Ferret Adrenal Disease

 

Tumors of the adrenal gland in ferrets can cause excess secretion of sex hormones, thus affecting many organs in the body. Unfortunately, this is a relatively common problem in middle aged and older ferrets. Even though most of these tumors are not malignant, they can cause significant disease if left untreated.

Dogs and cats get a problem similar to this, although it acts and is treated differently. In dogs and cats it is due to an excess secretion of cortisone, not sex hormones. In these species it is called Cushing’s disease.

At the very end of this page is a QuickTime video of part of a surgery to remove cancerous adrenal glands and cancerous nodules on the pancreas. You will need QuickTime from www.apple.com to be able to view it.


Physiology

This disease involves reproductive hormones. In a normal ferret, a hormone from the hypothalmus in the brain,  called gonadotropin-releasing hormone (GnRH) causes stimulation of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the pituitary gland. These hormones stimulate the release of estrogen and testosterone from the gonads. A very sensitive negative feedback loop maintains just the right amount of estrogen and testosterone. This sensitive balance is upset in adrenal disease of ferrets.

Cause

The exact reason this tumor arises is not completely unknown. It is seen more often in the U.S. than in Great Britain, where different breeding and husbandry practices are utilized. It is speculated that diet, exposure to sunlight, and neutering are all factors, with neutering being the most important one.

Ferrets breed seasonally, causing variation in melatonin release with varying daylight. Less daylight means more melatonin and a thick haircoat. This higher level of melatonin eventually exerts a negative feedback on the release of the sex hormones estrogen and testosterone. When ferrets are spayed and neutered the negative feedback is disrupted, more of these sex hormones are secreted than is normal, and clinical signs develop.

The three main types of adrenal lesion encountered are:

  • Nodular hyperplasia that occurs 56% of the time
  • adrenocortical adenoma that occurs 16 % of the time
  • adrenocortical adenocarcinoma that occurs 26% of the time

Anatomy

The adrenal glands are small glands located just in front of the kidneys. The left gland is embedded in fat just in front of the kidney, the right one is located deeper in the abdomen and under one of the liver lobes.

This radiograph shows two overlapping kidneys (K) in the middle of the abdomen. The adrenal glands are located just to the left of these glands. They are not routinely visible on radiographs.

The arrow points to a normal left adrenal gland of a ferret. It is quite small and buried in fat in front of the kidneys.

 

To the left of the kidney (K) you can see a cancerous and inflamed left adrenal gland that is buried in fat.

 

A close-up of this abnormal left adrenal gland shows how enlarged and inflamed it is compared to the normal one .

When a diseased left adrenal gland is not removed surgically it might eventually get extremely enlarged and cause substantial illness. The left 2/3 of this picture is a diseased adrenal gland. The right 1/3 of this picture is the kidney, showing just how large this adrenal gland became as this ferret aged. The adrenal gland is so diseased that it is literally rutpturing, as can be seen toward the top left of the gland.

In this picture we have both adrenal glands of the same ferret. The white arrow in the lower left of this picture points to a normal right adrenal gland. It is very small because it is normal. On the left, above this right adrenal gland, is a lobe of the liver (L) that has to be pulled forward during surgery in order to get access to the right adrenal gland. The posterior vena cava is the large blue vein running horizontally. The abnormal left adrenal gland can be visualized to the left of the arrow on the top right.

The right adrenal gland of this different ferret is the horizontal white area just to the the right of the hemostat. You can see a dark blue vein running vertically over the adrenal gland. The liver has to be pulled away to visualize this gland. You can also see how the adrenal gland is adhered to the vena cava, the large horizontal blue vein that drains the blood from the back of the body is the vena cava.


Physiology

These small but very important glands have numerous roles. The adrenal tissue in ferrets normally secretes several sex hormones. The important ones are:

  • 17 – OHP (17 alpha hydroxyprogesterone)
  • androstenedione
  • DHEa (dehydroepiandrosterone sulfate)

It is postulated that these hormones are secreted from the adrenal glands after chronic stimulation from follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. Indoor housing of ferrets, leading to more light than ferrets in the wild, is postulated to also stimulate release of LH, along with gonadotropin releasing hormone (GnRH) from the pituitary gland.

The end result of this hormone imbalance is excess secretion of estrogen in females and testosterone in males. This causes the vulva to enlarge in females, and a return to male sexual behavior in the male. The enlarged vulva is easy to see, which might be the reason we diagnose this problem more often in female ferrets.

The arrow points to an enlarged vulva typical in females.

In male ferrets cysts can occur in the small amount of prostatic tissue they have. This can cause difficulty in urination, which can affect the kidneys if it progresses.

You can see dye in the urinary bladder of this male ferret and the urinary catheter so its bladder can empty. You can also see the shape of this ferrets penis. It has a bone in it (just like the dog) called the os penis. The tip of the os penis in the ferret is curved, and the opening is very small, making catheterization difficult.

Click on the photo to enlarge and see this anatomy in more detail.


Symptoms

The most common symptom of adrenal disease in ferrets is hair loss, sometimes with itchiness (pruritis). The most likely spots for hair loss are the tail area and rear legs. Hair loss in dogs and cats is almost always caused by a different problem.

Some ferrets with adrenal disease do not show any symptoms, while others exhibit varying degrees of hair loss and even enlarged vulvas in spayed females. Male ferrets sometimes have difficulty urinating in addition to hair loss. Even if they are neutered there might be a return to normal sexual behavior. There might also be lethargy, a decrease in appetite and weight loss. These symptoms might even come and go over a period of months, and the hair loss can be a seasonal occurrence.

