​Insulinoma in Ferrets

What is an Insulinoma? By Jonathon Bresolin, DVM

Insulinoma is a tumor of the pancreas. Specifically, it is a tumor of the cells in the pancreas that produce insulin, a hormone vital to the control of blood sugar (glucose) levels in the body. Normally, as a meal is digested, blood sugar levels rise. The pancreas produces insulin, which drives the new sugars into the cells of the body, where they can be used as energy. It also inhibits the body’s ability to produce new glucose from body stores (fat, muscles, etc.). An insulinoma, however, will produce insulin at all times. This causes a constant state of low blood sugar, which can be dangerous and possibly fatal.

Insulinomas are most commonly seen in older ferrets (+3 years) and affect male and female ferrets equally.

What Causes Insulinoma?
Much discussion has occurred regarding the exact cause of insulinoma in ferrets. Its prevalence is far higher in American-bred ferrets, compared to ferrets bred in other countries. Some theorize that the American ferret breeding pool has a genetic predisposition towards developing insulinoma tumors. Others theorize that a diet high in carbohydrates, rather than protein, stimulates excessive insulin production, resulting in over-activity and eventual cancerous development of pancreatic cells.

What are the Clinical Signs?
Clinical signs of the insulinoma are directly related to the overproduction of insulin, and the subsequent low blood sugar levels.
–          Neurologic:
o   General lethargy/decreased energy levels
o   Confusion, mental dullness
o   Tremors, seizures
o   Coma, death
–           Adrenergic:
o   Increased heart rate
o   Hypothermia
o   Irritability, nervousness
–          Miscellaneous:
o   Signs of nausea (drooling, teeth grinding, pawing at the mouth)
o   In later stages of the disease, poor body condition
o   Hindlimb weakness, paralysis

The chronic nature of insulinomas often results in a slow onset of clinical signs. However, there can be acute events of low blood sugar (hypoglycemia) that can be extremely dangerous and possibly fatal. The clinical signs bolded above are signs of a dangerously low blood sugar, and need to be addressed immediately.

How Do We Diagnose Insulinoma?
The aforementioned clinical signs, combined with an older age, are enough to make us highly suspicious of insulinoma. In order to confirm the diagnosis, we rely on two particular blood tests. These tests are performed after 4-6 hours of fasting, to prevent false negatives:

–          Blood Glucose Levels: < 70 mg/dL
–          Blood Insulin Levels: > 200 pmol/L

A low glucose level, combined with a high insulin level, is diagnostic for insulinoma. Multiple tests may be required to catch the ferret at a time in which it is suffering from the effects of the insulinoma. Frequently, the tumor itself is composed of numerous “microtumors”, rather than a singular large mass, making detection via imaging difficult. However, radiographs and ultrasound can be used to check for metastatic tumors in other parts of the body, and may be useful if blood tests are inconclusive. Finally, if all else fails, surgical exploration of the abdomen may be necessary to detect the tumor. Sampling of the pancreas, as well as the liver and spleen, can check the body for the presence of other cancers, as well as metastatic lesions in organs other than the pancreas.

How Do We Treat Insulinoma?
Treatment can be split into two major categories: Emergency treatment of life-threatening symptoms, and long-term treatment of the tumor and its effects.

Emergency Treatment:
Emergency treatment revolves around stabilizing the critically low blood sugar in as controlled and safe of a manner as possible. If your ferret is suffering from a hypoglycemic event (tremors, seizures, coma, glassy-eyed stare), a small amount of soft, high protein food can be offered he can swallow. This can help restore them to safe glucose levels. However, this is just a stabilizing treatment. They should still be seen immediately by a veterinarian, as they will likely experience these symptoms again. If unable to swallow, the ferret should immediately be brought to the animal hospital.

At the hospital, injectable dextrose, a type of sugar, can be given intravenously to rapidly correct hypoglycemia if seizures are present. Once the blood sugar level is stabilized, and the ferret is able to swallow, high protein meals are used to stabilize the blood glucose level.  If the ferret is experiencing tremors and/or seizures, drugs such as diazepam can be used to control the symptoms.  A short acting injectable steroid to stabilize serum glucose levels may also be used.

Medical Management: 
Medical management is meant to control the symptoms of insulinoma, but is not curative for the tumor, itself. There are two drugs that are commonly used to help ferrets with insulinomas:

Prednisone/Prednisolone, a corticosteroid, is often the first line of medical management. It acts on peripheral tissues to reduce the glucose uptake stimulated by the excessive insulin. It also stimulates a process known as gluconeogenesis, which is the body’s ability to generate new glucose out of storage tissues such as adipose and glycogen. It also has anti-tumor properties that can reduce the rate and intensity of the tumor’s proliferation. It is cheap and can be given orally, but has a host of side effects, including increased eating, drinking, urination, immunosuppression, and occasional gastric ulceration.

Diazoxide is a diuretic that can be used on cases that do not respond to or cannot be put on prednisone therapy. It inhibits the release of insulin from the pancreas, as well as reduces the uptake of glucose by peripheral tissues and promotes gluconeogenesis. However, it does not have any anti-tumor properties and is much more expensive than Prednisone. Side effects are more mild than Prednisone, and include anorexia and vomiting.

Changing an insulinoma ferret’s diet can also improve its quality of life. Feeding frequent, small meals with a high-quality protein source and complex sugars can help prevent the massive spikes and drops in glucose. Maximum Calorie Eukanuba and Lafeber Emerald Exotic Carnivore are two good choices.

Finally, chemotherapy regiments have been explored, and can be discussed with a board-certified veterinary oncologist.

Surgical Management:
As mentioned above, insulinomas are often composed of multiple “microtumors”, rather than a single large tumor. This can make surgical removal of the tumor challenging, if not impossible. However, an animal with a single large tumor is a possible candidate for surgical removal. This carries the greatest chance at curing an insulinoma in a ferret. However, even ferrets with large, discrete tumors often have multiple microtumors in the pancreas that cannot be detected, and may cause reoccurrence later in life. This most commonly occurs within 2-6 months after the surgery. There is often a period of diabetes (excessive blood glucose) that occurs after surgery, but this corrects with time.

What is my Ferret’s Prognosis?
Treatment of insulinoma revolves around controlling, not curing disease. As such, the overall prognosis is guarded—rarely are ferrets truly cured of insulinoma. A combination of surgical and medical management gives the ferret the longest mean survival time. Below are listed the average survival times of the different treatment techniques.
–          Without Treatment: 3 months
–          Medical Management: 6 – 12 months
–          Surgical Treatment & Medical Management: 1 – 3 years

However, some ferrets have lived up to five years on medical treatment, alone. Ferrets with insulinoma should have their fasting blood glucose evaluated regularly, in order to monitor treatment and make the necessary adjustments.

By Association of Exotic Mammal Veterinarians: aemv.org