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Insulinoma

Last updated Oct. 12, 2018

Edward Alabraba et al.

Gross histological appearance of insulinoma showing typical red-brown appearance of tumor.


What are the other Names for this Condition? (Also known as/Synonyms)

  • Beta Cell Tumor of Pancreas
  • Islet Cell Insulinoma
  • Pancreatic Insulinoma

What is Insulinoma? (Definition/Background Information)

  • Insulinoma is a rare tumor of the beta cells of the pancreas, which secretes insulin. They are considered to be functionally-active tumors, because they secrete insulin. Due to this secretion, they cause low blood glucose levels, which is termed ‘clinical hypoglycemia’
  • About 90% of Insulinomas have a benign behavior, while 10% may turn malignant. These pancreatic tumors generally occur in adults, especially in women
  • These tumors may be small and during the early stages may not cause any significant signs and symptoms, making it difficult to detect an Insulinoma. Malignant tumors have more severe signs and symptoms than benign tumors
  • Insulinoma can cause sweating, vision abnormalities, confusion, etc. in the affected individuals, due to reduced glucose levels in blood. Malignant tumors may infiltrate into local tissue or even metastasize
  • There are various treatment modalities available to address the condition; although, a complete surgical excision is the preferred mode of treatment. In cases of metastasis, a combination of chemotherapy, radiation therapy, and surgical procedures may be used
  • The prognosis of Insulinoma depends upon many factors including the behavior of the tumor (if benign or malignant) and overall health of the individual. Generally, a benign Insulinoma has an excellent prognosis with appropriate treatment

The pancreas is an important organ of the digestive system.

  • Based on function of the pancreas, it can be functionally divided into 2 parts, namely:
    • Exocrine pancreas, which produces digestive enzymes, and
    • Endocrine pancreas that produces hormones such as insulin, glucagon, and somatostatin. Insulin and glucagon helps with controlling sugar levels in blood
  • 95% of the pancreas is exocrine portion and 5% is endocrine portion. Pancreatic tumors (both benign and malignant) can arise from both the exocrine and the endocrine part
  • Based upon anatomy of the pancreas, it can be divided into 3 main parts, namely the:
    • Head,
    • Body, and
    • Tail
  • Pancreatic tumors can affect the head, body, and tail region of the pancreas. Some tumors can affect one area of the pancreas more than the other areas.

Hence, localizing the tumor site can guide the healthcare provider to arrive at a probable diagnosis.

Who gets Insulinoma? (Age and Sex Distribution)

  • Pancreatic Insulinoma is an infrequently occurring tumor that typically affects adults
  • It can affect both males and females, though a preference for females is observed
  • The condition can occur worldwide; individuals of all racial and ethnic background may be affected

What are the Risk Factors for Insulinoma? (Predisposing Factors)

The specific risk factors for Insulinoma are generally unknown or unidentified.

  • Multiple endocrine neoplasia type 1 (MEN 1, an inherited genetic disorder) syndrome: About 10% of the cases are seen in individuals with this syndrome. In such cases, the tumor occurs in individuals who are less than 20 years old
  • A family history of Insulinoma or other pancreatic tumors

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Insulinoma? (Etiology)

  • The exact cause of Insulinoma development is unknown
  • Research scientists believe that the cause of the condition is mostly due to molecular or genetic mutations, which results in tumor formation

What are the Signs and Symptoms of Insulinoma?

The signs and symptoms of Insulinoma depend upon the size and location of the tumor. During the initial stages, small tumors may not cause any signs and symptoms that are readily recognized. Hence, these tumors are only detected incidentally, when being worked-up for other conditions (i.e., diagnostic tests and exams undertaken for other health conditions).

