cortisol- cortisone produced by the adrenal glands
exogenous cortisone- supplemental cortisone
CRH- corticotropin releasing hormone
polyphagia- excess appetite
adrenalectomy-surgery to remove the adrenal gland
Hepatomegaly- enlarged liver
anabolick steroid- testosterone and its equivalent
catabolic steroid- cortisol and its equivalent
atrophy- decreased size of an organ
hypertrophy- increased size of an organ
polydipsia- excess drinking
mineralcorticoid- hormone that affects sodium and potassium
iatrogenic- caused by something a person does as opposed to
ACTH- adrenocorticotrophic hormone
adrenomegaly- enlarged adrenal gland
PD- pituitary dependent
AT- adrenal tumor
What is Cushing's disease?
Cushings disease (hyperadrenocorticism) is the production of to much
corticosteroids (adrenal hormone). This can be caused by tumor of the pituitary
or adrenal glands or by administration of to much prednisone (iatrogenic
To understand what Cushing's disease does, I need to explain how the
pituitary and adrenal glands function in a healthy pet.
This is called negative feedback loop. The pituitary gland is located
at the base of the brain. This gland produces ACTH. This is released into
the blood stream and stimulates the two adrenal glands. The adrenal glands
are located near the kidneys. The adrenals secrete glucocorticoid (cortisone-like
or cortisol) hormones into the blood stream. When the appropriate amount
of cortisol is released, then the pituitary stops secreting ACTH.
In a Cushing's disease the feedback loop is unable to work due to the
fact the body is being flooded with to much cortisol.
What does cortisol do?
Cortisol helps the body respond to stress. The body needs cortisol
to live, and it affects many bodily functions. These include blood sugar
levels, fat metabolism, skeletal muscles, kidney function, nervous system,
cardiovascular system and immune response. ACTH/cortisol secretions will
increase due to stress, infection, pain, surgery, trauma, cold temperatures.
In a healthy body, there will always be a mild fluctuating balance at all
At what age is Cushing's usually diagnosed?
It is usually diagnosed in meddle-aged and older dogs. The average
age is 10 years. There have been younger dogs that have been diagnosed.
Are more male or females diagnosed with Cushing's?
There is no difference between genders.
Is Cushing's disease more common in some breeds more
There are several breeds that are predisposed to Cushing's these include.
Poodles, Yorkshire terriers, Beagles, Boston Terriers, Boxers, Dachshunds,
Labradors, Scottish Terriers, and terriers in general. However, all breeds
are at risk.
What are the symptoms of Cushing's disease?
Increased/excessive water consumption
Urinary accidents in previous house trained dogs
Food stealing/gaurding, begging, trash dumping
Sagging, bloated, potbellied appearance. Weight gain or its appearance
of weight loss.
Bony skull-like appearance of head
Exercise intolerance, lethargy, general or hind-leg weakness
New reluctance to jump on furniture or people
Excessive panting, seeking cool surfaces to rest on
Thinning hair or baldness on both sides of torso
Dullness/dryness of coat
Slow regrowth of hair after clipping
Wrinkled, fragile and/or darkly pigmented skin
Easily damaged/bruised skin slow in healing
Hard calcified lumps in skin (calcinosiscutis)
Susceptibility to skin and urinary infections
Diabetes, pancreatitis, and seizures
How many types of tumors cause Cushing's?
There are two types of tumors, pituitary and adrenal.
Pituitary dependent (PD) Cushing's, is most common. Most are microscopic
benign tumors (microadenoma) 50% of these tumors are less than 3mm in diameter.
10%-15% are larger (macroadenomas) over 1cm in diameter. Larger tumors
can cause pressure on the brain tissue and nerves, they can cause blindness,
circling, seizures and incoordination. These can also resemble side effects
of medicines used to treat Cushing's. The larger tumor, can complicate
diagnosis and treatment.
The pituitary over secretes ACTH causing the adrenals to keep making
cortisol. The pituitary does not respond to elevated levels by stopping
its release of ACTH. 85% of Cushing's cases are pituitary dependent. You
will see enlarged adrenal glands due to constantly working producing excess
50% are benign (adenomas) and 50% are malignant (adenocarcinomas) The
later will spread to the liver and lungs.
Communication between the adrenals and pituitary is lost. 15% of Cushing's
case are adrenal based. One adrenals gland is extremely enlarged due to
the tumor and over production. The other adrenal gland is very small, to
compensate fore the overactive one.
