A glucagonoma is a rare type of neuroendocrine tumor that develops in certain cells of the pancreas. These cells produce hormones and are known as alpha-2 islet cells. They are responsible for the production of the hormone glucagon, which is involved in the regulation of sugar in the blood.
When the blood sugar level drops, the pancreas usually increases the production of glucagon. Glucagon stimulates the transformation of stored glycogen in the liver to glucose. As a result, the concentration of glucose in the blood rises to increase the blood sugar and keep it within the normal range.
Glucagonomas are very rare and are diagnosed in less than one per million people per year. Of these, more than half (up to 80%) are malignant.
These tumors affect males and females equally, and usually occur in older individuals. The mean age of diagnosis is 55 years.
The causes of glucagonoma are not apparent. However, individuals with the rare familial syndrome Multiple Endocrine Neoplasia Type 1 (MEN1) are more likely to develop such a tumor.
Glucagonomas tend to grow slowly. For this reason, the symptoms usually set in gradually. However, about half of the individuals with this tumor will have cancer that has already metastasized at the time of diagnosis.
Most symptoms are linked to an increased production of glucagon, and may include:
- Skin rash (initially appearing as small red circles, which then turn into itchy and painful blisters) which is migratory
- Loss of weight
- Diabetes mellitus
- Sore mouth
- Deep vein thrombosis
- Frequent urination
- Blurred vision
Blood tests to measure the blood concentration of glucagon are most commonly used to make the initial diagnosis of glucagonoma. An abnormal result will require further investigation to determine the cause for a raised glucagon concentration. Other hormones such as insulin, VIP, and prolactin, along with substances like calcium may need to be assayed to rule out MEN-1.
An endoscopic ultrasound, skin biopsy or octreoscan may be needed to confirm the diagnosis. It is not always possible to know if the tumor is benign or malignant. There are several imaging tests that can help to make this diagnosis. This includes magnetic resonance imaging (MRI) and computed tomography (CT) scan.
Management of Symptoms
Initially, the symptoms of the condition need to be controlled to correct the blood sugar level and prevent complications related to diabetes. This may include oral medications to bring down the blood sugar, or insulin injections.
Additionally, some patients may require supplementation of zinc or amino acids to reduce the severity of the rash on the skin.
If patients are affected by diarrhea, somatostatin analogs such as octreotide or lanreotide can help to control it.
Removal of Tumor
Following the appropriate management of symptoms, surgery is often required to remove the glucagonoma. However, this is not always possible, particularly if it has already metastasized at the time of diagnosis.
The type of surgery used will depend on the number, location and size of the tumors. Depending on the situation, the tumor may be removed, in addition to the distal part of the pancreas or the surrounding lymph nodes.
This is a major procedure that has the potential to remove the glucagonoma completely, but it is not without risks. Additionally, chemotherapy, radiotherapy or cryotherapy is also sometimes used to control the growth of cancerous cells.
Since glucagonomas spread to the liver so commonly, many patients are offered surgery, or non-invasive procedures to remove the hepatic metastases. These include radiofrequency ablation, transarterial chemoembolization, or selective internal radiotherapy to deal with cancer deposits inside the liver.
There is little research about glucagonoma because it is such a rare condition, and there are few people that can take part in trials.
There are, however, some emerging treatments that are being trialed for use in glucagonoma. These include biological drugs such as sunitab, everolimus and bevacizumab. Other possibilities for future treatment include targeted radiotherapy and radiolabeled treatment.
Reviewed by Dr Liji Thomas, MD.