What is Cushing’s syndrome?
Hyperadrenocorticism or Cushing’s syndrome is a clinical
condition that results from an overproduction of cortisol by the adrenal
glands. This overproduction most commonly results from a benign tumor in
the pituitary gland, which is located at the base of the brain. Under
normal conditions, the pituitary gland is responsible for stimulating the
adrenal glands to produce cortisol by releasing a hormone called
adrenocorticotrophic hormone (ACTH). Once a sufficient amount of cortisol
is released into the body, the release of ACTH from the pituitary gland is
turned off. Tumor cells in the pituitary don’t respond appropriately to
the signals to shut down and they continue to secrete ACTH and the adrenal
glands continue to produce cortisol in response. According to statistics,
in less than 20% of pets diagnosed with Cushing’s disease, the excess
production of cortisol results from a tumor in one of the adrenal glands.
Like tumor cells in the pituitary, these cells don’t respond normally to
signaling and continue to produce cortisol without the stimulation by
ACTH. Cushing’s syndrome is relatively common in dogs and rare in cats.
What are the clinical signs of Cushing’s syndrome?
There are many clinical signs that might be seen with
Cushing’s syndrome. These include increased water consumption and
urination, ravenous appetite, pot bellied appearance, thin skin, muscle
wasting or weakness, ligament tears (commonly the cruciate ligaments of
the knees), hair loss, panting, lethargy, recurrent urinary tract
infections or neurological abnormalities. Many pets exhibit several of
the listed clinical signs, but rarely does any one pet have all of the
signs. Cats with Cushing’s syndrome are often diabetic and also have very
thin skin that tears easily.
How is Cushing’s syndrome diagnosed?
Your veterinarian will likely have an index of suspicion
that your pet has Cushing’s syndrome based on the history you provide
about your pet and by physical examination. Routine blood work and a
urinalysis may be recommended to evaluate for changes that might be
consistent with Cushing’s as well as to ensure there isn’t evidence of
problems with other organs such as the liver and kidneys or evidence of a
urinary tract infection. More specialized blood tests will likely be
recommended, which are used specifically for diagnosing Cushing’s as well
as differentiating between adrenal and pituitary dependent Cushing’s
syndrome. Your veterinarian may also recommend diagnostic tests such as
radiographs and ultrasound to evaluate the size of the adrenal glands and
to look for evidence of a mass associated with one of the glands. If your
pet is exhibiting neurological signs, a CT scan or MRI might be
recommended to evaluate the size of the pituitary gland. Although most
pituitary tumors remain small, some can increase in size and cause
pressure on the brain resulting in neurological signs, the most common
being blindness and seizures. These larger pituitary tumors are called
macroadenomas.
How is Cushing’s Syndrome treated?
Although we are unable to cure Cushing’s syndrome, many
pets can be managed with medical or surgical treatment. The method of
treatment for Cushing’s syndrome largely depends on whether the cause is
pituitary dependent or a tumor of the adrenal gland. Adrenal tumors can
sometimes be removed surgically, and in some cases, may be treated
medically. Consultation with your veterinarian regarding the nature of
your pet’s tumor will help you make the best decision regarding treatment
for your pet. Pituitary tumors are most commonly treated with a
medication called O,P’-DDD, (Mitotane or Lysodren). This drug was
originally produced as an insecticide, but was found to chemically destroy
the region of the adrenal gland responsible for the excess cortisol
production. This drug is very effective in dogs, but not in cats,
therefore surgical removal of one or both adrenal glands is the treatment
of choice in cats.
If treatment with Mitotane is initiated, you and your
veterinarian will need to monitor your pet very closely while on this
medication, as it can have toxic effects. Signs to watch for at home
include an attitude change or lethargy, development of vomiting or
diarrhea or a decrease in appetite or water consumption. The first phase
of Mitotane therapy is termed the “induction phase” and your pet will be
taking the medication daily. The goal of this phase of therapy is to
destroy enough adrenal tissue so that only minimal amounts of cortisol are
being produced. This phase usually takes from 3 to 7 days, but can take
as little as 1 day or up to 2 weeks in some patients. Your veterinarian
will want to monitor this induction phase with blood tests. Once the
induction phase is completed, your pet will be started on a maintenance
protocol, which is aimed to maintain cortisol production within a certain
range. Blood work will need to be checked periodically and the dosage of
medication may need to be adjusted from time to time.
Ketoconazole is an antifungal medication, which
interferes with the production of cortisol. This medication is much more
expensive than Mitotane and often less effective, but it is a viable
alternative, especially in the short term if the pet requires surgery or
if there is an adrenal tumor that is too large or invasive to be removed.
L-Deprenyl (Anipryl) is another medication that might be
recommended for some pets with pituitary dependent Cushing’s syndrome.
This medication may help to alleviate some of the clinical signs by
decreasing the amount of ACTH released from the pituitary gland. This
medication hasn’t proven to be effective in all pets with pituitary
disease and doesn’t suppress cortisol production like Lysodren does, but
it has the benefit of being less toxic.
If your pet is diagnosed with a macroadenoma, radiation
therapy might be recommended in hope of decreasing the size of the tumor,
thus reliving some of the pressure on the brain and the related clinical
signs. Radiation therapy hasn’t been successful in decreasing the
production of ACTH by the tumor so concurrent therapy with Mitotane is
still recommended.
What are the side effects of Mitotane?
Side effects from the drug are most commonly associated
with a rapid drop in cortisol levels. If too much of the adrenal gland is
destroyed by the medication, your pet will likely show signs such as
decreased appetite, lethargy, vomiting, diarrhea or instability while
walking. It is very important to report these signs to your veterinarian
if they occur. These side effects are reversed quite easily in most
patients by supplementing the pet with corticosteroids such as
prednisone. In rare cases, it is possible to permanently destroy the
adrenal glands with Mitotane and these pets will require therapy with
medications to replace the cortisol and other steroid hormones normally
produced by the adrenal glands. Some veterinarians may choose to give low
doses of cortisone with the Mitotane in attempt to prevent these clinical
signs from developing. Some veterinarians may also choose to treat their
patients to the extent that the adrenal gland is destroyed, creating
Addison’s disease.
What can I expect if I choose not to treat my pet?
The effects of excess cortisol will eventually be
detrimental to your pet’s health. Too much cortisol suppresses the immune
system, making the pet more susceptible to infections. Urinary tract
infections are common and infections that start in the bladder can migrate
to the kidneys resulting in pyelonephritis, which may cause permanent
kidney damage. Excessive cortisol can also result in an increased risk
for stone formation in the urinary tract, diabetes mellitus and PTE.
Pulmonary thromboembolism (PTE) is the development of blood clots in the
lungs and this condition is often fatal. Pets with Cushing’s
syndrome also have a decreased ability to heal after surgery or injury.
Pets with adrenal tumors are at risk for local spread of the tumor.
Adrenal tumors can be invasive and can grow into other organs or tissues
in the abdomen. Although there are risks involved with treating
Cushing’s syndrome, the disease, itself is often more detrimental to the
pet’s health and the risks involved with not treating outweigh those of
treatment.
