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The adrenal glands are small paired glands buried in
fat in the front of each kidney. Even though these glands are small, the cortisol they secrete, along with their other functions,
have great significance to normal physiology.
Cause
Pituitary Dependent (PD)
Up to 90% of all Cushing's
cases in dogs fall into this category. The pituitary gland is invaded with a slow growing cancer called an adenoma. This causes
it to secrete an excess amount of ACTH. The adrenal glands respond to this excess ACTH by enlarging and secreting excess cortisol.
It is this excess of cortisol that is circulating in the bloodstream that causes the symptoms we see in this disease.
Non-Pituitary
Dependent (AT)
In up to 15% of Cushing's there is an actual tumor of one of the adrenal glands (sometimes both are
involved). It enlarges and secretes excess cortisol in the bloodstream.
The benign version of this tumor occurs 50%
of the time, and is called an adenoma. The malignant version, which occurs the other 50% or the time, is called an adenocarcinoma.
It can spread from the adrenal gland to the liver, lung, kidney, and lymph nodes.
Iatrogenic
Long term use of supplemental
cortisone, in oral, injectable, or even topical form, might cause an animal to have the symptoms of Cushing's disease. A common
supplemental cortisone is called prednisone. The blood level of cortisone that results from this supplemental use will cause
the adrenal glands to shrink in size. This is because the negative feedback loop tells the brain there is plenty of cortisol
in the bloodstream, so the pituitary secretes less ACTH. The pet has the symptoms of Cushing's because it is being introduced
into its body, not because the adrenal glands are overproducing it.
Symptoms
Some dogs with Cushing's disease
show the classic symptoms, while other show only a few vague symptoms. The classic symptoms are:
Polyphagia- excess
appetite.
Polyuria/polydypsia (PU/PD)- This is excess urinating and excess drinking of water. Several other important
diseases cause these symptoms also, notably liver disease, kidney disease pyometra, and diabetes mellitus (sugar diabetes).
Pot
bellied abdomen.
Thin skin and usually symmetrical hair loss along the trunk. The hair might grow in lighter in color
or even be hyperpigmented. Secondary skin infections are common.
Other symptoms could include lethargy, muscle wasting,
poor appetite, weakness, and behavioral changes.
Diagnosis
Cushing's disease has a large effect on the
skin. Many skin conditions have similar symptoms, so numerous diseases have to be kept in mind when making a diagnosis. These
include hypothyroidism, skin allergies, sarcoptic mange, demodectic mange, and Ringworm.
A thorough approach is needed
for a correct diagnosis of Cushing's. In every disease we encounter we follow the tenet's of the diagnostic approach to ensure
that we make an accurate diagnosis and so that we do not overlook some of the diseases that are also encountered in pets as
they age.
1. Signalment
Cushing's tends to be a problem that affects older dogs, usually greater than 10 years
of age. The disease tends to have a slow and gradual onset, so the early symptoms are easily missed.
Several canine
breeds are prone to getting Cushing's:
* Yorkshire Terrier
* Poodle
* Beagle
* Boston Terrier
* Boxer
*
Dachshund
Females and males get it at about the same frequency, neutered pets might be at higher risk of Cushing's.
2.
History
Cushing's disease is suspected in any pet that has some of the symptoms described above, particularly the skin
symptoms and the PU/PD. It is important to remember that some dogs do not show any symptoms early in the course of the disease.
This is another reason for yearly exams and blood and urine samples in dogs and cats 8 years of age or more.
Other
findings include skin infections that recur after antibiotic therapy is stopped. Some dogs might be itchy if a skin infection
is present.
3. Physical Exam
Routine physical exam findings might include:
Pot bellied abdomen
An
enlarged liver (hepatomegaly) might be palpated, along with smaller muscle mass in general.
Bruising might be seen
under the skin or when a blood sample is obtained.
Hair loss that is symmetrical and calcium deposits under the skin.
Blood
pressure might be elevated.
4. Diagnostic Tests
Several tests are used as an aid in making this diagnosis. Each
test has its advantages and disadvantages.
