ANDRENAL GLAND DISEASE
When we refer to adrenal disease in the ferret, we almost always mean HYPER adrenal disease, where adrenal hormone levels are increased, as opposed to HYPO adrenal disease, where hormone levels are decreased. This is one of the most common problems of the domestic ferret. There are numerous proposed possible reasons including genetic predisposition, early neutering, nutrition and seasonal light cycle variations. A large study conducted in Holland demonstrated that ferrets neutered later in life still had nearly as high an incidence of adrenal disease as American ferrets, but it occurred an average of about one year later. It’s most likely this problem is the result of a combination of factors and not a single simple one.
Mammals have two adrenal glands, which are typically located near the kidneys. The normal size of the ferret adrenal gland is about one-thirtieth the size of the kidney. In ferrets, the left one lies in an easily accessible area between the kidney and the vena cava, which is the largest blood vessel in the rear half of the body. The right adrenal lies in a much more difficult spot. It is usually attached to the vena cava itself and is hidden under the central lobe of the liver. It has traditionally been very difficult to remove surgically.
The adrenal glands produce many hormones (steroids), which are essential to life. To date, more than 50 different steroids have been isolated from the adrenal cortex, the outer 2/3 portion of the gland. These can be divided into three main groups: the glucocorticoids (cortisones), the sex hormones (androstenedione, estradiol, testosterone), and mineralocorticoids (aldosterone). The inner 1/3 of the gland, the medulla, produces adrenaline (epinephrine).
Diagnosis
In the ferret, most adrenal tumors involve the area of the adrenal gland that produces sex hormones, although tumors that produce cortisol or epinephrine do occasionally occur. For this reason, most of the clinical signs of adrenal disease are related to either estrogen or testosterone overproduction. Either of these can occur in either sex. In most cases, adrenal disease is relatively easy to diagnose, since the signs are so characteristic.
The most common sign of adrenal disease is hair loss. The most serious sign in female ferrets is an enlargement of the vaginal labia, which results from too much estrogen production. The result, if untreated, can be anemia and death. High estrogen levels can cause the bone marrow to stop production of red blood cells. In ferrets, this can be seen as early as three months from the beginning of labial enlargement. The most serious sign in male ferrets is difficulty urinating. This results from enlargement of the prostate gland due to high hormone levels. If untreated, the swollen prostate can completely block the flow of urine and death will result from uremia. Treatment may be either medical or surgical. While surgical removal of the affected gland is still the treatment of choice, a new medical treatment is showing a lot of promise.
Treatment/Surgery
Removal of the left adrenal gland is a fairly straightforward and uncomplicated process and may be performed by anyone with a little ferret surgery experience. Removal of the right adrenal gland demands a great deal of confidence and experience on the part of the surgeon, since the right adrenal is intimately attached to the largest blood vessel in the body (vena cava). In our experience, freezing, scraping or any form of "subtotal" removal of the right gland does not yield satisfactory results, as the gland usually grows back within three to six months. The only sure method of removing the entire gland is to remove the portion of the vena cava to which the gland is attached, and then suture the remaining portion of the vessel back together. This is a procedure with a high degree of difficulty and should only be attempted by surgeons with a lot of experience. It is nearly impossible to determine which gland (possibly both) is involved prior to surgery. The glands are so small that ultrasound may not give accurate results.
Although there is always some degree of risk associated with general surgery, we have performed hundreds of adrenal surgeries, both right and left, with very few complications. Adding a melatonin implant at the time of surgery when one adrenal gland is removed may help prevent the remaining gland from becoming diseased.
Treatment/Medical
Medical options are available for ferrets who cannot undergo surgery. Medical treatment usually consists of a melatonin implant, Lupron injection, or a combination of the two. Melatonin is a hormone that influences the entire endocrine system. It is thought that this hormone may play a role in preventing adrenal disease or reversing early adrenal disease in the same way that manipulation of light cycles may play a role.
The use of artificial lights to stimulate hair growth 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. 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, end the estrus cycles, and stimulate the hair follicles to grow hair (i.e. putting on their winter coat). Conversely the decreased melatonin levels (13-15 hours of light) cause the seasonal weight loss, start the estrus cycles, and cause the hair follicles to shed.
Early studies showed that continuous, long-term dosing of oral melatonin did work in many cases, but only for a period of eight to ten months. After initial improvement, ferrets taking oral melatonin had a rebound effect and adrenal symptoms returned. We are now using time-release melatonin implants injected under the skin to mimic natural hormonal cycles. These implants are administered every three to six months, and are showing extremely good results treating adrenal disease that is not too far advanced. The implants are inexpensive.
Lupron is an estrogen blocker that is used mainly in treatment of breast cancer in women. It has proved effective in treating a high percentage of adrenal tumors. It appears to be as effective against testosterone-producing tumors as it is against estrogen-producing ones. It is very safe and has about an 80% efficacy rate. Its main disadvantage is expense, costing approximately $50 a month and continuing for the life of the ferret.
Combining the effects of Lupron and melatonin seem to offer the best possible medical option. In my experience, adding melatonin to Lupron therapy improves Lupron’s effectiveness significantly.
Conclusions
There is still much to be learned about ferrets and adrenal disease. There are currently ongoing studies by practicing veterinarians all over the U.S. who are combining their information to produce useful data on surgical techniques and promising medical treatments. It is an exciting possibility that the use of melatonin as a preventive in healthy ferrets will reduce the incidence of adrenal disease as well. It is of the utmost importance that you seek experienced veterinary help in deciding on a preventive or a treatment plan for your ferret.
