CLASSIFYING CUSHING'S DISEASE

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 and prognosis are very different for each form. As described, there are two forms, commonly abbreviated PDH and AT. PDH stands for "pituitary dependent hyperadrenocorticism" and, as mentioned, accounts for 85% of canine and feline Cushing's patients. In PDH, there is a pituitary tumor, often extremely small, causing over stimulation of the adrenal glands. AT simply stands for "adrenal tumor." Adrenal tumors can be benign or malignant (for more details, click here). Testing to determine the type or form of Cushing's disease is called discriminatory testing. This type of testing is done AFTER the diagnosis of Cushing's disease has already been made.  Here are some issues and concerns where the type of Cushing's disease present becomes an important matter:

• If an adrenal tumor is present, there is a 50% chance that it is a malignant tumor. It is helpful to know if the pet has a condition with this kind of a malignancy rate, especially if surgery is being considered.
• If the patient is known to have an adrenal tumor, this knowledge will direct the doctor on how and where to look for evidence of tumor spread so as to determine if the patient has cancer or not. On the other hand, if the patient is known to have a pituitary tumor, it becomes more relevant to image the brain to look for evidence of pressure on the brain.
• Medication protocols may be very different for adrenal tumors versus pituitary tumors.
• Surgery protocols are completely different for adrenal tumors versus pituitary tumors.

Approximately 85% of Cushing's patients will have pituitary dependent disease while approximately 15% will have adrenal tumors.
This statistic appears to be valid in dogs as well as cats.

SO WHAT TESTS WILL TELL US WHAT TYPE OF CUSHING’S SYNDROME IS PRESENT?

(photocredit: MorgueFile.com)

CANINE TESTING

THE LOW DOSE DEXAMETHASONE SUPPRESSION TEST

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. In the usual version of the Low Dose Dexamethasone Suppression test, three lab samples are drawn and their cortisol levels are compared. There is a cortisol suppression pattern that can only mean that a pituitary tumor is present. If this pattern comes up, no further testing is needed. Approximately, 60% of patients with pituitary tumors can be identified with the Low Dose Dexamethasone Suppression test.

THE HIGH DOSE DEXAMETHASONE SUPPRESSION TEST

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 both Dexamethasone Suppression tests is to dose the patient with a steroid hormone and see if the patient's body recognizes that this has occurred. When higher doses of dexamethasone are used, a pituitary tumor theoretically will suppress cortisone production but an adrenal tumor will not. 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. Further, this test cannot identify patients with adrenal tumors; it is able to confirm about 70-80% of patients with pituitary disease. The remaining patients will need further testing.

ENDOGENOUS ACTH LEVEL

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. The idea with this test stems from the normal situation where the pituitary gland secretes ACTH to stimulate the adrenal gland to make cortisone. The adrenal gland makes cortisone which, in turns, tells the pituitary gland to stop making ACTH. This feedback keeps cortisone production in balance.

If there is a pituitary tumor, it will be churning out high levels of ACTH. If the pituitary gland is normal but an adrenal tumor is churning out high levels of cortisone, the pituitary gland will be making little or no ACTH. In this way, measuring ACTH tells us which situation is present.

The problem is that ACTH is a delicate hormone. Serum from the patient must be frozen when transported to the laboratory and must not thaw. Special sample transport is necessary which might not be possible for some areas.

IMAGING

Fundamental to discerning pituitary dependent Cushing's syndrome from adrenal tumor is the size and shape of the adrenal glands. With pituitary dependent disease both adrenal glands are being over stimulated so they should both be symmetrical in size and shape and most likely enlarged. With an adrenal tumor, one gland will be severely atrophied and possibly undetectable while the other one is enlarged and possibly misshapen. This dichotomy makes imaging of the adrenal glands an accurate way to distinguish types of Cushing's syndrome. Ultrasound, MRI, or CT scan can be used, however, ultrasound is the most readily available and least costly. In one study, ultrasound was able to correctly identify adrenal tumors in 86% of cases. Sedation is generally not needed for abdominal ultrasound whereas, CT and MRI require general anesthesia and usually referral to some type of specialty clinic.

An added benefit of imaging, includes looking for evidence of malignancy should an adrenal tumor be identified. Malignant tumors tend to invade the vena cava, the largest vein in the body. Ultrasound has been found to be extremely accurate in evaluating for this complication. Imaging also allows for measurements of the adrenal glands to be taken. Glands that measure >4 cm in length are highly suspicious of being malignant.

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.

IS IT REASONABLE TO “PLAY THE ODDS” AND NOT DO FURTHER TESTING?

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.

(photocredit: MorgueFile.com)

FELINE TESTING

For the cat with Cushing’s syndrome the methods that can be reliably used to distinguish pituitary from adrenal disease are: high dose dexamethasone suppression testing, endogenous ACTH and imaging.

HIGH DOSE DEXAMETHASONE SUPPRESSION TEST

The feline high dose dexamethasone suppression test is the same as the canine version of the test except that even higher dexamethasone doses must be used. If the cortisol levels suppress in response to the injection of dexamethasone then only a pituitary tumor is possible. If the cortisol levels do not suppress, however, then no conclusion can be drawn as 50% of feline pituitary tumors will not suppress. This can be a frustrating situation but since the test is non-invasive, it is worth a try to confirm a pituitary tumor in this way.

ENDOGENOUS ACTH

As with dogs, this test is very accurate in distinguishing pituitary-dependent from adrenal Cushing's syndrome but the problem is transport and sample stability. ACTH is a delicate hormone and the sample must be frozen all the way to the lab with no thawing out. The idea is that the patient with pituitary disease will have a very high level of ACTH while the adrenal patient will have none or very little. Obviously, if there is a transport problem the results can falsely indicate an adrenal tumor where there is none.

IMAGING

When it comes to using imaging to distinguish pituitary from adrenal Cushing’s syndrome the rules for cats are the same as those for dogs. 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 and has the added benefit of screening for local tumor spread.

After one knows which form of Cushing's disease is present, the best possible treatment for your pet's situation can be determined. Please continue to the next section in the Cushing's disease library to learn about treatment options.

Page last updated: 3/23/2026