The University of Arizona
Department of Surgery



Insulinomas are the most common neuroendocrine tumors of the pancreas with an incidence of 4 cases per million. Insulin is overproduced resulting in recurrent low blood glucose levels. Most insulinomas are sporadic (90%), but they can also be inherited as part of multiple endocrine neoplasia (MEN) type 1 syndrome (10%).

Insulinomas are usually small (90% are < 2cm) and solitary, but multiple tumors occur in 10% of patients, especially in those with MEN 1. Insulinomas arise equally in the head, body and tail of the pancreas, but less than 1% are located outside of the pancreas. The majority of tumors are benign; 5% to 10% are malignant.

Symptoms associated with insulinomas develop when the blood glucose falls below 50 mg/dL. The most common symptoms, occurring in 85-90% of patients, include dizziness, confusion, weakness, hunger, and chest palpitations. Symptoms can rapidly progress with continued fasting leading to syncope (fainting), seizures and coma. These symptoms are exacerbated with fasting, stress, and exercise and are relieved by eating.


Patients with insulinomas have an elevated serum insulin level > 30 μU/mL, proinsulin level > 5 pmol/L, C-peptide > 1.7 ng/mL, an insulin-to-glucose ratio > 0.4, and a blood glucose level < 45 mg/dL with symptoms. The most reliable test to diagnose an insulinoma is the 72-hour fast (it is diagnostic in 98% to 100% at 72 hours).

If the tests are equivocal, provocative tests may be performed to confirm the diagnosis. These tests include glucagon stimulation, tolbutamide stimulation, and calcium infusion.

Our preferred preoperative localizing study is a computed tomography (CT) scan because it can localize two-thirds of tumors and has a sensitivity of 60% to 85%. If the CT scan is negative, an endoscopic ultrasound (sensitivity up to 80%) can help localize the insulinoma. Other more invasive studies (angiography and arterial stimulation and venous sampling) may be considered if the insulinoma cannot be localized, however, we prefer the intraoperative ultrasound because it localizes over 90% of insulinomas.


Laparoscopic enucleation is performed when preoperative imaging studies indicate that it is possible and the pancreatic duct is not involved, otherwise a resection is performed. Resection is also often required in patients with MEN 1. Prior to surgery, hypoglycemia is controlled with frequent meals and diazoxide (or verapamil). The patients are admitted the day before surgery and are given 10% dextrose intravenously.

Patients with metastatic insulinomas should receive diazoxide to control hypoglycemia and systemic chemotherapy. Some patients may benefit from tumor debulking to achieve hypoglycemic control.


Patients with benign insulinomas are cured with surgery, whereas the median disease free survival for malignant insulinomas is 5 years. Recurrence occurs in up to 60% of patients, but palliative resection produces a median 4-year survival.

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Ehehalt F, Saeger HD, Schmidt CM, Grutzmann R. Neuroendocrine tumors of the pancreas. Oncologist. 2009;14(5):456-67.