Insulinoma
Beta cell tumors, also known as insulinomas, are the most common neoplasm in ferrets. These tumors produce excessive amounts of insulin, causing dangerously low blood glucose levels. Unlike dogs or cats, insulinomas in ferrets don't usually metastasize. Although the cause is different, this condition is essentially the opposite of diabetes mellitus. Diabetes causes insufficient insulin to be produced, resulting in high blood glucose levels. Diabetes mellitus is uncommon in ferrets, though not unheard of, and it can be a transient condition after insulinoma surgery.
Some veterinarians feel that the high incidence of insulinoma in ferrets may be due to the high carbohydrate diet that ferrets are fed. Susan Brown, DVM says, “If normal beta cells are bombarded with higher than normal levels of glucose (which comes from carbohydrates) they can become hypertrophied (overactive) trying to keep up with insulin demand. If the high carbohydrate diet continues, the result may be a complete burnout of the cells, which is what happens when a pet or a person develops diet-induced diabetes. However, another possibility is that instead of the cells burning out, they go from hypertrophy to neoplasia (cancer). Neoplasia is an abnormal growth of cells and can be preceded by a hyperplastic condition. I would like to stress that this exact mechanism has not been scientifically proven in ferrets to date, but the scenario is entirely within the realm of possibility.” (1)
Surgery to remove visible tumors or a large portion of pancreas frequently does not result in a cure. Dr. Bruce Williams says, “the incidence of recurrence of insulinoma after surgery is high, averaging about 40% over a 10 months span.” Even after undergoing a partial pancreatectomy, some ferrets may not have any relief from low blood glucose levels. In some cases, with good care and a combination of medical and surgical treatment, or medical treatment alone, a ferret may be able to live with this condition for a number of years.
A normal fasting blood glucose level is in the range of 90-125 mg/dL (4.95 Mmol/L - 6.88 Mmol/L). According to Katherine Quesenberry, DVM, in Ferrets, Rabbits and Rodents - Clinical Medicine and Surgery --- “Ferrets with blood glucose concentrations lower than 70 mg/dL (3.85 Mmol/L) are suspected of having Insulinoma. In one study of 49 ferrets with confirmed insulinoma, all had blood glucose concentrations lower than 60 mg/dL (3.30 Mmol/L).” Ferrets can often have shockingly low blood glucose levels and have no significant symptoms. Though I have no medical evidence to back this up, I believe this may be due in part to the ferret becoming acclimated to glucose levels that have been decreasing gradually over a period of time.
The excess levels of insulin produced by these pancreatic tumors drive the glucose in the blood into the cells of the body, causing a dangerously low blood glucose level known as hypoglycemia and can result in one or more of the following symptoms:
Hypersalivation (drooling)
a trance or "spaced out" look for seconds at a time
pawing at the mouth
Hind leg weakness, wobbly gait
Head bobbing or twitching
Dizzy or drunken appearance
Lethargy
lack of appetite
Seizures
Coma
It's important that a hypoglycemic ferret eats regular, high protein meals to help avoid hypoglycemic episodes. Avoid foods with high sugar or carbohydrate (cereal) content. In end stage insulinoma, sugar may be the only thing that will allow a ferret to remain seizure free; however, in early stage Insulinoma, sugar may result in a see saw effect with blood sugar levels. Emergency Treatment for Hypoglycemic Seizures
Contact your vet immediately after beginning this treatment!
Seizures brought on by the sudden drop in blood sugar levels can be a very frightening experience. Even the experienced ferret caretaker can feel helpless and in a panic. For many, the term seizure presents a picture of someone on the floor, twitching with arms and legs flailing around. This is usually not what you will see in a ferret that is in the midst of a hypoglycemic seizure.
In most cases, ferrets that are in this state are simply unresponsive and appear to be in a coma like state. They may have moments of rapid breathing and have repeated reactions that make them appear to be gasping for air. There may be some twitching or paddling with their legs. In severe cases, they may even scream, and though this is very difficult to hear and witness, rest assured this is not a pain response and the ferret is totally unaware of what is going on.
Treatment consists of quickly getting the ferret's blood sugar levels back up. The quickest way to do this is with a dextrose IV. Since this must be given intravenously, not subcutaneously, this is not something that can be done at home. Unfortunately, these attacks always seem to happen when the vet clinic is closed. Besides, in less severe cases, you can probably bring the ferret around quicker by starting home treatment immediately rather than racing off to the clinic unless it is open and right around the corner. Begin treatment while someone else calls the vet or emergency clinic, or if you are alone, begin the treatment and while waiting for the ferret to respond, make the call.
Home treatment consists of repeatedly painting the ferrets gums with Karo syrup using a Q-tip. I have found that Karo syrup works better than honey or Nutrical and thinning the Karo slightly with a bit of water seems to make it more readily absorbed. Applying Karo syrup one time to the ferret's gums and waiting for the ferret to wake up is usually not going to be very effective. You must repeatedly apply Karo every 20-30 minutes or so until the ferret starts to come around. Many say that the ferret will begin to respond in 5 or 10 minutes, and in some instances, this is true; however I have not found this to be the case if the ferret is unconscious. Many times it has taken an hour or more before the ferret responds.
Once the ferret is alert again, it's important to feed him or her a high protein meal to help stabilize his or her blood glucose levels. Chicken baby food works best for this and anyone with a ferret prone to low blood glucose episodes should always have some of this on hand, in addition to Karo syrup.
When you are done feeding the ferret, BE SURE to thoroughly wash off any karo syrup that has gotten on the fur or skin around the ferret's mouth. If not cleaned off, it can cause intense itching and the ferret may scratch to the point of bleeding.
