I.  Adrenal Cortical Disease

Adrenal disease is most common in ferrets over 3 years of age with sporadic occurance in younger ferrets. This is a primary disease of the adrenal gland that results in overproduction of steroid hormones. Several hormones may be involved: androgens can be high and cortisol levels normal. This is not the typical Cushing's disease seen in dogs.

Clinical signs include varying degrees of alopecia, generalized pruritus, and in some spayed females, a swollen vulva may result. Owners may report a stronger than usual odor. Some males become aggressive and behave like intact males (effects of testosterone). PU/PD is not seen as in dogs. Urinary tract outflow problems can be seen in some ferrets with long standing adrenal androgen elevations (see below). Bone marrow suppression with subsequent anemia and thrombocytopenia may be a result of chronic overproduction of estrogens by the adrenal tumor.

Diagnosis is based on clinical signs, palpation of adrenal glands, ultrasound, and ultimately, adrenal biopsy. Routine blood tests used to diagnose adrenal disease in the dog or cat (e.g., stimulation and suppression tests) are not diagnostic. Plasma androgen panels are commercially available (University of Tennessee Vet School in Knoxville) and are helpful in some cases.

Treatment involves surgical removal of the affected gland. In a small number of cases, both glands may be affected. Removal of one gland and biopsy of the second or removal of both glands is recommended in these cases. Post-operative Addisonians are unusual in cases of bilateral adrenal gland removal, but follow-up with electrolyte testing and prednisone replacement should be considered. Metastasis is rare; surgery is usually curative. Histopathology of the affected adrenal gland includes hyperplasia, adenoma, and adenocarcinoma of the adrenal cortex.

Cystic Urogenital Disease ("Prostatic Disease")

This is a well recognized "syndrome" seen in neutered ferrets with hyperadrenalcorticism. A cyst-like structure can develope around the urethra at the trigone area of the bladder and results in cystitis, dysuria, and urinary obstruction. Some of these ferrets present for urinary tract problems before outward signs of adrenal disease developes (i.e., alopecia). Histologically, the cyst resembles prostatic tissue. It is thought that the overproduction of adrenal androgens stimulates hyperplasia of vestigial urogenital tissue in this area, resulting in mechanical outflow obstruction. Although this is seen mostly in male ferrets, we have occasionally diagnosed this in spayed females.

Diagnosis is based on clinical signs, palpation, radiographs, or ultrasound. On palpation the caudal abdomen may feel like a "double-bladder". Sometimes a soft-tissue density may be seen above the bladder in the sublumbar area. Ultrasound may be the best diagnostic test to image the cysts. Grossly, they appear to be fluid-filled cysts dorsal to the bladder and may be continuous with the bladder lumen. Aspiration of the cyst reveals urine or a thick cloudy material. Correction is surgical; the affected adrenal gland must be removed and the cysts aspirated or resected. Culture and sensitivity of the cyst fluid is recommended. Often the cystic structures will receede once the androgen levels are reduced.

Medical Therapy for Adrenal Disease

Traditional medical therapies (Lysodren^®) has variable effects and is not considered effective. New hormonal therapies for adrenal disease in ferrets is currently being researched (Dr. Cathy Johnson-Delaney, WA and Dr. Charles Weiss, Potomac, MD). Experimental treatment with the human GnRH agonist, leuprolide (Lupron^®) is underway. Lupron decreases levels of testosterone and estrogens. Lupron comes as powder that needs to be reconstituted. Long term stability is unknown (60 days in freezer is OK). It comes as a 1 month (ferret dose = 200-500ug) or 4 month (dose = 2 mg) depot injection. The 4 month injection may alleviate clinical signs as long as 7 months (per Dr. Weiss). These drugs are very expensive, e.g., wholesale cost of the 4 month shot is about $200 (from a compounding pharmacy that will break it down into aliquats, 800 832-9285, (otherwise about $2000 per vial).

