Skip to Main Content


Insulinomas are such rare tumors that even most specialists treat only a handful of these patients over their entire careers. Moreover, even most major referral centers treat only three or four cases per year. Nevertheless, the widely disparate clinical presentations as well as the complexity of diagnosis, localization, and treatment of these tumors continue to allure and sometimes perplex the team of physicians who care for these patients.


Resection of an insulinoma was first attempted by William J. Mayo in 1926.1 Unfortunately, the patient, a surgeon, was found to have an unresectable metastatic insulinoma and died 1 month later. Two years later, Roscoe Graham of Toronto performed the first successful curative enucleation of a benign insulinoma.2 In 1935, Frantz and Whipple characterized the classic symptoms of endogenous hyperinsulinemia, which subsequently became known as a "Whipple's triad."3 This triad of hypoglycemia (plasma glucose <50 mg/dL), symptoms of hypoglycemia, and symptom resolution after glucose administration still serves as the fundamental basis for diagnosis.


Islet cells were first identified by a medical student, Paul Langerhans, in 1869.4 Islets contain several different subtypes of secretory cells with different hormone production profiles. Insulin, which is secreted by the β cell, was discovered by Banting and Best in 1922, winning them a Nobel Prize.5 Insulin is manufactured by the β cell as proinsulin, an inactive peptide made up of two subunits and a linking peptide (C peptide). Before secretion, proinsulin is cleaved into its active form, also releasing C peptide (an inactive, rapidly degraded peptide) in equimolar amounts.6 C peptide is more rapidly degraded in the blood than insulin, with a half-life of about 4 to 6 minutes compared with a half-life of about 11 to 14 minutes for insulin.7 Knowledge of this biochemistry is critical in evaluating patients with suspected hyperinsulinemia because the concomitant measurement of insulin and C-peptide levels may help distinguish between endogenous hyperinsulinemia and exogenous insulin administration (e.g., malingering). Manufactured insulin compounds do not contain C peptide. Hyperinsulinemia with low or undetectable C-peptide levels indicates an exogenous source of insulin.


Insulinoma is an islet cell neoplasm characterized by the excessive unregulated secretion of insulin, which results in the clinical symptoms of hypoglycemia. The incidence is estimated at four per 1 million person-years.8Table 17-1 presents the major reported series of surgically treated insulinomas. The mean age of presentation is typically in the fourth or fifth decade of life, with a slight predominance in women. Approximately 3% to 7% of tumors are associated with type 1 multiple endocrine neoplasia syndrome (MEN1).9–16

Table Graphic Jump Location
Table 17-1. Summary of Insulinoma Experience at Major Referral Centers

Want remote access to your institution's subscription?

Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.


About MyAccess

If your institution subscribes to this resource, and you don't have a MyAccess profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus.

Subscription Options

AccessSurgery Full Site: One-Year Subscription

Connect to the full suite of AccessSurgery content and resources including more than 160 instructional videos, 16,000+ high-quality images, interactive board review, 20+ textbooks, and more.

$995 USD
Buy Now

Pay Per View: Timed Access to all of AccessSurgery

24 Hour Subscription $34.95

Buy Now

48 Hour Subscription $54.95

Buy Now

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.