New technologies have made monitoring easier. Continuous glucose monitoring systems allow glucose levels to be tracked in a minimally invasive way throughout the day and night, making it easier to catch dangerous drops in blood sugar early and follow treatment progress.[1]
The long-term outlook for children with hyperinsulinism depends largely on how quickly the condition is diagnosed and how well blood sugar is controlled. If low blood sugar is prevented and the condition is properly managed, most children develop normally with a normal range of cognitive, emotional, and social skills.[12]
In many cases, especially for certain genetic forms, clinical remission can occur after several years of intensive treatment, meaning all medications can eventually be stopped.[12] However, children who have had significant periods of uncontrolled low blood sugar may experience long-term complications such as epilepsy, cerebral palsy, and developmental deficits.[7]
Families need proper training and support for home care. Before discharge from the hospital, caregivers must learn how to recognize symptoms, check blood sugar, administer medications (including through pumps if needed), and know when to seek emergency help.[6]
Because hyperinsulinism is rare and complex, ongoing care at specialized centers with multidisciplinary teams experienced in managing this condition provides the best outcomes for children and families.[2]
