Nesidioblastosis is a rare pancreatic disorder characterized by the excessive, unregulated release of insulin, leading to severe and persistent low blood sugar (hyperinsulinemic hypoglycemia). The condition involves a microscopic change where insulin-producing cells are abnormally numerous or enlarged. It is the most common cause of persistent hyperinsulinemic hypoglycemia in infants, though a form can occur in adults, sometimes following gastric bypass surgery.
The Cellular Basis of Nesidioblastosis
The pancreas contains specialized cell clusters called the Islets of Langerhans, where beta cells produce and secrete insulin. Nesidioblastosis is characterized by beta cell hyperplasia—an abnormal growth and arrangement of these insulin-producing cells, often involving new islet-like structures budding from the pancreatic ductal epithelium.
In infants, this condition is a form of Congenital Hyperinsulinism (CHHI), categorized as either diffuse (involving the entire pancreas) or focal (limited to a specific area). In both types, the beta cells are functionally defective, failing to suppress insulin release even when blood glucose levels fall dangerously low.
The underlying cause is often a genetic mutation, most commonly affecting the K-ATP channel genes within the beta cells. When mutated, these channels fail to regulate insulin secretion, leading to a continuous, unregulated flow of insulin. In adults, the condition, sometimes called Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS), often follows bariatric surgeries, suggesting gut hormone changes may trigger abnormal beta cell activity.
Recognizing the Signs of Hyperinsulinemia
The clinical presentation is directly linked to the severity of hypoglycemia caused by excess insulin. Since the brain relies on glucose, severe hypoglycemia quickly leads to neuroglycopenic symptoms. In infants, where the condition is most common, these signs can be subtle and difficult to distinguish from normal neonatal behavior.
Infant symptoms include lethargy, excessive sleepiness, poor feeding, jitteriness, and tremors. Severe hypoglycemia can lead to serious neurological events such as seizures, loss of consciousness, or coma. Due to constant insulin overproduction, the low blood sugar is often refractory to simple measures like feeding, requiring high rates of intravenous glucose for stabilization.
Adult-onset nesidioblastosis is rarer and presents with low blood sugar symptoms that often occur post-meal. Signs include shakiness, sweating, palpitations, anxiety, and confusion. Because symptoms can mimic other conditions and imaging often fails to show a clear tumor, diagnosis may be delayed.
Confirming the Diagnosis
Diagnosis begins with Whipple’s triad: symptoms of hypoglycemia, documented low blood glucose, and symptom resolution when glucose levels are raised. Initial laboratory tests performed during hypoglycemia show a key pattern: low blood glucose combined with inappropriately high levels of insulin and C-peptide. Measuring C-peptide confirms the excess insulin is being produced internally.
If hypoglycemia is intermittent, a diagnostic fast (48 to 72 hours under medical supervision) may be required to provoke an episode for testing. Once endogenous hyperinsulinemia is confirmed, doctors must distinguish nesidioblastosis from an insulinoma (an insulin-secreting tumor). Conventional imaging, such as CT or MRI, often fails to detect the diffuse or small focal lesions, raising suspicion for nesidioblastosis.
Specialized functional imaging is often necessary. The most effective is a PET scan using the tracer 18F-DOPA, which is taken up by hyperactive beta cells. This helps localize a focal lesion for surgical removal or shows a diffuse pattern affecting the entire pancreas. The Selective Arterial Calcium Stimulation Test (SACST) is another advanced technique that maps regions of excessive insulin secretion by stimulating release via injected calcium.
Managing the Condition
Management aims to prevent severe hypoglycemia and permanent brain damage. Initial stabilization requires a continuous intravenous infusion of glucose to maintain safe blood sugar levels. For long-term control, the first-line treatment is diazoxide, a medication that inhibits insulin release from beta cells.
If diazoxide therapy is ineffective or intolerable, a somatostatin analog such as octreotide may be used. Octreotide suppresses insulin secretion and is administered via injection, though effectiveness varies. Dietary modifications, including frequent, small meals or adjusted carbohydrate and protein content, also help regulate blood sugar fluctuations.
Surgical intervention (pancreatectomy) is often necessary when medical treatment fails or a focal lesion is present. If the 18F-DOPA PET scan localizes a focal area, a targeted, partial pancreatectomy offers a high chance of cure with minimal tissue removal. For the diffuse form, a subtotal pancreatectomy (removing 70% to 90% of the pancreas) reduces the mass of hyperactive beta cells. Patients undergoing extensive pancreatectomy require long-term monitoring for diabetes mellitus and pancreatic enzyme insufficiency.