Ron Hines DVM PhD 1/16/08
Cushing's syndrome is a disease with very distinct clinical signs in your pet. It is also called hyperadrenocorticism. Two small glands, the adrenal glands, that lay just ahead of your dog's kidneys are responsible for this problem. When these glands over-produce the hormones, cortisones, hyperadrenocorticism results. All the symptoms of Cushing's disease are due to this excess of cortisone in the body. Cortisones relax the ligaments of the abdomen and causes enlargement of the liver. This is why dogs with the disease have a pot belly. Cortisones decrease the growth of hair and thins the skin. It increases appetite and thirst, which results in weight gain and excessive drinking and urination. Cortisone decreases muscle mass resulting in limb weakness and debility. The production of connective tissue that stabilizes the joints decreases. Cortisones also regulate the mineral content of the blood.
The adrenal glands are regulated by the pituitary gland situated in the brain. The pituitary produces a hormone, ACTH. ACTH stimulates the adrenal gland to produce cortisones. Occasionally, an ACTH-producing tumor will form in the pituitary gland. This is one form of Cushing's disease. It accounts for 85% of all cases. A second form of the disease occurs when a cortisone-producing tumor forms within the adrenal gland. A third form of the disease is man made. It occurs when a dog receives too much corticosteroid supplementation either in pill form or by injection. Sometimes this is the price of controlling some other serious disease.
Symptoms of Cushing's Disease:
One of the first signs noted by owners is excessive drinking and urination by their pet. Female dogs may have "urinary accidents" at home. Owners sometimes tell me that they have to fill their pet's water bowl again and again throughout the day and that their pet cries to be let out to urinate during the night. These dogs also become more susceptible to urinary tract infections.
Another effect of increased cortisone is increased appetite. Dogs with Cushing's Disease never seem to be full. This constant eating leads to weight gain and obesity.
Cortisone also causes the muscles of the legs to wither and the liver to enlarge so that in advanced states, the dog assumes the proportions of a fat, pot bellied barrel on spindly legs. In this condition the pet's exercise tolerance and activity decrease. It becomes difficult for the dog to jump onto the bed or climb stairs.
With time, the pet's hair coat becomes sparse – especially on both flanks. Hair on the head and legs remains normal. It may take very long for hair to regrow after clipping. The dogs skin thins due to the action of cortisone which causes it to become more susceptible to scrapes and infections. A textbook sign of Cushing's Disease which I have never seen is Mineralization of nodules within the skin (Calcinosis cutis).
High risk breeds for this disease include Silky Terriers, Bull Terriers, Boston Terriers and Yorkshire terriers, dachshunds, and standard, toy and miniature poodles. Female dogs are more susceptible to adrenal gland tumors. Dogs that develop the disease are generally older than five years.hyperadrenocorticism
Diagnosis of Cushing's Disease:
Cushing's Disease is diagnosed through a series of blood tests. These tests not only diagnose the disease but they tell us if the problem is in the pituitary within the brain or within the adrenal gland(s) themselves. Routine blood analysis often show that the pet has higher than normal levels of Alkaline Phosphatase (ALP), Alanine aminotransferase (ALT), cholesterol and blood glucose as well as very dilute urine. If these results and the dogs other symptoms make us suspect Cushing's Disease, we run additional tests: One of these is called a dexamethasone suppression test. The other is an ACTH stimulation test. Both will usually confirm or rule out the presence of this disease and tell us weather to pituitary or the adrenal gland is the root of the problem.
The ACTH stimulation test is expensive, requires hospitalization and is time consuming. Recent studies have shown that another test, the urine cortisol:creatinine ratio (UC:Cr) is equally effective in screening out dogs that do not have Cushings Disease. It is best run on your pet's morning urine collected at home when the pet is at ease. I suggest that this test be run first. Dogs that have a normal (negative) cortisol:creatinine ratios are quite unlikely to have Cushings Disease. However, when the test comes back as elevated (positive), the ACTH stimulation test should be run. This is because a number of other health problems can cause the elevation (liver, intestinal, kidney, heart or autoimmune disease).
This test is also a good way to monitor your pets condition over the years once initial stabilization has been achieved. It is not a good test to use alone when the pet is initially stabilized.
Treatment of Cushing's Disease:
It is not unusual for dogs with Cushings Disease to have other endocrine gland problems such as diabetes or recurrent pancreatitis so their long term survival can be tenuous. If tests determined that there is an adrenal gland tumor, it can be removed. The surgery is quite specialized and dangerous so many veterinarians prefer to have a specialist attempt it or elect to treat the dog medically. Pituitary gland tumors are not usually removed. Most cases of Cushings Disease are managed medically. We treat the disease with Lysodren (o'p'-DDD, which is a relative of DDT or mitotaine) or an anti-fungal drug, ketaconazole. Lysodren attacks the cortex layer of the adrenal gland suppressing the production of cortisols. Just enough Lysodren must be administered or the dog will lapse into the opposite disease, hypoadrenocorticism (Addison's Disease) when not enough cortisol is produced. So dogs on this medication must be closely monitored.
A new drug, Anipryl (l-deprenyl) was approved for treating Cushing's disease in 1997. It does not appear to be as toxic or have as many side effects as Lysodren. Anipril is effective in approximately eighty percent of cases but may take several months to work. Improvement in the dog's general condition is a much better judge of the effect of this drug than laboratory tests.
The Outlook For Your Pet:
If Cushing's Disease is not treated, it can progress to life-threatening conditions including congestive heart failure, liver failure, kidney failure, diabetes and neurological disorders. Dogs with Cushing's Disease are also more susceptible to infections of the mouth, ears, skin and urinary tract. The most dangerous period is the first six months after treatment begins. None of the treatments actually restore normal adrenal function but once the six months period has passed, dogs with the disease may live several more good quality years.
New Developments:
A new drug, trilostane, appears to have great potential in treating Cushing's disease without some of the side effects caused by mitotane. Trilostane interferes with production of cortisol in the adrenal glands without destroying the cells in the adrenal cortex that produce cortisol. The drug is not currently available for general use in the United States. In England it is marketed by Arnolds Veterinary Products of Yorkshire under the name, Vetoryl. The company is attempting to gain FDA approval to market in the US.
