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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
Dr. Williams is available to help with diagnoses and answer questions.
Adrenal disease is caused by a tumor or growth in the adrenal gland. These growths can be malignant tumors, benign tumors, or something called hyperplastic tissue (bigger than normal cells but not quite fitting the definition of cancer). These cells no longer follow the normal negative feedback loop. That is, when levels of hormones or steroids that the adrenal normally secretes gets too high, the adrenal normally stops secreting them until they are back in the normal range. These tumors just keep pumping out the hormones and steroids. What hormones and/or steroids get pumped out results in the symptoms the ferret exhibits (aggression, swollen vulva, hair loss, prostate enlargements, etc.) The last piece of information is that the adrenal gland has a high regeneration capacity. You cut out half of one and it will regrow over a relatively short period of time.As for the cost of the surgery, it varies widely just like human surgery prices do. A lot has to do with the local economy, veterinary pricing structure and equipment. Ironically, the more ferret work a vet does, the more he/she usually has invested in equipment to do ferret work. The result is better medicine for the pet but with a corresponding higher cost.
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.
Adrenal Cortical Disease (ACD) is most commonly seen in middle-aged to older ferrets, but has been seen in ferrets under one year of age that were ovariectomized/orchiectomized at 4-12 weeks of age. It commonly occurs concurrently with insulinomas. Changes can be: adrenocortical hyperplasia, adenoma, or adenocarcinoma. Metastasis is rare, but has occurred with adenocarcinoma. The major clinical signs are alopecia, particularly of the tail and rump, and in the female, a swollen vulva. As the disease progresses in the male, prostatic cysts are common and may occlude the urethra. A non-specific pruritis, muscle atrophy, hindlimb weakness, and a return to sexual behavior in neutered ferrets may be seen. Signs are attributable to hyperadrenocorticism although estradiol, not cortisol, is the primary elevated hormone, occasionally along with other sex steroids.
Diagnosis is based on clinical signs, serum hormonal levels, ultrasonagraphic changes with confirmation at surgery, with histopathology of the excised gland or portion of the gland. ACTH stimulation tests are not useful. Serum estradiol [ref. 1 , below] and urinary cortisol:creatinine ratios may be more useful [ref. 2]. A serum endocrine panel is recommended in cases where estradiol may not be the only steroid involved [ref. 3]. An enlarged adrenal gland or glands may be detected on ultrasound. Predominantly the left gland is affected, but in approximately 10% both glands are involved. With bilateral adrenal involvement, the larger gland should be removed, and a subtotal adrenalectomy should be performed on the remaining gland. The right adrenal gland may be overlying and/or firmly adherent to the caudal vena cava, and in some instances there seems to be direct vascularization into the gland. There is often little maneuvering room to ligate or use hemaclips around the gland without damaging the cvc. During surgical manipulation of the gland(s), heart rate and blood pressure may dramatically increase, followed by a plunge in both following ligation. A biopsy of the pancreas should be done if insulinoma is suspected.
Postoperatively, the swollen vulva regresses in days, but the alopecia [hair loss] may take months to resolve. Some never fully regrow the hair to previous coat color/consistency. Prostatic cysts will regress at variable rates. Recurrence of the condition involving the remaining gland or tissue within a year is predictable.
If nonsurgical treatment is desired, a protocol using lysodren can be tried. Anecdotally, it works better in adenomas than in adenocarcinomas. In the author's opinion, chemotherapy should be utilized when surgery is no longer an option. Lysodren (mitotane) is used at 50 mg/kg PO SID 7 days, then at 25-50 mg/kg PO EOD ad infinitum depending on effects. In the author's experience, 100-250 mg per week per ferret may be needed. Leuprolide acetate [ref. 4] may be an extremely useful adjunct therapy along with the lysodren. Administered at 100 mcg/kg IM every 3 weeks, it suppresses sex steroidogenesis. It inhibits the growth of hormone-dependent tumors and tissues. Effects include reduction in size of the prostate or vulva, and hair growth through follicle reactivation. Use of this drug in ferrets is just being tried, but based on initial uses, it seems very successful.
References:
1. Wagner, RA, Dorn DP: Evaluation of serum estradiol concentrations
in alopecic ferrets with adrenal gland tumors. Journal Am Vet Med
Assoc 1994, 205(5): 703-707
2. Gould, WJ, Reimers, TJ, Bell, JA, et al. Evaluation of urinary
cortisol: creatinine ratios for the diagnosis of
hyperadrenocorticism associated with adrenal gland tumors in
ferrets. Journal Am Vet Med Assoc 1995, 206 (1): 42-46
3. Ferret Endocrine (Adrenal Disease) Panel
4. Leuprolide acetate (Lupron Depot, TAP Pharmaceuticals, Inc,
Deerfield, IL, 60015 1-800-622-2011 [Takeda Chemical Industries,
Ltd., Osaka, Japan 541]): 100 mcg/kg IM q 3 weeks. Drug must be
reconsitituted with sterile water (or its manufacturers diluent),
divided into dose ampules, frozen at -70 F to -80 F.