The signs and symptoms may include the following:

  • Symptoms of low glucose level in blood, such as sweating, dizziness/confusion, blurring of vision, and even loss of consciousness
  • Nausea and vomiting
  • Abdominal pain, back pain
  • Loss of appetite, weight loss
  • Diarrhea, indigestion
  • Yellowing of skin (jaundice)
  • Dark-colored urine
  • Fatigue (getting tired easily)
  • Signs and symptoms of any underlying disorder, such as multiple endocrine neoplasia type 1

General features of Pancreatic Insulinoma include:

  • About 1 in 10 tumors are malignant, while the remaining (majority) are benign
  • Benign tumors are usually 1.5 cm and lesser in size. Sometimes the tumors are missed, because of their small size
  • They can arise from the endocrine portion of the pancreas
  • The tumors are generally single, while sometimes multiple tumors are observed

How is Insulinoma Diagnosed?

Frequently, pancreatic tumors are difficult to detect/diagnose in the early stages. The signs and symptoms can be very similar to other conditions. Since the pancreas is located in the peritoneum, behind many organs, there is a lot of space for the tumor to grow (often unnoticed).

The following are the diagnostic methods that may be used to detect Insulinoma:

  • A thorough physical examination and a complete medical history is very important
  • A diagnosis is usually made using the classical Whipple’s triad in individuals with Insulinoma. These are classical features which helps in the diagnosis, namely:
    • Symptoms of low blood glucose such as dizziness, blurring of vision, fainting etc.
    • Blood glucose levels less than 50 mg/deciliter
    • The symptoms occur after fasting or exercise, and they generally tend to disappear after glucose is administered to the individual (either orally or through intravenous effusion)
  • Blood levels of insulin and glucose
  • Blood insulin to glucose ratio
  • Pancreatic arteriography to detect small tumors
  • Radiological studies that may include:
    • Abdominal ultrasound: A procedure where high-frequency sound waves are used to produce real-time images
    • Endoscopic ultrasound: It is a minimally-invasive procedure that uses high-frequency sound waves to obtain detailed images of the pancreas
    • CT scan of abdomen: It may be helpful in detecting recurrences, or if metastasis to other organs has occurred
    • MRI scan of abdomen: It helps produce high-quality pictures of certain body parts including the tissues, muscles, nerves, and bones
  • Additionally, the following magnetic resonance imaging procedures may be used particularly in individuals suspected of having pancreatic tumor/cancer:
    • MR cholangio-pancreatography (MRCP)
    • MR angiography (MRA)
  • Positron emission tomography (PET) scan: It is particularly helpful in visualizing the spread of the cancer to other body parts (metastasis) and/or recurrence
  • Insulin level testing using selective transhepatic portal venous sampling. In this test, the insulin levels from various parts of the portal system is measured to localize the tumor
  • Tissue biopsy: A tissue biopsy is performed and sent to a laboratory for a pathological examination to the pathologist, who examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis

The tissue for diagnosis can be procured in multiple different ways, and they include:

  • Fine needle aspiration (FNA) biopsy of the pancreatic tumor:
    • A FNA biopsy may not be helpful, because one may not be able to visualize the different morphological areas of the tumor. Hence, a FNA biopsy as a diagnostic tool has certain limitations, and an open surgical biopsy is preferred
  • Core biopsy of the pancreatic tumor
  • Open biopsy of the pancreatic tumor

Other tests to diagnose Insulinoma may include the following:

  • Blood test to check for serum amylase levels
  • Complete blood count with differential
  • Fasting serum
  • Blood tests that may involve tumors markers, such as:
    • Carcinoembryonic antigen (CEA)
    • CA 19.9
    • CA 15.3
    • Alpha fetoprotein
  • Radiological studies that may include an abdominal x-ray
  • Percutaneous transhepatic cholangiography (PTC): A contrast material is injected into the bile ducts to visualize the structure
  • Endoscopic retrograde cholangio-pancreatography (ERCP): This technique is used when symptoms of pancreatic cancer are present in the individual. A special equipment and dye injections are used to obtain a series of images. If required, a biopsy sample may also be collected during the procedure
  • Invasive diagnostic procedures such as:
    • Laparoscopy: A special device is inserted through a small hole into the abdomen, to visually examine it. If necessary, a tissue sample is obtained for further analysis. Exploration of the abdomen using a laparoscope is called ‘exploratory laparoscopy’
    • Laparotomy: The abdomen is opened through an incision for examination, and if required, a biopsy sample obtained. Exploration of the abdomen using laparotomy procedure is called ‘exploratory laparotomy’

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Insulinoma?

