There are several options for the treatment
of adrenal disease in ferrets. Most will agree that surgery
is the best option; however, surgery is not possible in
all cases. The ferret may be a high surgical or anesthetic
risk, or the owner simply may not have the funds needed.
Fortunately, there are several non-surgical options and
this article will discuss one of those options - the use
of melatonin for both the treatment of adrenal disease and
the possibility of using it as a preventative measure.
Lupron Depot is another option, and while it works wonderfully
(in this author's experience) it may be cost prohibitive
if your veterinarian does not use Lupron regularly and can
spread the cost over many clients. The use of Lupron Depot
is discussed in detail in several places on this website.
HOW MELATONIN WORKS
Melatonin is a natural hormone that is
released by the pineal gland (a tiny structure located at
the base of the brain) in response to darkness. Conversely,
the release of melatonin is inhibited by light. According
to Dr. Jerry Murray, "Melatonin directly and indirectly
activates the breeding season (spring/summer) during the
'long day' photoperiods, and it terminates the breeding
season (fall/winter) during the 'short day' photoperiods.
In the fall/winter there is more melatonin released during
the dark time, and less released in the spring/summer. In
addition to the breeding season, the increased melatonin
causes the winter fur to come in and the winter weight gain.
Likewise the low levels cause the summer fur to come in
and the summer weight loss."
It is likely that the abnormal lighting
to which we subject our ferrets may be at least partially
responsible for the high incidence of adrenal disease. Their
in-home environment is naturally light during daylight hours
and we add many hours of artificial light on top of that
during the evening hours. This constant lighting causes
a natural reduction of the ferret's production of melatonin
and adds to the stimulation (LH) to the adrenal glands.
So how does melatonin combat the effects
of adrenal disease? Once again from Dr. Murray: "Melatonin
inhibits GnRH release, which decreases LH and FSH and stops
the stimulation to the adrenal glands [Adrenal glands have
LH receptors] which decreases the amount of adrenal sex
hormones being produced."
The overproduction of sex hormones is
what causes the typical symptoms we see with adrenal disease
in ferrets. Hair loss, vulva swelling in females, prostate
swelling in males and sexual or aggressive behavior; any
one or more of these symptoms may be present. If this constant
stimulation can be stopped, the results can often be dramatic.
Hair grows, the vulva or prostate swelling resolves, and
except in some cases of carcinoma, the adrenal glands may
get no larger and in some cases may actually reduce in size.
A suggested dosage is 1 milligram of
melatonin given orally around 7-9 hours after sunrise. This
timing would mimic the body's natural release of melatonin
during the short days of fall and winter. In cases where
there is no response to this level of melatonin, up to 3
milligrams may be given daily. In mink, doses as high as
78.2 mg produced no adverse side effects in adults, and
doses as high as 124 mg/kg produced no side effects in kits.
The only side effects seen in ferrets have been sleepiness
for the first 3-5 days when beginning this treatment and
weight gain. Some ferrets will even get fat pads on the
sides of their necks.
study conducted by the University of Wisconsin, 10 ferrets
with confirmed adrenocortical disease were given 0.5 mg
of melatonin (liquid) daily and were monitored over the
course of a year. Nine of the ten ferrets had moderate to
dramatic improvement in clinical signs including hair growth,
reduction of vulva swelling, or reduction of prostatic size.
There was no significant change in the size of the adrenal
glands. This can be interpreted to mean that although the
size of the gland was not reduced, they also did not get
any larger during the one year study.
The most difficult part of this treatment
protocol is compliance with the timing of giving melatonin
7-9 hours after sunrise. For many, this means the dosage
would be due while still at work. A more convenient method
that Dr. Murray uses is the male mink melatonin implant.
This implant is roughly the size of a grain of rice that
is injected subcutaneously (under the skin) over the shoulder
blade area. The implant slowly releases melatonin over a
3-4 month period and eliminates the need to give melatonin
HOW CAN MELATONIN PREVENT ADRENAL DISEASE?
Any endocrine tissue which is constantly
stimulated over a long period of time becomes hyperplastic,
and the more cell cycles and stimulation, the greater the
chance for neoplasia. This is particularly true with organs
that secrete hormones, such as the adrenal glands.
Although there have been no controlled
studies to prove this theory, by giving melatonin before
a ferret develops adrenal disease, we may be able to prevent
the constant stimulation of the adrenal glands. This may
prevent the glands from becoming hyperplastic and eventually,
WHERE DO I GET MELATONIN?
Melatonin is both inexpensive and readily
available in the U.S. One can find melatonin at health food
stores, the local drugstore or supermarkets and even at
Wal-Mart. It comes in both a pill and a liquid form but
one must pay close attention to the actual amount of melatonin
contained within the particular form, particularly liquid.
