Cushing’s Disease – Testing

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Cushing’s disease is caused by an overproduction of the body’s natural steroid hormone or stress hormone called cortisol. Cortisol is needed to maintain a lot of the body’s normal functions, but, when the body starts making too much, cortisol can suppress the immune system, leading to infections of the skin, ears and urinary tract. Cortisol can also make dogs excessively hungry, thirsty, or have accidents in the house. These patients have weakened muscles, which gives them a potbellied appearance. Because there’s a wide range of body systems that are affected by cortisol, not all dogs with Cushing’s disease will look the same and there can be a wide range of severity to the signs as well. If you and your family veterinarian are suspicious for Cushing’s disease, this episode discusses the different tests available.

Introduction

[00:01:07] Dr. Lancellotti: Hello everyone and welcome to Part Two of our three part series on canine Cushing’s disease. I’m very excited to continue our discussion on Cushing’s disease and have the return of my very special guest, Dr. Amy Oberstadt, who joined me for our first part of this series on the clinical signs of Cushing’s disease and she is back now to talk about the diagnostic testing. Just a reminder for you, Dr. Oberstadt is a board certified small animal internal medicine specialist, who is currently a private practitioner in Texas.  She and I were classmates in veterinary school together and we both see Cushing’s patients very commonly, but we have a little bit of a different perspective.  I’m very excited to share in the ongoing conversation about Cushing’s disease with Dr. Oberstadt. Welcome back. 

[00:01:57] Dr. Oberstadt: Thank you. Welcome everyone to Part Two.

Review of Clinical Signs

[00:02:00]Dr. Lancellotti: Can you tell our listeners a little bit about what we’re talking about? Just a refresher if it’s been a while, since they listened to the first episode, and what they can expect from today.

[00:02:09] Dr. Oberstadt: Today we’ll be talking a little bit more about a very common hormonal disease in dogs. That’s called Cushing’s disease. Because pets with Cushing’s disease are treated by both dermatologist and internal medicine specialists like myself, we thought it would be really interesting to talk about the disease from both of our different perspectives. Last time we talked about how Cushing’s disease is an overproduction of your body’s natural steroid hormone, which is called cortisol. This is your normal stress response hormone, but when you have too much of it, you get a really wide variety of clinical signs in dogs. The most common of these are increased thirst and urination, increased hunger, panting, elevated liver values and infections of the skin, ears, and urinary tract. These pets are slowing down a lot and their muscles start getting weaker. They will frequently develop a potbellied appearance to go along with all these clinical signs. Because cortisol affects so many different body systems, they have a really wide range of clinical signs that we’ll see. 

[00:03:15] Dr. Lancellotti: [00:03:15] Yeah, every patient is different in how they present with their clinical signs of Cushing’s disease.  Last episode, we talked a little bit about my dog, Russell Sprout, who is the Your Vet Wants You To Know mascot, and what his early signs of Cushing’s disease were. He had recurring ear infections, he had accidents in the house overnight and he had an increase in his liver enzymes when I did general health blood work as part of his routine, preventative care. Once I was really suspicious that all of those changes were linked, I decided that it was time to do some more testing, to see if he really did have Cushing’s disease. What we’re going to tackle on today’s episode is the testing. Dr. Oberstadt, why don’t you tell our listeners what testing options are available when their veterinarian is suspicious of Cushing’s disease. 

thinning hair coat in a dog with Cushing's disease

Two dogs with Cushing’s disease. You can see patchy hair loss on the body of the dog in the first image, and a pot-bellied appearance due to muscle wasting with the second dog. Both dogs had difficult ear and skin infections due to the high levels of cortisol in their body causing suppression of their immune system. 