Is there any other kind of Cushing's disease?
Yes, there is. It is called Iatrogenic Hyperadrenocoticism. This is
Veterinary induced, by flooding the body with to much glucocorticoid for
conditions such as arthritis and allergies. The adrenals and pituitary
will try to reduce ACTH and cortisol. You will see small adrenal glands,
because they have shut down. This condition is reversible, by slowly withdrawing
the steroids this will allow the adrenals to start functioning.
What is the most common symptom(s) that people take
their pets in for evaluation?
The most common symptom(s) is increased water intake, urination, or
coat changes. 80%-85% in water consumption. The pet is usually drinking
2-10 times the normal amount. The formula for that is 1 oz. of water drunk
per pound of body weight per day. 80%-90% increased appetite 90%-95% pot
bellied appearance. Most pets display symptoms after 6 or 7 years of age.
Most pets show some symptoms for one to six years before being diagnosed.
Some symptoms of inflammatory conditions like arthritis, decrease due to
increased cortisol levels.
My dog was just diagnosed with Cushing's what is going
to happen now??
I'm sorry that your dog has Cushing's. Now that we know what it is,
the next step is treatment.
There are 3 types of treatment
and Anipryl (L-deprenyl).
Lysodren: This is a chemo therapy drug. It is used for adrenal
gland cancer. It erodes the outer cortex of the adrenal gland. By doing
this, it reduces the amount of cortisol the adrenals are making. This reductions
will cause the cortisol to go back to normal levels.
This is done by what is called a loading dose.
The dose is calculated by the dogs weight. In Brenna's case, she took
250 mg twice a day. The Lysodren tab
only comes in a 500 mg tab. So she got one half pill twice a day. You
give this until she starts showing signs of lethargy, diarrhea, taking
longer to eat than usual, and reduced water intake. When this happens,
stop giving the Lysodren and an ACTH test is done. If the levels are where
they need to be, then she will be started on a maintenance dose. This could
be once a week or twice a week.
This depends on how she responds and how the Vet treats Cushings.
The cost of Lysodren is about $5-$6 a pill.
Anipryl: This is a daily medication. I can't say if this is better
or worse than Lysodren therapy. It seems that, if the tumor is in the posterior
part of the pituitary, Anipryl will not work. If it is intermediate part
will work. The only way to find out is by how the pet will react to
the meds and if the ACTH test responds accordingly. Anipryl
will run any where from $55 to $65 a month. This is dependent
on the dosage needed.
Ketaconazole: is an anti fungal. It seems to work best in pituitary
Cushing's. Its tricky to adjust properly, Can cause acute hepatitis or
gastritis. It is very expensive. Most people
cannot afford it.
Elevated blood glucose
Elevated liver enzymes
Significant Alkaline Phospatase
Excess cortisol influences this enzyme
Normal specific gravity is around 1.025
Decreased specific gravity
Possible UTI due to excess glucose
· Calcified adrenal glands
· Rule out other problems
· Osteoporosis due to excessive cortisol
· Better visualization of adrenal glands
· Get measurements of adrenal and other glands
· Rule out other problems
URINE CORTISOL CREATIN RATIO
· Measures level of cortisol in the bloodstream
· Creatin is measured to adjust for different levels of urine
· Checks for Addison's or Cushing's
· Best test for Cushing’s diagnosis and monitoring therapy
· Stimulation measures the reserve the adrenal glands have in
the production of cortisol
· False positives are rare compared with other tests. Not as
sensitive as LDDS test because of this it can be used in combination with
· ACTH is the only test that can distinguish between
Iatrogenic and naturally occurring Cushing’s
· Reliable results even if a dog has been on cortisone recently
· Unable to tell the difference between pituitary dependent
or adrenal tumor
· Blood sample is taken to measure resting cortisol level
· ACTH stimulation is given IM injection
· Some Vets do a post at one hour others wait two hours post
injection. This gives ACTH time to stimulate the adrenal gland to produce
· Post stimulation is higher than the resting level, it’s suggestive
of Cushing’s 80-95% of the time
· ACTH is not reliable in cats 51% show an exaggerated response
· If second test is lower than the resting level Addison or
Iatrogenic Cushing’s is suspected
· Reduction can also come from Mitotane or Ketaconazolia therapy
· 5-20% of dogs with Cushing’s will not show an exaggerated
response if Cushing’s is suspected a repeat test at a later date should
be done or an LDDS test.
