Cushing's confusion? Ask a veterinary endocrinologist

"OK, explain that to me again." (Photo: Shutterstock.com)At a recent Fetch dvm360 conference, David Bruyette, DVM, DACVIM, shared his professional wisdom and characteristic wit while answering common endocrinology questions in a session especially designed to address attendee questions. Let's look into the curiosities concerning canine hyperadrenocorticism …

What's the best test for diagnosing Cushing's disease?

“When you see that there is more than one test to diagnose a disease,” Dr. Bruyette says, “it immediately tells you that all the tests suck.”

According to Dr. Bruyette, there is no perfect diagnostic test for Cushing's disease. ACTH stimulation tests, low-dose dexamethasone suppression tests and urine cortisol:creatinine ratios-the three most common diagnostic tests-each have their pluses and minuses.

The urine cortisol:creatinine ratio is sensitive but not specific. According to Dr. Bruyette, it's most useful as a tool to rule out Cushing's disease. Before treating a patient for Cushing's disease, Dr. Bruyette recommends confirming the disease with one of the other two tests.

The advantage of the low-dose dexamethasone suppression test is that it's more sensitive than an ACTH stimulation test-80% vs. 90%, according to Dr. Bruyette. And you can differentiate between pituitary-dependent and adrenal-dependent hyperadrenocorticism about 65% of the time. However, this test takes eight hours to perform, which some owners don't like.

Dr. Bruyette says that the main advantage of the ACTH stimulation test is that it's faster to perform than the low-dose dexamethasone suppression test-no eight-hour wait. However, there are more false negative results.

Should I use Cortrosyn or a compounded gel to stimulate the adrenals for an ACTH stimulation test?

“If you compare ACTH stimulation test results in normal dogs and cushingoid dogs and compare the gel and Cortrosyn, the results are identical,” Dr. Bruyette says. “Both will stimulate the adrenals equally well. The problem comes with monitoring.” The concentration of ACTH in compounded gels isn't consistent, he says, which skews monitoring results.

The bottom line from Dr. Bruyette: Either is fine for diagnosing, but for monitoring purposes, use Cortrosyn (Amphastar Pharmaceuticals).

What do the results of the low-dose dexamethasone suppression test mean?

According to Dr. Bruyette, the results may seem confusing but can be interpreted easily. He says there are three numbers to assess-the resting cortisol concentration, the four-hour cortisol concentration and the eight-hour cortisol concentration. If the patient's eight-hour concentration is higher than the laboratory's normal result (these vary by laboratory), then the patient has hyperadrenocorticism. If you see 50% suppression at any time point (four hour or eight hour), the patient has pituitary-dependent hyperadrenocorticism (PDH).

For example, a patient has a resting cortisol concentration of 10, a four-hour cortisol concentration of 4, and an eight-hour cortisol concentration of 10. If normal results at eight hours are < 2, then the patient has PDH because 10 > 2 and there is more than 50% suppression at the four-hour time point. “This is the most common thing we see in the lab,” Dr. Bruyette says. “Rapid suppression followed by escape.” According to Dr. Bruyette, the eight-hour cortisol concentration went back up because the dog cleared the dexamethasone from its system, most likely indicating it has had PDH for a while.

If there isn't 50% suppression, the hyperadrenocorticism may have an adrenal cause but not necessarily. More diagnostic tests would be needed to determine the cause.

Why would an owner want to differentiate between pituitary- and adrenal-dependent hyperadrenocorticism?

Because the prognosis is different, says Dr. Bruyette.

“I usually tell owners of dogs with pituitary-dependent Cushing's disease that's being treated that their dogs will live a normal lifespan unless they develop a macroadenoma, which occurs in about 15% of these patients,” Dr. Bruyette says.

Unfortunately, about 50% of adrenal tumors causing Cushing's disease are malignant, and these dogs have a life expectancy of < 1 year. Dogs with benign adrenal tumors can live a normal life with treatment but it's often more challenging to manage them medically than a dog with PDH.

Is it possible for a dog with Cushing's disease to have normal ACTH stimulation test results?

Yes. Twenty percent of dogs with Cushing's disease will have normal results with an ACTH stimulation test. According to Dr. Bruyette, the patient is most likely still in the early stages of the disease process and hasn't developed adrenal hyperplasia yet.

Can a dog with Cushing's disease have normal results with a low-dose dexamethasone suppression test?

Yes. Dr. Bruyette says that although this test is more sensitive than the ACTH stimulation test, 10% of dogs with Cushing's disease will have normal results with a low-dose dexamethasone suppression test.

What should I do if I suspect the patient has Cushing's disease but the results from the ACTH stimulation test or low-dose dexamethasone suppression test are normal?

According to Dr. Bruyette, you have three options: 1. Wait and see if the disease progresses. 2. Retry the test. 3. Perform the alternative test (perform a low-dose dexamethasone test if you previously performed an ACTH stimulation test and vice versa).

Dr. Bruyette says that the deciding factor is probably how severe the clinical signs are. If they aren't bothering the owner and aren't affecting the dog's quality of life, wait.

Why do some dogs not respond to trilostane therapy?

“It has to be given with food to be absorbed,” says Dr. Bruyette. So if a patient isn't responding, verify with the owners that they always give it with food.

“But even when fed, some dogs don't absorb it,” Dr. Bruyette says. “We've had dogs that didn't respond, and we've measured the trilostane in their blood and it's not there. If you get trilostane into the blood, it works because it blocks the synthesis of cortisol.”

It's important that they give the medication with food each day, including the day they have the ACTH stimulation test performed. Some owners and vets will mistakenly fast the dog the day of the test and give the trilostane on an empty stomach, which can dramatically alter the test results. Also, variation in clinical response and ACTH stimulation test results can be seen with dogs on compounded trilostane versus Vetoryl (Dechra), so switching to the name brand preparation would be a good idea if inadequate control of Cushing's is present. If the pet is clinically not responding and the ACTH stimulation test indicates inadequate adrenal suppression, the dose and/or frequency of administration of trilostane may need to be adjusted.

My patient has Cushing's disease but it's largely asymptomatic. Should I treat it?

“I say don't treat,” Bruyette says. “It could be months or years before that patient is symptomatic.”

According to Dr. Bruyette, the benefit of treating an asymptomatic patient is that the disease is in the early stage, so you might keep it from getting worse. However, all treatment has a risk-benefit ratio. The risks are the possible adverse effects and the cost. In an asymptomatic patient, there is no benefit. “Since the patient is already asymptomatic,” Dr. Bruyette says, “it will either stay asymptomatic or get worse.”

Alyson Collins is a freelance writer in Olathe, Kansas, and a former editor at dvm360 magazine. Her interests include (in no particular order) amusement parks, chocolate, her three kids, politics, and Harry Potter.

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