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 Cushing's). 

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 times. 

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 than others?
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
Increased/excessive urination
Urinary accidents in previous house trained dogs
Increased/excessive appetite
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.
Pituary tumors
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 cortisol.

Adrenal tumors
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 
Lysodren (mitotane), 
Ketaconazole (nizoral) 
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 then it 
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. 
 

DIAGNOSTIC TESTS:

 Skin scrapings:
 Usually negative

 Blood panel
  CBC
   Elevated RBC
   Elevated WBC
   Increased neutrophils
   Decreased lymphocytes
   Decreased eosinophils
  BIOCHEMISTRY
   Elevated cholesterol
   Elevated blood glucose
   Elevated liver enzymes
   Significant Alkaline Phospatase
    Excess cortisol influences this enzyme
  URINALYSIS
   Normal specific gravity is around 1.025
   Decreased specific gravity
   Protein elevated
   Possible UTI due to excess glucose

 RADIOGRAPHY/ULTRASOUND

  Radiography
· Calcified adrenal glands
· Rule out other problems
· Osteoporosis due to excessive cortisol
Ultrasound
· 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 dilution.
ACTH STIMULATION
· 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 LDDS
· 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 cortisol
· 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 tumors

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 the HDDS
· These pets generally have large macro adenomas.

TREATMENT:

 Treatment will depend on the type of Cushing’s disease. Most
Dogs are elderly with other health problems. Treatment can be a little complicated. 
 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 life span.

SURGERY

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 is made. 
 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.

RADIATION:
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.

IATROGENIC:
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 diabetes.
 

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.
Muscle: 
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.

Bone:
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.

Skin:
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.

Vascular System:
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.

Liver:
Excess cortisol causes the liver to work harder. Enlarged livers are common to dogs with Cushing's.

Kidney:
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.

Immune System:
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 to infections.

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.

Dosage:
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 is given.

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 a week.

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.
  Depo-medrol 20mg/ml
  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 
  Ophthalmic ointment.

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 produces ACTH.

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 your Vet.

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 always risks. 
· 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 cat. 
 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 on Cushings Email Lists to help you along.