Understanding Cushing's Disease to Understand Testing

[00:04:05] Dr. Oberstadt: When we are talking about testing options, in order to get a little bit more into that, what I want to back up and do first is talk a little bit more about where Cushing’s disease comes from, because these are the areas where our testing is going to really be able to shine and to target. Last episode, we talked about how Cushing’s disease most commonly comes from the pituitary gland at the base of the brain. This gland acts like the air traffic controller and tells the adrenal glands, which live above your kidneys, to make cortisol. 80% of canine cases come from the pituitary gland, so the air traffic controller in these cases is getting a little wild. The problem is the air traffic controller is also really small, usually microscopic. We rely on special blood tests to tell us how out of control our air traffic controller really is. Additionally, we can also look at how much the adrenal glands are being pushed by that overactive process.  There are two adrenal glands in the body and they’re located on each side of the body kind of tucked in behind each kidney. They’re also about the size of your pinky finger nail. So they’re really small. In many cases, we can use an abdominal ultrasound to see what these glands look like. If both of them are being pushed to make too much cortisol, both are often enlarged. An abdominal ultrasound is a really nice test to say, are these adrenal glands big or not? 

[00:05:34] Dr. Lancellotti:  That’s great. Say both of the adrenal glands look big on ultrasound and you have a pet that has lots of clinical signs that are consistent with Cushing’s disease. How do we then test to know how out of control the air traffic controller or the pituitary gland has actually become.

Low Dose Dexamethasone Suppression (8 hour) and ACTH stimulation (1 hour) tests

[00:05:56]Dr. Oberstadt: There are two main tests available to be able to definitively diagnose Cushing’s disease. The first one is an eight hour test and it’s called a low dose dexamethasone suppression test. The second test is a one hour test and it’s called an ACTH stimulation test. Both of these are good tests and they involve administering a specific medication to help either suppress or stimulate those adrenal glands. Both of them can also have false positives and false negatives. In some cases we end up needing both. Ultimately it’s going to be up to your doctor to select between these two tests. In my practice, I’m usually seeing patients that travel a long distance. I tend to use the one hour test just so they’re able to go home the same day. Sometimes we’ll actually catch Cushing’s disease when it’s in really early stages and so the cortisol levels with either test are not quite elevated enough to start treatment. That’s okay because we can monitor these patients over a few months until they’re ready for therapy. 

[00:07:03]Dr. Lancellotti: It’s interesting that you say that both of the tests have false positives and false negatives. Can you describe to pet owners a little bit more about what that means? What exactly is a false positive and what is a false negative and how come neither one of these tests is 100% accurate. 

[00:07:23] Dr. Oberstadt: It’s almost impossible to find a test that’s truly a hundred percent accurate all the time. Anytime we’re talking about a diagnostic test, we have to consider these different things called false positives and false negatives. A false positive is where we have a positive test result in a patient that is actually not positive for the disease. On the other side of the equation, a false negative is where we have a negative result, even though the pet has Cushing’s disease. Because no test is perfect, either one of these can occur with these specific tests and we’ll go through it in a little bit more depth, the different scenarios where you could get these kinds of results in a few minutes.

[00:08:08] Dr. Lancellotti: I know many family veterinarians are becoming a lot more familiar with this disease and they often will catch it before those clinical signs that we talked about are completely overwhelming. So the drawback to that though, is that our laboratory tests, the blood tests that we have for Cushing’s disease, haven’t quite caught up with our ability to recognize pets that have symptoms of Cushing’s disease early on. It can be a little bit frustrating going through several rounds of tests when we first suspect that disease. Fortunately, though, if we don’t get our diagnosis right away, we do our best to manage the  clinical signs and then come back to testing later. For me, being in the Los Angeles metropolitan area, most of my clients are local, so I tend to schedule an eight hour test that you talked about, the low dose dexamethasone suppression test, as that can help me differentiate, between a problem with the pituitary gland, which is our air traffic controller, or a direct problem with the adrenal glands, where the cortisol comes from. If the results of that eight hour test make me suspicious the adrenal glands are actually the problem, then I’ll usually recommend the pet goes to see an internal medicine specialist to have an abdominal ultrasound done to get a better look inside. 

[00:09:26] Dr. Oberstadt: That’s really important because when we talk about Cushing’s disease, we said that 80% of dogs have this air traffic controller that’s the problem. But 20% of dogs actually have another type of Cushing’s disease, which is called adrenal dependent disease. This means that the pituitary gland is actually normal, but one of the adrenal glands, so one of the airplanes that they’re trying to control, is actually the problem. When we do an abdominal ultrasound in these patients, this will often show that one adrenal gland is significantly larger than the other one.  Sometimes,  when one airplane takes over all the work, it actually makes the other one smaller since it has so much less work to do.