Additional references:
Johnson-Delaney, CA. Exotic Companion Pet Medicine Handbook. Wingers
Publishing, Lake Worth, FL, 1996.
Rosenthal, KR: Ferrets. Vet Clin North Am Small Anim Pract 1994 24
(1): 1-24.
Williams, BH. Pathology of the domestic ferret (Mustela putorius furo
L.), Ferret Pathology Home Page on the Internet, 1995.
Cathy A. Johnson-Delaney, DVM
Washington Regional Primate Research Center, Univ of Washington, Seattle
and
Exotic Pet & Bird Clinic, Kirkland, WA
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 [100%] reliable blood test [see below]. 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.And, from Dr. Williams:The bottom line is... Yes, hair loss is usually the first symptom and the ferrets don't feel sick at this point.
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, because it has a high rate of false negatives. [Thyroid 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 said:
Dr. Karen Rosenthal from Animal Medical Center in New York City does tons of ferrets. The ultrasound technician they use has been doing this for 17 years and she feels he is one of the best animal ultrasound people. In the technician's experience, he detects less than 50% of adrenal tumors.And Dr. Cathy Johnson-Delaney adds:
As to the evaluation for adrenal disease: I start always with the physical and history. I like to do a CBC, chemistry and urinalysis. If I'm suspecting, I do the estradiol level. I'm not sure if testosterone is as much of a problem. I like to do a scout radiograph (helps me assess heart, kidneys, bladder and in males, prostate). I do a deep palpation, sometimes I can pick up an enlarged mass. If the spleen is enlarged without anesthetic, we start down a slightly different path.I don't usually proceed to ultrasound and/or surgery until I get the estradiol back. If ultrasound shows an enlargement, I know which adrenal to target in surgery. If not given that option, I go in. I measure the glands. Even if they seem "normal" size, which I'm not sure of at all any more, I will take safe sections for histopath. I recommend a knowledgeable ferret pathologist . Out here we are lucky to have Dr. Mike Garner of Northwest ZooPath. Or we send to Drs. Bob Schmidt/Drury Reavill in Calif. [The Tennessee adrenal panel is also good.]
If you have elevated estradiol, somewhere, something is going wrong. If the biopsy comes back normal adrenal, and you do have elevated sex steroids, I think I'd opt for the Lupron to begin with and hold on the mitotane. Monitor bloodwork and symptoms. There may be extraadrenal tissue hiding somewhere in the abdomen. The classic model of this is in primates (humans) with endometriosis. There can be endometrial tissue a lot of places in the abdomen other than the lining of the uterus. A hysterectomy may not stop the problem. That is what Lupron was first designed for.
University of Tennessee College of Veterinary Medicine
Clinical Endocrinology Lab
Dept. of Comparative Medicine
2407 River Drive, Rm. A105 VTH
Knoxville, TN 37996
The test requires 0.3 cc of serum, spun down and placed in a clean tube. No gel should be used, as it is unstable during shipment.
Betsy Bailey writes in early 1998:
Ferret Adrenal Panel Normal Values
steroid SI units mean +/- SD Upper Normal Cutoff
value
-----------------------------------------------------------------
Cortisol nmol/L 53+/- 42 140
17 OH Progest nmol/L 0.2+/- 0.3 0.8
Estradiol pmol/L 107+/- 38 180
Androstenadione nmol/L 6.6+/- 4.1 15
DHEAS nmol/L 10 +/- 9 28
The data in this table are from 26 normal ferrets, which Karen Rosenthal sent to our lab for analysis. (See the related report by Rosenthal and Peterson in JAVMA 209:1097-1102, 1996.)According to Dr. Bruce Williams, DVM, on 3 Feb 1995:The most important tests seem to be: estradiol, androstenadione, 17 hydroxy Progesterone and DHEAS. The cortisols are run if there is sufficient sample volume remaining.
Due to increased demand, the panel is run twice each month, the first and third weeks. Completion of the panel requires one full week: three days (starting on Tuesday) to run the assay, plus one day to compile the results, check them for accuracy, and provide interpretation. Results are faxed on Friday or the following Monday, and are also mailed out.