Other experimental drug therapies include Arimidex^®) and Casodex^®. Arimidex (0.1mg/kg daily) blocks testosterone conversion into estrogen. Casodex^® inhibits testosterone and may be useful for those male ferrets that are straining to urinate. The ferret dose is 5mg/kg daily until signs resolve, then pulse dosing (1 week on/ 1 off) for life.

Hormonal treatment of adrenal disease only alleviates clinical signs. It appears that these drugs have no obvious effect on the tumor size or growth. Surgical excision is still the treatment of choice but in some cases where surgery is not an option, "informed-consent" use of these drugs may be indicated.

II.  Insulinoma

Pancreatic beta cell tumors (insulinomas) are the most common disorder seen in ferrets over 3 years of age. There is an overproduction of insulin by pancreatic islet cells resulting in hypoglycemia. Clinical signs are attributable to hypoglycemic episodes: hindlimb weakness, ataxia, hypersalivation, increased amounts of sleeping, glazed eyes or stuporous appearance. Seizures are usually seen only in advanced cases. Onset is often insidious and many owners miss the early signs of the disease.

Diagnosis is based on clinical signs, and hypoglycemia (<60mg/dl). Insulin levels are not reliable; i.e., values can be normal in an affected ferret (IRI assay normals up to 250 pmol/L). Elevated plasma ALT levels are sometimes seen on a biochemistry profile. Radiology and ultrasonography are non-diagnostic but are useful screening tests in older ferrets.

Treatment can be medical or surgical or a combination of both. Medical therapy is designed to increase the blood glucose concentration. Prednisone (Pediapred^® @ .5 - 2 mg/kg/ PO BID) is used for its' gluconeogenic effects and is the first line of treatment. Diazoxide (Proglycem^®) is added if and when hypoglycemic episodes return (5 - 30 mg/kg PO BID, start low and increase prn). Proglycem can be formulated through compounding pharmacies to make the drug cost effective and available. Surgical treatment involves excising individual nodules or partial pancreatectomy. Histopathology usually reveals adenocarcinoma, although adenoma and hyperplasia are also seen. Metastasis to other tissues (liver) can occur but is uncommon. Most insulinomas will recurr making treatment palliative and not curative. Fortunately, this is a slow, chronic process and once diagnosed, ferrets can live 6 - 24 months with appropriate therapy. Prognosis varies and depends on the age, degree of metastasis, and chosen therapy (medical or surgical). The best possible case would be early diagnosis, and partial pancreatectomy.

References and Recommended Reading

1.  Li X, Fox JG, et al: Cystic urogenital anomalies in ferrets (Mustela putorius furo). Vet Pathol 1996; 33: 150-158.

2.  Rosenthal KL, Peterson ME, et al: Hyperadrenalcorticism associated with adrenocortical tumor or nodular hyperplasia in ferrets: 50 cases (1987-1991), JAVMA 1993; 203: 271-275.

3.  O'Brien RT, Paul-Murphy J, et al: Ultrasonography of adrenal glands in normal ferrets. Vet Radiol Ultra 1996; 37: 445-448.

4.  Rosenthal KL, Peterson ME: Evaluation of plasma androgen and estrogen concentrations in ferrets with hyperadrenocorticism. JAVMA 1996; 209: 1097-1102.

5.  Caplan ER, Peterson ME, et al: Diagnosis and treatment of insulin-secreting pancreatic islet cell tumors in ferrets: 57 cases (1986-1994). JAVMA 1996, 209: 1741-1745.

6.  Quesenberry KE, Rosenthal KL: Endocrine diseases. In Hillyer EV, Quesenberry KE (eds.): Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery. WB Saunders Co, Philadelphia, 1997

7.  Weiss CA, Williams BH, Scott, MV: Insulinoma in the ferret: clinical findings and treatment comparison of 66 cases. JAAHA, Dec. 1998, pp 471-475.

*Video available from Dr. Charles Weiss (Poolesville, Maryland) "Common Ferret Surgical Procedures Vol 1: Insulinoma and Adrenal Disease"