Melatonin treatment of hyperadrenocorticism in Ferrets

By Michael Janke

reviewed for accuracy
by Dr. Jerry Murray

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 authors experience) it may be cost prohibitive in some cases.

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 for 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 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 has 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.

In a 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 daily.

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 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 or neoplastic.

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's 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).

The FDA approved mink melatonin implants can be ordered from Neo-Dynamics at 1-800-206-7227. They come in packages of 100, 500, and 1,000. Your vet will also need a special syringe (implant device) and special needles (12ga.) that can be ordered from the same company. AVID microchip implanting syringe and needle also works well. The implanting syringe is reusable whereas a new needle will be needed each time. Some ferret owners perform the implant injection at home, though you should be instructed by your vet on how to do this properly.

Recently Neo-Dynamics has started to market "a ferret melatonin implant." The ferret melatonin implant is called Ferretonin and is being marketed by Melatek (, 800-206-7227).The implants are 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.

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. Fortunately one can use both products (melatonin and Lupron) at the same time.
Thanks to Dr. Jerry Murray for taking the time to review this article for accuracy and for adding his expertise on the subject.


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