Causes
The overproduction may be caused by disease in either the adrenal glands, the pituitary gland located at the base of the brain (which stimulates the adrenal glands) or the hypothalamus (a section of the brain that stimulates the pituitary gland). Additionally, an artificial Cushing's syndrome can be seen if a patient is being given excessive levels of steroid medication such as certain skin creams, eye-drops and ear medications.

In about 85 percent of cases, the syndrome results from a tiny, usually benign tumor in the pituitary gland  and is called pituitary dependent hyperadrenocorticism or PDH. The tumor causes the pituitary gland to secrete too much ACTH, a hormone that, in turn, signals the adrenal glands to produce cortisol in excessive amounts.

The adrenal form of Cushing's is caused by a tumor of the adrenal gland itself, which secretes too much cortisol, ignoring the body's natural regulatory mechanisms.

Symptoms
Because the subtle symptoms develop slowly and share similarities with other problems seen in older dogs, owners may not know their pets need veterinary care until the disease is advanced.

The symptoms of the disease result from the body's being subjected to high levels of cortisol for a long time, almost as if the dog has been overdosed with cortisone pills. The most common clinical signs include:

• increased water consumption and urination
• symmetrical hair loss, primarily on the trunk
• abdominal enlargement (pot-bellied appearance)
• thin skin, especially over abdomen and flank area
• excessive panting
• weakness
• legs may appear spindly
• animal may have difficulty getting up or jumping onto furniture or into the car

If a complete blood count, serum chemistry profile and urinalysis indicate Cushing's, the veterinarian will next run hormone tests, including the ACTH stimulation and the low-dose dexamethasone screening tests which are both blood tests. Veterinary experts disagree over which is the most accurate. All the tests can be affected by stress and other diseases and can have misleading results. The veterinarian has to be extremely careful interpreting the tests to be sure of the diagnosis. X-rays or ultrasound of the abdomen to check the adrenal glands can help differentiate PDH from the adrenal form.

Treatment
Adrenal Form of Cushing's
The treatment of choice for the adrenal form of Cushing's is to surgically remove the cancerous gland. Surgical removal of either a benign adrenal tumor or a malignant adrenal tumor that has not yet spread carries an excellent prognosis for recovery. A malignant adrenal tumor that has spread to other sites carries a poor prognosis with most dogs succumbing to the disease within a year of diagnosis.

Pituitary Dependent Form of Cushing's
Medical therapy can control the clinical signs of PDH but it does not affect the pituitary tumor itself, and therefore must be given for the remainder of the dog's life. Three options of oral medications are available for PDH.

The most long standing medication is a highly effective drug called mitotane or Lysodren. It acts by partially destroying the adrenal gland, thereby decreasing the body's ability to produce cortisol. Inadvertent overdose with Lysodren is possible and, if too much of the adrenal gland is damaged, the dog must be treated for cortisol deficiency. In its most severe, life threatening form this is termed an Addisonian or hypoadrenal crisis. Owners usually monitor their dogs’ water intake and appetite for signs of overdosage. Veterinarians also use ACTH stimulation tests to monitor treatment.

Ketaconazole or Nizoral is another drug choice but many dogs vomit when given it and success varies with this rarely used medication.

A relatively new option is the drug L-deprenyl or Anipryl which became available in 1997 to treat the pituitary form of Cushing's. It is used to treat Parkinson's disease in humans and shows promise in treating patients with Alzheimer's disease. Instead of damaging the adrenal gland, Anipryl works at the level of the pituitary gland. It helps regulate production of ACTH to decrease stimulation of the adrenal gland to produce cortisol. A major benefit of Anipryl is that it is impossible to make a dog hypoadrenal with it. However, since Anipryl can take a couple of months to show improvement, if a case requires prompt resolution, faster-working Lysodren make be prescribed.

“Artificial” Cushing's
If the pet is receiving excessive steroid medication for another condition, then merely altering the dosage may correct the problem.

Conclusion
Owners of dogs with Cushing's disease must commit time and money to treat them. A 30 day supply of Anypril will cost between $40 and $50. The disease is rarely cured but can be controlled with lifelong medication. A lot of the success of treatment will depend on the dedication of the owner.