Blood Panel
A CBC (complete blood cell) and biochemistry panel should
be run on every dog 8 years of age or more, especially if they have any of the symptoms of Cushing's.
The CBC might
show an increased WBC (white blood cell count). The biochemistry panel might show an elevated alkaline phosphatase (Alk Phos).
This is an enzyme that is located in the bile production area of the liver. The excess cortisol influences this enzyme, although
other diseases can cause this elevation also. Cholesterol, red blood cells, blood glucose, and liver enzyme tests might also
be elevated. If a thyroid test is run also, it might be low or borderline normal.
This dog has a high Alk Phos.
Some dogs go much higher than this, especially if the disease has been present for a long period of time. This dog needs further
diagnostic tests if there are any other Cushing's symptoms present also. Note the 3 arrows on the bottom that point to Cholesterol,
Bun, and Creatinine. BUN is usually low, not high, in Cushing's Disease, so this pet might also be dehydrated or have kidney
disease at the same time.
Urinalysis
This test is not as important in Cushing's disease as it is
in other diseases, especially kidney disease. The specific gravity of the urine might be low, the protein might be elevated,
and a urinary tract infection might be present because of excess glucose in the urine.
Radiography
Radiography
might be of value if the adrenal glands are calcified (might occur with an adrenal tumor), otherwise the adrenals do not show
up on a radiograph. An enlarged liver can be seen on the radiograph, along with problems associated with other diseases in
pets this age, so a radiograph can be highly beneficial to help rule them out.
Ultrasound
This test
can be highly beneficial in this diagnosis. The adrenal glands can be measured, and their internal architecture can be analyzed.
Screening
Tests
This is the most reliable way to confirm a diagnosis of Cushing's disease. These tests evaluate the interactions
that are occurring between the hypothalamus, the pituitary gland, and the adrenal gland. The interaction between these glands
is know as the hypothalmic-pituitary-adrenal axis. The first goal is to determine if Cushing's Disease exists. After this
is achieved, the next step is to determine if it is pituitary dependent (PD) or an adrenal tumor (AT).
Urine cortisol:creatine
ratio
In this test the level of cortisol in the urine is measure, and used as an indication of the cortisol level in
the bloodstream. Creatinine is measured to adjust for different levels of urine dilution. Our kidney page has more information
on creatinine. It is used in a pet that has PU/PD, but not the other signs of Cushing's. It works in both dogs and cats.
This
test is easy to perform because all that is needed is a urine sample. We recommend you obtain this sample at home in the morning
just after your pet wakes up. Bring it to us immediately for analysis by our lab. Obtaining it at home will minimize the stress
of a car ride and a visit to our hospital, both of which will normally increase the level of cortisol in the bloodstream (remember
the stress response?), thus affecting this test.
A high level of cortisol in the sample is suggestive of Cushing's.
If the test comes back normal, then it is unlikely that Cushing's is present.
ACTH Stimulation
When a dog or cat
is given ACTH by an injection the adrenal glands are stimulated to produce cortisol. By measuring this cortisol with a blood
sample we can determine what reserve the adrenal glands have in the production of cortisol.
This is the ACTH we inject.
It is given at a specific dose depending on the weight of the dog.
A positive on this test gives a reasonably
good chance that a dog has Cushing's. It will not catch all dogs with Cushing's, so a dog with a negative test might still
have the disease.
Low Dose Dexamethasone Suppression Test (LDDS)
This is also a good test when the history, physical
exam, and routine blood panel and urinalysis are consistent with Cushing's. It only works in dogs because cats get a significant
number of false positives.
This dose of dexamethasone (which is a version of cortisone) suppresses the adrenal gland
from producing cortisol in normal dogs but not those with Cushing's. In this test an injection of Dexamethasone is given and
cortisol levels are measured at 4 hours and 8 hours after the injection. Like the ACTH stimulation test, a pre-injection blood
sample is taken to measure the resting cortisol level.
