Managing endocrine disease in ferrets (Proceedings)

Ferrets remain popular pets in the United States. Although much of the historical literature suggests that these animals are long-lived (10-15 years), the average lifespan appears to be much shorter (5-9 years). One of the reasons for the shorter longevity of captive U.S. ferrets appears to be associated with the high incidence of endocrine diseases reported in these animals. Endocrine diseases in ferrets have been attributed to genetics, early-age neutering, diet, and photoperiod. The majority of the ferrets entering the U.S. pet trade are supplied by large breeding facilities. The fact that many of these animals share a common lineage, and that many of the endocrine diseases reported in captive ferrets are reported in these "farmed" ferrets, suggests that genetics may play a role in the epidemiology of endocrine disease. Ferrets produced in commercial breeding operations are neutered at an early age (<6 weeks) to reduce unwanted musk odors and concerns about estrogen induced anemia in jills. Early age neutering has been associated with the development of adrenal gland disease in other species, and may also be responsible for the disease in ferrets. The normal photoperiod for ferrets should follow a standard 12 hour cycle. Unfortunately, many captive ferrets are exposed to extended periods (>12-14 hours) of light. Extended light can lead to alterations in baseline hormone levels, resulting in endocrine disturbances. Ferrets are carnivores. Unfortunately, the diets offered to captive ferrets are comprised of a large proportion of plant materials (e.g., corn). Providing a less than optimal diet may contribute to the development of certain endocrine disease in ferrets. From these comments it is possible that there may be a number of factors that contribute to the epidemiology of endocrine diseases in ferret, and further work is required to characterize these risk factors.

Adrenal gland disease is a common presentation in geriatric (> 4 years of age) ferrets. Ferrets presenting with adrenal gland disease frequently have alopecia. The alopecia may be focal or generalized. Where there is hair loss, the skin may appear thin and smooth. Pruritis is reported in approximately 50% of cases. Muscle atrophy is frequently reported in ferrets and is generally observed over the spine and pelvis. Female ferrets presented with adrenal gland disease commonly have an enlarged vulva. In some of these cases, there may be a thick purulent vaginal discharge (vaginitis). Male ferrets with adrenal gland disease frequently have a return to aggressive behavior. Stranguria may also occur in male ferrets as a result of secondary prostatomegaly. Some of the ferrets presenting with adrenal gland disease are depressed or lethargic; however, the majority of the ferrets presented are bright, alert and responsive.

To confirm the presence of adrenal gland disease, a thorough diagnostic work-up should be performed, including a complete blood count, plasma chemistry analysis, hormone panel, urinalysis, radiographs, and ultrasound. Anemia or leukopenia may occur in cases with elevated circulating levels of estrogen. In general, the leukocyte count is within normal limits. Ferrets with concurrent insulinoma may be hypoglycemic (<80 mg/dl). The AST and CK may be elevated as a sequella to muscle necrosis. The ALT may be elevated in cases that involve the liver (e.g., metastasis). An androgen blood panel can be performed to evaluate different hormone levels. The androgens are generally elevated in ferrets with adrenal hyperplasia or neoplasia. Radiographs are often unremarkable, although it is important to perform them to rule-out other disease processes. Ultrasound is an important diagnostic that can be used to characterize the size of the adrenal glands, confirming an adrenomegaly, and assess their general location in association with the vena cavae.

Both medical and surgical treatment options for adrenal gland disease exist. The medical therapies are supportive in nature and are not curative. These techniques are well suited for geriatric ferrets or those that are not considered good anesthetic/surgical candidates. A number of different medical therapies have been attempted, including mitotaine, flutamide and luprolide acetate. The author has used both mitotaine and flutamide to manage adrenal gland disease in ferrets with limited success. The results with luprolide acetate are much more encouraging. Luprolide acetate is a GNRH agonist and can be administered (100-150 mcg/kg) every 6-8 weeks. The primary disadvantage associated with this drug is the expense. The author has administered luprolide acetate to more than 100 ferrets with exceptional results. The clinical signs, including the alopecia, muscle wasting, swollen vulva, or male aggressiveness, have resolved in more than 95% of the cases. If the ferret responds to the lupron treatment, the animal should be maintained on the drug for life. One exception would be in adrenal hyperplasia cases that fluctuate seasonally.

Surgical removal of an affected adrenal gland(s) should be considered in cases that are considered a good anesthetic/surgical candidate. In general, the left adrenal gland is affected, although the right side can also be affected. An adrenalectomy can be performed in a manner similar to that described for dogs. Right adrenal glands that are in close apposition to the vena cavae may be difficult to remove. Laser or cryosurgery may be beneficial. Partial resection of the vena cavae may be necessary. Post-operative recovery is generally unremarkable. In cases where only one adrenal gland is removed, the contralateral gland frequently becomes affected at a later time.

Insulinomas are one of the most common emergency presentations for pet ferrets. Again, geriatric ferrets (>4 years of age) represent the majority of the cases. There is no apparent sex predilection for ferrets with an insulinoma. Insulinomas are beta-cell tumors of the pancreas. The tumors produce excess insulin, resulting in a hypoglycemia. Affected ferrets may present with weakness, paresis of the rear limbs, stargazing, or seizures. Blood glucose levels in ferrets are generally >80 mg/dl; however, ferrets with insulinomas may present with blood glucose values as low as 40 mg/dl. Ferrets that present with severe hypoglycemia (<50 mg/dl) should be catheterized (e.g., cephalic or lateral saphenous) and given intravenous glucose (5%).

The long-term management of these cases requires either additional medical treatment or surgical intervention. When offering these two treatment options to your clients it is important to consider both the age of the patient and financial resources of your client. When managing a ferret with insulinoma, there are two chemotherapeutics that are generally used. Prednisone stimulates gluconeogenesis and glycogenolysis and reduces the peripheral uptake of glucose. In general, ferrets should be started at 0.5 mg/kg BID. As the ferret becomes refractory to the drug the dose may be increased. Diazoxide also stimulates gluconeogenesis and glycogenolysis, but it also inhibits insulin release at the level of the beta cells. Diazoxide may be used in combination with the prednisone or as a sole chemotherapeutic. This drug is expensive and clients may expect to pay between $30-50/month. Although surgery provides the greatest likelihood for treatment, it may be difficult to remove all of the neoplastic masses because of their small size. The prognosis for these cases is generally poor to guarded.