Neuroendocrine Tumors: Insulinomas and Glucagonomas

What are neuroendocrine tumors? 

Neuroendocrine tumors develop due to disorganized, uncontrolled proliferation of neuroendocrine cells, which are special cells that make up the neuroendocrine system. 

Neuroendocrine cells are like nerve cells (neurons), but they also make hormones like cells of the endocrine system (endocrine cells). They receive messages from the nervous system and respond by making and releasing hormones. These hormones enter the blood and travel all over the body to control many body functions.

Neuroendocrine tumors can be benign (non-cancerous and only grow locally) or malignant (cancerous and spread to other areas of the body). 

• Functional tumors over-secrete their normal hormone products and cause signs of disease due to excessive hormone levels.
• Non-functional tumors cause signs of disease due to the presence of a physical mass and/or metastasis (spread to other areas of the body). 

A growing tumor can damage the nearby healthy tissues, even if it’s benign, and it can sometimes secrete excess hormone. Generally, neuroendocrine tumors are rare in dogs and cats. Very rarely, more than one type of neuroendocrine tumor may occur at the same time. 

What is an insulinoma and what clinical signs does it cause?

An insulinoma is a neuroendocrine tumor that occurs in the pancreas, in the beta cells, which are cells that make insulin – a hormone that triggers the movement of glucose from the blood into the tissues. 

An insulinoma releases excessive insulin, which lowers blood sugar levels, causing hypoglycemia. This condition can lead to intermittent weakness, lethargy, incoordination, mental confusion, muscle twitching, and episodes of seizures or collapse.

What is a glucagonoma and what clinical signs does it cause?

A glucagonoma is a neuroendocrine tumor that occurs in the pancreas, in the alpha cells, which are cells that release glucagon – a hormone that increases blood glucose (sugar). 

A glucagonoma releases excessive glucagon, which increases blood sugar levels, causing hyperglycemia. This condition can lead to lethargy, increased drinking and urination, weight loss, diarrhea, and skin changes such as crusting sores of the nose, elbows, genital area, and footpads, which can be painful. 

How are these tumors diagnosed?

These tumors may be diagnosed in a variety of ways.

• Insulinomas may be diagnosed based on persistent hypoglycemia with inappropriate insulin levels.
• Glucagonomas may be diagnosed based on increased glucose in the blood and urine. A specialized blood analysis (testing for amino acid, glucagon, and zinc levels) can be helpful for diagnosis. 
• Imaging may be needed to identify the presence of a mass, including radiographs (X-rays), ultrasounds, computed tomography (CT scans), and magnetic resonance imaging (MRI). Imaging may also demonstrate that an insulinoma or glucagonoma has spread to other areas of the body (such as the lungs). In some cases, the tumor may be found during exploratory surgery.
• Tissue biopsy is typically needed to definitively diagnose these tumors. A tissue biopsy involves taking a small sample of tissue from the body for examination under a microscope. The tissue may be obtained by surgically removing the entire tumor or a portion of the tumor. To identify the type of cancer, a veterinary pathologist examines the tumor or pieces of the tumor under the microscope, a process called histopathology.

For neuroendocrine tumors, special procedures are often necessary to make a diagnosis. Histopathology is not only helpful in making a diagnosis but can indicate how the tumor is likely to behave.

How do these tumors typically progress? 

Most of these tumors have the tendency to metastasize (spread to other areas of the body). The rate and extent of metastasis depends on the type of tumor. Common sites of metastasis include the lymph nodes, lungs, liver, kidneys, spinal cord, adrenal glands, and spleen. 

Staging (searching for potential spread to other locations in the body) is highly recommended for these tumors. Staging may include bloodwork, urinalysis, X-rays of the lungs, abdominal ultrasound, or other imaging procedures. If any lymph nodes are enlarged or feel abnormal, further sampling may be pursued to determine if spread is present. 

What are the treatments for these tumors? 

Treatment depends on the type, size, and malignancy of the tumor, as well as the presence of metastasis. Treatment typically involves several options, including surgery, chemotherapy, radiation therapy, and medical and dietary approaches. Your veterinarian may refer your pet to a veterinary oncologist to develop a care plan. 

Insulinomas may initially require emergency management of life-threatening hypoglycemia. If surgery isn’t an option or doesn’t completely control the hypoglycemia, your veterinarian may recommend dietary changes, such small meals frequently, and medications that promote increased blood sugar.

For patients affected by glucagonoma, a high-protein diet may be recommended if other treatment is not possible, including added egg whites, zinc supplementation, intravenous amino acids, and management of secondary conditions like skin infection.

Is there anything else I should know? 

Neuroendocrine tumors are rare, so if these tumors are suspected or diagnosed, your veterinarian may refer you to a veterinary oncologist. Many of the signs of these tumors are symptomatic of many common illnesses, and the signs may come and go, so these tumors can be difficult to diagnose.

Prognosis for patients with insulinoma varies, depending on how far the disease has advanced. Prognosis for patients with glucagonoma is generally poor, even with surgery.