Updated: Feb 21, 2016
  • Author: Zonera Ashraf Ali, MBBS; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
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Practice Essentials

Insulinomas are the most common cause of hypoglycemia resulting from endogenous hyperinsulinism. Approximately 90-95% of insulinomas are benign, and long-term cure with total resolution of preoperative symptoms is expected after complete resection. See the image below.

CT scan image with oral and intravenous contrast i CT scan image with oral and intravenous contrast in a patient with biochemical evidence of insulinoma. The 3-cm contrast-enhancing neoplasm (arrow) is seen in the tail of the pancreas (P) posterior to the stomach (S) (Yeo, 1993).

Signs and symptoms

Insulinomas are characterized clinically by the Whipple triad, as follows:

  • Presence of symptoms of hypoglycemia (about 85% of patients)
  • Documented low blood sugar at the time of symptoms
  • Reversal of symptoms by glucose administration

About 85% of patients with insulinoma present with one of the following symptoms of hypoglycemia:

  • Diplopia
  • Blurred vision
  • Palpitations
  • Weakness

Hypoglycemia can also result in the following:

  • Confusion
  • Abnormal behavior
  • Unconsciousness
  • Amnesia
  • Adrenergic symptoms (from hypoglycemia-related adrenalin release): Weakness, sweating, tachycardia, palpitations, and hunger
  • Seizures

See Clinical Presentation for more detail.


Lab studies

Failure of endogenous insulin secretion to be suppressed by hypoglycemia is the hallmark of an insulinoma. Thus, the finding of inappropriately elevated levels of insulin in the face of hypoglycemia is the key to diagnosis.

The biochemical diagnosis of insulinoma is established in 95% of patients during prolonged fasting (up to 72 h) when the following results are found:

  • Serum insulin levels of 10 µU/mL or more (normal < 6 µU/mL)
  • Glucose levels of less than 40 mg/dL
  • C-peptide levels exceeding 2.5 ng/mL (normal < 2 ng/mL)
  • Proinsulin levels greater than 25% (or up to 90%) of immunoreactive insulin levels
  • Screening for sulfonylurea negative

Imaging studies

Insulinomas can be located with the following imaging modalities:

  • Endoscopic ultrasonography: Detects 77% of insulinomas in the pancreas [1, 2, 3]
  • Real-time transabdominal high-resolution ultrasonography: 50% sensitivity
  • Intraoperative transabdominal high-resolution ultrasonography with the transducer wrapped in a sterile rubber glove and passed over the exposed pancreatic surface: Detects more than 90% of insulinomas
  • Helical or multislice computed tomography (CT) scanning: 82-94% sensitivity
  • Magnetic resonance imaging (MRI) with gadolinium: Can aid tumor detection in 85% of cases
  • Arteriography: Selective arteriography has 82% accuracy, with a 5% false-positive rate; arteriography with catheterization of small arterial branches of the celiac system combined with calcium injections and simultaneous measurements of hepatic vein insulin during each selective calcium injection localizes tumors in 47% of patients
  • Somatostatin receptor scintigraphy: 60% sensitivity

See Workup for more detail.


Pharmacologic therapy

Pharmacologic treatment is designed to prevent hypoglycemia and, in patients with malignant tumors, to reduce the tumor burden. Agents used in this therapy include the following:

  • Diazoxide: Reduces insulin secretion
  • Hydrochlorothiazide: Counteracts edema and hyperkalemia secondary to diazoxide and potentiates its hyperglycemic effect
  • Octreotide: Prevents hypoglycemia


  • Laparoscopic surgery: A large study from Spain showed laparoscopic surgery to be safe and effective in benign and malignant tumor resection [4]
  • Enucleation: Because of the small likelihood that a tumor that presents without metastatic spread is malignant, insulinomas may be removed by enucleation
  • Pancreaticoduodenectomy: If enucleation is not possible, a larger pancreatic resection, including pancreaticoduodenectomy, may be necessary
  • Whipple procedure: Major resections, such as the Whipple procedure, may become necessary when the tumor is found in the pancreatic head and local excision is not possible
  • Subtotal pancreatectomy with enucleation: If insulinoma is associated with multiple endocrine neoplasia type 1 (MEN1), subtotal pancreatectomy with enucleation of tumors from the pancreatic head and uncinate processus often is recommended over simple enucleation, because of frequent multiple tumors in MEN1

Even when metastases are found, surgical excision is often feasible before any medical, chemotherapeutic, or other interventional therapy is considered. Resect all gross disease; this would include performing wedge resections of hepatic metastases

See Treatment and Medication for more detail.



