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Name
Cushing's Disease, Canine
Short Description
Canine hyperadrenocorticism
Affected Animals: Although dogs of almost every age have been
reported to have Cushing's disease, it is most common in middle-aged
and older dogs. Most dogs diagnosed with Cushing's disease are at
least nine to 10 years old. Slightly more female dogs are affected
than male dogs. Large breed dogs tend to be affected more often than
smaller breeds. Several breeds are more commonly diagnosed with PDH
than others, including poodles, terriers, German shepherds,
dachshunds, beagles, and boxers. Many of these same breeds are also
reported to have adrenal gland tumors at a greater frequency.
Overview: Cushing's disease results from excessive
production of cortisol, a hormone normally produced by the adrenal
glands. This excessive cortisol production can result from
abnormalities in the pituitary gland that cause excessive hormone
secretion by the adrenal glands, by tumors within the adrenal glands
themselves, or by a combination of these factors.
A variety of symptoms can result from excess cortisol, the most
common of which include increased thirst and urination, increased
appetite, panting, and skin changes such as hair loss and thinning
of the skin. Efforts to distinguish which form of the disease is
present are important, as this can influence treatment
recommendations. Blood tests and imaging procedures, including
abdominal ultrasound, may be needed to make this distinction.
Pituitary-dependent Cushing's disease is usually treated with
medication. Adrenal gland tumors are best addressed surgically,
although they can also be treated medically in situations in which
surgery is not advised.
Complications due to Cushing's disease and its treatment are common,
but with careful diagnosis and management, many dogs with Cushing's
disease can survive for as long as two to three years or more,
depending on a number of factors.
Symptoms: Increased thirst, increased urination, increased
appetite, panting, hair loss, darkening of the skin, thinning of the
skin, abdominal enlargement, skin infections, flaky or greasy skin
changes, weakness, tiredness, obesity, reproductive changes,
bruising.
Description: Cushing's syndrome refers to the
signs and changes that occur secondary to excessive cortisol
production by the adrenal glands. Cortisol is a hormone that is
necessary for many normal body functions. Its secretion from the
adrenal glands is regulated by input from two regions in the brain,
the hypothalamus and the pituitary gland. The hypothalamus, a small
structure in the brain, secretes corticotropin-releasing hormone, or
CRH, which in turn acts on the pituitary gland, also located in the
brain. The pituitary gland releases adrenocorticotropic hormone, or
ACTH, which then stimulates the adrenal gland to make cortisol. The
cortisol produced by the adrenal gland feeds back to both the
hypothalamus and the pituitary gland to regulate production of CRH
and ACTH.
Although the exact mechanism that causes Cushing's disease to
develop is not completely understood, there are many possible
causes. In general, there are two forms -- PDH and adrenal gland
tumors. The most common is the pituitary-dependent Cushing's
disease. Some dogs with pituitary-dependent disease have microscopic
tumors that cause the excessive ACTH production, leading to
excessive cortisol secretion from the adrenal glands, while others
have larger tumors that cause the same result. Some dogs with PDH do
not have discrete tumors in their pituitary glands, but the cells
there still produce excessive ACTH. Dogs with the less common form of the disease,
adrenal gland tumors, may have either benign or malignant tumors
that produce excessive amounts of cortisol from one or both adrenal
glands. The excessive cortisol concentrations in the dog's blood
then lead to the clinical signs, and the changes in the bloodwork
and other diagnostic findings discovered by the veterinarian.
Although most dogs with Cushing's disease are not in critical
condition at the time of diagnosis, serious complications of
Cushing's disease are possible. These include high blood pressure;
urinary tract infection and stone formation; changes in the portion
of the kidney where blood is filtered; congestive heart failure;
pancreatitis; diabetes; and blood clot formation, especially in the
vessels supplying the lungs.
There are both surgical and medical treatments for Cushing's
disease. Surgery is the preferred way to manage dogs with adrenal
tumors, while medical treatment is used for dogs with PDH. The goals
with treatment are to eliminate or minimize signs due to excessive
cortisol production, and to prevent potentially life-threatening
complications from the disease. Dogs treated successfully for
Cushing's disease live for an average of two to three years.