We recently assayed (Dec 1997-Jan 1998) an additional 14 normal ferrets which provided data that closely correlate with the data from Dr. Rosenthal. Additional studies are planned in 1998 to further refine the expected normal adrenal steroid hormone values in ferrets.
We receive samples from ferrets ranging in age from 6 months to 8 years. So it is apparent that the disease can appear at any time in a ferret's life. Hormonal patterns vary so the best results are obtained by running the complete panel.
We will be compiling a journal article sometime in 1998 regarding retrospective results of ferret panels which were submitted in 1997. We hope to include correlation of assay results with histopathological findings where possible. This will entail us contacting the individual vets who sent us samples and asking for information from them.
Let me reiterate, 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.
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.A prostate problem often looks a lot like a urinary tract infection, and can sometimes cause one. If the prostate is involved, it can usually be palpated (a normal prostate is tiny), and a greenish goo can often be expressed from it.
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.Dr. Mike Dutton adds:I recommend all adrenal tumors be removed, no matter how bad they look. These tumors tend to look a lot worse than they are.
Statistically, 85-90% of the ferrets [with adrenal disease] have a tumor ONLY in the left gland. 75% are female. In my experience at least one gland will look abnormal on the surgery and that is the one I remove. Based on biopsy reports, I have been wrong two times in about 200 surgeries. One of those two ferrets got better and has remained symptom free so far.
The Colorado State University veterinary hospital sees many ferrets and has experience with bilateral adrenalectomies without replacement hormones. They typically recommend removing the second adrenal gland, as opposed to letting the ferret continue with one gland affected by the disease, and they only recommend replacement hormones if the ferret becomes lethargic afterward. Their number is 970-491-4477.
Dr. Joseph Bock of Golden, CO has done also some work with replacement hormones, should they be necessary. You can contact him at 303-494-4344 for more information.
Non-surgical options [see below] are another possibility, though none of them appears to be as successful as surgery.
Dr. Cathy Johnson-Delaney has written:
I do not think ligating the caudal vena cava is conducive with longevity (painful as well). I have not heard of it being as successful as good medical management after you surgically debulk the tumor (remove left, as much of right as can safely be done without fatal hemorrhage).
Dr. Michael Dutton, DVM, DACVP says:
Lysodren (by Bristol Meyers Squibb) is generically known as mitotane or o,p -DDD. It is a medication that destroys adrenal tissue. The goal of administering Lysodren is to destroy a percentage of the gland while the rest of the gland regenerates new adrenal tissue. You are trying to reduce the functional mass so less hormones/steroids can be produced (i.e., the factory is smaller for manufacturing).Dr. Cathy Johnson-Delaney, DVM, writes:Disadvantages of Lysodren: 1) some ferrets become nauseous (vomiting, diarrhea, anorexia, etc.), 2) does not work in some ferrets, 3) lifelong medication (since the adrenal gland regenerates), 4) lifelong expense can equal or surpass the surgery cost, 5) can cause profound hypoglycemia (not to be used in an insulinoma ferret).
Advantage of Lysodren: 1) don t need to do surgery if Lysodren works
Disadvantages of surgery: 1) cost, 2) higher technical skill required by veterinarian.
Advantage of surgery: 1) 85-90% of the time you can CURE the ferret lifelong just by removing the left adrenal gland.
Lysodren kills off adrenal tissue period. The difference in ferret adrenocortical disease vs. dog/human is that the primary hormones secreted are usually sex steroids, instead of cortisol. However, cortisol may be slightly elevated in some ferrets as well. Lysodren seems to work better on adenomas than adenocarcinomas. There can be side effects, but various pulsing regimens can be used to minimize this. Deliver with some food seems to help as well.Jerry Murray, DVM, has said, "The new canine drug Anipryl will not help adrenal disease in ferrets."Lupron Depot is a synthetic GNRH agonist that blocks sex steroidogenesis. It is leuprolide acetate, utilized primarily for endometriosis and as palliative treatment to shrink prostate tissue with many kinds of prostate cancer. Although theoretically it primarily acts to interrupt the feedback system from the pituitary to the adrenal/auxillary endocrine tissue, it essentially acts to block estradiol receptors. It is for this ability that we decided to try it in my ferret, whose prostate had totally occluded his pelvic canal, making urination and defecation almost impossible (and painful). He had his left adrenal totally removed in April of 95, along with one large insulinoma. In Aug of 96 he plugged. He started Lupron in September. I am happy to say he is now 5 days past 2 years from surgery (the right adrenal was determined to be too much of a surgery risk to even try). He is 13 months on Lysodren (varying from 100 - 250 mg/week), and is 8 months on Lupron (100 mcg injection IM every 3 weeks). He will be six years and nine months on May 4, and is growing hair where none has grown for 2 years. He plays, has no problem urinating/defecating, climbs, and runs (he didn't do that for most of the time post surgery, until he started Lupron and I upped his Lysodren).