Insulinomas are the most common cause of hypoglycemia resulting from endogenous hyperinsulinism. In a large single-center series of 125 patients with neuroendocrine tumors, insulinomas constituted the majority of cases (55%), followed by gastrinomas (36%), VIPomas (vasoactive intestinal polypeptide tumor) (5%), and glucagonomas (3%). [5]

CT scan image with oral and intravenous contrast i CT scan image with oral and intravenous contrast in a patient with biochemical evidence of insulinoma. The 3-cm contrast-enhancing neoplasm (arrow) is seen in the tail of the pancreas (P) posterior to the stomach (S) (Yeo, 1993).
Endoscopic ultrasonography in a patient with an in Endoscopic ultrasonography in a patient with an insulinoma. The hypoechoic neoplasm (arrows) is seen in the body of the pancreas anterior to the splenic vein (SV) (Rosch, 1992).

In 1927, Wilder established the association between hyperinsulinism and a functional islet cell tumor. [6] In 1929, Graham achieved the first surgical cure of an islet cell adenoma. Insulinomas can be difficult to diagnose. It was not uncommon for patients to have been misdiagnosed with psychiatric illnesses or seizure disorders before insulinoma was recognized.



An insulinoma is a neuroendocrine tumor, deriving mainly from pancreatic islet cells, that secretes insulin. Some insulinomas also secrete other hormones, such as gastrin, 5-hydroxyindolic acid, adrenocorticotropic hormone (ACTH), glucagon, human chorionic gonadotropin, and somatostatin. The tumor may secrete insulin in short bursts, causing wide fluctuations in blood levels.

About 90% of insulinomas are benign. Approximately 10% of insulinomas are malignant (metastases are present). Approximately 10% of patients have multiple insulinomas; of patients with multiple insulinomas, 50% have multiple endocrine neoplasia type 1 (MEN 1). Insulinomas are associated with MEN 1 in 5% of patients. On the other hand, 21% of patients with MEN 1 develop insulinomas. Because of the association of insulinomas with MEN 1, consideration should be given to screening family members of insulinoma patients for MEN 1.

Increased expression of the phosphorylated mechanistic target of rapamycin (p-mTOR) signaling pathway and itsdownstream serine/threonine kinase p70S6k has been observed in insulinoma tumor specimens. [7] This discovery has led to studies exploring new therapeutic options.



United States

Insulinomas are the most common pancreatic endocrine tumors. The incidence is 3-10 cases per million people per year. [8] These make up 55% of neuroendocrine tumors.


Exact data for international incidence of insulinomas are not available. One source from Northern Ireland reported an annual incidence of 1 case per million persons. A study from Iran found 68 cases in a time span of 20 years in a university in Tehran. [9] A 10-year single-institution study from Spain of 49 consecutive patients who underwent laparoscopic surgery for neuroendocrine pancreatic tumors included 23 cases of insulinoma. [4] These reports may be an underestimate.



The postoperative morbidity rate in one published series was 14% and consisted mainly of local complications, such as fistula formation after pancreatic resection. The postoperative mortality rate in another series of 117 insulinoma patients was 7.7%. The median survival in metastatic disease to the liver ranges from 16-26 months.


Race-, Sex-, and Age-related Demographics

Insulinomas have been reported in persons of all races. No racial predilection appears to exist.

The male-to-female ratio for insulinomas is 2:3.

The median age at diagnosis is about 47 years, except in insulinoma patients with MEN 1, in whom the median age is the mid 20s. In one series, patients with benign disease were younger (mean age of 38 y) than those with metastases (mean age of 52 y). The age range for peak incidence of insulinoma is between 30 and 60 years.