Testing Confirming Cushing's Syndrome
Specific Tests to Confirm Cushing's Disease
Once there is reason to suspect Cushing's disease based on the history, physical examination, and initial laboratory testing, it is necessary to do specific testing to confirm it. There are several options. We will begin with dogs and then discuss cats.
CANINE CUSHING'S DISEASE TESTING
The Low Dose Dexamethasone Suppression Test
(usually takes 8 hours in the hospital)
Dexamethasone is a cortisone-type hormone that is used therapeutically for numerous conditions. When given dexamethasone, the dog's pituitary gland will perceive that there is a steroid and shut off its stimulatory message to the adrenal glands. In the normal animal, this means that a drop in blood cortisol level will be seen 8 hours after a tiny dose of dexamethasone is given intravenously.
If there is a pituitary tumor, the pituitary is not about to shut off its stimulatory message and it ignores the dexamethasone. No drop in cortisol level is seen at the end of eight hours.
THIS TEST IS CURRENTLY CONSIDERED THE MOST ACCURATE TO CONFIRM CUSHING'S DISEASE. APPROXIMATELY 90% OF DOGS WITH CUSHING'S DISEASE WILL TEST POSITIVE WITH IT.
To Run this Test Ideally the low dose dexamethasone suppression test is run in the morning. A baseline cortisol level is measured, a low dose of dexamethasone is given intravenously, and blood samples are checked again in 8 hours. Sometimes a 4-hour sample is also drawn as the pattern of suppression over the entire 8 hours may help classify the type of Cushing's disease. The pet will require at least 8 hours in the hospital.
The ACTH Stim Test (Requires two hours in the hospital)
Central to the concept of Cushing's disease is the over-production of cortisol. It follows then that the adrenal glands of the Cushing’s patient would possess large amounts of stored hormone due to their chronic stimulation. We have been talking about the stimulatory message sent from the pituitary gland to the adrenal glands. This message consists of a hormone called Adrenocorticotrophic hormone or ACTH. In this test, a dose of ACTH is given to the patient. If a larger than expected rise in cortisol levels is measured in 2 hours, we may diagnose Cushing's syndrome.
To Run this Test Ideally, the patient is fasted overnight and the test is performed in the morning between 8 a.m. and 10 a.m. A blood sample is drawn, a dose of ACTH is given, and two hours later a second blood sample is drawn.
When Would we Run this Test? Given that the low dose dexamethasone suppression test is more accurate, when might we run this test instead? It turns out that this is the only test that can be used if the iatrogenic form of Cushing's disease is suspected. This test is also crucial in monitoring patients with Cushing's disease, depending on which medications are used. This test is more specific than the low dose dexamethasone suppression test, meaning that the strongly positive dogs definitely have Cushing's disease (false positives are unusual) but since it is not a very sensitive test, the University of California Veterinary School at Davis no longer recommends this test to determine whether or not a dog has Cushing's disease. As mentioned, this is the test that is used to monitor treatment, however, and a dog being treated for Cushing's disease will likely have many ACTH Stimulation tests ahead.
The Urine Cortisol/Creatinine Ratio This is a screening test for Cushing's disease; a positive test here does NOT confirm Cushing's syndrome but a negative test DOES rule it out. In this test a single urine sample is collected to determine the relative amounts of cortisol and creatinine (creatinine is a protein metabolite that is excreted in urine constantly). If there is a high ratio - a relatively high amount of cortisol being excreted - further testing is in order. Ideally for this test the urine sample is collected at home so that cortisol secreted in response to the stress of visiting the vet's office does not interfere with results.
FELINE CUSHING'S DISEASE TESTING
The testing situation is somewhat different in cats.
The Urine Cortisol/Creatinine Ratio While this test is of limited value in dogs, it is the preferred test in cats. The owner should bring urine samples collected first thing in the morning on three consecutive mornings. Having the sample collected at home removes the possibility of interference from vet visit-induced stress. The first two samples are used to determine if the cat has Cushing's disease and the ratios are averaged. On the second day, after the second sample is brought in, dexamethasone pills are given to the cat at home and the sample from the third day is used to determine the type of Cushing's disease the cat has.
Collecting a cat's urine at home is easier than it sounds. The cat is confined overnight and in the morning is allowed access to the litter box. The easiest way to collect the urine is to place a sheet of cellophane over the box. The cat will rumple this up a bit scratching around but only a small amount need be caught on the surface of the cellophane. A syringe can be used to suck up the sample and store it for transport to the veterinary clinic.
This test is sensitive in both dogs and cats, which means that a negative test can be considered a confirmed negative.
The Low Dose Dexamethasone Suppression Test This test is performed similar to the way it is performed with dogs; however, the dose of dexamethasone required to test a cat is substantially higher as cats are more resistant to the effects of steroids. The test still requires 8 hours in the hospital and the cat should be relaxed and kept quiet during the stay. If the cat is the type to experience a great deal of stress in visiting the vet's office, consider the urine cortisol:creatinine ratio. It is important to find a diagnosis of Cushing's disease but it is equally important to consider that successful treatment of Cushing's disease is about control of symptoms. If the symptoms do not warrant control, then treatment should be postponed until they are more severe. After it has been determined that a pet has Cushing's disease, it is important to determine the type of Cushing's disease (adrenal vs. pituitary tumor). The next section in this series reviews how this is done. Treatment options and prognosis are highly dependent on the type of Cushing's disease the pet has.