Cushing's Disease or Hyperadrenocorticism

Cushing's disease is probably more accurately referred to as hyperadrenocorticism -- the production of too much adrenal hormone, in particular corticosteroids. It can be naturally occurring or due to over administration of corticosteroids such as prednisone (iatrogenic Cushing's). The latter is easy to cure - just cut out the corticosteroid administration slowly to allow the body to return to normal function. The former is more difficult.

Hyperadrenocorticism occurs for two reasons --- a tumor of the adrenal gland that produces adrenal hormones or stimulation of the normal adrenal glands from the hormones that control it. The primary reason for this to occur is a pituitary gland tumor that produces excessive ACTH, which stimulates the adrenal gland to produce corticosteroids. Adrenal gland tumors account for 15% of the cases of spontaneous hyperadrenocorticism. Pituitary tumors account for 85%.

Cushing's disease causes increased drinking, increased urination, increased appetite, panting, high blood pressure, hair loss - usually evenly distributed on both sides of the body, pendulous
abdomen, thinning of the skin, calcified lumps in the skin, susceptibility to skin infections and diabetes, weakening of the heart and skeletal muscles, nervous system disease and other symptoms. Most owners reach a point where the water consumption and urination become bothersome to them.

The diagnosis of Cushing's can be done with several blood tests. A general hint of Cushing's can be obtained by a blood panel. To confirm it, a test known as a low dose dexamethasone test is done. A baseline blood sample is drawn in the morning, an injection of dexamethasone given and a follow-up blood test done 8 hours later. In a normal dog, the dexamethasone should suppress cortisol levels in the blood stream. In Cushing's disease this effect does not occur. Once the disease is diagnosed, it is possible to differentiate between the adrenal tumors and pituitary gland tumors using a second test, a high dose dexamethasone suppression test. Most dogs with pituitary tumors will have cortisol suppression on this test. There are other tests used, including ACTH response tests and urine cortisol/creatinine ratios to diagnose this disease. X-rays and ultrasonography can help determine if an adrenal gland tumor is present.

If it can be determined that there is an adrenal gland tumor, it can be removed. Many veterinarians prefer to have a specialist attempt this since the surgical risks can be high. Pituitary gland tumors are not usually removed in veterinary medicine. This situation is treated using Lysodren (o'p'-DDD, which is a relative of DDT) or ketaconazole. Some research with Deprenyl for treatment of this is being done, too, I think. Lysodren selectively kills the outer layer of the adrenal gland that produces corticosteroids. By administering it in proper amounts it is possible to kill just enough of the gland off to keep the production of corticosteroids to normal levels. Obviously, close regulation of this using blood testing is necessary since overdoing it can cause severe problems with Addison's disease - hypoadrenocorticism. Adverse reactions to Lysodren occur at times but it is the standard treatment at this time. Over medication with Lysodren can cause inappetence, vomiting, diarrhea, lethargy and weakness. If any of these signs occur then your veterinarian should be immediately notified.

Treatment of Cushing's disease caused by pituitary tumors is symptomatic therapy -- it does not cure the pituitary tumor. The average lifespan of dogs diagnosed with Cushing's, with or without treatment is estimated at 2 years by Dr. Mark Peterson, but in a recent conversation with another endocrinologist I came away with the impression that this was an "educated guess" rather than the result of extensive survey of Cushing's patients. At present, though, I think that treatment should be viewed as a means of providing a better quality lifestyle rather than as a method of extending longevity.

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