LOW DOSE DEXAMETHASONE SUPPRESSION TEST (LDDS)
· Best test 90-95% accuracy
· The dog is fasting, pre-injection level is drawn
· Dose of Dexamethasone is injected (IM) dosage is based on
the pets weight 0.03-0.15 mg/kg/lm
· Follow-up samples are taken at 4 hours an 8 hours post injection
· Normal response the dog’s body will perceive the presence
of the Dexamethasone and will suppress cortisol output throughout the test.
· Cushinoid dog will not suppress cortisol in response to the
Dexamethasone injection due to the feed back loop is not working
· Cannot differentiate between pituitary and adrenal Cushing’s.
Dogs who suppress at 4 hours and rebound at 8 hours usually have pituitary
HIGH DOSE DEXAMETHASONE SUPPRESSION TEST (HDDS)
· Not used as a routine screen
· Can differentiate between pituitary and adrenal Cushing’s
· Fasting pre injection or resting cortisol level
· A high dose of Dexamethasone is injected blood samples are
taken at 4hours and 8 hours post injection
· Normal dog will suppress as in LDDS
· Adrenal tumor Cushing’s will not notice the Dexamethasone
and will continue to make cortisol
· Pituitary Cushing’s will have limited ability to response
to high dose of Dexamethasone so some suppression will occur
· 15-20% of dogs with pituitary tumors will not suppress on
· These pets generally have large macro adenomas.
Treatment will depend on the type of Cushing’s disease. Most
Dogs are elderly with other health problems. Treatment can be a little
The pets comfort level should be considered for example, if a
dog has severe arthritis it may be more humane not to treat the Cushing’s.
This should be discussed with your Vet. Treatment of Cushing’s is best
viewed as a way to improve the quality of life not to increase the pet’s
ADRENAL TUMORS: Some say remove both adrenal glands and
others say just the diseased adrenal gland. These tumors do not recur on
the adrenal gland that is left. 50% of adrenal tumors are malignant and
may have already metastasized to the liver or lungs by the time diagnosis
There are Post-OP complications. Slow to heal because of the
Cushing’s and sometimes because of the dog’s age.
The remaining adrenal gland is atrophied and the dog will have
to be on supplemental prednisone until the gland returns to normal function.
ACTH test is done every few months to tell when the gland is functioning
normally. This could take up to one year.
PITUITARY TUMOR: These types of tumors are not surgically removed
in Veterinary Medicine. These tumors tend to be small and slow growing.
They cause little or no damage on their own. Aside from over stimulating
the adrenal glands, the symptoms are treated and not the root cause.
Pituitary Macro adenomas are treated with radiation in an attempt to
reduce the size of the tumor. Radiation treatments are very expensive and
there are very few specialty radiation centers that can do the procedure.
ADVANTAGES OF KETOCONAZOLE OVER LYSODREN:
Ketoconazole cannot induce Addison’s disease. Monitoring tests
are not necessary. Potential side effects vomiting and diarrhea, but does
not need antidote pills. Stop the Ketoconazole till side effects resolve,
adjust the dose and re-start.
ADVANTAGES OF LYSODREN OVER KETOCONAZOLE:
Ketoconazole is given twice a day. Lysodren is given once or
twice a week. Ketoconazole is very expensive. Few people can afford this
medication. Most Vets do not have a lot of experience using this drug.
Approximately 1 in 5 dogs will not respond to Ketoconazole. Possibly
a problem with absorption of the drug from the intestinal tract.
ADVANTAGES OF ANIPRYL OVER LYSODREN:
Addison’s disease is not a concern. It’s the only medication
approved by the FDA for the treatment of Canine Cushing’s.
ADVANTAGES OF LYSODREN OVER ANIPRYL:
Anipryl is more expensive. Approx. 1 in 5 dogs will not respond to
Anipryl. The protocol if no response is seen for 2 months of therapy, is
to double the dose and therapy is continued for one more month before determining
the pet to be a non-responder and selecting another medication.
This is the easiest to treat. Taking away a medication treats this.
By stopping the prednisone, this will return your pet to normal function.
This might take several months. Some of the skin changes might take longer
and it may not completely return to normal.
In some cases, decreasing the dose of prednisone over a period
of several weeks will give the adrenals time to resume normal function.
Does a Cushinoid dog have to be diabetic?
A dog can be diagnosed with Cushing’s and not have diabetes.