At least one vet has tried ketoconazole (Nizoral) for a ferret with both adrenal tumors and insulinoma, though the results haven't been reported. Jeff Johnston, an epidemiologist, writes that a ferret being treated with ketoconazole may need to also receive prednisone, since ketoconazole suppresses corticosteroid production.
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.
Technically, adrenal means "near the kidney," so it could be used to describe a number of things. In practice, adrenal usually refers to a gland that is found on the head end of the kidneys. The adrenal gland is composed of two parts, the internal medulla and the outer cortex. These two parts have different functions, and are actually anatomically distinct. The adrenal cortex produces three types of hormones: glucocorticoids (which increase blood glucose levels), mineralcorticoids (which help regulate electrolyte levels), and androgens (which have a masculating effect and increase muscle mass); while the adrenal medulla produces adrenaline and noradrenaline.
Glucocorticoids (such as hydrocortisone, cortisone and cortisterone) cause the liver to increase glycogen levels, they raise blood sugar levels, and they also act as anti-inflammatory agents. It is easy to understand why some ferrets with adrenal tumors have a difficult time maintaining blood sugar, while many others seem very energetic and increase their activity levels. Most of the people who have responded to the adrenal survey indicated their ferrets typically display the latter characteristic, which *could* indicate that the tumor increased glucocorticoid production.
Mineralcorticoids (such as aldosterone) are essential in regulating the salt and water concentrations in the blood and extracellular tissues. If they are goofed up, you could either have electrolyte or fluid imbalances, which affect everything from cardiac output to urinary volume, thirst, and increased/decreased salt requirements. Many ferrets with adrenal tumors become very thirsty, and have increased urination. They also develop osteoporosis (see below).
Androgens (such as androsterone and testosterone) promote male characteristics and are necessary for maintenance of muscle mass. In most females, their effects are masked by estrogens, but when the estrogens are gone, they become more apparent. This is why post-menopausal ladies grow moustaches, and neutered ferrets with adrenal tumors can become quite aggressive, and even start displaying sexual behaviors and traits.
Adrenaline (AKA epinephrine) and Noradrenaline are powerful hormones which increase blood sugar levels, slow down the bowels, increase blood pressure and heart and metabolic rates, and generally prepare the ferret for action. Noradrenaline is similar to adrenaline, but is not as immediately powerful nor as long lasting. When you are startled by someone, the sudden buzz you feel is a result of adrenaline being pumped into your body to prepare it for "fight or flight" situations. Ferrets with adrenal tumors often display increased body heat and eat more, reflecting an increase in the metabolic rate. Some also have increased blood pressure and heart rates. Other symptoms can include problems with maintaining proper sugar levels, excitability, and nervousness.
Because the adrenal gland is composed of two parts, and because a tumor can reside in both or either parts, the initial symptoms of adrenal disease can vary, and many are not noticed at all until hair loss (due to elevated corticosteroids) occurs. They can be slow to show, develop gradually, and, depending on the area of the adrenal affected, may never show any severe symptoms until it is too late to do much.
However, most people agree that artificial light cycles can't cure adrenal disease once it's begun.
Dr. Cathy Johnson-Delaney writes:
I think there is something to the pituitary-adrenal feedback loop, that it gets turned on, then the adrenal gets "super stimulated" and hyperplastic, and eventually neoplastic. Dr. Judith Bell is now theorizing that this pituitary "turn-on" or over stimulation (the pineal gland is also involved) may have something to do with light cycle: ferrets evolved fairly nocturnal, and from northern latitudes; we give them 16-hour-plus light cycles all year. She is proposing testing light amounts and measurements of melatonin, looking into keeping your ferrets on 8 hour light cycles, etc. She may be on to something. We have this problem in birds: they go into constant laying. We have to regulate light exposure. Maybe ferrets need that too, but it's going to be very difficult given human hours and the companion aspect.Dr. Jerry Murray, DVM, writes:If the pituitary is busy churning out the hormones that in turn cause the adrenal to think it's breeding season and the gonads aren't working right (which they're not, because they're gone!), then the adrenal picks up the slack to tell the brain and pituitary that the reproductive tract is gearing up.... You can kind of see the progression: ferrets are seasonal reproductive animals, and are normally shut off by either breeding and copulation (pregnancy turns off the season in females) or the end of the season (light cycle), in males. Any tissue which is constantly stimulated over a long period goes hyperplastic, and the more cell cycles and stimualtion, the greater the chance for neoplasia. Particularly with secreting tissue, i.e. endocrine tissue. This is why I think Lupron is important in this: it interrupts that stimulation cycle. I think that is why some folks thought about "birth control" medications; however, most birth control medications interrupt the cycle by supplying an end-stage hormone (i.e. the hormone of pregnancy, progesterone) so that the pituitary thinks it's pregnant and quits trying for more breeding! That's too late, and adds the complication of all the metabolic consequences of progesterone. The Lupron hits before the signals reach the sex steroid secreting tissue: it sends the message to back down on the reproductive steroidogenesis. Metabolically, this is probably the key. Couple that with killing off the tissue that could respond, and you stop the adrenal neoplasia and its consequences. These are my theories, but I'm going to follow through with Dr. Bell.
