ADRENAL OR PITUITARY CUSHINGS?
WHY DO WE CARE?
Once a pet has been confirmed as having Cushing’s syndrome, the next step is to determine which form of Cushing’s syndrome the pet has since treatment is different for each form.
- If an adrenal tumor is present, there is a 50% chance that it is a malignant tumor. It is important to rule out evidence of cancer spread and determine whether or not surgery is an option.
- Adrenal tumors are much less responsive to medications; in fact, only lysodren is an option and the doses required for meaningful effect are totally different from those used to treat pituitary dependent disease.
SO WHAT TESTS WILL TELL US WHAT TYPE
OF CUSHING’S SYNDROME IS PRESENT?
If one is lucky, the same test used to determine if Cushing’s disease is present can also classify the Cushing’s disease so that no further tests are needed. To get the information needed, a 4-hour sample is drawn in addition to the pre-dexamethasone sample and the 8-hour sample. If the cortisol level suppresses to a level below 50% of baseline at 4 hours, only to escape to a level high enough to indicate a positive result, only a pituitary tumor is possible. While pituitary tumors do not always show this kind of classic suppression at four hours, adrenal tumors never do. If suppression is seen in the 4-hour sample, further testing is not needed, though this is the only pattern that is distinctive enough to obviate further testing.
This test is similar to the low dose dexamethasone suppression test except that a higher dose of dexamethasone is used and the patient having the test is already known to have Cushing’s disease through prior testing. The idea behind this test is that a patient with a pituitary tumor will show suppression in circulating cortisol when exposed to the high dose of dexamethasone (though suppression does not occur with the low dose). If an adrenal tumor is present, suppression does not occur. Unfortunately, the theory does not hold well enough to make this a reliable test; a full 20-30% of pituitary tumors will fail to suppress even with the high dose of dexamethasone.
This test is felt by many to be the most accurate method of classifying Cushing’s syndrome but the problem is that the test is technically challenging to run. Serum from the patient must be frozen when transported to the laboratory and may not thaw. The hormone ACTH is very fragile and may not survive the trip to the lab. The idea with this test is that a patient with a pituitary tumor will have high ACTH levels, as this is what the tumor is secreting. A patient with low or no measurable ACTH levels has an adrenal tumor as the pituitary is trying its best not to stimulate the over-active adrenal tumor.
Imaging such as ultrasound, MRI, CT scan, or nuclear medicine studies are highly accurate in classifying Cushing’s syndrome. Probably ultrasound is the most readily available. If a Low Dose Dexamethasone Suppression test has confirmed Cushing’s syndrome but not confirmed which type, imaging of the adrenal glands can provide the information needed to complete classification. Two large or normal sized adrenal glands are typically present with the presence of a pituitary tumor as both adrenal glands will be equally stimulated by ACTH production. Other imaging results should be followed by either of the blood tests described below.
If one adrenal gland looks large and the other is not visible, an adrenal tumor may be suspected (remember, the non-tumorous gland will atrophy). In the event of an adrenal tumor, ultrasound is also helpful to determine the extent of tumor spread, which is crucial to deciding for or against surgical removal of the tumor.
It is important to note that ultrasound can never be used to make the initial diagnosis of Cushing’s syndrome as there is too much variability in the size of normal adrenal glands. When it comes to gaining information about a patient’s Cushing’s syndrome, imaging is best used on patients already known to have Cushing’s syndrome for whom classification is needed.
Since 85% of canine patients with Cushing’s syndrome have a pituitary tumor, it is not unreasonable to “play the odds” and treat for a pituitary tumor. The risks in doing so is that if the patient does not readily respond to medication is will be impossible to know if the medication dose simply needs adjustment or if the patient has an adrenal tumor and a completely different treatment is needed. A great deal of time and effort could be wasted by pursuing the wrong therapy.
For the cat with Cushing’s syndrome there are only two methods that can be reliably used to distinguish pituitary from adrenal disease: imaging and the high dose dexamethasone suppression test combined with the urine cortisol creatinine ratio.
In cats the initial testing to determine if the cat has Cushing’s syndrome can be done at the same time as the discrimination test. This is done by using urine cortisol:creatinine ratios as described in the section on the confirmation of Cushing’s syndrome. A first morning urine sample is collected on each of two consecutive mornings and brought in for testing. On that second day, dexamethasone tablets are given at 8 AM, 4PM, and midnight. The next morning, a third urine sample is brought in. The urine cortisol:creatinine ratios of the first two samples not only serve to make the diagnosis of Cushing’s disease but they also are averaged together to create a baseline against which to compare the ratio from the third day. If the ratio from the third day is less than half of the average of the first two, the cat most likely has a pituitary tumor. If the ratio from the third day is greater than the average from the first two days then it is not possible to determine whether the cat has a pituitary or an adrenal tumor and imaging should be performed.
Basically, the same situation exists for the cat as in the dog when it comes to using imaging to distinguish pituitary from adrenal Cushing’s syndrome. A cat with pituitary disease will have both adrenal glands approximately the same size, possibly both of them clearly larger than what would be considered normal. If there is an adrenal tumor, one gland will be large (the one with the tumor) while the other is very small (atrophied). Ultrasound is probably the least invasive and least complicated method of distinguishing adrenal from pituitary disease in cats but since the urine cortisol:creatinine ratios are needed to confirm Cushing’s syndrome in the first place, it is fairly easy give the medication, collect one more urine sample and potentially confirm a pituitary tumor.
Page last updated: 1/29/09