Cushing's disease (hyperadrenocorticism) is a
condition that results from the
chronic overproduction of too much
glucocorticoid in the body. In the normal dog, the
pituitary gland produces a hormone called ACTH, which stimulates the
adrenal gland to produce the steroid hormone glucocorticoid
necessary for the function of many systems in the body. If something
goes wrong in the pituitary gland or adrenal gland and too much
glucocorticoid is produced, then Cushing's disease develops. This is
a very complicated disease with a wide range of symptoms and causes.
This article will try to give a concise description of the disease,
its symptoms, how it is diagnosed, and its treatment.
Cushing's disease is considered a disease of
middle age and older dogs and cats. It is much more common in dogs.
This disease is similar in cats except that in cats up to 80% also
diabetes mellitus. This article will refer to the problem
as it occurs in dogs. The usual age of contracting the disease is
around six or seven years with a range of two to sixteen years.
There is equal distribution between males and females and there does
not appear to be an increase of the disease in any one breed.
|For dogs ultimately diagnosed
with Cushing's disease, hair loss was one of the most common
reasons the owners first brought their dog in for evaluation.
As a result of the chronically elevated
glucocorticoids (steroids), the affected dogs develop a classic
combination of dramatic clinical signs and lesions. The disease
progresses slowly. A study showed that most dogs had at least one
symptom of the disease from one to six years before the disease was
diagnosed. Because the symptoms occur so gradually, the owner often
attributes the changes to "old age." Some dogs will have only one
symptom, while others may have many.
Consumption and Urination: The most
common symptom is increased consumption of water and the resultant
increased urination (polyuria/polydipsia). The dogs drink between
two and ten times the normal amount of water and the resultant
increase in urination follows. This symptom is present in over 85%
of all animals with Cushing's disease. Previously housebroken
animals may begin to have accidents because their bladders fill
quickly with the overproduction of urine.
Increase in Appetite:
Increase in appetite (polyphagia) is
another common clinical symptom that shows up in around 80% of the
affected animals. Dogs may begin stealing food, getting into the
garbage, begging continuously, and become very protective of their
food. Despite having other symptoms, the owner may feel that the dog
is okay because of his good appetite.
Abdominal enlargement is a common
symptom in up to 80% of the affected dogs. The potbellied appearance
is a result of the shifting of fat to the abdominal area and a
weakening and wasting of muscle mass in the abdomen.
Hair Loss and Thin Skin:
Hair loss and thinning of the skin are
also common symptoms in dogs with Cushing's disease. It is estimated
that between 50% and 90% of the affected animals develop these
symptoms. Hair loss (alopecia) is one of the most common reasons
that owners bring their dog in for evaluation. The hair loss usually
starts over the areas of wear such as the elbows and progresses to
the flanks and abdomen until eventually only the head and
extremities have hair. The skin may also become thin and be easily
damaged and slow to heal.
Increased panting, recurrent urinary tract
infections, or losses in reproductive ability are other symptoms
often noted with this disease.
Cushing's Disease has two
There are two different distinct forms of the
disease. There is pituitary dependent hyperadrenocorticism (PDH) and
there is an adrenal-based disease.
hyperadrenocorticism: PDH involves the
oversecretion of ACTH by the pituitary gland. ACTH is a hormone that
stimulates the adrenal gland to produce glucocorticoids. The
pituitary gland is most likely overproducing ACTH because of a
pituitary tumor. The PDH form of the disease is responsible for
around 80% of the cases of canine Cushing's disease.
hyperadrenocorticism: The adrenal-based
form of the disease is usually a result of an adrenal tumor that
causes an oversecretion of glucocorticoids. Adrenal tumors are
responsible for around 20% of the cases of Cushing's disease. There
is also a form of the disease called "iatrogenic" Cushing's disease
that occurs as a result of giving the animal high doses of steroids.
In this form of the disease, symptoms of Cushing's disease will go
away once the steroids are discontinued.
|It is recommended that any dog
suspected of having Cushing's disease should have a complete
blood count, chemistry profile, and urinalysis performed as a
routine part of the evaluation.
Cushing's disease can present with a variety of
symptoms and may also be involved with several different disease
processes. Therefore, it is recommended that any dog suspected of
having Cushing's disease should have a
complete blood count (CBC),
blood chemistry panel, and
urinalysis performed as a routine part of the evaluation. Common
abnormalities in these tests include increases in alkaline
phosphatase, and ALT (liver enzymes), increased cholesterol,
decreased BUN (a kidney function test), and dilute urine (low
There are several different tests that can be
performed to get a definitive diagnosis of Cushing's disease. Many
times the veterinarian may perform more than one test to help
confirm the diagnosis or to determine which form of the disease is
present. A diagnosis of Cushing's disease, however, should never be
made on the basis of laboratory tests alone. The dog needs to be
showing symptoms of the disease, and have a medical history
consistent with the diagnosis.
The three most common "screening" tests are the
urine cortisol:creatinine ratio, the low dose dexamethasone
suppression test, and ultrasound.
Ratio: In this test, the owner
generally collects a urine sample at home (where the animal is not
stressed). The sample is sent by the veterinarian to a special
laboratory for testing. Most dogs with Cushing's disease have an
abnormal result. However, there are other diseases that can also
cause abnormal results. So if this test is abnormal, further
diagnostic testing should be performed.
