About Adrenal Disease
In its simplest terms, adrenal disease are tumors on the adrenal glands which are located in front
of the kidneys and generally starts affecting ferrets over the age of 2. There are a number of theories regarding the high incidence of adrenal disease including the over abundance of light, inbreeding, early spaying/neutering practices, diet, etc., but none have been proven to date. The best thing you can do for your ferret, is to use sun blocking shades in their room, and keep lights to a bare minimum. It is recommended that you have routine Adrenal Panels runs to possibly detect the disease in it's early stages (before signs and symptoms), providing you with more treatment options.
The high exposure to light and early spaying/neutering, seems have the most validity as a root cause. Ferrets have a very sensitive pineal gland, which in the natural state is stimulated by increased exposure to light. The pineal gland signals the reproductive tract to get ready for reproduction by sending a signal to the hypothalamus to produce GnRH (Gonadotropin Releasing Hormone) which stimulates the pituitary gland to release LH (Luteinizing Hormone) and FSH (Follicle-Stimulating Hormone) which triggers the gonads to secrete the sex hormones.
For intact ferrets, the surge in LH signals the hypothalamus
and pituitary gland to stop producing the hormones. In a spayed or neutered
state, the adrenal glands receive the hormones and respond by producing the
sex hormones, but as they lack gonads, the LH surge cannot be produced to stop
the hormone production from the hypothalamus and pituitary gland. As a result
the hormones remain in an on state and are continually producing hormones which
can cause the adrenal glands to enlarge.
In order to have a better understanding of adrenal disease, it is important to understand the make-up of the gland. The adrenal gland comprises 2 sections, the cortex (where the majority of problems arise) and the medulla. The cortex is then subdivided into 3 zones: the outer (zona glomerulosa-which secretes mineralocortoid hormones), the middle (zona fasciculata-secretes glucocortocoid hormones and comprises about 70% of the cortex), and the inner (zona reticularis-secretes sex hormones and androgens). In ferrets, the tumors overproduce the sex steroids and androgens and is called hyperadrenocorticism.
There are 3 forms adrenal disease can take on:
Whether the tumors are malignant or benign, the most common symptoms of adrenal disease include hair loss usually beginning at the end of their tail (though it can appear anywhere on your ferret) moving up towards their shoulders in a symmetrical fashion, muscle loss and/or a potbelly appearance, lethargy, an orangey skin color and weight loss which can be dramatic. It is quite common for a ferret to loose all their fur, except for a few areas and their face. Females often develop an enlarged vulva (50%), and males experience an enlarged prostate often causing them to strain while urinating. Male ferrets can also return to intact male behavior including aggressiveness due to the increased levels of testosterone.
Diagnosis of adrenal disease can usually be made by your veterinarian without additional testing by the signs and symptoms exhibited by the ferret. Additional testing is usually performed to confirm the diagnosis and/or check for any additional problems your ferret may have and include blood profiles, x-rays and urinalysis There is currently only one test that will undoubtedly confirm adrenal disease in your ferret and that is the adrenal panel which is analyzed by the University of Tennessee, School of Veterinary Medicine.
Ferret Adrenal Panel Normal Values
||Mean +/- SD
||Upper Normal Cutoff Value
53 +/- 42
0.2 +/- 0.3
107 +/- 38
6.6 +/- 4.1
10 +/- 9
In most cases, the left adrenal accounts
for the vast majority of lesions (80%), with the right
adrenal accounting for 26%. Ferrets presenting with both
glands involved represents about 8% of all cases. It is
quite common after the removal of the affected gland (usually
the left), to have the other gland affected down the line.
If the gland is malignant the window of recurrence to the
other gland is usually shortened.
You should have frank, open and honest discussions with your vet on the best treatment options. Keep in mind when opting for the drug choice, you will need to continue this for the life of the ferret. If signs/symptoms begin appearing after some use, the dosage time can be increased, and if that doesn't help, chances are the tumor is malignant and surgery should be pursued.