This is typical of the hair loss that can occur

Alopecia

It can sometimes be more extreme


Diagnosis

Symptoms

Although enlarged adrenal glands can be palpated during an examination, this is not usually the case. a large number of adrenal tumors are diagnosed during routine exploratory surgery, especially if the ferret exhibits the typical pattern of hair loss and an enlarged vulva in the female, or straining to urinate in the male. Exploratory surgery is a common way to verify the diagnosis and correct the problem. During this surgery we routinely check other organs for problems, especially the pancreas for tumor nodules that might be an insulinoma.

Blood Sample

Blood sample and hormone assays might be helpful in the diagnosis also, particularly to rule out other diseases.

A special blood sample can be performed to check hormone levels. This test can be used if the typical symptoms of hair loss and enlarged vulva or urine straining are not particularly prevalent. This sample is sent to a special laboratory that takes several weeks to report their results.


Radiology

Radiographs are unhelpful in this diagnosis since it is difficult to see the adrenal glands. Ultrasound is what is needed to visualize the glands in ferrets and also dogs and cats.

Ultrasound

This ferret is having an ultrasound performed on its abdomen


Surgical Treatment

The primary method of treating adrenal disease in ferrets is surgical removal of the gland. The problem can occur on either the right or left adrenal gland (or both). In the overwhelming number of cases the problem is in the left gland only. Eventually, both glands are commonly involved.

The left gland is much easier to work with because it is in a fat pad above the left kidney. The right gland is much more difficult to approach because it is under a lobe of the liver and is attached to the posterior vena cava, the main vein that returns blood from the back end of the body to the heart. In most surgeries we remove the diseased left gland, leaving the right gland alone.  Complete removal of both glands can cause serious complications. Sometimes removal of only one of the glands can cause a problem if the remaining gland cannot make up for the loss.

We take the same precautions in ferret adrenal gland surgery as we do in all pets. First we perform a pre anesthetic blood panel to check the internal organs. If everything is in order we then carefully anesthetize our patient. In ferret surgery we have to pay particular attention to low body temperature (hypothermia) and low blood sugar (hypoglycemia)

This area contains graphic pictures of a ferret with adrenal gland disease. It may not be suitable for some children (and some adults also!).

We make our incision in a particular location in the center of the abdomen, called a ventral mid line incision. In this picture our surgeon has incised through the skin, and is pointing to the muscle layer he will be going through to gain entrance into the abdomen. It is important that we go through this particular area because this is the area that will be able to hold the sutures we use to sew the muscles back together, and thus prevent a hernia.

Ferrets are little guys, so their surgical anatomy is small. The pictures you previously saw of the adrenal glands were enlarged to allow easier visualization. The picture below is from an actual surgery. The white arrow points to the diseased adrenal gland that is held at the tip of the hemostat running vertically. The other hemostat to the left is clamping off a blood vessel .

The white arrow points to the suture that remains once the gland is removed.

During the surgery and immediately after we monitor body temperature to prevent hypothermia.

We also check the blood sugar level when the procedure is finished and before the ferret is completely awake. Their veins are small and difficult to find, so it is much easier to do it when the ferret is still groggy from the anesthesia.

We test the blood sugar level right in the surgical suite so we can plan our post operative care

Here is our little friend nice and cozy right after her surgery. She has been given a pain injection and is being monitored closely.


This is the report we received when the diseased left adrenal gland was analyzed.


 

Whenever we perform an exploratory surgery (called a laparotomy) on an animal we check other internal organs for disease. This is especially important in ferrets due to their propensity for having other diseases. This is a picture of an enlarged spleen found during a routine adrenal gland surgery.

We knew there was an enlarged spleen in this ferret because we could palpate it during an examination. This enlarged spleen was verified by a radiograph. The black arrows outline the enlarged spleen. a kidney (K) is also visible overlying the spleen.

This spleen was biopsied to determine whether this was a normal enlargement, called hypersplenism, or whether it was cause by cancer. This picture shows cautery of the spleen after a small biopsy was taken.

Another very important organ to check in ferrets is the pancreas due to a disease called insulinoma. These arrows outline a normal pancreas as observed during a laparotomy.

This ferret had a cyst on one of its liver lobes


Now that you know how we perform this surgery lets look at an abbreviated video of a ferret with an adrenal gland tumor and an insulinoma. You will also get a chance to see how we make a bloodless incision with the laser.

Ferret Adrenal and Insulinoma Surgery


Medical Treatment

One of the best medications used to treat this condition is called Lupron, originally used to treat prostate and breast cancers. We have maintained ferrets on Lupron successfully for many years, so it has become a mainstay of our medical management after the left adrenal gland is removed.

Lupron (Leuprolide) is a GnRH analog (remember the physiology section above) that minimizes the secretion of the sex hormones from the adrenal gland. Lupron does this by suppressing the production of FSH and LH from the pituitary gland. Long term effects of the chronic use of this drug are unknown.

In some cases we also use only medical therapy, particularly if a ferret is not a good surgical candidate.

Melatonin can be used to stimulate hair regrowth, it does not suppress the adrenal tumor. If used prior to a physical exam it can mask symptoms, and cause the adrenal gland to become even larger before surgical removal.


Prognosis

Most ferrets that have this surgery regain hair growth and do well for years. Even though most adrenal tumors are benign, recurrence can occur. a tumor can reappear in the adrenal gland that remains after surgery, and symptoms can recur.