Cushing's Disease (or syndrome) occurs when the adrenal glands produce
excess amounts of cortisol, also known as cortisone. Cushing's is also
known as hyperadrenocorticism. Hyper = above normal; adreno = relating to
the adrenal glands; corticism = relating to the cortex & cortisol
production. So, Cushings is a disease of elevated cortisol production by
the adrenal cortex. Cushing's is much more common in dogs than in
cats, so this page focuses on Cushings in dogs.
Dogs have two adrenal glands, which are are small pea-sized glands located
next to the kidneys. The adrenal glands produce several types of hormones
that are involved in regulating many of the body's processes including
control of blood potassium and sodium concentrations, water metabolism,
protein, fat and carbohydrate metabolism, stress response, regulation of
blood pressure, and to a small extent sex hormone levels.
The outer portion of the adrenal gland is called the cortex and it
produces corticosteroids (cortisol and corticosterone) and
mineralocorticoids (aldosterone). Cortisol is involved in the metabolism
of carbohydrates, fat, and protein. Aldosterone is involved in regulation
of mineral and water balance. The inner portion of the adrenal gland is
called the medulla and it produces epinepherine, which during a stress
response, raises blood glucose levels, blood pressure, and cardiac output.
Production of cortisol by the adrenal gland is controlled by the pituitary
gland, which is a small gland located at the base of the brain. The
pituitary gland produces adrenocorticotropic hormone (ACTH) which
stimulates the adrenal cortex to produce corticosteroids (cortisol).
Additionally, the hypothalamus, a small structure in the brain, secretes
corticotropin-releasing hromone (CRH) which signals the pituitary gland to
produce ACTH. When enough cortisol is produced, it in turn goes back to
the pituitary and hypothalamus and tells them to stop producing ACTH and
CRH. In technical terms this is called a negative feedback system. The
hypothalamus produces CRH which tells the pituitary gland to produces
ACTH. The ACTH tells the adrenal glands to produce cortisol, which returns
back to the hypothalamus and pituitary to turn off CRH and ACTH
Cushing's is one of the most common endocrine diseases of middle-aged and
older dogs. Most dogs are 9-10 years old when diagnosed, but it can occur
in younger dogs. Larger dogs and females tend to be more affected than
smaller breeds or males.
why the balance between ACTH and cortisol can be upset:
- Pituitary gland
tumor- also called Pituitary Dependent Hyperadrenocorticism (PDH)–
This is the most common type of Cushings and it is found in about 85% of
all cases. A tumor in the
pituitary gland causes an increased production of ACTH, which in turn
tells the adrenal cortex to produce more cortisol. The pituitary tumor
can be very tiny or large and it can be benign or malignant.
Poodles, terriers, German shepherds, Dachshunds, beagles, and
boxers are more commonly diagnosed with PDH than other breeds.
- Adrenal gland
– A tumor in one or both adrenal glands can cause an excess production
of corticosteroids, which causes Cushing’s. The tumor can be tiny or
large and it can be benign or malignant.
– Iatrogenic means the disease has resulted from a complication of
medical treatment. When a dog is given corticosteroids to treat another
medical condition such as allergies, the excess corticosteroids can
overload the body and result in Cushing’s symptoms.
Not all of these signs may be present, but as
the disease progresses, they may become more pronounced or more signs may
be seen. How common the sign is is shown for many of the items.
- Increased appetite (polyphagia) - 80-95%
will show this sign.
- Increased drinking (polydypsia) and
urination urination (polyuria) - due to interference with production
of antidiuretic hormone. 80-90%.
- Muscle weakness, lethargy, lack of
activity - excess cortisol causes protein breakdown (catabolism) which
leads to muscle weakness. 75-80%
- Obesity, bloated abdomen, and
"potbelly" - due to an increase of fat in the abdomen,
increase in liver size (hepatomegaly), cronically full bladder,
stretching of the abdominal wall, and the abdominal well becoming
- Panting - due to increased fat in the
rib area (thorax), muscle weakness, and increased abdominal contents
exerting pressure on the diaphragm. A "common" sign.
- Poor hair coat, thinning hair (usually
on the sides), hair does not regrow . "Common".
- Skin infections - due to excess
corticosteroids suppressing the immune system.
- Thin skin, flaky or greasy skin &
bruising - many processes that control skin structure and health are
- Fasting hyperglycemia (elevated blood
glucose) - seen in 40-60% of dogs.
- Insulin resistance - seen in up to 85%
So as you can, some of the signs of diabetes and Cushing's are
Diagnosis and Testing
Diagnosis of Cushing’s can be complicated and difficult. It is important
to determine the type of Cushings (adrenal, pituitary, or iatrogenic) so
that the appropriate treatment can be undertaken.
lab tests are usually performed – complete blood count,
biochemistry, urinalysis – and abnormalities in these tests may
abdominal x-ray may show an enlarged liver or adrenal gland changes.
abdominal ultrasound is often performed to evaluate liver and adrenal
urine test measuring cortisol to creatinine ration is sometimes
performed, but it is not a very specific test because many health
problems can cause abnormal test results.
This is a screening test only – a negative result rules out
Cushing’s. A positive
result does not confirm Cushing’s and more tests will need to be
definitive diagnostic testing looks at adrenal gland function.
