PetStyle

OK, you asked for it! A loaded question gets a very loaded answer! This should help.

Cushing’s syndrome is the resulting set of symptoms observed when the body is exposed to excess cortisone (or related hormones) over a long period of time. Cortisone, or more correctly cortisol, is a hormone produced by the adrenal glands that are located adjacent the kidneys. Cortisol is stored in the adrenal gland and is released in times of stress as it helps our bodies prepare for a fight or flight situation. It adjusts the metabolism to expect physical exertion by mobilizing fat and sugar stores and retaining sodium and water. It puts us in a state of “break down” so that our stored resources can be used quickly. However, if the body is exposed to this hormone most of the time instead of only for short stressful periods, the state of break down becomes debilitating.
In the normal dog, the pituitary gland produces a hormone called ACTH (adrenocorticotropic hormone), which stimulates the adrenal gland to produce the glucocorticoid steroid hormone (cortisol) necessary for the function of many systems in the body. Occasionally, the pituitary gland or adrenal gland causes overproduction of glucocorticoid, resulting in Cushing's disease.
Cushing's disease is a disease of middle age and older dogs. Usually between six or seven years to sixteen years of age. There is equal distribution between males and females and there does not appear to be an increase of the disease in any one breed.
As a result of the chronically elevated glucocorticoids (cortisol), affected dogs usually develop a classic combination of clinical signs. The disease progresses slowly. A study showed that most dogs had at least one symptom of the disease from one to six years before the disease was diagnosed. Because the symptoms occur so gradually, the owner often attributes the changes to "old age." Some dogs will have only one symptom, while others may have many.

Symptoms include:
Increased water consumption and urination: The most common symptom is increased consumption of water and the resultant increased urination (polydipsia /polyuria). The dogs drink between two and ten times the normal amount of water and the resultant increase in urination follows. This symptom is present in over 85% of all animals with Cushing's disease. Previously housebroken animals may begin to have accidents because their bladders fill quickly with the overproduction of urine.
Increased appetite: Increase in appetite (polyphagia) is another common symptom present in around 80% of the affected animals. Dogs may begin stealing food, getting into the garbage, begging continuously, and become very protective of their food. Despite having other symptoms, the owner may feel that the dog is okay because of his good appetite.
Abdominal enlargement: Abdominal enlargement is seen in 80% of the affected dogs. The potbellied appearance is a result of the shifting of fat to the abdominal area and a weakening and wasting of muscle mass in the abdomen.
Hair loss and thin skin: Hair loss and thinning of the skin are seen in 50-90% of dogs with Cushing's disease. Hair loss (alopecia) is one of the most common reasons that owners bring their dog in for evaluation. The hair loss usually starts over the areas of wear such as the elbows and progresses to the flanks and abdomen until eventually only the head and extremities have hair. The skin may also become thin and be easily damaged and slow to heal.
Increased panting, recurrent urinary tract infections, or losses in reproductive ability are other symptoms often noted with this disease.
There are several mechanisms that can lead to Cushing’s syndrome and, as they are treated differently, it is important to determine which one is at work in a given animal.
Pituitary dependent hyperadrenocorticism: PDH involves the over-secretion of ACTH by the pituitary gland. ACTH is a hormone that stimulates the adrenal gland to produce glucocorticoid (cortisone). The pituitary gland is most likely overproducing ACTH because of a benign pituitary tumor. The PDH form of the disease is responsible for around 85% of the cases of canine Cushing's disease.
Adrenal dependent hyperadrenocorticism: The adrenal form of the disease is a result of an adrenal tumor (usually benign, but can be malignant) that produces cortisone constantly, without the body’s normal regulation of glucocorticoid production. Adrenal tumors are responsible for around 15% of the cases of Cushing's disease.

Iatrogenic Cushing's disease: occurs as a result of chronic exposure to relatively high doses of steroids. In this form of the disease, symptoms of Cushing's disease usually go away once the steroids are discontinued. Cortisone derivatives may well be the most over-used drugs in veterinary medicine. Their anti-inflammatory actions soothe such common maladies as allergic skin disease (especially flea allergic dermatitis) and degenerative arthritis. Relief is usually rapid and many owners find themselves requesting “cortisone" shots or pills over and over again. In time, Cushing's syndrome can result, not from any inherent disease in the pet's system, but from the effects of the hormones given over the long term.
The pituitary gland perceives the high steroid levels yielded by the medication and does not send stimulation to the adrenal glands. In time, the adrenal glands atrophy and they are not able to release cortisone on their own should they be required to do so. This effect lasts as long as three months after the cortisone medication has been discontinued. To allow the adrenal to gradually recover, cortisone pills are usually prescribed in a decreasing dose, rather than a sudden stoppage; an owner should never discontinue the pills suddenly.
Commonly prescribed cortisone derivatives include: Vetalog, prednisone, prednisolone , dexamethasone, Depo-Medrol, triamcinolone and others. These medications have important parts to play in medicine but they must be respected and not used indiscriminately, nor discounted suddenly after prolonged use.

