Glucagonoma

What is glucagonoma?

A glucagonoma is a rare pancreatic tumor that releases glucagon, a hormone. It’s a type of pancreatic neuroendocrine tumor (islet cell tumor).

Glucagon is a natural hormone your body makes that helps manage blood glucose (sugar) levels. Specific cells in your pancreas called alpha cells make glucagon. Glucagon triggers your liver to release stored glucose (glycogen) to raise your blood sugar. Your body normally releases glucagon in response to a drop in blood sugar, prolonged fasting, exercise and protein-rich meals.

A glucagonoma can release excess glucagon. This leads to glucagonoma syndrome, which involves several symptoms and complications, like a painful skin rash and diabetes.

Most glucagonomas begin in the tail or body of your pancreas.

Is glucagonoma a cancer?

A glucagonoma is usually cancerous. About 50% of people have metastasis (the cancer has spread) when they receive a diagnosis. It most commonly spreads to your liver.

How common is glucagonoma?

Glucagonoma is very rare. There’s less than 1 new case per 1 million people a year. It mostly affects people who are 50 to 70 years old.

What are the symptoms of glucagonoma?

Glucagonomas tend to grow slowly. If you have one that isn’t releasing enough excess glucagon to cause issues for your body, you likely won’t have any symptoms.

If a glucagonoma releases excess glucagon that your body can’t keep up with, it triggers glucagonoma syndrome. This condition has noticeable symptoms. If you develop these symptoms, it’s important to see a healthcare provider as soon as possible.

Glucagonoma skin rash

The most common symptom of glucagonoma syndrome is a widespread skin rash called necrolytic migratory erythema (NME). It affects about 90% of people with the syndrome.

The rash can be on any part of your body, but it most often starts in your genital and anal regions, buttocks and lower legs. Other features of NME include:

• It may come and go and move around your body.
• It’s often itchy and painful in the beginning.
• It starts as a ring-shaped reddish area that blisters and crusts over. As the area heals, it may leave behind a brownish mark.
• It can cause a sore smooth tongue (glossitis), a sore mouth, cracked dry lips and angular cheilitis.
• It can cause inflamed eyelids (blepharitis), hair loss and issues with your nails.

Diabetes symptoms

The syndrome can lead to high blood sugar (hyperglycemia), which causes diabetes. Symptoms of diabetes include:

• Unexplained weight loss.
• Excessive thirst (polydipsia).
• Frequent urination (polyuria), especially overnight.
• Increased appetite or intense hunger (polyphagia).

Other symptoms of glucagonoma syndrome

Other symptoms of glucagonoma syndrome include:

• Chronic diarrhea.
• Anemia, which can cause fatigue, dizziness and other symptoms.
• Blood clots, especially deep vein thrombosis.

It can cause neurological and psychiatric symptoms, including:

• Depression.
• Dementia.
• Agitation.
• Hyperreflexia.
• Ataxia.
• Psychosis.
• Paranoid delusions.

What causes glucagonoma?

In most cases, healthcare providers don’t know the cause of glucagonoma. In about 10% of cases, the tumor is linked to an inherited condition called multiple endocrine neoplasia type (MEN) type 1.

However, even among people with MEN type 1, only a very small percentage will develop a glucagonoma.

How is glucagonoma diagnosed?

If you have necrolytic migratory erythema (NME), a healthcare provider will likely suspect glucagonoma and order tests. These tests may include:

• Fasting blood sugar test: An elevated level helps point to glucagonoma and can help confirm diabetes related to glucagonoma.
• Fasting glucagon blood test: With glucagonoma, glucagon levels are abnormally elevated — usually greater than 500 picograms per milliliter (pg/mL). Normal fasting blood glucagon levels are less than 150 pg/mL.
• Amino acid blood test: Glucagonoma usually causes hypoaminoacidemia (low levels of amino acids).
• Complete blood count: This test checks for anemia, which can happen with glucagonoma.

Imaging tests can confirm the presence of a tumor. They may include:

• CT scan.
• MRI scan.
• Endoscopic ultrasound.

How is glucagonoma treated?

The treatment for glucagonoma largely depends on whether the tumor is localized (just in your pancreas) or has metastasized (spread to other parts of your body).

Initial treatment for glucagonoma involves managing the symptoms and complications related to excess glucagon. Treatments include:

• Medications to manage glucagon excess: Octreotide and lanreotide injections can help reverse the effects of glucagon excess, as well as prevent the release of glucagon. These medications may also slow down the tumor’s growth. They can also help treat NME, diabetes, diarrhea and neurological symptoms.
• Management of diabetes: You may need oral diabetes medications or insulin injections to keep your blood sugar levels in a healthy range.
• Nutritional support: This may include total parenteral nutrition (TPN) and supplementation of amino acids and zinc to reverse the effects of malnutrition.
• Management of NME: Antibiotics and corticosteroids may help improve NME.
• Anticoagulant therapy: Blood-thinning medication (like heparin) can help prevent deep vein thrombosis.

Treatment for localized glucagonoma

If the tumor is only in your pancreas, surgery is the main treatment. If your surgeon can completely remove the tumor, then it’s usually cured. Once the glucagonoma is gone, your glucagon levels should return to normal. Your symptoms should also go away.

Treatment for metastasized glucagonoma

When possible, your healthcare provider will recommend surgery to remove tumors. This may include tumors in your pancreas, nearby lymph nodes and liver.

If your surgeon can’t remove any or all of the tumor(s), your healthcare team will likely recommend one or more of the following:

• Chemotherapy: This treatment aims to destroy cancer cells and prevent them from multiplying.
• Radiofrequency ablation: This treatment uses heat from radio waves to kill tumor cells.
• Cryosurgical ablation: This treatment uses extremely cold chemicals, like liquid nitrogen, to destroy cancerous cells.
• Chemoembolization: This treatment blocks a tumor’s blood supply.

Can I prevent glucagonoma?

As scientists don’t know the cause of most cases of glucagonoma, there’s nothing you can do to prevent it.

If one of your first-degree relatives (biological parents and siblings) has a multiple endocrine neoplasia (MEN) diagnosis, talk to your healthcare provider about genetic testing that can screen for the condition. If you do have MEN, genetic testing could help detect tumors in their early phases.

What’s the prognosis for people with glucagonoma?

The prognosis (outlook) for people with glucagonoma depends on several factors, including:

• Your age and overall health.
• The tumor size.
• If the tumor has spread or not.

The outlook is usually good if the tumor is contained within your pancreas. Surgery to remove the tumor typically cures these cases. But this represents only about 20% of glucagonoma cases.

Glucagonomas are very rare, so there’s not much data that can predict survival rates and outcomes for metastasis. Your healthcare team will be able to provide more information based on your unique situation.

A note from Cleveland Clinic

Receiving a tumor diagnosis is an upsetting experience. And there are special challenges when you’re diagnosed with a rare one like glucagonoma. Know that your healthcare team will be beside you to answer your questions and support you. If you’re feeling like you’re mentally and emotionally on your own with glucagonoma, ask your provider about programs and services that might help you.