Clinical Pearls & Morning Reports
Published July 25, 2018
Insulinoma, which is the classic cause of hyperinsulinemic hypoglycemia, is a rare neuroendocrine tumor. Approximately 98% of insulinomas are located in the pancreas, and 90% are smaller than 2 cm in diameter. Read the latest Case Records of the Massachusetts General Hospital here.
Q: What are the causes of hypoglycemia due to hyperinsulinemia?
A: Hyperinsulinemic hypoglycemia can be caused by autoimmune diseases, the ingestion of medications that cause beta cells in the pancreas to secrete insulin (e.g., sulfonylureas), altered secretion of insulin and gut hormones after gastrointestinal surgery, and insulinomas.
Q: How often are insulinomas associated with multiple endocrine neoplasia type 1?
A: Nearly 90% of insulinomas are single, benign tumors; 6% are associated with multiple endocrine neoplasia type 1.
A: The tumor autonomously secretes insulin, causing an impaired or absent response to falling glucose levels; as in most endocrine tumors, some degree of suppression may be maintained in insulinoma. Consequently, in patients with insulinoma, the insulin and C-peptide levels are inappropriately elevated when the blood glucose level is low. Most patients with insulinoma have fasting hypoglycemia, but 10% have postprandial hypoglycemia. Insulinoma usually leads to intermittent episodes of neuroglycopenic symptoms. Hypoglycemia normally leads to the release of counterregulatory hormones, including epinephrine, cortisol, and glucagon. The release of epinephrine is what causes the sympathoadrenal symptoms of hypoglycemia, such as palpitations and diaphoresis. However, the recurrence of hypoglycemia leads to a decrease in the release of counterregulatory hormones, causing a profound unawareness of hypoglycemia. A patient’s unawareness of hypoglycemia can lead to a delay in diagnosis or even to the misdiagnosis of a seizure disorder or malingering. The median time to an accurate diagnosis of insulinoma is 1.5 years.
A: In order to establish the diagnosis of insulinoma, blood levels of C-peptide, insulin, and β-hydroxybutyrate can be obtained. For increased sensitivity and specificity, these tests would be performed when the patient’s glucose level is less than 55 mg per deciliter (3.1 mmol per liter), ideally when symptoms of hypoglycemia are present. The hypoglycemia may be provoked by a fast. The standard duration of the fast is 72 hours to maximize sensitivity. However, two thirds of patients with insulinoma have hypoglycemia within the first day and 85 to 95% have hypoglycemia within 48 hours. If hypoglycemia is precipitated by fasting and insulinoma is suspected, the next step in the diagnostic process would be to perform imaging studies, such as endoscopic ultrasonography, computed tomography (CT), or magnetic resonance imaging (MRI). Endoscopic ultrasonography has a higher sensitivity and specificity than CT or MRI for detecting lesions that are confirmed to be insulinoma on surgical pathological examination.