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Written by Dr. Bruce Williams, DVM:
The following article may be reprinted by anyone desiring to disseminate this information in a newsletter or non-commercial publication. This material may not be altered or changed in any way. Under Title 17 of the U.S. Code, Section 105, copyright protection is not available for any work of the United States Government.
"My ferret is losing its hair."
While hair loss in the ferret can occur from many causes, I would like to concentrate on what is the most common and what is becoming the most commonly talked about reason for serious hair loss -- proliferative lesions of the ferret adrenal gland.
Ferrets with adrenal lesions - including areas of hyperplasia as well as both benign and malignant neoplasms of the adrenal cortex - typically all show the same clinical signs regardless of which type of growth is present. These signs are fairly diagnostic, and in the majority of cases, are so characteristic that no other diagnostic tests are required before therapy is instituted.
The signs of adrenal disease in the ferret are well documented (Fox et al., 1987, Lawrence et al. 1993, Rosenthal et al., 1993, Lipman et al, 1993) although the cause of these signs is still somewhat unclear. Adrenal lesions may be seen in animals ranging from one to seven years of age, with the average being around 3.5 years. In one study (Rosenthal, 1993), 70% of affected ferrets were female. Hair loss, or alopecia, is by far the most common clinical sign in affected ferrets. Hair loss often begins at the tail, and progresses forward over the trunk, flanks, and abdomen, until hair is only present on the neck, head, and the extremities. Additionally, in spayed females, the vulva will often become swollen to the extent that the owner may erroneously believe that the animal is in estrus. A watery mucus discharge from the vulva may also be seen in this animal. (Vulvar swelling in a spayed female on its own is sufficient cause to warrant abdominal exploratory surgery). Other clinical signs that may be seen in ferrets with adrenal lesions include increased scratching, excessive drinking and urination, anemia, weight loss, and in long-standing cases, difficulty in using the hind legs.
The cause of the hair loss and vulvar swelling is not currently known. In other species with hyperadrenocorticism, high circulating levels of adrenal corticosteroids cause the hair follicles to atrophy and the skin itself to become thin, resulting in hair loss. But since we know that these ferrets do not have these high levels of cortisone, this explanation does not suffice for what we see clinically. A plausible theory has been advanced by specialists at the Animal Medical Center in New York City. (Rosenthal, 1993). Citing the fact that 36% of affected ferrets have high blood levels of estrogen, the believe that early neutering (most ferrets in the U.S. are neutered before six weeks of age) cause a population of cells in the adrenal gland which have retained the ability to secrete gonadal hormones to grow, in essence "filling the void". High levels of estrogen are well known to also cause hair follicle atrophy, and would also cause vulvar swelling in females, as is seen in estrus. In fact, Dr. Rosenthal has demonstrated that serum estrogen levels are indeed higher in ferrets with adrenal disease.
The treatment for adrenal disease in ferrets primarily involves removal of the affected adrenal gland. [If money is an object, Dr. Tom Kawasaki in Woodbridge VA, will probably do it for less than $300 (and he has done many more than most vets).] In most cases, adrenalectomy is performed based solely on clinical signs. Routine pre-surgical blood work should be performed in all animals over 4 years of age, as would be done for any other type of surgical procedure. Special diagnostic tests which are used in other species to diagnose adrenal disease are rarely of use in the ferret. Specific testing for estrogen levels in the ferrets is not commonly available, even at diagnostic labs, and in most cases is not necessary to confirm the diagnosis.
In most cases, one gland is noticeably larger than the other and is removed. For unknown reasons, the left adrenal gland accounts for the majority of lesions (64%), with the right adrenal gland accounting for 26%, and 8% of ferrets having disease in both adrenals. Removal of one adrenal gland is generally well tolerated in ferrets and in most of these cases, if disease is confined to that gland, clinical signs will cease (i.e., the hair will grow back and the swollen vulva will diminish to its previous size). In animals with bilateral disease, removal of one gland and part of another has been done, but carries a more significant risk of post-operative complications.
The surgery itself is not excessively difficult. Removal of the left adrenal is fairly easy and has a low risk of complication. Due to the position of the right adrenal near several large blood vessels, it is a more difficult surgery and requires considerably more expertise on the part of the surgeon. As always, if your veterinarian has little expertise in performing this surgery, it is wise to ask for a referral to a more experienced surgeon. In cases in which surgical excision of the offending adrenal gland is not an option, medical treatment with certain drugs that kill off a large portion of the cells of the adrenal cortex may be tried. Unfortunately, this medication is not specific for estrogen-secreting cells, and affect all of the other cortical cells as well. For this reason, this form of treatment should be reserved only for those animals who are poor surgical candidates.