Diagnosis
Cushing's disease can present with a variety of symptoms that are shared with many disease processes. Therefore, it is recommended that any dog suspected of having Cushing's disease have a complete blood count (CBC), blood chemistry panel, and urinalysis and urine culture performed as a routine part of the evaluation. Common abnormalities in these tests include increases in alkaline phosphatase, and ALT (liver enzymes), increased cholesterol, decreased BUN (a kidney function test), and dilute urine (low specific gravity) as well as urinary tract infection.
There are several different tests that can be performed to get a definitive diagnosis of Cushing's disease. Many times the veterinarian may perform more than one test to help confirm the diagnosis or to determine which form of the disease is present. A diagnosis of Cushing's disease, however, should never be made on the basis of laboratory tests alone. The dog needs to be showing symptoms of the disease, and have a medical history consistent with the diagnosis.
The three most common "screening" tests are the urine cortisol:creatinine ratio, the low dose dexamethasone suppression test, and ultrasound.
Treatment
Treatment depends on the type and cause of Cushing’s disease. If an adrenal tumor is identified, then surgical removal may be a viable option. Surgery can be a simple one or very difficult as tumors can invade local large blood vessels making the surgery very dangerous and risky.
85% of the cases are pituitary in origin, and usually medical therapy is used. It is also possible, with technology today, to use very carefully directed radiation therapy to treat these small brain tumors instead of controlling the disease symptoms with medical therapy.
There are currently several different oral medications being used to treat canine Cushing's disease.
Lysodren: Until recently, Lysodren (also known as mitotane, and o,p'-DDD) was the only treatment available for pituitary dependent Cushing's disease. It is convenient to use and is relatively inexpensive and is still probably the most widely used treatment. The downside of this drug is that it can have some serious side effects and regular blood-monitoring needs to be performed. During the initial phases of the therapy, the dog must be very carefully monitored, and there must be close communication between the veterinarian and the owner.
The use of Lysodren is somewhat like chemotherapy. It works by destroying cells of the adrenal gland that produce the corticosteroid hormones. As the number of corticosteroid-producing cells is reduced, even though the pituitary gland continues to produce excess ACTH, the adrenal gland is less able to respond, so the amount of glucocorticoid being produced is reduced. The problems arise when too much of the adrenal cortex is destroyed. The animals may then need to be placed on prednisone, either short or long term. Lysodren is initially given daily while the animal is being monitored for a decrease in the symptoms (water consumption, appetite). On the 8th or 9th day of the initial therapy, the dog needs to be examined and an ACTH stimulation test is performed to determine if the drug is working. If the goal is achieved, maintenance therapy is started. If the goal has not been reached, then the dog generally remains on the daily medication for 3 to 7 additional days and is rechecked until the proper results are achieved. If the dog becomes lethargic, vomits, or has diarrhea, or if the treatment does not work by 30 days, then the treatment plan is reevaluated. If treatment is successful, then symptoms should resolve within 4 to 6 months. A certain percentage of dogs will relapse and need to undergo the daily therapy again at some point in their lives. If a dog ever becomes ill while on Lysodren, the Lysodren should be stopped immediately and the dog should be examined by a veterinarian. The dog will need to be on Lysodren for the rest of his life.
Ketoconazole: Ketoconazole is an oral antifungal agent that has been used extensively since the mid 80s. One of the side effects of ketoconazole is that it interferes with the synthesis of steroid hormones. It therefore gained some popularity as a treatment for Cushing's disease. However, it is rarely used today due to its expense and gastrointestinal side effects that are common.
L-deprenyl (Anipryl): L-deprenyl (Anipryl) has been advocated for the treatment of Cushing's disease in dogs, but its effectiveness has come into question. It is not recommended widely due to poor efficacy.
Trilostane: Trilostane is a newer treatment that is used to treat some dogs with Cushing's disease. It is more expensive, but may be an alternative treatment for dogs with adrenal tumors. As with Lysodren, the dog is reexamined repeatedly during the initial phase of treatment, and ACTH stimulation tests are performed. In many cases, after several months of therapy the dose needs to be increased.