Diagnosis: A definitive diagnosis of Cushing's disease can
be difficult to obtain. When animals present with the classic signs
of the disease, the diagnosis is initially suspected on the basis of
those signs and the results of routine laboratory tests. As with
many illnesses, a complete blood count, biochemistry profile, and
urinalysis are very important tools in the initial evaluation of a
dog suspected of having Cushing's disease. Usually there will be
changes on these tests that may indicate the possibility of
Cushing's disease. Routine imaging procedures, such as abdominal
x-rays, may show changes including generalized liver enlargement,
and, less commonly, adrenal gland enlargement or mineralization.
Abdominal ultrasound is also used frequently in the evaluation of
Cushing's suspects to evaluate the liver size and texture, the size
and shape of the adrenal glands, and to look for evidence of other
abnormalities that might be contributing to the dog's signs.
A more definitive diagnosis depends on the results of tests that
look more specifically at adrenal gland function. The urine
cortisol-to-creatinine ratio is used in some cases, but it is not a
very specific test because dogs with almost any illness can have an
abnormal result. The two most commonly used screening tests are the
ACTH stimulation test, and the low-dose dexamethasone suppression
test. Yet, it can be very difficult to know for sure that an
individual dog has Cushing's disease, since the results of the tests
can be difficult to interpret.
Once a tentative diagnosis of Cushing's disease
is established, an attempt to distinguish which form of the disease
is present should be made. Pituitary dependent hyperadrenocorticism,
or PDH, is the more common form, accounting for as many as 80 to 85
percent of patients with Cushing's disease. The remaining dogs have
adrenal gland tumors, which can affect either one or both adrenal
glands. In very rare circumstances, both PDH and an adrenal tumor
can be present in the same dog. The tests most commonly used to
distinguish the pituitary-dependent form from an adrenal tumor are
the high-dose dexamethasone suppression test, the endogenous ACTH
level, and abdominal ultrasound. CAT scans can also be used to
evaluate adrenal gland structure, and MRI scans can be used to look
for pathology in the pituitary gland.
Prognosis: The outlook for surgical treatment of adrenal
gland tumors is fairly good, provided that the animal survives the
surgery and the period immediately after it. As a rule, dogs with
benign adrenal gland tumors live longer than dogs with malignant
tumors. Metastasis, or spread of a malignant tumor, makes for a
worse prognosis. Such animals can be treated successfully with
medication to help keep symptoms under control after surgery. Dogs
that survive surgery are reported to have an average survival time
of as long as 36 months.
Dogs treated successfully for PDH live approximately two years. Some
dogs do not do that well, while others may live for 10 years or more
depending on their age at the time of diagnosis, the presence of
additional disorders, and the development of complications related
to the treatment. Relapses are common in patients treated medically,
with many dogs requiring medication adjustments due to recurrence of
signs in the first year. Almost half of all dogs with Cushing's
disease that die do so because of problems related either to the
disease itself or its treatment. However, despite a guarded
long-term prognosis, the majority of dogs can lead lives of an
excellent quality with careful monitoring and attention to detail.
Transmission or Cause: The exact events that lead to the development of
Cushing's disease are not known at this time. The majority of dogs
with the illness have a pituitary gland problem, while the remaining
dogs have adrenal gland tumors. Rarely, a single dog can have both
pituitary-dependent Cushing's disease and an adrenal gland tumor.
Treatment: Treatment of Cushing's disease depends on which form of
the disease is present. With PDH, the main treatments are
medications. Although surgery to remove the pituitary gland or the
adrenal glands has been performed, the results with medical
treatment are better, and the risk of these surgeries, at least at
this time, makes them difficult to recommend. The drug used most commonly to treat
pituitary-dependent Cushing's disease is o,p'-DDD, also known as
Lysodren or mitotane. Lysodren is used at first on a daily basis.
This drug works by actually causing death of the cortisol-producing
cells in the adrenal gland. Dogs without Cushing's disease appear
more resistant to the drug's effects than dogs with the illness.
