Adrenal gland disease, Hyperadrenocorticism
Cushing’s disease of ferrets

AffectedAnimals:
The majority of ferrets develop signs of this disease in young middle age, when they are between three to four years old. Most ferrets with adrenal gland disease are neutered before the age of six weeks, but almost all ferrets in the United States are neutered by the time the disease presents. Both male and female ferrets develop this disease.

Overview:
Adrenal gland disease is a common problem in middle-aged to older ferrets. The disease results in one or both of the adrenal glands producing abnormal amounts of the androgens and/or estrogens, which are the male and female sex hormones. This disease can cause hair loss, itching, vulvar enlargement in females, and in rare cases, severe anemia and urinary blockage.

Because adrenal gland disease can be difficult to diagnose through routine bloodwork, it is often necessary to do specialized blood tests and ultrasound examination of the abdomen to diagnose adrenal disease. Physical exam findings and clinical signs often will lead to a suspicion of adrenal gland disease. Although clinical signs such as itching and hair loss are not life threatening, a ferret’s quality of life is impacted and, on rare occasions, the disease can lead to more serious complications. Treatment is best accomplished by surgery, although medical treatment is also possible.

Clinical Signs:
Alopecia is usually the first and sometimes the only sign of adrenal gland disease in ferrets. It can be present on the tail, rump, ventrum, and dorsum. The hair will epilate easily and the skin can appear flaky, inflamed, and erythematous. In unusual cases, the skin may become thin. It is not uncommon for alopecia to begin in the late winter and early spring. In younger ferrets with this disease, the hair will regrow in the late summer, but then alopecia will return the next winter or spring. Pruritus can accompany the alopecia although a number of ferrets may develop just pruritus with no other signs.

The vulva is enlarged in over 90 percent of females with this disease. Vulvar enlargement may be accompanied by vulvar discharge and vaginitis. Approximately one-third of the ferrets with adrenal gland enlargement have a palpable mass that can be felt next to the kidney. Some male ferrets will exhibit stranguria and dysuria. Older neutered ferrets may also begin to act intact and show signs of sexual aggressiveness towards other ferrets.

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Symptoms:
Typically, ferrets will begin to lose their hair around their tail base. Hair loss usually progresses to involve the sides and belly of the ferret. Some ferrets with adrenal gland disease will scratch incessantly. A few male ferrets will develop a urinary tract blockage with this disease and will have difficulty urinating. In many cases, female ferrets develop a large vulva.

Description:
There are two adrenal glands that are each located next to a kidney. The gland has two major layers that function as two different endocrine organs. The outer layer is called the adrenal cortex and it makes steroid hormones such as sex hormones, glucocorticoids, and mineralocorticoids. The inner layer is called the adrenal medulla and it makes catecholamines such as epinephrine.

In ferrets, adrenal gland disease occurs when one or both of the adrenal glands produce abnormal amounts of the sex hormones called androgens and/or estrogens. Very rarely, the overproduction of androgens can cause the development of two serious complications: bone marrow suppression resulting in anemia, a decrease in red blood cell formation, prostate enlargement in male ferrets, a condition which blocks the flow of urine.

Adrenal gland disease mainly affects middle age to older ferrets. Although not usually a serious health concern, ferrets may have no relief from the itching that is associated with this disease if it is not treated.

It is important to realize that adrenal gland disease is not the same condition as Cushing’s disease, which affects dogs. Dogs can also develop adrenal problems, but their dysfunction does not involve the overproduction of sex hormones. Serum cortisol concentrations are normal in most affected ferrets and they also have a normal response to the ACTH stimulation test. A more appropriate term is hyperadrenocorticism or adrenal gland disease.

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Diagnosis:
Physical examination is an important part of diagnosing adrenal gland disease. Diagnosis typically is suspected based on clinical signs because there are few other diseases in ferrets that exhibit the same group of symptoms. In clinical cases, the urine cortisol:creatinine ratio has not been shown to be useful to diagnose this disease. Since cortisol concentrations rarely are elevated due to this disease, blood tests such as an ACTH stimulation test and low or high dose dexamethasone tests will not diagnose this disease either.

At present, the best way to diagnose this disease definitively, short of doing exploratory surgery, is with a specialized blood test called an adrenal androgen panel offered by the University of Tennessee. Ferrets with adrenal gland disease have elevated plasma concentrations of androgens and/or estrogens. A baseline plasma sample should be taken to measure androgen and estrogen concentrations. Elevations of these hormones may indicate the presence of adrenal gland disease. An ultrasound of the abdomen may show an enlarged adrenal gland—also confirming the presence of this disease.

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Prognosis:
Uncomplicated cases with surgical removal of the adrenal gland usually carry an excellent prognosis. If the ferret is not treated for this disease, the lasting problems may only be cosmetic, such as hair loss and an enlarged vulva. Serious health concerns that can arise due to untreated adrenal gland disease include urinary blockage in male ferrets, which is rare, and anemia, which is even less common.

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Transmission or Cause:
The cause of adrenal gland disease is unknown. The affects of this disease are caused by the over-production of androgens and sex steroids by the adrenal gland.

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Treatment:
Until medical treatments are well studied, surgery is still the best treatment. The abdomen is examined for any abnormalities and the abnormal adrenal gland is removed. If both adrenal glands are abnormal, either the larger gland is removed and the other gland is partially removed, or both glands are removed. When both glands are removed, life-long supplementation may be necessary.

The right adrenal gland is more difficult to remove because it is attached by a ligament to the vena cava and may even invade the vena cava. Laceration of this large vessel, one of the major veins that returns blood to the heart, may occur if great care is not used in the right adrenal gland removal.

A number of drugs have been proposed to treat adrenal gland disease including mitotane, Lupron®, Flutamide®, and Arimidex®. Mitotane shows equivocal results in ferrets. Lupron® is a GNRH analog that may have some use in controlling adrenal gland disease. Flutamide® is an androgen blocker that may be most useful in ferrets with prostatic enlargement. Arimidex® is an aromatase inhibitor and should decrease the effects caused by androgens in the ferret.

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Prevention:
There is no known way to prevent this disease or to predict which ferrets will develop this disease.

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