Because melatonin that is available in these stores is treated
as a supplement (and not a drug) it is not controlled by
the FDA. This means that the actually quantity and quality
of melatonin in the product is not regulated or guaranteed.
Price is not always an indication of quality either, but
one may do better to buy a known brand name. Melatonin may
not be available over the counter in countries other than
the United States (i.e. Canada).
A form of melatonin that has been found
to work much better than oral melatonin is an implant that
was created for the mink and fox fur industry. This
implant provides a steady level of melatonin over a three
to four month period, eliminating the need to dose your
ferret at a specific time daily with an oral product.
Neo-Dynamics, LLC originally supplied these implants to
veterinarians for use in ferrets. This company no
longer serves this segment and the implants are now marketed
and sold exclusively through several distributors:
Professional Veterinary Products 800-228-0077
AAHA's MARKETlink 888-722-2242
Ferretonin comes prepackaged
in a single dose, sterilized syringe (implant device) with
needle. It contains the same amount of melatonin (5.4 mg)
as the male mink melatonin implant. Contact your veterinarian
for pricing information. If you need bulk quantities,
they may be purchased as aseptic individual implant packages.
Contact Melatek for more information. Please note
that they will only sell this product to a veterinarian.
WHY IS THE ORAL DOSAGE DIFFERENT THAN THE
Several have asked why ferrets have to
receive 1 mg of melatonin orally every day, but if given
as an implant, 5.4 mg will last three to four months.
The short answer is that when given orally, it is quickly
metabolized by the body, whereas when given as an implant,
a constant, steady level of melatonin is provided over a
long period of time.
WHAT IF MELATONIN DOES NOT WORK FOR MY FERRET?
There may be instances where neither
melatonin or Lupron will produce the expected or desired
results. This would be the case if the adrenal gland is
affected in a way that causes it to secrete sex hormones
independent of any outside influence (some carcinomas).
In these cases, the only option is surgical removal of the
affected gland. There also may be cases where melatonin
alone does not work, but Lupron will. One can use
both products (melatonin and Lupron) at the same time.
DRAWBACKS OF USING THE MELATONIN IMPLANT
Dr. Cathy Johnson-Delaney found during
a study of the melatonin implant's effects on hormone levels
that when a 560g female was given the melatonin implant,
she became so lethargic within two weeks of implantation
that she had to be roused daily to eat. No medical or physical
cause for this change in her behavior was found and her
activity level gradually increased to normal levels after
three months. This appears to indicate that the level of
melatonin being released by the implant was too high for
this ferret. One may want to consider this possible effect
in small (less than 600g) ferrets.
Previously, the melatonin implant came
in one dosage level (5.4 mg). Melatek's website indicates
they now have an implant available with a smaller dosage
size if needed for a very small ferret.
Cost is another possible drawback in
the use of the melatonin implant. In its current
form, that is, one implant along with an implant syringe,
the cost may approach that of Lupron Depot for those vets
that treat a large number of ferrets with Lupron.
For more information on melatonin usage
1) Diagnostic Laboratory Insight with Regard
to Adrenal Disease by Jack Oliver ( U of Tenn), Proc 20th
ACVIM 2002, p541-543.
2) Melatonin use in ferret adrenal gland
disease by J. Paul-Murphy (U of Wisconsin) Proc N. Am. Vet
Conf. Vol 15, 2001 pg 897.
3) Melatonin therapy for canine alopecia.
Kirk's CVT 13 by Manon Paradis (U de Montreal) p546-549.
She also describes the mink melatonin implant.
4) Diagnosis and Treatment of Adrenal Tumors
in Ferrets by James Johnson (Texas A&M) Annual Exotic Pets
Conf. 2001 p3-6.
5) Studies on the duration of the breeding
season and photorefractoriness in female ferrets pinealectomized
or treated with melatonin. by Penelope Thorpe + J. Herbert
(U of Cambridge) Journal of Endocrinology 1976, 70, p 255-262.
6) Effect of oral melatonin administration
on sex hormone, prolactin, and thyroid hormone concentrations
in adult dogs. by Patricia Ashley et al (U of Tenn) JAVMA
Vol 215 No 8, 10/15/99, p 1111-1115.
7) Induction of winter fur growth in mink
with melatonin. by J. Rose, J. Anim Sci, 1984 Vol 58 p 57-61.
8) The role of luteinizing hormone in the
pathogenesis of hyperadrenocorticism in neutered ferrets.
By N.J. Schoemaker, et al. (Utrecht University), Molecular
and Cellular Endocrinology, 2002, vol 197, p 117-125.