Glucagonomas - Causes, Symptoms, Diagnosis, and Management

Introduction:

Glucagon is a hormone secreted by special cells in the pancreas called alpha cells. It works together with the hormone insulin in regulating blood sugar levels in the body. When glucose enters the body in the form of food, insulin acts as a key to let glucose enter the cells. The excess glucose that remains in the blood is sent into the liver and stored as glycogen. When the blood sugar levels fall, the pancreas produces glucagon, which helps in converting glycogen into glucose that enters the bloodstream, thereby raising blood glucose levels. This mechanism helps in maintaining a balance in blood glucose levels.

What Are Glucagonomas?

Glucagonomas are neuroendocrine tumors (tumors occurring in body parts that produce hormones in response to stimulation by nerves) that occur in the alpha cells of the pancreas leading to excess production of the hormone glucagon. High glucagon levels can cause life-threatening conditions. Most glucagonomas spread to different body parts, especially the liver, by the time they are diagnosed. They are called malignant glucagonomas.

What Are the Alternative Names for Glucagonomas?

The other names of glucagonomas include:

• 4D syndrome.

• Glucagonoma syndrome.

• Pancreatic islet alpha cell tumor.

• Glucagon-secreting pancreatic islet cell tumor.

• Glucagon-secreting pancreatic neuroendocrine tumor.

What Are the Causes of Glucagonomas?

In most cases, the cause of glucagonomas is not known. However, in a few patients, a family history of a condition called multiple endocrine neoplasia (MEN) type 1 can increase the risk of occurrence of glucagonomas.

Multiple endocrine neoplasia (MEN) type 1 is a rare, inherited disorder that causes tumors in the pancreas, pituitary, and parathyroid glands.

What Are the Symptoms of Glucagonomas?

Noticeable symptoms are not present initially as glucagonomas grow slowly. However, as the amount of glucagon levels increases, causing elevated blood sugar levels, symptoms are noted. In most patients, the tumors spread to different body parts, mainly the liver, by the time they are diagnosed. The following symptoms may be noted, which include:

• A characteristic skin rash, also called necrolytic migratory erythema, occurs in almost 80 percent of patients with glucagonomas. The rash starts in the groin and later spreads to other body parts like the chest, buttocks, and lower legs. The rash has a crusty and blister-like appearance, with the skin around the rash changing color.

• Excessive thirst, frequent urination, and vision problems, all signs of type 2 diabetes, occur due to high blood glucose levels. About 60 to 80 percent of patients with glucagonomas develop type 2 diabetes.

• Increased appetite.

• Nocturnal or nighttime urination.

• Diarrhea.

• Glucose intolerance (a condition in which the body has difficulty in breaking down sugars).

• Inflammation of the mouth and tongue.

• Loss of weight.

• Deep vein thrombosis (DVT) blood clots that occur in deep veins of the legs.

• Vulvovaginitis is a condition in which there is inflammation and infection of the vulva and vagina in females. Women having glucagonomas tend to develop vulvovaginitis.

What Are the Complications of Glucagonomas?

The complications of glucagonomas include the following:

1. Weight loss.

2. Venous thrombosis, blood clots which occur in the deep veins of the legs that reach the lungs, can be life-threatening.

3. Chronic diarrhea.

4. In dilated cardiomyopathy, the left ventricle of the heart, which is the main pumping chamber, cannot pump blood efficiently as it becomes weak and enlarged.

5. Proximal muscle weakness (of the muscles close to the midline of the body.)

6. Psychosis (a mental health disorder.)

7. Depression.

8. Liver failure.

How Are Glucagonomas Diagnosed?

The first test is done when a doctor suspects glucagonomas are fasting blood sugars, which determines the levels of blood sugars when the patient has not eaten anything for more than eight hours. Glucagonomas cause very high fasting blood sugar levels.

Another test that is advised is the fasting gut hormone test to assess the levels of glucagon and chromogranin A. High level of both chemicals indicate glucagonomas. Other hormones like pancreatic polypeptide are also found in patients with glucagonomas.

Following detection, imaging tests are done to detect the location of tumors. The following imaging tests are done, which include:

• Ultrasound Scan: A type of imaging test that is done to view the internal organs of the body using high-frequency sound waves.

• CT (Computerized Tomography) Scan: Cross-sectional images of the body parts are obtained based on several X-rays and computer processing.

• MRI (Magnetic Resonance Imaging) Scan: Uses magnetic fields and radio waves to provide precise details of the parts of the body.

• Octreotide Scan: In an octreotide scan, the doctor injects a substance known as octreotide, which is mildly radioactive, into the body. This octreotide is taken up by the cells of the glucagonoma. The doctor then uses a scanner to detect the glucagonoma cells which have taken up the radioactive octreotide. This scan also helps detect if the glucagonomas have spread to different locations.

• Endoscopic Ultrasound: A tube with a camera at the end, guided by endoscopy, is used to study the organs of the abdomen.

Glucagonoma patients who are suspected of having the inherited condition multiple endocrine neoplasia (MEN) type 1 will need blood tests to confirm the same.

How Are Glucagonomas Managed?

The main treatment for glucagonomas is surgery to remove the tumor, which is done by a pancreatic surgeon along with an endocrinologist (a doctor who treats hormonal disorders). Malignant glucagonomas, which have spread to different parts, have various treatment options that include:

1. Two-Way Surgery: The surgeon initially removes the tumor in the pancreas and then any tumor that would have spread to other body parts.

2. Debulking Surgery: This procedure involves removing a large part of the tumor, leaving behind very small parts, which are easily destroyable with other therapies like chemotherapy.

3. Chemotherapy: Chemotherapy uses drugs to stop the growth of dividing tumor cells or destroy them.

4. Medications: Somatostatin analog medicines, Sunitinib, and Everolimus are used to reduce symptoms and control tumor growth.

5. Interferon Treatment: It directs the immune system to fight against tumor cells and destroy them.

6. Transarterial Chemoembolization: A procedure that blocks blood vessels that supply tumors of the liver.

7. Blood Thinners: They are medicines that reduce the risk of blood clots in the legs and lungs.

Glucagonoma treatment also includes the management of symptoms like high blood sugar and skin rashes. Diabetes is treated with anti-diabetic medications or insulin injections. Supplements containing amino acids, zinc, and skin creams are recommended to reduce rashes.

What Are the Adverse Effects of Treatment?

The main side-effects of surgery include infection, blood loss, or pain post-surgery. Other possible side-effects that can occur are due to medicines prescribed.

Conclusion:

Glucagonomas are tumors of the pancreatic cells that cause symptoms related to high glucagon levels. Glucagonomas, which are confined to the pancreas, can be successfully treated by surgery. However, most of the cases tend to have spread to other body parts by the time the tumor is diagnosed. Periodic checkups that include blood and imaging tests are required to assess the condition of the tumors. Mental health professionals help in guiding patients to take care of themselves and cope with anxieties related to the treatment.