Ultrasound is NOT an accurate test for adrenal, and in one study by Dr. Karen Rosenthal, etc at The Animal Medical Center in New York, only 50% of the diseased glands were diagnosed.
Bilateral Adrenal Disease
Unfortunately, it is quite common after the removal of a gland to have the other gland become affected, and to a lesser degree to have them both affected at the same time. If both are affected together, the recommended protocol is to remove the gland that's worst first and then remove the other one 1-2 months later to avoid Addison's crash.
When both glands are removed, the ferrets body stops producing
the needed hormones at once, which can send the ferret into shock, Addison's
Disease and possibly death. It is very possible that some ectopic tissue remains
from surgery, producing enough natural hormones on their own without drug intervention.
The only way to know for sure is through frequent Chem Panels to monitor the
levels. Your ferret will most likely need to be given Florinef (pill) daily
for life or an injection of Percortin monthly for life. Blood tests are vital
at the beginning to establish the correct drug dosage, and should continue
quarterly thereafter to ensure all is well. A majority of the vets prefer the
Florinef for the easier flexibility in dose changes and less visits for you
to the office.
When both glands are removed, it is very common to immediately administer the Florinef or Percortin to avoid Addison's
shock due to the immediate loss of needed hormones not being produced. Constant and continual monitoring by blood tests are vital to the health, survival and well-being of your ferret.
Surgery is the MOST effective, recommended and successful treatment for adrenal disease,and involves the removal of the infected gland. It is reported that 90+% of affected ferrets can be cured by surgery, even in ferrets older than 7. Once surgery has successfully been performed, you can expect your ferret to live a normal life for quite a few years, however, there is no guarantee that the disease will not reappear or affect the other gland.
The removal of the right gland presents increased complications, due to it's very close proximity to the large vena cava, which is the main abdominal vein. Due to this delicate nature, some veterinarians are not comfortable in performing surgery and will opt for drug use. It is important BEFORE you proceed with this surgery to seek out a veterinarian who is very comfortable performing this operation and has had great success, especially if the right side is involved with it's many complications.
Cryosurgery is frequently used by veterinarians,
especially when the right adrenal gland is involved. This procedure actually
freezes the tissues with a liquid nitrogen to kill the cells that are frozen.
There are many benefits to cryosurgery including: decreased bleeding, quicker
operative time, quicker recovery time and being an easier procedure to perform.
Regardless of which surgical procedure is utilized, within a few weeks hair
growth should begin, body weight should increase, as will their activity level.
As this option is being used more and more, the high incidence of recurrence
is being seen. The risk still remains in first cutting through all the muscle
in order to reach the gland.
If your ferret is not a good candidate for surgery, usually due to age, overall health, and/or other medical conditions, your ferret will most likely be treated by drug therapy using Lupron Depot. During normal function, the hypothalamus produces GnRH which is released to the pituitary gland in a pulsating release which signals the release of both LH and FSH (primarily LH) which tells the gonads and the adrenal glands to produce the sex hormones.
Lupron Depot (GnRH analog) works by binding to pituitary receptors. Lupron sends a steady stream of GnRH to the pituitary which becomes desensitized and stops producing LH and FSH (the pituitary can only handle the pulsating signals). By suppressing LH & FSH from being produced, the sex hormones will also stop being produced in response. With continued use, the decrease in hormones being produced have lasted for more than 5 years and results being seen as early as 2-4 weeks. During this time, the vulva will return to normal size, hair loss will stop and within 1-2 months hair regrowth will begin.
Lupron Depot is available as a 1, 3 or 4 month injection (100 - 500 micrograms/ kg per month), with higher dosages often being used: ie; 4 month depot at 2000 mcg/kg.
It is important to note that while this can be a very effective treatment option for your ferret, surgery is still considered the first line of treatment. Lupron Depot will NOT cure your ferret of adrenal disease, it will attempt to maintain the condition of your ferret and hopefully stop it's progression. Melatonin is often used in conjunction with Lupron and sometimes used alone. Lupron will not work if the gland is malignant.