In some cases, the diabetes is diagnosed first. When the pet cannot
be regulated then the pet can be tested for Cushing’s. If the testing is
positive for Cushing’s, you will have to treat both the Cushing’s and the
Why is there an increase in the blood glucose in a Cushing’s dog?
Cortisol is considered a “Catabolic Steroid”. A Catabolic Steroid
takes amino acid from the skeletal muscles and with help from the liver
converts them to glycogen. Glycogen is the storage form of glucose. The
result of this is an increase in the level of glucose in the bloodstream.
If the disease is caught early and treatment is started immediately, the
glycogen can be reduced to normal levels. If it not caught in the
early stages, then the dog becomes diabetic. This is caused by the overload
of glycogen to the system and the insulin’s inability to be utilized by
the dogs system.
What do you feed a Cushinoid dog?
Whether you have a Cushinoid or diabetic dog, it is very important
to discuss this with your Vet. Between the two of you, you will come up
with the best diet for your pet. Case in point. A diabetic dog should
have high fiber and a Cushinoid dog should have low fiber. So if
you have a Cushinoid/diabetic dog you have to find a place in between.
I did find this on a Cushing’s diet. Feed a high protein, low
fiber, low fat, and low purine diet. It’s important not to over supplement
calcium and to make sure potassium levels are adequate and that sodium
is not restricted in any way, if Lysodren (Mitotane) is being used to treat
Cushing’s. Do not restrict water intake.
Purines are the end products of nucleoproteins. They break down
to form uric acid. Exogenous Purines are present in or derived from food.
A low Purine diet excludes foods such as meat, fish, fowl, spinach, lentils,
mushrooms, peas and asparagus.
What is the life span of a Cushinoid dog?
For years, the prognosis for a Cushing’s dog was 2 years, whether
you treated the disease or not. This was based on the fact that most dogs
were diagnosed in their later years. Now days, it depends at what age they
are diagnosed. A dog can live many years after diagnoses, with treatment.
The Goal here IS NOT Quantity life, but QUALITY!
Is Cushing’s contagious?
No, it’s caused by a tumor in the pituitary or adrenal glands. It can
also be caused by over dosing the dog on steroids.
How is the body affected by too much cortisol?
I'll break it down into groups.
Too much cortisol can cause the muscles to atrophy (shrink). This happens
because the body will use the amino acids in the muscle fiber to increase
blood sugar levels when this happens to the abdomen muscles it give the
pot belly appearance.
Increased cortisol affects the protein matrix. It decreases calcium
absorption from the intestines and increase calcium excretion by the kidneys.
The bone loses calcium and becomes weaker.
Increased cortisol can cause atrophy in the hair follicles and sebaceous
glands, which causes hair loss. Thinning of the skin also happens and can
lead to some areas of skin developing skin nodules of built up calcium.
Too much cortisol can cause thinning of the blood vessel walls, which
can lead to them rupturing and cause bruising.
Central Nervous System:
Increased cortisol can interfere with sleep and cause changes in the
pet's mood. This had been noted in both Cushinoid dogs and dogs given cortisone
to treat a disease.
Excess cortisol causes the liver to work harder. Enlarged livers are
common to dogs with Cushing's.
Increased cortisol increases blood flow to the kidneys. Which increases
the amount of water and waste products filtered by the kidneys. This is
why Cushinoid dogs drink lots of water and urinate excessively.
Normal levels of cortisol can decrease the body's over reaction to
foreign body or infection. However excessive amounts can suppress the immune
system to the point that it can't respond properly making the susceptible
Are there any other treatments other than Anipryl or Lysodren?
Yes, the medication is called Trilostane.
Trilostane (Vetoryl) inhibits the action of the enzyme 3-beta-hydroxysteroid
dehydrogenase, which is important in steroid hormone synthesis. Trilostane
treats Cushing's by blocking the synthesis of Cortisol.
Trilostane is a once a day medication. However, some dogs may require
a dose twice a day.
Should Trilostane be given with food or on an empty stomach?
It is best given with food.
Does it matter if you give Trilostane in the Am or PM?
The morning mainly for convenience. It will be easier for doing ACTH
monitoring. The ACTH test should be done 4 to 6 hours after the medication
Are there any warnings for Trilostane?
· Do Not use in animals with primary
hepatic disease. Trilostane is metabolized by the liver,
· Do Not use if you suspect renal
insufficiency. It is renally excreted.
· Do Not use in pregnant or lactating
animals or any animal intended for breeding. This medication has the potential
to block the production of sex hormones.