[00:10:11]Dr. Lancellotti:  With those patients, there’s a little bit of a difference in the treatment that we might recommend for them, so I’m excited to talk about that on the next episode, when we dive further into what we do with these pets when we finally do get a diagnosis of Cushing’s disease. 

veterinarian performs abdominal ultrasound on a dog

Dr. Oberstadt performs and abdominal ultrasound on a dog.

What if the testing comes back normal?

[00:10:27]Dr. Oberstadt: Exactly, and when we talk about these patients that we are testing and we don’t get a diagnosis right away, that’s a really good example of what we would consider a false negative result, where we’ve had a test that came back negative, but the patient actually does have Cushing’s disease. So we do see false negatives fairly commonly in practice in these really early cases. Like we said, it’s great that we have the ability to retest these patients, but it requires a lot of patience on everyone’s part because it can take us a little while to come to a definitive diagnosis. 

[00:11:07] Dr. Lancellotti: It definitely is trying on my patience as well, as the veterinarian who’s looking for an answer. I certainly get those pets come in to see me where everything that is going on with them makes me think Cushing’s disease. I’m like, “Yes, this is absolutely Cushing’s disease.” We’ll do some testing, we’ll get a result and it comes back negative and I get frustrated. So I have to learn to be really good about just taking a deep breath, focusing on clearing the infections and keeping the animal comfortable, and then just retesting a little bit later and I eventually do get my answers. You’re absolutely right, patience on everybody’s part and just managing the pet and keeping them comfortable until we can get our answer is really important for everybody to understand.

Making sure your pet is ready for testing

[00:11:53] Dr. Oberstadt: It’s unfortunately, a disease that is a long-time disease, not a short time disease. So whether we’re talking about coming to a diagnosis or pursuing treatment, these are truly chronic patients for both of us.  So now that we’ve talked about the two main blood tests available, the low dose dexamethasone suppression test and the ACTH stimulation test, I want to point out that when we look at things in real life, they always get more complicated. Because hypoadrenocorticism comes from excess cortisol, your body’s normal steroid hormone, can you tell us a little bit how you change your approach when patients are exposed to steroids, but not from the adrenal glands, so in the form of medications that they might already need for skin and ear problems? 

[00:12:42] Dr. Lancellotti:  Absolutely. So, one thing that I need to consider as a dermatologist is what other medications is a pet receiving when it’s time for me to test for Cushing’s disease. I talked a lot about steroids for treatment of allergies with Dr. Plowgian in a previous episode of Your Vet Wants You to Know. Steroids are really great for providing relief from itch and inflammation, so they are commonly used in topical ear medications for ear infections, and there’s some topical sprays and ointments for the skin and eyes that also contain steroids. Since many pets with Cushing’s disease can develop ear infections, it’s not uncommon for them to be receiving those ear medications with steroids to make the ears feel better. Heck, I even treated the first couple of ear infections that Russell got with an ear medication containing a steroid. But, once I suspected that Russell might have Cushing’s disease, I knew that I needed to stop any treatment that I was using that contained a steroid medication, because any steroids that we treat a pet with can actually interfere with the testing that we do for true Cushing’s disease. So I switched him to an ear drop without a steroid, which can actually be pretty tough to find and waited for the steroid I had previously given him to be washed out from his body before doing the low dose dexamethasone suppression test, to look at the blood levels of cortisol. That takes about a month and each steroid is a little bit different, so it’s important to just be patient. The big takeaway that I’m trying to drive home here is that it is really crucial for the pet owner to communicate to their veterinarian, who wants to perform testing for Cushing’s disease, if they’re using any medication that might contain a steroid, whether that’s an oral medication or a topical medication for the ears or the skin or the eyes. When we’re spending the time and the money to do a test like this, as veterinarians, we want to be able to accurately interpret the results so that we can give the pet owners the most reliable answer possible. We’ve talked again and again about how important it is with this particular disease to have good communication between the pet owner and the veterinarian. Make sure that you, as the pet owner, are telling your veterinarian of everything that you are possibly giving your pet so that they know whether or not now is a good time to do those tests.

