Ferret insulinoma: State of the union (Proceedings)
Pancreatic islet beta cell tumors, more commonly known as insulinomas, have been well recognized and well documented in ferrets over the last 20 years. Insulinoma nodules within the pancreas secrete high levels of insulin and cause hypoglycemia. Clinical signs include lethargy, weight loss, weakness, ptyalism, bruxism, seizures, and death. Treatment modalities include medical therapy, chemotherapy, surgery, and dietary changes. The underlying etiology of insulinoma is unknown, however a nutritional hypothesis has recently been offered along with a prevention strategy based upon feeding a more natural, archetypal diet.
Insulinoma is by far the most common neoplasm in middle-aged to older ferrets, with a reported incidence of 21.7% to 25% of neoplasms diagnosed. Most ferrets begin exhibiting clinical signs around 4-6 years of age, although it has been reported in ferrets as young as 2 weeks of age. It is likely that islet cell tumors exist subclinically for months or years before symptoms occur.Insulinomas appear to occur regionally; most have been reported in North America, where the majority of ferrets are fed dry kibble, and many are fed treats that contain sugar. Insulinomas are uncommon in Europe, New Zealand and Australia, where ferrets are fed a low-carbohydrate diet of meat scraps, poultry scraps, and/or fish scraps, and sugary treats are generally not provided. The typical ferret diet in the US contains 22-42% protein, 15-28% fat, 10-45% carbohydrate, and 1.5-3.5% fiber. Such high levels of carbohydrate are unnatural and may have negative consequences for the ferret. Finkler hypothesizes that excessive carbohydrate intake stimulates excessive insulin production by the pancreas and results in compensatory hyperplasia. He postulates that lifelong stimulation of pancreatic beta cells leads to a hyperinsulinemic "preinsulinoma" state and eventually to the development of beta cell neoplasia.
Domestic pet ferrets in the U.S. are supplied by a small number of breeders, thus limiting their genetic diversity, and suggesting that the development of insulinomas may have a genetic component. Finally, it is thought that keeping ferrets indoors the U.S. (versus outdoors in other countries) may contribute to the propensity of endocrinopathies in ferrets in the United States.
The pancreas plays a major role in glucose, lipid, and protein metabolism through the balance of its two major hormones, insulin and glucagon. Insulin, a polypeptide produced by beta islet cells, is released when levels of glucose, amino acids, and free fatty acids are increased in the blood. In the case of a sudden increase in the blood glucose level, the plasma insulin level can increase almost 10 fold within minutes. Insulin then causes a rapid uptake of glucose into peripheral tissues and promotes the storage of glucose in the muscle and liver. Additionally, insulin inhibits hepatic gluconeogenesis and glycogenolysis, and promotes the conversion of excess glucose into fatty acids. The net effect of all these processes is a decrease in blood glucose levels. Glucagon is secreted by alpha cells in response to decreasing glucose levels and is involved in effects that are exactly opposite to those of insulin, namely, an increase in the blood glucose level.
Insulinomas produce their effects through the overproduction of insulin. Theses tumors secrete insulin indiscriminately and are not responsive to inhibitory stimuli such as hypoglycemia or hyperinsulinemia. Additionally, a rapidly increasing blood glucose level, even in the presence of a low blood glucose concentration, can stimulate excessive insulin release from these tumors, causing a profound rebound hypoglycemia. Although local tumor recurrence is common, metastasis to other organs is not. This finding is in contrast to insulinomas found in dogs, which are usually malignant and metastatic. When insulinoma metastasis does occur in a ferret, the regional lymph nodes, liver and spleen are the organs most commonly involved.
Onset of symptoms may be gradual or sudden. Appetite may be normal or decreased, and weight loss may be noted. Advanced insulinomas result in hypoglycemia, causing weakness, anorexia, lethargy, stupor, and seizures. Owners may report that the ferret's eyes appear "glazed" during episodes. Hypersalivation and pawing at the mouth (presumably due to nausea, numbness, or tingling) also occur. Owners may present the ferret with concern that the patient has swallowed something noxious or has something stuck in its mouth. Affected ferrets may present with hind limb paresis or ataxia, as if nerve damage has occurred. Corticosteroid injection, which raises blood glucose levels, may improve symptoms, leading the practitioner to believe the problem is spinal trauma or disk disease when, in fact, hind limb paresis in the ferret is a nonspecific indication of weakness.