Cortisol levels in the blood are measured before and after a drug that
would normally effect cortisol levels is given. Two commonly used
tests are the ACTH stimulation test
and the Low-dose dexamethasone suppression
test. During the ACTH stimulation test, a pre-test blood
sample is taken, then a dose of ACTH is given. After 2 hours, cortisol
levels are measured again. If the cortisol levels are higher
than expected, Cushing’s may be diagnosed. Dexamethasone is a
cortisone-type drug that provides negative feedback on the pituitary
gland to turn off ACTH production, and that in turn causes a decrease
in adrenal cortisol production. In a normal animal (non-Cushing’s) a
dip in cortisol would be seen 8 hours after giving dexamethasone. If a
pituitary tumor exists, no drop in cortisol level is seen
during the low-dose dexamethasone test. During a high-dose
dexamethasone suppression test, cortisol levels will be suppressed
in about 75% of dogs with PDH and will not be suppressed in the
remaining 25% of dogs with PDH or in 100% of dogs with an
For detailed information about the tests used to diagnose Cushing’s,
Diabetic animals can pose a
special problem when testing for Cushing's.
As you can see, diabetes and Cushing’s share many of the same signs
(increased drinking, urination, eating, lethargy, enlarged liver).
Uncontrolled diabetes can lead to complications that in turn cause increased
cortisol levels and signs that are identical to Cushing’s.
Testing and diagnosis of Cushing’s in a non-diabetic dog can be
complicated, and it can be extremely complicated in a dog that has diabetes.
The situation is even worse for a stressed or poorly controlled
diabetic because stressed diabetics and Cushing’s dogs can have similar
blood panel abnormalities and blood chemistry abnormalities.
Plasma ACTH levels, the ACTH stimulation test results, and low-dose
dexamethasone suppression test results can be abnormal in a stressed DM dog;
the high-dose dexamethasone suppression test
results can be abnormal in an unregulated DM dog.
There are clinical signs that help distinguish the two disease so
your general vet and specialist must consider the “whole picture” of
your dog’s physical condition and test results.
Cushings caused by a
pituitary gland tumor (PDH). Surgery to remove a tumor in the
pituitary gland is very risky and is rarely performed. Controlling the
growth of the tumor may be attempted with radiation. Medication is used to
control this type of Cushings.
- The drug most commonly used is o,p’DDD, also
know as Lysodren or mitotane.
This drug works by destroying the cortisol-producing cells in the
adrenal cortex. Careful monitoring is required during treatment to be
sure that too much drug is not given and too many adrenal cortex cells
are not killed. Too much
drug would result in too little cortisol being produced (resulting in
Addison’s disease, the opposite of Cushing’s).
Treatment involves an “induction” or “loading” phase
where Lysodren is given on a daily basis. This loading phase rapidly
brings the some of the Cushing’s symptoms under control. Owners are
usually instructed to closely monitor their dog’s eating and
drinking. When drinking
is normal (about 50-60 mL water per pound body weight per day)
induction is complete and the “maintenance” phase begins.
In maintenance, Lysodren is given two to three times a week to
keep the cortisol levels within acceptable levels.
ACTH stimulation tests are repeated every three to four months
to ensure adequate control and dosing.
or L-deprenyl is another drug
that is used to treat pituitary-dependent Cushing’s.
It was approved for use in the United States in 1997. Anipryl
is used to treat cognitive dysfunction in dogs and has shown to be
effective in clinical trials in controlling Cushing’s in about 70%
of dogs. The drug works by influencing dopamine concentrations (a
chemical used to by brain cells to communicate with each other), which
in turn influences production of ACTH by the pituitary gland.
The effectiveness of this drug is controversial, but since the
side effects are less severe than those of Lysodren, it is used in
some dogs, especially those who are older or have multiple health
problems. Anipryl does not involve an induction or loading phase.
is another drug used to treat PDH or dogs who have adrenal gland
tumors. It works by
blocking production of cortisol in the adrenal gland.
It has the potential to damage the liver.
Cushings caused by an
adrenal gland tumor may be treated surgically or with Lysodren
Surgery is difficult and may have many complications.
Removal of the adrenal gland may require life-long supplementation
with glucocorticoids and mineralocorticoids (both normally produced by the
– treatment requires slowly discontinuing the cortisone that is being
given. This must be done in a
controlled manner so that other problems do not occur.
The disease that is being treated with cortisone will probably
recur. If damages has been done to the adrenal glands, that will need to
considerations for treating diabetics
With a possible diabetic and/or Cushoid animal there are three different scenarios that
- Your animal may be both diabetic and have
Cushing's. As the
Cushing's is brought under control your animal's insulin needs will be greatly reduced.
Therefore it's very important to monitor your animal's blood glucose until the correct
maintenance dose is determined so an overdose of insulin doesn't happen.
You can read Kiri's story -
she lived with diabetes, Cushing's and hypothyroidism for over 6 years.
- Your animal may only have Cushing's. The increased blood
glucose levels may be a side effect of the Cushing's and once the Cushing's is brought
under control there may be no need for insulin anymore.
- Your animal may only be diabetic. The Cushing's tests may
have been altered by one of the previously mentioned causes, resulting in false positive
to ask your vet
With a diabetic it is very important to take every means possible to stabilize them on
their insulin before a Cushing's test is even tried. Some questions to ask your vet:
- If your animal is unregulated--ask your vet at what amount
of insulin they would consider your animal to be needing to bring the
glucose levels under control.
- If your animal has only been on one type of insulin, are they
willing to try another type.
- Would a change in food, feeding schedule, or amount
of food make a difference.
Updated April 2006
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