[00:15:16] Dr. Oberstadt: Exactly. Similarly, there’s also situations where your body will naturally produce more cortisol. Filling your vet in on the history of the different things that your pet has gone through and how they’ve been feeling over the last month or so is also really important. Remember, cortisol is our stress hormone. So being sick can also be really stressful or if a pet has had a recent surgery or any kind of severe illness. In these situations, we often will delay testing to allow them to recover from whatever that naturally stressful event was. 

The Urine Cortisol Creatinine Ratio Screening Test

[00:15:55] Dr. Lancellotti: So Dr. Oberstadt, if we have a pet who, we’re maybe not quite sure if they have Cushing’s disease, we’re a little bit suspicious, but they don’t have tons of those clinical signs that we talked about, are there any tests that we can use to maybe screen the patient for Cushing’s disease before we get to those blood tests? 

[00:16:17] Dr. Oberstadt: Great question, and there is an additional test available that can help us. This is particularly important in cases where our suspicion for Cushing’s disease is low and we want to just rule it out and make sure that this dog doesn’t have Cushing’s disease. It’s a test that is often less expensive than the testing that we talked about already. It’s a urine screening test. It’s called a urine cortisol to creatinine ratio. So it’s measuring cortisol in urine. If it’s negative, if the dog does not have too much cortisol in their urine, then we can comfortably say that the dog does not have Cushing’s disease. If it’s positive, we have to do those tests that we talked about earlier in order to help tell for sure if they’re positive because they have Cushing’s disease producing too much cortisol, or if they’re positive, because maybe it’s just a stressful day.  That would be a situation where the test would truly be an example of a false positive. 

[00:17:21]Dr. Lancellotti: Perfect. So the urine cortisol creatinine ratio test is a good test if maybe it might be Cushing’s disease, but it might be something else let’s just check before we do all of these more intensive blood tests. That’s a great example of something that might be helpful in those cases where we’re kind of on the fence. 

[00:17:42] Dr. Oberstadt: Yes, it’s a great screening tool for us, but it often leads us to additional testing if we’re truly worried about Cushing’s disease.  After going through all these different testing options that we have, I know all of our listeners are wanting to know how did you diagnose Russell Sprout?

Russell Sprout gets anxious at the vet. Using Fear Free techniques, including holding him how he prefers to be held, anti-anxiety medication prior to coming to the clinic, and lots and lots of peanut butter, Russell Sprout gets his blood drawn to test for Cushing’s disease.

Diagnosing Russell Sprout

[00:18:00]Dr. Lancellotti:  What we did with Russell Sprout started with the general health blood work I discussed on the last episode. We looked at his liver enzymes and they were high. That was the first blood test that we did. Once I had him off of any steroid that he could have been getting in ear medication and I knew that I would accurately be able to interpret the results of the test, I started with the low dose dexamethasone suppression test with him. The results of his cortisol levels during that eight hour test showed me that he has a problem with his air traffic controller telling his adrenal glands to produce too much cortisol. So we got our diagnosis with him and when we come back for our next episode, we’ll talk all about the different treatment options available and what we’ve been doing with Russell Sprout since we got his diagnosis. 

[00:18:51] Dr. Oberstadt:  I’m so glad you guys were finally able to come to a diagnosis for Russell Sprout. I know he had such a difficult experience and it was such a frustrating time for you guys with all the clinical signs that you were dealing with at home with him. So I can’t wait for next time when we talk about all the treatment options available. 

[00:19:09] Dr. Lancellotti: Yeah, me too. It was definitely frustrating for myself, but also for my husband who is not a veterinary professional and not used to dog accidents in the house on a regular basis. So we’re very relieved to have him get some treatment that helps those clinical signs go away. 

[00:19:25] Dr. Oberstadt:  Absolutely. It’s always a relief when everybody gets to sleep at night. 

Conclusion

[00:19:29] Dr. Lancellotti: Dr. Oberstadt, can you kind of wrap up for our listeners here a summary of what Cushing’s disease is and what testing we talked about today?