The use of artificial lights to stimulate hair growth is interesting; however, using artificial lights is not a new concept. During the 1930's several studies were done using artificial light to induce estrus cycles (heat). During the 1950's the neuropathways of light-induced estrus were studied. During the 1960's, 70's, and 80's the hormones and neuropathways involved in reproductive neuroendocrinology in ferrets were studied. I will try to briefly explain this sixty plus years of medical research. The amount of light per day (photoperiods) regulates the amount of melatonin. During the spring/summer months the photoperiod increases (13-15 hours of light per day) and the melatonin levels decrease. During the fall/winter months the photoperiod decreases (8-12 hours of light per day) and the melatonin levels increase. Melatonin directly and indirectly controls the hypothalamus-pituitary-adrenal/gonadal axis. Thus the increased melatonin levels (8-12 hours of light) cause the seasonal weight increase ends the estrus cycles, and stimulates the hair follicles to grow hair (ie. putting on their winter coat). Conversely the decreased melatonin levels (13-15 hours of light) cause the seasonal weight loss, starts the estrus cycles, and causes the hair follicles to shed.Using a short photoperiod (8-11 hours) to increase the melatonin levels causes the hair growth and weight gains. However you are not actually curing these ferrets. When you increase the photoperiod (13-15 hours) estrus signs and hair loss will re-occur and become progressively worse. This same phenomenon occurs in ferrets with early mild adrenal disease. The use of artificial lights (short photoperiod) or melatonin supplements to stimulate hair growth would be best used 1) after adrenal surgery 2) when surgery is too risky (ie. heart disease, lymphoma, etc.) 3) when the owner can not afford surgery, or 4) when the left adrenal gland has been removed and the right adrenal gland has been debulked by capsular incision.
Osteoporosis (abnormally light, decalcified bones) is common in ferrets suffering from adrenal disease; in 8 ferret skeletons where the poor beastie died from adrenal-related problems, I found osteoporosis to some degree in all of them, yet never found osteoporosis in 12 other ferret skeletons where the beastie died of non-adrenal problems. My sweetie, Razz, died earlier this year from a series of massive strokes, which came on suddenly and unexpectedly. Her bones displayed extreme osteoporosis, and a close inspection of both the adrenal and pancreas showed small cancerous nodules. When the skeleton was prepared, the left tibia had a large lumpy mass on it, and the dried skeleton weighed 1/3 less than it should have. Between the necropsy and the skeleton, it was clear that Razz developed a cancer, which spread to her internal organs and bones. When it reached the adrenals, it caused an increase in corticosteroid production, causing osteoporosis (the cancer in the bones could have also caused the osteoporosis, and the two together probably account for the severity that I found). The stroke must have been the result of a combination of increased adrenaline production resulting in higher than normal blood pressure, coupled with water balance problems, yet I never saw a symptom until it was too late and nothing could be done.
The reason for the osteoporosis is because bone is the body's storehouse of electrolytic salts. When mineralcorticoid levels are thrown off, one of the effects is that bone is dissolved to replace blood salt levels, which are being eliminated in the urine. Over time, the bone gradually gets thinner and thinner. The ferret is always thirsty, has increased urination, sometimes forms kidney stones, and loses bone mass. The end result, over time, is that the bones get thinner and thinner.
Ferret bones are much stronger than they need to be, [so even ferrets with osteoporosis rarely break bones from jumping]. Osteoporosis is easily confirmed with an x-ray of the affected areas, which might not be a bad idea if you suspect it. I also recommend you ask your vet about bone-meal and vitamin supplements, which can be mixed with Nutri-Cal for ease of administration, and help to offset the dissolution of bone for metabolic needs.
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