Unfortunately, not all adrenal surgeries end happily. Postoperative mortality averages from 10% (Tom Kawasaki, personal communication) to 12.5% (Rosenthal, 1993). The cause of the post-surgical mortality is not known; most theories center on the inability of the other, unaffected adrenal gland to produce enough cortisol on short notice, i.e., the hyperfunctioning gland has caused it to atrophy.
On a personal note - while some owners believe that hair loss is only cosmetic and would "rather not put their pet through the stress of an operation", let me categorically state that the changes seen in ferrets with adrenal disease are cumulative and progressive. Animals with adrenal lesions do not just lose their hair - they also lose muscle mass, and have little energy. While the lesions themselves are rarely life-threatening (in over one-hundred twenty cases, I have only seen two cases of tumor metastasis), their clinical manifestations are debilitating and greatly decrease the quality of a ferret's life. (When I noticed the signs of adrenal disease in one of my ferrets who was six at the time - I had the surgery done immediately. The hair has grown back, the vulva has reattained its normal size, and she is more fit than ever.)
Adrenal disease in the ferret is common, and if detected by a watchful owner or a knowing practitioner, can be easily treated.
Get those hairless ferrets checked, and have a festive ferret-filled holiday season.
1. Fox J.G, et. al. Hyperadrenocorticism in a ferret. JAVMA, 191: 343, 1987.
2. Lawrence, H.J. et al. Unilateral adrenalectomy as a treatment for adrenocortical tumors in ferrets: Five cases (1990-1992). JAVMA 203: 267-270, 1993.
3. Lipman, N.S. et al. Estradiol-17B-secreting adrenocortical tumor in a ferret. JAVMA 203(11): 1552-1554, 1 Dec 1993.
4. Rosenthal, K.L. et al. Hyperadrenocorticism associated with adrenocortical tumor or nodular hyperplasia of the adrenal gland in ferrets: 50 cases (1987-1991). JAVMA 203: 271-275, 1993.
Bruce Williams, DVM
In various articles and messages, Dr. Williams has written:
from Ferret Senior Citizens and their Special Needs
Midwest Bird and Exotic Animal Hospital:
This cancer is almost as common as insulinoma and commonly occurs along with it. This is a cancer of the adrenal glands, which are very tiny organs about the size of half a pea, located near the kidneys. They produce very potent hormones that control a number of metabolic functions in the body. Most ferrets develop adenoma, which is the benign form of the disease (which means that it does not spread to other organs of the body). Adenocarcinoma is the malignant form that we see less commonly. Many ferrets develop the cancer in only one gland.
Signs are fairly specific and they are related to an overproduction of corticosteroids and estrogen by the diseased adrenal. They include: hair loss over a portion or all of the body, a decrease in coat quality (becomes dry and brittle), thinning of the skin, thinning of the musculature of the body, lethargy, and occasionally drinking more water and urinating more frequently. The hair loss may be intermittent, with periods of regrowth. The skin may become intensely itchy and develop red patches, scaling and flaking. Fat tends to accumulate in the abdomen and combined with the thinning musculature and skin, gives a pot-bellied appearance to the animal. Some spayed females may develop vulvar swelling as if they were in heat again.
Diagnosis is based primarily on the signs as described above. Treatment of choice is the removal of the affected adrenal gland. However, sometimes the disease is advanced, and both adrenals are affected or other disease precludes the possibility of surgery. In these cases the use of a drug called Lysodren [also known as Mitotane] can be very effective. It chemically destroys the adrenal tissue gradually until a more normal hormone level is reached and the symptoms regress. Even if no treatment is elected for specific reasons, this tends to be a slowly progressive disease, and many pets live 6 months to over 2 years, bald, but happy.
According to Dr. Charles Weiss, DVM:
There are many signs of adrenal tumors in ferrets. The first sign is usually hair loss. The loss of hair can involve only the tail or involve the whole body. Other symptoms include pruritis (itchy skin), swollen vulva (females), return to sexual behavior in neutered males, skin that is thin and dry, and abdominal distention. Unfortunately there is no reliable blood test. It is important to note that the tests we use to diagnose adrenal gland problems in dogs and cats (called Cushings Disease -- a completely different disease) have been proven to be ineffective to diagnose adrenal tumors in ferrets.
The bottom line is... Yes, hair loss is usually the first symptom and the ferrets don't feel sick at this point.