The complications due to Insulinoma may include the following:

  • Gastrointestinal obstruction
  • Biliary tract obstruction causing jaundice
  • Compress adjoining organs if the tumor size is large, which may cause the organs to dysfunction or function abnormally
  • Sometimes, multiple tumors may develop, a condition called insulinomatosis
  • Severe hypoglycemia can cause brain damage
  • Malignant tumors can cause local invasion or distant metastasis
  • Complications may arise due to the presence of the underlying genetic disorder (MEN type 1)

How is Insulinoma Treated?

The treatment of Insulinoma depends upon a set of factors that include the following:

  • If the tumor is benign or malignant
  • Stage of the tumor (how far the tumor has spread from the pancreas)
  • Whether it is a single tumor, or there are multiple tumors
  • Whether the tumor is associated with a syndrome (such as MEN 1)
  • Overall health status of the individual
  • Location of the tumor in the pancreas (head, body, or tail)
  • Size of the tumor

The treatment measures available for Insulinoma include the following:

  • In most cases, a surgical excision and removal of the entire tumor is the preferred treatment option; removing the tumor can result in a cure (enucleation of pancreatic Insulinoma)
  • In some cases, a portion of the pancreas may have to be removed
  • If the tumor has metastasized, then a combination of chemotherapy, radiation therapy, and invasive procedures may be used to treat the tumor. This is often based upon the individual’s specific circumstance
  • Other treatment options may include:
    • Radiofrequency ablation of the tumor
    • Cryotherapy
    • Selective internal radiotherapy
    • Transarterial chemoembolization (TACE)
    • If the above measures are not effective, chemotherapy may be considered
  • Treatment of the underlying MEN type 1 (if present)
  • Post-operative care is important: One must maintain minimum activity levels, until the surgical wound heals
  • Follow-up care with regular screening and check-ups are important and encouraged

How can Insulinoma be Prevented?

Currently, there are no specific methods or guidelines to prevent Insulinoma. However, the condition may be avoided through the following measures:

  • Genetic testing in individuals with a family history of pancreatic tumors or other underlying genetic conditions associated with pancreatic tumors
  • Regular medical screening at periodic intervals with blood tests, scans, and physical examinations for those who have already endured the tumor

What is the Prognosis of Insulinoma? (Outcomes/Resolutions)

  • The surgical removal of benign Insulinomas can result in a cure and the prognosis is excellent in most cases
  • If Insulinoma is a malignant tumor, then its prognosis depends upon a set of several factors, which include:
    • Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
    • The surgical respectability of the tumor (meaning, if the tumor can be removed completely) 
    • Overall health of the individual: Individuals with overall excellent health have better prognosis compared to those with poor health
    • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
    • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have a poorer prognosis compared to tumors that do not recur
    • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond so well to treatment
  • An early diagnosis and prompt treatment of the malignant tumor generally yields better outcomes than a late diagnosis and delayed treatment
  • In case of underlying genetic syndromes, such as multiple endocrine neoplasia 1, the prognosis is further dependent upon the severity of the syndrome
  • Regular follow up visits with the healthcare provider are important

Additional and Relevant Useful Information for Insulinoma:

  • Not all Insulinomas are functional tumors; some are non-functional and do not cause low blood glucose levels
  • It is estimated that the average lifetime risk of developing pancreatic cancer is about 1.5%

What are some Useful Resources for Additional Information?


References and Information Sources used for the Article:


Helpful Peer-Reviewed Medical Articles:


Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Nov. 24, 2015
Last updated: Oct. 12, 2018

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