An insulinoma is a tumor of the pancreas that is derived from beta cells and secretes insulin.
It is a rare form of a neuroendocrine tumor and of cancer of the pancreas, of the functional
PanNET group ("functional" because it increases production of insulin; "PanNET" as an abbreviation
of Pancreatic neuroendocrine tumor. In the Medical Subject Headings classification, insulinoma
is the only sub-type of "Islet cell adenoma". Beta cells secrete insulin in response to
increases in blood glucose. The resulting increase in insulin acts to lower blood glucose
back to normal levels at which point further secretion of insulin is stopped. In contrast,
the secretion of insulin by insulinomas is not properly regulated by glucose and the
tumors will continue to secrete insulin causing glucose levels to fall further than normal.
As a result patients present symptoms of low blood glucose, which are improved by eating.
The diagnosis of an insulinoma is usually made biochemically with low blood glucose,
elevated insulin, proinsulin and C-peptide levels and confirmed by localizing the tumor
with medical imaging or angiography. The definitive treatment is surgery.
Features Insulinomas are rare neuroendocrine tumours
with an incidence estimated at 1 to 4 new cases per million persons per year. Insulinoma
is one of the most common types of tumor arising from the islets of Langerhans cells. Estimates
of malignancy range from 5% to 30%. Over 99% of insulinomas originate in the pancreas,
with rare cases from ectopic pancreatic tissue. About 5% of cases are associated with tumours
of the parathyroid glands and the pituitary and are more likely to be multiple and malignant.
Most insulinomas are small, less than 2 cm. Signs and Symptoms
Patients with insulinomas usually develop neuroglycopenic symptoms. These include recurrent
headache, lethargy, diplopia, and blurred vision, particularly with exercise or fasting.
Severe hypoglycemia may result in seizures, coma, and permanent neurological damage. Symptoms
resulting from the catecholaminergic response to hypoglycemia are not as common. Sudden
weight gain is sometimes seen. Diagnosis
The diagnosis of insulinoma is suspected in a patient with symptomatic fasting hypoglycemia.
The conditions of Whipple’s triad need to be met for the diagnosis of "true hypoglycemia"
to be made: symptoms and signs of hypoglycemia,
concomitant plasma glucose level of 45 mg/dL or less, and
reversibility of symptoms with administration of glucose.
Blood tests The following blood tests are needed to diagnose
insulinoma: glucose
insulin C-peptide
If available, a proinsulin level might be useful as well. Other blood tests may help
rule out other conditions which can cause hypoglycemia.
Suppression tests Normally, endogenous insulin production is
suppressed in the setting of hypoglycemia. A 72-hour fast, usually supervised in a hospital
setting, can be done to see if insulin levels fail to suppress, which is a strong indicator
of the presence of an insulin-secreting tumour. During the test, the patient may have calorie-free
and caffeine-free liquids. Capillary blood glucose is measured every 4 hours using a
reflectance meter, until values < 60 mg/dL are obtained. Then, the frequency of blood
glucose measurement is increased to every hour until values are < 49 mg/dL. At that
point, or when the patient has symptoms of hypoglycemia, a blood test is drawn for serum
glucose, insulin, proinsulin, and C-peptide levels. The fast is then stopped at that point,
and the hypoglycemia treated with intravenous dextrose or carbohydrate-containing food or
drink. Diagnostic imaging
The insulinoma might be localized by non-invasive means, using ultrasound, CT scan, or by MRI
techniques. An Indium-111 pentetreotide scan is more sensitive than ultrasound, CT, or
MRI for detection of somatostatin receptor positive tumors, but not a good diagnostic
tool for insulinomas. An endoscopic ultrasound has a sensitivity of 40-93% for detecting
insulinomas. Sometimes, angiography with percutaneous transhepatic
pancreatic vein catheterization to sample the blood for insulin levels is required.
Calcium can be injected into selected arteries to stimulate insulin release from various
parts of the pancreas, which can be measured by sampling blood from their respective veins.
The use of calcium stimulation improves the specificity of this test.
During surgery to remove an insulinoma, an intra-operative ultrasound can sometimes localize
the tumour, which helps guide the surgeon in the operation and has a higher sensitivity
than noninvasive imaging tests. Treatment
The definitive management is surgical removal of the insulinoma. This may involve removing
part of the pancreas as well. Medications such as diazoxide and somatostatin
can be used to block the release of insulin for patients who are not surgical candidates
or who otherwise have inoperable tumours.Streptozotocin is used in islet cell carcinomas which produce
excessive insulin. Combination chemotherapy is used: either doxorubicin + streptozotocin,
or fluorouracil + streptotozocin in patients where doxorubicin is contraindicated.[1]
In metastasizing tumours with intrahepatic growth, hepatic arterial occlusion or embolization
can be used. [2] Prognosis
Most patients with benign insulinomas can be cured with surgery. Persistent or recurrent
hypoglycemia after surgery tends to occur in patients with multiple tumours. About two
percent of patients develop diabetes mellitus after their surgery.
History Hypoglycemia was first recognized in the 19th
century. In the 1920s, after the discovery of insulin and its use in the treatment of
diabetics, hyperinsulinism was suspected to be a cause of hypoglycemia in non-diabetics.
A pioneering description of hyperinsulinism as a cause of hypoglycemia was published by
Seale Harris in 1924. The first report of a surgical cure of hypoglycemia by removing
an islet cell tumour was in 1929. Notable Death(s)
The Co-founder of Apple, Inc., Steve Jobs, died of Metastatic Insulinoma on October 5,
2011. See also
Hypoglycemia Causes of hypoglycemia
Pancreas External links
www.endotext.org article The Johns Hopkins University Pancreatic Islet
Cell Tumor / Pancreatic Endocrine Neoplasms webpage
Insulinoma community website provides up to date, easily accessible information and support
Additional images
References
Larsen PR, Williams RL. Williams textbook of endocrinology. Philadelphia: WB Saunders.
ISBN 0-7216-9184-6. Doppman JL, Chang R, Fraker DL, et al.. "Localization
of insulinomas to regions of the pancreas by intra-arterial stimulation with calcium".
Annals of Internal Medicine 123: 269–73. doi:10.7326/0003-4819-123-4-199508150-00004.
PMID 7611592. Service FJ. Insulinoma. In: UpToDate, Rose,
BD, UpToDate, Waltham, MA, 2005.