Low Dose Dexamethasone
Suppression Test: The low dose
dexamethasone suppression test is useful in diagnosing Cushing's
disease in dogs. When given low doses of dexamethasone, normal dogs
show a marked decrease in blood cortisol levels when tested 8 hours
later. Most dogs (more than 90%) with Cushing's disease do not have
a decrease in cortisol level after being given dexamethasone. The
results can sometimes help determine which type of disease is
Abdominal ultrasound is helpful in
three respects. First, it is a good test to evaluate all of the
abdominal organs in the dog. Secondly, it is used to study the size
and shape of the adrenal glands. The adrenal glands in pituitary
dependent hyperadrenocorticism are usually normal in size or
enlarged. If a tumor is present however, one adrenal gland is often
abnormally large or of uneven shape. Finally, if a tumor is
suspected, ultrasound can help identify any metastasis to other
There are two tests that were used more commonly
in the past to aid in the diagnosis of Cushing's disease in dog.
They are the high dose dexamethasone suppression test and the ACTH
High Dose Dexamethasone
Suppression Test: This blood test is
used to try to distinguish between pituitary dependent
hyperadrenocorticism and adrenal-based hyperadrenocorticism.
ACTH Stimulation Test:
This is another test that is less
commonly used in the diagnosis of Cushing's disease today. The ACTH
hormone preparation that is used in this test has become very
expensive and sometimes difficult to acquire. It will not
distinguish between the two types of hyperadrenocorticism, but it
may aid in the diagnosis in difficult cases. It is most commonly
used to evaluate the effectiveness of therapy.
Treatment consists of several different options.
Depending on the type of disease, surgery can be performed. If an
adrenal tumor is identified, then surgical removal may be a viable
option. There are several different forms of tumors that can invade
the adrenal gland and their treatment will be based on the
particular tumor type. There are a few surgeons that have
successfully performed surgery to remove the affected pituitary
gland in the pituitary form of the disease. However, this is a very
specialized procedure and is not commonly performed in the pituitary
form of the disease.
|Nonsurgical treatment is the
most often used treatment for most cases of canine Cushing's
Non surgical treatment is the most often used
treatment for most cases of canine Cushing's disease. About 80% of
the cases of Cushing's disease in the dog are of the pituitary type,
and since both the adrenal and the pituitary type will respond
effectively to some of the oral treatments, many veterinarians do
not perform the diagnostics necessary to distinguish between the two
different forms. There are currently several different oral
medications being used to treat canine Cushing's disease.
Lysodren (also known as mitotane, and o,p'-DDD) was the only
treatment available for pituitary dependent Cushing's disease. It is
convenient to use and is relatively inexpensive and is still
probably the most widely used treatment. The downside of this drug
is that it can have some serious side effects and regular
blood-monitoring needs to be performed. During the initial phases of
the therapy, the dog must be very carefully monitored, and there
must be close communication between the veterinarian and the owner.
The use of Lysodren is somewhat like chemotherapy.
It works by destroying cells of the adrenal gland that produce the
corticosteroid hormones. As the number of corticosteroid-producing
cells is reduced, even though the pituitary gland continues to
produce excess ACTH, the adrenal gland is less able to respond, so
the amount of glucocorticoid being produced is reduced. The problems
arise when too much of the adrenal cortex is killed off. The animals
may then need to be placed on prednisone, either short or long term.
The Lysodren is initially given daily while the animal is being
monitored for a decrease in the symptoms (water consumption,
appetite). On the 8th or 9th day of the initial therapy, the dog
needs to be examined and an ACTH stimulation test is performed to
determine if the drug is working. If the goal is achieved,
maintenance therapy is started. If the goal has not been reached,
then the dog generally remains on the daily medication for 3 to 7
additional days and is rechecked until the proper results are
achieved. If the dog becomes lethargic, vomits, or has diarrhea, or
if the treatment does not work by 30 days, then the treatment plan
is reevaluated. If treatment is successful, then symptoms should
resolve within 4 to 6 months. A certain percentage of dogs will
relapse and need to undergo the daily therapy again at some point in
their lives. If a dog ever becomes ill while on Lysodren, the
Lysodren should be stopped immediately and the dog should be
examined by a veterinarian. The dog will need to be on Lysodren for
the rest of his life.
Ketoconazole is an oral
antifungal agent that has been used extensively since the
mid 80s. One of the side effects of ketoconazole is that it
interferes with the synthesis of steroid hormones. It therefore
gained some popularity as a treatment for Cushing's disease.
However, it is rarely used today.
(Anipryl) has been advocated for the treatment of Cushing's disease
in dogs, but its effectiveness has come into question.
Trilostane is a newer treatment that is used to treat
some dogs with Cushing's disease. It is more expensive, but may be
an alternative treatment for dogs with adrenal tumors. As with
Lysodren, the dog is reexamined repeatedly during the initial phase
of treatment, and ACTH stimulation tests are performed. In many
cases, after several months of therapy the dose needs to be
Cushing's disease is a disease that affects middle
age to older dogs. The affected animal has a characteristic
presentation including increased water consumption and resulting
increased urination, increased appetite, hair loss, and a potbellied
appearance. There are several diagnostic tests available, as well as