DIAGNOSIS AND MANAGEMENT OF CUSHING'S DISEASE
IN THE DOG

Cushing's disease, or hyperadrenocorticism, results from excess production from the adrenal glands of a hormone called cortisol. Dogs with Cushing's disease may drink excess water, urinate larger volumes, show an increased appetite, lose hair, be more susceptible to infections, lose muscle mass, and develop abdominal distention.

To understand how this occurs, it is helpful to understand how adrenal function is regulated in the normal dog.

Normal Pituitary/Adrenal Gland Function

ACTH is released by the pituitary gland and stimulates the release of cortisol from the adrenal glands. The pituitary gland monitors the level of cortisol and decreases the production and release of ACTH when cortisol levels rise. In this fashion, the pituitary gland functions similarly to a heating thermostat to control cortisol levels. The process is called negative feedback inhibition. The adrenal cortex also releases a hormone called aldosterone, which regulated blood sodium and potassium balance.

Cushing's Disease
Cushing's disease is most commonly caused by a microscopic pituitary tumor that secretes excessive amounts of ACTH. The adrenal glands are innocent bystanders, but produce excess cortisol in response to the elevated ACTH. There is failure of negative feedback to occur at the level of the pituitary due to uncontrolled secretion of ACTH by the microscopic pituitary tumor. These cases are called pituitary-dependent Cushings disease. Rarely (less than 1% of all cases), pituitary tumors are large and result in neurologic signs. These cases require CT scanning to confirm the diagnosis and require radiation therapy for effective treatment.

Pituitary-Dependent Cushing's Disease (90%)
Adrenal tumors result in uncontrolled production of cortisol. The pituitary negative feedback inhibition is intact, resulting in decreased release of ACTH. This results in low ACTH levels, which lead to atrophy of the normal adrenal gland.

Adrenal Tumor-Dependent Cushing's Disease (10%)
Dogs affected with Cushing's disease due to either pituitary cause or adrenal tumors tend to show similar clinical signs, including increased thirst, increased volume of urination, increased appetite, hair loss, skin infections, "pot bellied" appearance, muscle atrophy, and occasionally panting.

Diagnosis of Cushing's Disease
The first step in the diagnosis of Cushing's disease is to determine if Cushing's disease, of either pituitary or adrenal origin, is present. Tests used in this first round of testing include ACTH stimulation, Urinary Cortisol to Creatinine Ratio, and Low Dose Dexamethasone Suppression testing. 

After Cushing's disease has been confirmed, the second round of testing is performed to determine if pituitary or adrenal disease if present. It is helpful to determine which type of Cushing's disease is present, since therapy differs for each type of disease. Tests used to differentiate between pituitary and adrenal disease are endogenous ACTH levels, abdominal ultrasound, and CT or MRI scanning.

Lysodren Therapy for Pituitary-Dependent Cushing's Disease
Lysodren therapy is very effective for the management of pituitary-dependent Cushing's disease, but side effects can be seen with the drug, and dogs need to be closely monitored during therapy. Lysodren therapy is usually very effective in reversing the clinical signs associated with pituitary-dependent Cushing's disease. Lysodren acts by selectively killing the areas of the adrenal gland that produce cortisol and usually sparing the cells that produce aldosterone. There are two phases of lysodren therapy, loading and maintenance.

Loading therapy with Lysodren - During loading therapy, lysodren is given every day for 7 to 10 days to achieve rapid control of Cushing's disease. Always give lysodren with food to improve absorption into the bloodstream. During the loading period, dogs also are supplemented with prednisone to prevent illness due to rapidly falling cortisol. Prednisone should be stopped following completion of the loading period. 

Twenty-four to seventy-two hours (1 to 3 days) following loading, ACTH stimulation testing is repeated to see if the patient has been adequately loaded. It is very important that no prednisone be given within 24 hours of ACTH stimulation therapy. Prednisone will be measured as cortisol and invalidate the test. There are three potential outcomes following loading with lysodren:

1. The patient is adequately loaded. Maintenance therapy (see below) can be started.
2. The patient is under loaded. Additional loading is required prior to starting maintenance therapy.
3. The patient is over loaded. Prednisone therapy needs to be continued and no lysodren should be given. ACTH stimulation will be repeated in 3 weeks. Most dogs can start maintenance at that time.

Maintenance therapy with Lysodren - Do not start maintenance therapy until the results of the post loading ACTH stimulation tests are available and your veterinarian has contacted you. Following adequate loading, dogs must be maintained on lysodren to keep the Cushing's disease under control. In maintenance therapy, lysodren is given at lower doses two to three times per week. ACTH stimulation testing is performed after one month of maintenance therapy. For the first year of maintenance therapy, ACTH stimulation is repeated every 4 months and twice yearly thereafter. It is not uncommon that the dose of lysodren must be adjusted during maintenance therapy. Do not change the dose of lysodren without permission from your veterinarian.

Side effects of Lysodren - Most dogs tolerate lysodren without any side effects, but side effects can be seen. Signs of lysodren toxicity are depression, trembling, poor appetite, vomiting, and occasionally diarrhea. If signs of lysodren toxicity are seen, do not give further lysodren and give prednisone as described below. If prompt improvement is not seen within three hours, please have your dog evaluated by a veterinarian immediately. 

Loading dose of Lysodren:     tabs,     times per day, for     days.

Loading dose of Prednisone:     tabs,     times per day, for     days.

Maintenance dose of Lysodren:     tabs,     times per day, for     days.

Emergency prednisone:dose:     tabs (     mg).