· Wash hands after use
· Do Not handle capsules if pregnant
or trying to conceive.
Are there side effects with Trilostane?
The side effects are mild. They include depression, no appetite, vomiting
and diarrhea. Therapy is usually stopped, for three to five days. The dosage
is adjusted and the treatment is started again.
Can a dog on Lysodren therapy be changed to Trilostane?
I'm not too sure if anyone has done it or if there is any one doing
clinical trials. This should be discussed with your Vet.
Advantages of Trilostane over Lysodren.
· Less potential for Addison's or other serious reactions.
· Trilostane does not erode the adrenal cortex. Its action is
as an enzyme inhibitor and the inhibition it caused is fully reversible.
Disadvantages of Trilostane over Lysodren.
· Approx. annual cost for a 20 lb. Dog can be $1,800
to $2,000. Lysodren costs less.
· Trilostane is one or twice a day. Lysodren is once or twice
What is exogenous cortisol?
Exogenous cortisol comes in several different forms oral, topical
and inject able. The most common ones are
Solu-Delta -Cortef 500mg.
Dexaject 2mg/ml solution
Vetalog 1.5mg tabs
Dexamethasone Sodium Phosphate 4mg/ml
Dexamethasone tablets .25mg
Prednisone tablets 20mg.
Prednisone oral solution 5mg/5ml
Otomax 7.5 g
Vetropolycin HC hydrocortisone acetate 1% veterinary
What is Ectopic ACTH Syndrome?
This is a very rare type of Cushing's that does not fall into the other
categories. It is a malignant tumor other than pituitary or adrenal that
How can they tell if an adrenal tumor is benign or malignant?
About 15% of Cushing's is caused by adrenal tumors. 50% will be benign,
50% will be malignant. The use of Ultrasound, CT Scan and MRI can be used
to determine tumor size and invasion of other tissues in the surrounding
areas. Malignant adrenal tumors tend to spread to the chest. If they find
a tumor in the chest, it is considered malignant. .
If the findings are benign for the adrenal tumor, and if you
decide to have the surgery there is an excellent change for a complete
recovery. The smaller the tumor, the easier the surgery.
If the findings are malignant, surgery may not be an option.
Medical therapy would have to be considered. This should be discussed with
If I choose to have the surgery done, what should I know?
With any type of surgery whether for your pet or yourself, there are
· Removal of the adrenal gland is a delicate surgery and can
be risky. All the information that I was able to find, suggested that a
board certified surgeon was the one to do the surgery.
· Risk of bleeding is increased for larger tumors that turn
out to be malignant and have invaded the surrounding tissue
· Cushinoid animals do not heal very well and tend to have high
blood pressure. If the tumor is considered benign, medical therapy of Lysodren
or Anipryl could strengthen the pet.
· Due to the suppression of the natural cortisol, post surgery
the dog may have to be on several months of prednisone. ACTH stim. Test
will monitor the dog's need for medication.
· Adrenal tumors are very hard for Pathologists to grade as
benign or malignant.
Do cats get Cushing's?
Yes, but is rare, except if they have diabetes. They can have symptoms
of excessive water intake, urinating, weight gain, potbelly and muscle
wasting. They can also have an enlarged liver. The skin can easily bruise
or be torn. This is known as fragile skin syndrome.
The tests that help to diagnose Cushing's in dogs may not useful
in diagnosing cats. For example an elevated alkaline phosphatase
may be because of unregulated diabetes and not from Cushing's. ACTH
tests can be used, but the blood samples need to be done at 30min and 60
min. The increase of cortisol in a cat is variable. The LDDS when
used with ACTH test is the best way to diagnose Cushing's disease in a
30% of adrenal tumors are mineralized and can be seen on an x-ray.
Ultrasound can also be used to see if there is an adrenal tumor.
Medical therapy does not always have the best effect. Surgery
can be an option. This again you will have to talk to your Vet about options
available to you and your cat.
This might seem an overwhelming at this time,
but once you get into a routine it will seem easier. I can say that while
getting the loading dose of Lysodren, Brenna's bg's were bouncing around.
We did not change her dosage at all but monitored her and I home test so
I could have a good idea of what was going on. Once she was under control.
Her bgs leveled right out.
They say the prognosis is about two years on Cushings,
but don't you believe that. I know of a lot of cases that the pet has lived
anywhere from 4 to 8 years after diagnosis. You know you are not alone
in this. You've got a whole bunch of folks here on the Rainbow List and
Email Lists to help you along.