Last updated: September 11, 2023

Summarytoggle arrow icon

Insulinomas are insulin-secreting pancreatic beta-cell tumors. They are the most common cause of endogenous hyperinsulinism and are benign in 90% of patients. Most insulinomas occur sporadically but they can also occur in patients with multiple endocrine neoplasias (e.g., parathyroid tumors, pituitary adenomas, gastrinomas). Typical clinical features include recurrent attacks of symptomatic hypoglycemia in individuals without diabetes. The diagnosis is established if serum insulin and C-peptide are elevated despite hypoglycemia, either during a spontaneous episode or during a hypoglycemic episode provoked by a 72-hour fasting test. The treatment of choice is surgical enucleation of the insulinoma. In inoperable cases and patients with persistent hypoglycemic attacks, pharmacotherapy (e.g., diazoxide, somatostatin analogues) can be used to decrease insulin secretion.

Definitiontoggle arrow icon

Epidemiologytoggle arrow icon

  • Sex: >
  • Age range: ∼ 30–60 years
  • Incidence: ∼ 4 cases/1,000,000 persons per year [1]

Epidemiological data refers to the US, unless otherwise specified.

Pathophysiologytoggle arrow icon


Clinical featurestoggle arrow icon

Diagnosticstoggle arrow icon

Approach [6]

Laboratory studies [6]

Initial studies

Factitious hypoglycemia secondary to exogenous insulin use will not raise C-peptide levels, whereas factitious hypoglycemia secondary to the use of insulin secretagogues (e.g., sulfonylureas, meglitinides) can elevate both C-peptide and proinsulin levels.

72-hour fasting test

Obtain in consultation with a specialist, e.g., endocrinology.

Glucagon stimulation test

Glucagon stimulation test may be obtained in conjunction with a fasting test or alone.

Interpretation of laboratory studies

Interpretation of laboratory studies for hyperinsulinism [6][8]
Serum levels Endogenous hyperinsulinism (or ↑ IGF) Exogenous hyperinsulinism Hypoglycemia without hyperinsulinism




Low or normal

Normal or high



Serum glucose response to glucagon injection

Increase ≥ 25 mg/dL

No or minimal increase (< 25 mg/dL)

Imaging studies [3][6]

Imaging is usually guided by a specialist (e.g., endocrine surgery).

Insulinomas are commonly < 1.0 cm in diameter and difficult to detect with noninvasive imaging. [6]

Treatmenttoggle arrow icon

Provide oral glucose, IV dextrose, or IM glucagon to patients with acute hypoglycemia. See also “Treatment of hypoglycemia.”

Surgical therapy [3][9]

Pharmacological treatment [6]

Tumor resection has a good prognosis and a low risk of recurrence.

Referencestoggle arrow icon

  1. Okabayashi T. Diagnosis and management of insulinoma. World Journal of Gastroenterology. 2013; 19 (6): p.829.doi: 10.3748/wjg.v19.i6.829 . | Open in Read by QxMD
  2. Grant CS. Insulinoma. Best Practice & Research Clinical Gastroenterology. 2005; 19 (5): p.783-798.doi: 10.1016/j.bpg.2005.05.008 . | Open in Read by QxMD
  3. Jensen RT, Cadiot G, Brandi ML, et al. ENETS Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Neoplasms: Functional Pancreatic Endocrine Tumor Syndromes. Neuroendocrinology. 2012; 95 (2): p.98-119.doi: 10.1159/000335591 . | Open in Read by QxMD
  4. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. McGraw-Hill Education ; 2015
  5. Kumar V, Abbas AK, Aster JC. Robbins & Cotran Pathologic Basis of Disease. Elsevier Saunders ; 2014
  6. Cryer et al.. Evaluation and Management of Adult Hypoglycemic Disorders: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2009; 94 (3): p.709-728.doi: 10.1210/jc.2008-1410 . | Open in Read by QxMD
  7. Desimone et al.. Non-Diabetic Hypoglycemia. Endotext. 2000.
  8. Seaquist ER, Anderson J, Childs B, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and The Endocrine Society. Diabetes Care. 2013; 36 (5): p.1384-1395.doi: 10.2337/dc12-2480 . | Open in Read by QxMD
  9. Howe JR, Merchant NB, Conrad C, et al. The North American Neuroendocrine Tumor Society Consensus Paper on the Surgical Management of Pancreatic Neuroendocrine Tumors. Pancreas. 2020; 49 (1): p.1-33.doi: 10.1097/mpa.0000000000001454 . | Open in Read by QxMD
  10. Eun Byul Kwon, Hwal Rim Jeong, Young Seok Shim, Hae Sang Lee, and Jin Soon Hwang. Multiple Endocrine Neoplasia Type 1 Presenting as Hypoglycemia due to Insulinoma. Journal of Korean Medical Science.. 2016.

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