It's important to consider that while Lupron may stop the progression, and you can increase the amount and frequency of the drug administered, after awhile it is quite possible it will have no effect (the adrenal glands will continue to produce the sex hormones on their own without any LH or FSH signals). By the time this happens, chances are the tumor is malignant and your ferret may no longer be a surgical candidate. Careful, open, honest conversation will need to take place with your veterinarian to decide on the right course of treatment, as many factors come into play.
Recently there has been talk about some veterinarians using and
suggesting the 24-hour Lupron injection as a 1-month protocol. It is important
that you understand the difference between this version and the 1, 3 & 4
month depot version. The actual amount of time the pituitary gland is desensitized
with this version and stops the LH and FSH production is only a few hours (vs
a steady flow over 1-4 months) followed by the high activity which is common
for all forms. If you do not repeat the injections daily, you are providing
no therapeutic benefit and might actually be doing more harm than good due
to that initial burst of hormone activity.
Melatonin is a naturally produced hormone in ferrets and it's use can assist in Adrenal Disease management. As with Lupron Depot, the end result is a reduction or elimination of LF and FSH production, which triggers the gonads and adrenal glands to produce the sex hormones. Lupron works by desensitizing the pituitary gland, while Melatonin works by inhibiting the release of GnRH to the pituitary gland, which is why owners often will use in combination or just alone. Lighting is a main factor for setting the hormone production into motion, as well as the highly sensitive pineal gland.
With increased light exposure, the natural production of melatonin from the pineal gland decreases. This decrease adds to GnRH production from the hypothalamus to the pituitary gland which releases LH and FSH which causes the gonads and adrenal glands to produce the sex steroids. By increasing the ferrets melatonin level, it can inhibit GnRH to the pituitary gland, which reduces LH and FSH production and decreases the sex hormones being produced. Melatonin should be given 1 mg 8-9 hours after sunrise. As the time to administer the Melatonin may not be feasible (often not home from work yet), you can talk to your veterinarian about using the FDA approved mink Melatonin implant or the ferret Melatonin implant, which lasts 3-4 months.
It is possible that Melatonin alone or with Lupron can stop the progression of adrenal disease, but also keep in mind it is equally possible to have no effect. It is however, certainly a viable option given the low cost, minimal side effects (ie; sleepiness first 5 days), and no drug-to-drug complication.
Lysodren is another drug that is used to be used prior to Lupron. It's success rate is very low, and it can produce other health problems in your ferret, namely insulinoma and can tear up the liver. Regular monitoring of blood glucose is needed while on this treatment, as Lysodren can cause low blood glucose and lead into other health problems. Lysodren therapy should be stopped immediately if any side effects develop such as, low blood sugar, anorexia, vomiting and lethargy. In addition, if no improvement is
seen by week 12, the drug should also be stopped as it is deemed ineffective. No ferret should be ever be placed on this treatment if it already has insulinoma! This treatment is hardly used anymore and is not recommended, unless all other efforts have failed.
Ovaban or Megesterol Acetate
Generally used as a rescue treatment. It counteracts the estrogen and works even if the gland is malignant. Long term side effects include obesity, fatty liver, diabetes (acquired). Older non-surgical ferrets can go 2-3 years with good quality of life.
Propecia/ Proscar (Finasteride)
Used to treat an enlarged prostate due to Adrenal disease. Is an enzyme inhibitor which stops the formation of DHT, a main hormone causing the enlargement. Usual dosage is 1 mg day for 30 days, then taper down.
Used to treat an enlarged prostate. Blocks androgen (DHT) receptors on the prostate, reducing testosterone
levels. Usual dosage is 5 mg daily.
Treats estrogen induced anemia, thrombocytopenia and mammary gland hyperplasia. An enzyme inhibitor that
stops the formation of estrogen. usual dosage is 1/10 mg/ kg daily.
Epogen/ Procrit (Epoetin Alfa)
Can be used with Arimidex to treat estrogen induced
anemia. used to stimulate bone marrow to produce
RBC after estrogen levels are reduced. Usual dosage
is 100 - 200 units/ kg 3 times a week, then taper
off as PVC normalizes.