Very careful monitoring is necessary once Lysodren has been
prescribed. Key factors to observe include thirst, appetite, and
general overall disposition. Prior to beginning treatment, the
veterinarian may ask that close attention be paid to the dog's
appetite and how much food the dog eats. The amount of water a dog
drinks over several days should be measured prior to treatment. This
helps owners recognize one of the key endpoints of induction
treatment: when water consumption drops below 50 milliliters per
pound of body weight per day. In some cases, if decreases in
appetite, water consumption, or the development of lethargy are not
observed, the ACTH stimulation test will be checked after seven days
of treatment to see if the endpoint of induction has been reached.
Based on the dog's symptoms and ACTH stimulation test results, a
lower dose of the drug is administered during the maintenance phase.
Once induction is complete, dogs are given doses of Lysodren,
usually two to three times a week, to keep the disease in check.
Often, the veterinarian will need to make adjustments in the
medication dose according to the recurrence of symptoms during
maintenance treatment. Sometimes dogs are given prednisone in
addition to Lysodren to avoid adverse consequences of Lysodren
treatment, but with very careful monitoring, this additional
treatment may not be necessary. Complications during treatment with
Lysodren can include the development of signs due to decreased
cortisol production from the adrenal glands. These signs, which can
be severe and life-threatening if they go unrecognized, include
weakness, lethargy worse than the lethargy existing present prior to
treatment, loss of appetite, vomiting, diarrhea, and in severe
cases, collapse or even shock. Neurological symptoms can occur
either as a side effect of Lysodren, or from growth of the pituitary
tumor that caused the Cushing's disease in the first place. ACTH
stimulation tests are repeated every three to four months to ensure
adequate control of the disease.
Dogs treated successfully with Lysodren usually
return fairly quickly to normal amounts of water intake, urination,
and food intake -- often within seven to 14 days. Strength may
improve within a few days to a few weeks, and the appearance of a
pot belly may diminish. Skin changes and panting usually take much
longer to resolve, as do reproductive disorders. Liver enzyme
abnormalities and elevated systemic blood pressure readings may take
as long as three to 12 months or more to resolve.
Another drug used for medical treatment of PDH is
Anipryl, or L-deprenyl. This drug is also used to treat older pets
with a behavioral disorder called cognitive dysfunction syndrome.
The drug works by influencing dopamine concentrations in the central
nervous system, which in turn then influence production of ACTH by
the pituitary gland. There is controversy as to the effectiveness of
this drug. However, since the potential side effects are less severe
than those that can occur with Lysodren, it is used in some dogs,
particularly geriatric dogs with multiple health problems.
Ketoconazole is another drug used for medical treatment of PDH. It
acts by blocking the formation of cortisol in the adrenal glands. It
can also be given to dogs with adrenal gland tumors that will not be
receiving surgery, or to help control symptoms prior to surgery.
Some dogs that cannot tolerate Lysodren can be treated successfully
with ketoconazole. Its main side effect is the potential to cause
injury to the liver.
In dogs with PDH that have large pituitary gland
tumors -- particularly those dogs with neurological signs due to the
physical presence of a large pituitary mass -- the primary treatment
is radiation therapy to control the growth of the tumor.
Dogs with adrenal tumors can be treated surgically or medically. The
main treatment for adrenal tumors is surgical removal. The surgery
is technically a very difficult one, with many potential
complications during and after the procedure. A surgeon experienced
in removing adrenal gland tumors should perform it. After surgery,
animals often need to be supplemented with both glucocorticoids and
mineralocorticoids, the two primary types of steroids normally
produced by the adrenal gland. Sometimes supplementation can be
tapered as the remaining adrenal gland begins to function again, but
some dogs will require supplementation for life.
Drugs used for the medical treatment of adrenal tumors include
Lysodren and ketoconazole. Dogs with large and likely inoperable
tumors on x-rays or ultrasound, dogs that are very sick, old, or
debilitated, and dogs with suspected spread of a malignant adrenal
gland tumor are all candidates for medical treatment, as are pets
whose owners cannot afford the surgery.
Prevention: The exact cause of Cushing's disease is not
known, and there is no way of preventing the disease from
developing. Since similar signs can occur in dogs that are treated
for long periods of time with high doses of cortisone, this
treatment should be avoided wherever possible. In these dogs with
so-called "iatrogenic Cushing's disease," the signs should resolve
as the cortisone dose is tapered.