And, from Dr. Williams:
To start, the disease is not Cushings, because Cushing's disease is an oversecretion of cortisone, not estrogen from the adrenal. This is a common mistake that many vets have. ACTH is not the hormone that is secreted, but estrogen, and ultrasound is not a very selective choice, becuase it has a high rate of false negatives. [Thyroid and cortisol blood tests, including the ACTH stimulation test, won't tell you anything about adrenal-associated endocrinopathy -- adrenal disease -- in ferrets.] The best choice is the endocrine panel at Univ. of Tennessee in terms of catching silent or marginal cases. Ultrasound may confirm a diagnosis, but contemplation of surgery should include more than an ultrasound exam, as so many adrenal lesions may be missed.
Dr. Michael Dutton has made these comments, in various articles:
I went to the Tufts Ferret Vet Seminar about 4 weeks ago and listened to Dr. Karen Rosenthal from Animal Medical Center in New York City. She does tons of ferrets. The ultrasound technician they use has been doing this for 17 years and she feels is one of the best animal ultrasound people. In the technician s experience, he detects less than 50% of adrenal tumors. We are seeing a lot of male, neutered ferrets develop prostate problems secondary to the testosterone/androgen secretions secondary to hyper adrenal disease. The prostates can be cystic, abscesses, malformed, etc. They can also close down on the urethra (the tube from the bladder to the tip of the penis) and cause a urinary tract obstruction. The treatment is to deal with the adrenal disease.
According to Dr. Bruce Williams, DVM, on 3 Feb 1995:
The test is available to private practitioners from the Endocrinology lab at the University of Tennessee (see below).
The ferret adrenal panel consists of assays for four hormones - dihydroepiandrosterone sulfate, estradiol, androstenadione, and 17-OH-progesterone. These are hormones and pre-hormones that are produced by the hyperfunctioning adrenals. According to Dr. Rosenthal, in over 90% of cases - one or more of the hormones will be elevated. In one case, when only the estradiol is up, however, you have to rule out an ovarian remnant (very rare), or the possibility of an intact ferret. If more than one is up, though, it is very diagnostic of adrenal-associated endocrinopathy.
Let me reiterate, however, that this test is mostly of use for ferrets in which the signs of adrenal disease are questionable. I would still recommend surgery alone for cases of marked bilateral hair loss, or the presence of an enlarged vulva in spayed ferrets. I don' think the test adds any extra information to your diagnosis over these fairly obvious clinical signs.
The cost to your vet for this test is $75. 0.5-1.0 cc of serum is required. As a bonus, if the results are confusing to your vet, Dr. [Karen] Rosenthal is available for consultation and interpretation at (212) 838-8100.
The tests are done one week during each month. Contact Dr. Oliver or Kim Abney at (423) 974-5729 or 974-5576,
University of Tennessee College of Veterinary Medicine
Clinical Endocrinology Lab
Dept. of Comparative Medicine
2407 River Drive, Rm. A105 VTH
Knoxville, TN 37996
According to Dr. Bruce Williams, DVM:
Recently, I completed a study of adrenal tumors in ferrets. I studied all types and out of 86 tumors, 39 were malignant. But of all 39 carcinomas, only 2 showed signs of metastasis. The vast majority, even though they looked bad, were surgically removed and the animal went on to grow all its hair back and live for another several years.
I recommend all adrenal tumors be removed, no matter how bad they look. These tumors tend to look a lot worse than they are.
As Dr. Williams says above [1], ferrets need at least a portion of one adrenal gland to live. If your ferret has had one adrenal removed and now has problems in the other one too, your best bet is probably a partial adrenalectomy -- that is, have only part of the second gland removed.
If that's not possible because too much of the second gland is affected, a full bilateral adrenalectomy may be your only choice. Try contacting Dr. Joseph Bock of Golden, CO at 303-494-4344 for more information on maintaining a ferret using replacement hormones.
Lysodren, a medication commonly given to dogs and cats with adrenal tumors, should be used only as a last resort. Dr. Williams says, "Most vets that are doing a lot of ferrets report poor response to Lysodren, and in the cases that I have seen, the results are very unpredictable." Another name for Lysodren is Mitotane.
Ferrets can take a long time to grow hair back, often not until their next coat change.
According to Dr. Bruce Williams, DVM:
There are several factors that may delay hair regrowth in ferrets following adrenalectomy. One would be continued hyperactivity of the remaining adrenal. A second reason may be the duration and severity of the presurgical hyperestrogenism. As excessive estrogen causes atrophy of hair follicles, the hair follicles may take a long time to return to full (hair-producing) function. It may also take the stimulus of a change in season which normally causes the shedding cycle to begin to bring her back into line.
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