Hyperadrenocorticism (Cushing's disease, HAC)

Part 1 - Diagnosis

For a basic description of HAC and how it is diagnosed, please see HAC for Dummies .

Hyperadrenocortisicm is a disorder in which the body produces excess cortisol. Cortisol is a chemical that has a varitey of vital functions in the body. It helps the body cope with stress (it is sometimes called a "stress hormone"). It is involved in the production of sugars from proteins, and in maintenance of energy stores in the liver. It is a potent anti-inflammatory and is important in disease resistance.

We cannot live without cortisol, but too much is detrimental. There is a very finely tuned regulatory system in the body that normally keeps cortisol levels within a very narrow concentration range. When this system breaks down we get too much cortisol (hyperadrenocorticism, or HAC) or too little (hypodrenocorticism).

First, a little anatomy and medical terminology. The pituitary gland is located at the base of the brain, and produces a number of important messengers, or hormones. The adrenal glands are located just in front of each kidney, in the abdomen. The cortex or outer layer of this gland (properly called the "adrenal cortex") is the area responsible for making cortisol. Medically speaking, when something is too big or in too high a concentration we use the prefix "hyper-". The opposite, smaller than normal or too little, is prefixed by "hypo-". So, when we have a dog who is producing too much hormone from the adrenal cortex, he is suffering from hyper-adreno-corticism.

In a normal animal, the pituitary gland produces a hormone messenger called ACTH. This ACTH messenger travels through the bloodstream to the adrenal glands and stimulates them to produce cortisol, which is released into the bloodstream. The pituitary gland can sense the levels of cortisol in the blood and will stop releasing ACTH when there is enough. In this way the pituitary gland and adrenal glands act together to keep the levels of cortisol in the body constant.

In HAC there is something wrong with this control mechanism. Most commonly, there is a benign tumor in the pituitary gland that releases ACTH regardless of how much cortisol is already in the bloodstream. In scientific terms, there is loss of feedback inhibition for ACTH release. The adrenal glands are bombarded with ACTH and work furiously to release lots of cortisol in response, even though there is already plenty in the bloodstream.

In a smaller number of dogs there is a tumor in the adrenal gland. The tumor cells will release lots of cortisol even if there is no ACTH messenger coming from the pituitary gland. The pituitary realizes that there is lots of cortisol around and stops producing ACTH, but the adrenal tumor does not respond properly and keeps secreting cortisol.

In either scenario, there is too much cortisol in the body. Pets with too much cortisol exhibit signs like excessive thirst and urination, a "pot-bellied" appearance, thin skin, muscle weakness, ligament laxity and weakness, reproductive problems, excessive panting, behavior changes and respiratory problems.

Diagnosis

Because of the complexity of the disease, there are usually several tests that need to be run to arrive at a diagnosis of Cushing's disease. Initially we will take a sample for a complete blood count and biochemical profile, as well as a urinalysis. This will help to detect problems with the red and white blood cells as well as organs like the kidneys, pancreas and liver. Radiographs (X-rays) may be taken to assess the size of internal organs like the liver, to assess bone density, and (very rarely) to see adrenal gland tumors.

Once this basic evaluation is done, there are several tests specific to the pituitary/adrenal system that need to be done. We will tell you the ones that are required for your pet not all dogs need all the tests! Sometimes the results of one test have to be evaluated before deciding whether further tests are needed.

As a general rule, in a dog that is otherwise healthy, we do a test called a low-dose dexamethasone suppression test (it's easier to call it a LDDST). It sounds pretty intimidating, but it is not difficult for the dog. We have your dog in the hospital first thing in the morning and take a blood sample. We then give an injection of dexamethasone (a drug that mimics cortisol) and take additional blood samples 4 and 8 hours after the injection. Then you can collect your dog and we will await the results from the lab. The results will take a few days to come back.

What this test does is measures the response of the adrenal glands to a higher than physiologic dose of cortisol. A dog with a normal pituitary and adrenal glands will respond by completely shutting down its production of cortisol. The pituitary sees the dexamethasone and says, "Wow! More than enough cortisol here!" and stops sending out ACTH. Without ACTH, the normal adrenal glands will stop putting out cortisol for a long period of time. The 4 and 8 hour samples should have extremely low cortisol levels; this is called suppression and is the result we see in dogs that do not have HAC. In other words, the LDDST is a good screening test to confirm HAC.

In dogs that do have HAC, we see a variety of patterns of incomplete or non-suppression. Sometimes the cortisol levels go down, but not very much. Sometimes the 4 hour cortisol level is fairly low, but then it escapes suppression and rises again by the time the 8 hour sample is taken. Sometimes the cortisol levels don't really go down at all. The particular pattern of incomplete suppression can often tell us which type of HAC we are dealing with - a pituitary tumor or an adrenal tumor. In other words, the LDDST can also tell us (the majority of the time) where the tumor is.

LDDST is not infallible, however. Some dogs with pituitary tumors will have a normal suppression pattern. In those dogs, where we still have a high suspicion of HAC, we need to do other tests. Most of the time, though, LDDST is an excellent tool in the confirmation and diagnosis of HAC, with no risk to the dog.