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.
- Insulinoma: the most common type of pancreatic neuroendocrine tumor (arising from beta cells); causes endogenous hyperinsulinism
- Hyperinsulinism: a condition of elevated blood insulin levels
- Endogenous hyperinsulinism: a condition characterized by inappropriately high serum insulin levels relative to blood sugar levels; manifests as hypoglycemic symptoms
- Insulinomas are neuroendocrine tumors that arise from beta cells of the pancreas. 
- Most insulinomas occur sporadically.
- Over 90% of insulinomas are benign. 
- ∼ 5% of insulinomas are associated with multiple endocrine neoplasia type 1 (). 
- , e.g., lethargy, syncope, and double vision
- Relief of symptoms of hypoglycemia after administering glucose (see also )
- Weight gain
- Symptoms characteristic of other endocrine neoplasias may occur (see “ ” for more information).
- Consider insulinoma in patients with both:
- Order laboratory studies to confirm endogenous hyperinsulinism.
- Obtain imaging to confirm insulinoma.
- Evaluate patients with confirmed insulinoma for clinical features of MEN 1 and .
- If insulinoma is ruled out or there is clinical suspicion for other causes of endogenous hyperinsulinism, consider additional workup, e.g.:
- Obtain during a symptomatic episode of hypoglycemia in patients with suspected insulinoma.
- Findings consistent with endogenous hyperinsulinism
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.
- Indication: patients with no spontaneous hypoglycemic episodes during the evaluation to provoke hypoglycemia
- Supportive findings: findings consistent with endogenous hyperinsulinism, e.g., low glucose and high insulin levels
- Limitations 
Glucagon stimulation test
- Supportive finding: an increase in serum glucose of ≥ 25 mg/dL within 30 minutes of glucagon injection 
- Unreliable in patients with malnutrition, hepatic disease, and cirrhosis with portocaval anastomosis
- Medication interference: diazoxide, hydrochlorothiazide, diphenylhydantoin, sulfonylureas, aminophylline
- Patients with nonislet cell tumors can have insulinoma-like responses.
- The glucagon tolerance test can induce nausea, vomiting, and hypoglycemia.
- In 8% of insulinomas, the expected peak is not observed.
Interpretation of laboratory studies
|Interpretation of laboratory studies for hyperinsulinism |
|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 
Imaging is usually guided by a specialist (e.g., endocrine surgery).
- Indication: confirmed endogenous hyperinsulinism to localize insulinoma for surgical planning 
Insulinomas are commonly < 1.0 cm in diameter and difficult to detect with noninvasive imaging. 
Surgical therapy 
- Tumor resection is the first-line treatment for localized insulinoma.
Pharmacological treatment 
- Consider agents that inhibit insulin secretion for:
- Short-term tumor resection is feasible until
- Long-term management of inoperable tumors or recurrent symptoms after excision
Tumor resection has a good prognosis and a low risk of recurrence.