For years we have been struggling to treat adrenal disease in ferrets. Surgery seems to offer only a temporary relief, and so far we don’t have a cure. But a number of veterinarians have been researching this syndrome, and have shed light on the cause as well as methods to control adrenal disease.
Signs of adrenal disease include hairless, swollen vulva or enlarged prostate, straining to urinate, aggressive behavior, marking or loss of litter box manners, and itchiness. These symptoms are caused by elevated levels of hormones produced by the adrenals, a pair of glands which reside in front of the kidneys.
Normal ferrets are very seasonal breeders. In non-neutered ferrets, male sex hormone levels peak in December, and female hormone levels start rising in January, and peak in March. In the brain, the hypothalamus sends a signal to the pituitary gland in the form of GnRh (gonadotropin releasing hormone). This stimulates the pituitary to release LH and FSH (leutenizing hormone and follicle stimulating hormone) which tells the sexual organs (ovaries and testes) to produce sex hormones. When mating occurs, and/or the daylight length changes as the breeding season ends, this causes a surge of LH which tells the hypothalamus and pituitary glands to stop sending those signals. Then sex hormone levels decline until the next breeding season.
Now, here is where things get messed up. Spaying and neutering DOES NOT stop the brain from sending LH and FSH during the breeding season. But when there are no testes or ovaries to receive the signal, the adrenal glands receive the signal instead and produce sex hormones. Without testes or ovaries, the ferret cannot produce the LH surge that tells the brain to stop. So the ferret continues to produce high levels of adrenal hormones. Even when both adrenal glands are completely removed, fat tissue can respond, and start producing sex hormones! Keeping ferrets in the dark or giving melatonin only helps a small amount – ferret brains still know when it is breeding season.
Adrenal disease is not a benign condition, though it is a slowly advancing disorder. Continuous production of sex hormones not only causes the signs we see, but it also causes enlargement of the adrenal glands themselves. Enlarged adrenal glands proceed to a precancerous state, then to a benign cancerous state (adenoma), and eventually to a malignant cancerous state (adenocarcinoma). All ferrets should get frequent veterinary exams to monitor for adrenal gland enlargement, even if there are no outward signs of adrenal disease. Once enlarged, adrenal glands usually require surgical removal. Another item of note - female ferrets can safely live with adrenal disease longer than male ferrets. Male ferrets get a swollen prostate which can block their urethra. This causes a life threatening urinary blockage which requires immediate treatment by a veterinarian. These are the most important reasons why adrenal disease is not an illness to be ignored.
So how do we prevent or treat adrenal disease? We need to do something to turn off the brain’s signals in spayed and neutered ferrets. This is where Lupron comes in. Lupron, or leuprolide acetate, is a GnRh analog. It is given as a depot injection, which means it lasts for 1 to 3 months, depending on which version is used. While the Lupron is in the ferret’s body, it suppresses LH and FSH production, thereby halting the signals from the brain to the adrenal glands (and sex organs if present).
How often to give Lupron and for how long is the question. Most veterinarians recommend giving a Lupron shot whenever the ferret starts to show signs of adrenal disease, like hairless or a swollen vulva. This could be every 6 months, or whenever the owner gets tired of looking at a naked ferret. But hairless and vulvar swelling are NOT good indicators of adrenal disease, and a ferret can look completely normal but have adrenal glands progressing towards the cancerous state. Exam, bloodwork to check levels of adrenal hormones, and sometimes ultrasound are recommended monitoring methods.
At the forefront of ferret adrenal research is Dr. Cathy Johnson-Delaney, a board certified specialist in Avian and Exotic Medicine. She has been a practicing veterinarian for several years, with a special interest in ferrets. Based upon her research and experience, her current recommendations are as follows:
1. Intact males will cycle out of the breeding season on their own.
2. Intact females may cycle out on their own. If they don’t, they need to mate with a male ferret (vasectomized or intact). Or they can get an injection of Lupron to end their breeding cycle each year.
3. All young ferrets (under 1 year) that were spayed/neutered, should have an injection of Lupron during the first breeding season (Dec/March) after puberty, and once a year every season after that. This will tell the brain to stop sending signals to the adrenal glands.
4. Adult ferrets that have never had Lupron, and have no signs of adrenal disease, should have hormone levels checked three times a year. If they have elevated adrenal hormones, then they should receive monthly Lupron injections until the hormone levels drop. (Dr. Johnson-Delaney’s research was performed using the one month depot of Lupron).
5. Adult ferrets with signs of adrenal disease should also have their adrenal hormone levels monitored three times a year, and should receive Lupron injections every month probably for the rest of their life.
6. Once Lupron injections are started, it is recommended to continue them with no longer than 4-6 weeks between injections. This way we try to avoid the resistance that can develop over time, requiring higher doses. Another method of dealing with resistance is to use higher doses during the breeding season, and the regular dose the rest of the year.
Here’s some additional interesting information:
Adrenal disease may also be responsible for the diarrhea and gastrointestinal upset that is commonly seen in our pet ferrets. Overstimulated adrenal glands produce excess epinephrine, which increases the amount of histamines. The histamines cause bleeding stomach ulcers and GI upset. In addition, excessive amounts of histamines can lead to those small black skin nodules called mast cell tumors. Antihistamines at high doses have been found to have some beneficial effects on ferrets with adrenal disease.
Another group of veterinarians are researching the genetics behind adrenal disease and other common ferret illnesses. In humans there is a disease in which people lack certain tumor suppressor genes, called P53 and MEN. P53 suppresses lymphosarcoma, mast cell tumors, osteoma, and leiomyosarcoma. MEN suppresses adrenal tumors, pancreatic tumors (insulinomas), mast cell tumors, and lymphosarcoma. Gee, didn’t that list just mention almost all of the common diseases ferrets get? So these researchers are checking ferrets to see if they have similar tumor suppressor genes.
If you are interested in helping us continue to learn more about ferret diseases, please feel free to send donations to Washingtonferretrescue.org, attention Adrenal project.