An insulinoma is a tumour of the pancreas that is derived from beta cells and secretes insulin.
Beta cells secrete insulin in response to increases in blood glucose. The resulting increase in insulin acts to lower blood glucose back to normal levels at which point further secretion of insulin is stopped. In contrast, the secretion of insulin by insulinomas is not properly regulated by glucose and the tumours will continue to secrete insulin causing glucose levels to fall further than normal.

As a result patients present with symptoms of low blood glucose (hypoglycemia), which are improved by eating. The diagnosis of an insulinoma is usually made biochemically with low blood glucose, elevated insulin, proinsulin and C-peptide levels and confirmed by localising the tumour with medical imaging or angiography. The definitive treatment is surgery.

Insulinomas are rare neuroendocrine tumours with an incidence estimated at 1 to 4 new cases per million persons per year. Insulinoma is one of the most common types of tumour arising from the islets of Langerhans cells (pancreatic endocrine tumours). Estimates of malignancy (metastases) range from 5% to 30%. Over 99% of insulinomas originate in the pancreas, with rare cases from ectopic pancreatic tissue. About 5% of cases are associated with tumours of the parathyroid glands and the pituitary (Multiple endocrine neoplasia type 1) and are more likely to be multiple and malignant. Most insulinomas are small, less than 2 cm.

Signs and Symptoms

Patients with insulinomas usually develop neuroglycopenic symptoms. These include recurrent headache, lethargy, diplopia, and blurred vision, particularly with exercise or fasting. Severe hypoglycemia may result in seizures, coma, and permanent neurological damage. Symptoms resulting from the catecholaminergic response to hypoglycemia (i.e. tremulousness, palpitations, tachycardia, sweating, hunger, anxiety, nausea) are not as common. Sudden weight gain (the patient can become massively obese) is sometimes seen.


The diagnosis of insulinoma is suspected in a patient with symptomatic fasting hypoglycemia. The conditions of Whipple’s triad need to be met for the diagnosis of "true hypoglycemia" to be made:
  1. symptoms and signs of hypoglycemia,
  2. concomitant plasma glucose level of 45 mg/dL (2.5 mmol/L) or less, and
  3. reversibility of symptoms with administration of glucose.
Blood tests

The following blood tests are needed to diagnose insulinoma:
If available, a proinsulin level might be useful as well. Other blood tests may help rule out other conditions which can cause hypoglycemia.

Suppression tests

Normally, endogenous insulin production is suppressed in the setting of hypoglycemia. A 72-hour fast, usually supervised in a hospital setting, can be done to see if insulin levels fail to suppress, which is a strong indicator of the presence of an insulin-secreting tumour.

During the test, the patient may have calorie-free and caffeine-free liquids. Capillary blood glucose is measured every 4 hours using a reflectance meter, until values < 60 mg/dL (3.3 mmol/L) are obtained. Then, the frequency of blood glucose measurement is increased to every hour until values are < 49 mg/dL (2.7 mmol/L). At that point, or when the patient has symptoms of hypoglycemia, a blood test is drawn for serum glucose, insulin, proinsulin, and C-peptide levels. The fast is stopped at that point, and the hypoglycemia treated with intravenous dextrose or calorie-containing food or drink.

Diagnostic imaging

The insulinoma might be localized by non-invasive means, using ultrasound, CT scan, or by MRI techniques. An Indium-111 pentetreotide scan is more sensitive than ultrasond, CT, or MRI for detection of somatostatin receptor positive tumors.

Sometimes, angiography with percutaneous transhepatic pancreatic vein catheterization to sample the blood for insulin levels is required. Calcium can be injected into selected arteries to stimulate insulin release from various parts of the pancreas, which can be measured by sampling blood from their respective veins. The use of calcium stimulation improves the specificity of this test.

During surgery to remove an insulinoma, an intra-operative ultrasound can sometimes localize the tumour, which helps guide the surgeon in the operation and has a higher sensitivity than noninvasive imaging tests.


The definitive management is surgical removal of the insulinoma. This may involve removing part of the pancreas as well (Whipple procedure and distal pancreatectomy).Medications such as diazoxide and somatostatin can be used to block the release of insulin for patients who are not surgical candidates or who otherwise have inoperable tumours.Streptozotocin is used in islet cell carcinomas which produce excessive insulin. Combination chemotherapy is used: either doxorubicin + streptozotocin, or fluorouracil + streptotozocin in patients where doxorubicin is contraindicated.[1]
In metastasizing tumours with intrahepatic growth,
hepatic arterial occlusion or embolization can be used. [2]

Most patients with benign insulinomas can be cured with surgery. Persistent or recurrent hypoglycemia after surgery tends to occur in patients with multiple tumours. About two percent of patients develop diabetes mellitus after their surgery.

INSULINOMA (eMedicine oncology)
  • About 85% of patients present with symptoms of hypoglycemia that include diplopia, blurred vision, palpitations, or weakness.
  • Other symptoms include confusion, abnormal behavior, unconsciousness, or amnesia.
  • About 12% of patients have grand mal seizures.
  • Adrenergic symptoms (hypoglycemia causes adrenalin release) include weakness, sweating, tachycardia, palpitations, and hunger.
  • Symptoms may be present from 1 week to as long as several decades prior to the diagnosis (1 mo to 30 y, median 24 mo, as found in a large series of 59 patients).6 Symptoms may occur most frequently at night or in the early morning hours.
  • Hypoglycemia usually occurs several hours after a meal.
  • In severe cases, symptoms may develop in the postprandial period. Symptoms can be aggravated by exercise, alcohol, hypocaloric diet, and treatment with sulfonylureas.
  • Weight gain occurs in 20-40% of patients. Because of hyperinsulinism, many patients may be overweight.
  • A case report of a patient with type 2 diabetes who developed recurrent hypoglycemia was published from France.7
  • Symptoms caused by effects of local tumor mass are very rare in insulinoma.
Insulinomas are characterized clinically by the Whipple triad (which occurred in 75% of 67 insulinoma patients in one report).
  • Presence of symptoms of hypoglycemia 
  • Documented low blood sugar at the time symptoms are present
  • Reversal of symptoms by glucose administration.
Most patients with insulinoma have normal physical examination findings.

The genetic changes in neuroendocrine tumors are under investigation.
  • The gene of MEN, an autosomal dominant disease, is called MEN1 and maps to band 11q13. MEN1 is thought to function as a tumor suppressor gene.
  • New data suggest that the MEN1 gene also is involved in the pathogenesis of at least one third of sporadic neuroendocrine tumors.
  • Researchers were able to detect loss of heterozygosity in band 11q13 in DNA samples from resected insulinoma tissue by using fluorescent microsatellite analysis.

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