Insulinoma

One of the most common and most devastating of ferret diseases is cancer of the insulin-producing cells called an insulinoma. Other names for this tumor are beta-cell carcinoma or pancreatic endocrine carcinoma. This cancer occurs when the cells of the pancreas that produce insulin (beta-cells) grow out of control. The disease in the ferret caused by this cancer is not caused by the cancer growing into a large tumor and thereby disrupting the surrounding tissues or organs (as is often the case with cancer), rather, it is due to the effects of the over production of the hormone insulin by the cancerous tissue.

As with any major disease problem in the ferret, insulinoma is a problem that should be addressed by a veterinarian familiar with ferrets, their diseases and with significant experience performing surgery on ferrets. This common problem of ferrets is very rare in dogs, cats, or other small animals.

Significant anatomy and physiology

The pancreas is a large glandular organ located at the upper end of the digestive tract, where the stomach empties into the small intestine. This large gland has two functions, one, called "exocrine" (meaning the gland secretes material outward or out of the body), and the other called "endocrine" (meaning that the gland secretes into the body or into the blood stream). The exocrine function involves the production and secretion of the digestive enzymes used to digest food, primarily proteins and sugars in the diet. The endocrine function involves regulation of the level of sugar in the blood stream. Two substances, or hormones, are involved in this process, insulin and glucagon. After eating a meal that contains sugar or carbohydrates, blood sugar levels rise in the blood. This rise in blood sugar causes the pancreatic beta cells to release insulin. The insulin acts on body tissues to actively absorb the sugar from the blood stream and lower the level in the blood.

When an insulinoma is present, too much insulin is released into the blood and the body’s tissues absorb too much glucose. This causes blood sugar levels to drop too low for the brain to function normally, resulting in the signs we see in the ferret.

Occurrence of insulinoma

It is safe to say that most ferrets that "die of old age" die of cancer. The cause of this truism is not clear, but unlike most animals that die of organ failure (liver failure, kidney failure, heart failure, etc.), ferrets die of a variety of unusual forms of cancer. Insulinoma is reported to be the second most common cancer of ferrets, second only to adrenal cancer. As many as 25% of all ferrets may develop this form of cancer. They occur in both male and female ferrets, as young as two years of age up to "old age," five to eight years. Early spay or castration has not been shown to increase a ferret’s chances of having this form of cancer, nor has diet.

Symptoms

A ferret with early stages of insulinoma may show very subtle signs. The ferret may stare into space as if it is in a trance. It may seem tired or may lack energy. As the disease progresses the ferret acts increasingly weak. It may drag it’s back legs or be too weak to climb. The ferret may retch or paw at it’s mouth as if nauseous. With advanced disease the ferret may become unconscious or have seizures caused by very low blood sugar levels. Other signs that may occur with insulinoma include vomiting, and black, tar-like diarrhea. If left untreated signs may progress to coma and the death of the ferret.

Diagnosis

Insulinoma is tentatively diagnosed on the basis of history, physical signs and tests that show low blood sugar levels. The disease is confirmed by tests showing high blood insulin levels and evaluation of cancer tissue removed at surgery. These tests must be performed by a veterinarian and there is some interpretation of results required. There are times when a ferret with an insulinoma may have normal blood sugar and normal insulin levels. The tests are best performed following a two to three hour fast. Longer fasts may give a falsely low blood sugar reading. Tests taken when blood sugar is very low, especially if it has been low for some period of time, may give a falsely low blood insulin level.

Treatment

Insulinoma is treated with a combination of medical and surgical therapy and, in some cases dietary changes. Medical treatment consists a steroid, prednisone, and in difficult to control cases, an insulin blocking drug, diazoxide. The prednisone acts to change the way the ferret’s body uses sugar. This greatly reduces the high and low sugar levels responsible for the symptoms caused by the tumor. Diazoxide helps to block the effect the insulin has on body tissues. Prednisone is very inexpensive and comes in both small dosage pill and liquid forms. Diazoxide is very expensive and comes as a liquid and a pill, however the pill form is difficult to reduce to a small ferret dosage.

Once stable, surgery may be recommended. The goal of surgery is to slow the progress of the disease. Insulinoma tumors metastasize or spread to other locations in the ferret’s body very early in the disease. This makes a surgical cure highly unlikely. However, removal of the primary tumors appears to significantly slow the progress of the disease.

Surgery is most often recommended after two to three weeks of medical treatment has been completed and the ferret has become medically stable and stopped showing signs of low blood sugar. In the author’s practice, ferrets undergoing surgery for insulinoma spend two to three days in the hospital. The surgery is performed on the first day. The ferret is prepared for surgery early in the day. An catheter is placed in a vein in the front leg and the ferret is started on a constant infusion of fluids including glucose (sugar). This reduces the risks of anesthesia and surgery in these patients.

Isoflurane, an inhaled gas anesthesia, is administered, first by a mask and then through a tube placed in the patient’s airway. The abdomen of the ferret is shaved from the middle of it’s chest to the inside of it’s thighs and the skin of it’s abdomen is washed and sterilized. An incision is made from just below the umbilicus (the belly-button) to the zyphoid process (the point at the bottom of the sternum). The tumor (or tumors) are located in the pancreas and the abdomen is examined for other forms of cancer and other problems. A common finding at surgery is the presence of a large spleen or adrenal cancer. If present, these problems would be addressed at the same time. The abdomen is closed with three layers of sutures and surgical staples.

Pain medication is given prior to the time the ferret awakens from the anesthetic and repeated in the evening. Further pain medication is usually not required. Intravenous fluids are continued until the patient is eating on it’s own.

Prognosis

Long term outlook for ferrets with insulinoma are considered "guarded" in that the disease is not curable in most cases. Survival of patients in the author’s practice range from several months to as much as four years. Best results are obtained when the disease is diagnosed and the ferret treated early in the disease process. If surgery is postponed, the number of secondary (metastatic) tumors spreading to other tissues in the body increases and the effects of the tumor will be more difficult to manage medically.

Most ferrets do well on medication following surgery. Eventually (months to years post-surgery) adjustments in the dosage of medication will be required and eventually the blood sugar levels may become very difficult to control and result in the eventual euthanasia of the patient.

Experimental treatments

The author has experimented with chemotherapy aimed at killing the cancer tissue. Two drugs have been used to treat insulinoma in other species and hold promise for treating the disease in ferrets. These drugs are highly toxic to insulin producing cells and have been used in medical research to produce diabetic animal models (animals that can not make insulin). This research is in very early stages and their routine use of these drugs is many months to years away.

Prevention

At this time there is no known way to prevent this disease. Some authors recommend not feeding sugary treats and keeping your ferret physically fit. Good diet and husbandry are always recommended.

Conclusion

In summary, insulinoma is a very common cancer of ferrets. Signs of the disease may include trance-like staring, lack of energy, loss of attention, weakness, nausea, and convulsions. It is caused by cancer of the insulin producing cells of the pancreas. The disease is significant and ferrets showing signs of insulinoma should be attended by a veterinarian familiar with ferrets and experienced in the surgery to correct this disease. The disease is diagnosed with a combination of history, physical signs and lab tests. Treatment consists of both medical and surgical treatment and, someday, may include a chemotherapy protocol aimed at killing the tumor cells. Treatment is not curative but will greatly enhance the quality and in most cases quantity of life, especially when initiated early in the course of the disease.

Signs of insulinoma
(In order of progression)

• Trance-like Staring
• Lack of energy
• Weakness
• Hind leg paralysis
• Nausea / Pawing at mouth
• Muscle tremors
• Seizures
• Coma
• Death

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