This test will catch most dogs that have the disease.
A negative on this test means that most likely the dog does not have Cushing's. A positive on this test indicates that a dog
might have Cushing's.
Treatment
This disease tends to occur in older dogs that commonly have other problems.
Some dogs die of other diseases before the symptoms of Cushing's become a significant problem. Treating Cushing's does not
necessarily give your pet a longer life. The goal of therapy is to give your pet a better quality of life.
Underlying
problems need identification and treatment. If your dog is hypothyroid the problem needs to be corrected with supplemental
soloxine. Skin infections and internal organ problems like kidney disease need treatment for a successful Cushing's outcome.
Urinary tract infections need to be cleared up with the use of antibiotics, and underlying diabetes mellitus needs to be regulated
with insulin. Some dogs with large tumors of the pituitary gland might initially respond to medical therapy for pituitary
dependent Cushing's. The Cushing's symptoms, especially neurologic, might recur as the tumor progresses. Several different
drugs have been used over the years to treat this disease. The 3 most common and effective ones will be described.
Pituitary
Dependent (PD)
L-Deprenyl (Anipryl)
This drug should be considered first in the treatment of PD Cushing's. IT
is used for Parkinson's disease in people and is also used to treat canine cognitive dysfunction (CD). This is helpful because
one medication can be used to successfully treat 2 diseases that occur in older dogs.
It is given daily for 2 months,
with the dose increased if the symptoms don't diminish. Side effects are negligible. The majority of PD Cushing's dogs will
show an improvement in symptoms within the first 2 months. If there is no improvement within one month after the dose is increased
then concurrent illnesses need to be looked for. If they do not exist then therapy with mitotane should be instituted. This
drug should not be used if your pet is being treated for Demodex with Mitaban, or with antidepressant medications or Prozac.
Mitotane
(o,p'-DDD)
This drug, know by the trade name of Lysodren, selectively destroys part of the adrenal gland. This limits
the amount of cortisol that the adrenal gland secrete can secrete. Pets that are on insulin for diabetes mellitus need to
have their insulin dose adjusted downwards when given mitotane. It should be administered with meals to enhance its absorption.
Side
effects can occur with this drug:
* lethargy
* vomiting
* diarrhea
* poor appetite
* weakness
* incoordination
You
need to closely observe your pet when it is on mitotane for any of the above side effects. If they occur you are to immediately
stop the use of mitotane. We will give you cortisone pills to give at home if side effects are severe enough.
Two long
term effects can occur while on mitotane maintenance therapy:
1. The Mitotane can be so effective that the adrenal
glands do not produce enough cortisol. Dogs with this problem have to be put on supplemental prednisone for the rest of their
lives.
2. It is not uncommon for relapses of Cushing's to occur within 12 months, even while on the maintenance therapy.
Both
of these effects emphasize the need for continual monitoring of your pet. This means close observation at home and ACTH stimulation
tests every 3-6 months.
Ketaconazole
This is a drug routinely used to control fungal infections. It has a different
mechanism of action than Mitotane. It inhibits cortisol production in dogs and humanoids by preventing enzyme pathways from
functioning properly. Ketaconazole works for PD and AT Cushing's.
It needs to be given at a test dose initially to
watch for anorexia or emesis. If tolerated well a loading dose is given for 7-10 days. After an ACTH test to determine if
the cortisol is in the normal range the drug is give every 12 hours for the rest of the dogs life. This is a more expensive
proposition than mitotane.
Iatrogenic
This form of Cushing's is the easiest to treat since we are not giving
a medication but taking one away. In most cases the elimination of exogenous cortisone will return your pet to normal function,
although this might take several months. Some of the skin changes might take longer, and may not even return completely to
normal. In some cases we use a decreasing dose of supplemental cortisone for several weeks to give the adrenal glands time
to resume normal production of cortisol.
Adrenal Tumor (AT)
The surgery to remove the cancerous adrenal gland is
called an adrenalectomy. It is a specialized surgery that is not routinely performed. Post operative complications are common.
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