[00:19:39]Dr. Oberstadt: Cushing’s disease is caused by an overproduction of your body’s natural steroid or stress hormone, cortisol. Cortisol is needed to maintain a lot of your body’s normal function, but when the body makes too much of it, cortisol can suppress the immune system, leading to infections of the skin, ears, and urinary tract. Cortisol also makes dogs excessively hungry and thirsty and they can have accidents in the house. Their muscles can weaken so they can have trouble getting around and they can also develop a potbellied appearance. Ultimately, there’s a wide range of clinical signs they can have. If you and your family veterinarian are suspicious for Cushing’s disease, the most common tests performed are the eight hour low dose dexamethasone suppression test and the one hour ACTH stimulation test, which are blood tests, looking at cortisol production.  An abdominal ultrasound can be used to look at the adrenal glands and measure their size to help us to make a more definitive diagnosis as well. Once Cushing’s disease has been diagnosed, the next conversation to have is about treatment options, which we’ll talk about on our next episode of Your Vet Wants You to Know. 

[00:20:51]Dr. Lancellotti: Thank you so much for joining us today, Dr. Oberstadt. I look forward to the next episode. 

[00:20:57]Dr. Oberstadt: Thank you so much for having me. 

[00:20:58]Dr. Lancellotti: If you enjoyed this episode, please write a review and subscribe so you don’t miss any upcoming episodes of Your Vet Wants You to Know, including our next episode, in which we talk about treatment options for Cushing’s disease. Many family veterinarians are very comfortable managing pets with Cushing’s disease, but if you would like to visit a specialist, the links for the American College of Veterinary Internal Medicine and the American College of Veterinary Dermatology are available on the Your Vet Wants You to Know website and you can view the references for today’s show in the show notes. I would encourage you to join the Facebook group, Your Vet Wants You to Know and tell us about your pet with Cushing’s disease. Do you have a similar experience that I have with Russell Sprout? I also love hearing what you would like to learn about on future episodes, so comment in the group or contact me through the website. 

[00:21:57] Dr. Lancellotti: I like to end each episode with a segment I call “Scratching the Itch.” This is a short segment that will highlight something, either a human interest story, a product or website that either provides relief or just makes you feel good. Hence, “Scratching the Itch.” Dr. Oberstadt, do you have a “Scratching the Itch” you’d like to feature today? 

[00:22:17] Dr. Oberstadt: I do. Today’s “Scratching the Itch” is a product for older dogs. This product is Dr. Julie Buzby’s Toe Grips, and these are an amazing product for dogs that have mobility issues as they get older. What we often find is especially with bigger dogs, they start having issues getting around on slippery surfaces, so hardwood floors, or anything at home that is just too slippery for them to be able to grip. If your dog can walk better on rugs and carpeting, instead of having to put carpet all through your house, you can actually use this product instead. Toe grips are small, flexible nail covers that don’t cover the entire nail, but they do create an extra surface to help the dog have instant traction on hard surface floors and stairs.  They can help these dogs to go places more comfortably than they otherwise would.

[00:23:17]Dr. Lancellotti: These are a really great product for dogs that have a little bit of trouble on those slippery surfaces and I see a big difference in the confidence level of those older dogs that have arthritis or any dogs with sort of orthopedic or mobility problems, when they realize that they don’t have to be scared to walk on those slippery surfaces anymore. It’s like that confidence gives them the boost of energy that they need and you can just see their faces light up when they realize, “Oh, I can walk on this again!” It’s really incredible how well these dogs take to it. Highly recommend for people who have dogs that may have an issue with hardwood floors or with tiles. Definitely a game changer for those dogs. 

[00:23:59] Dr. Oberstadt:  Absolutely. We’d love to have you check out Dr. Julie Buzby’s toe grips, and we will provide information in the show notes for you to be able to look into them if that’s something that would be a helpful tool for you and your dog. 

[00:24:11] Dr. Lancellotti: [00:24:11] Please join us again for our next episode on our three part series of Cushing’s disease, where we’ll be talking about treatment options. I look forward to your next visit with Your Vet Wants You to Know.

References

  1. Arenas, C., Melian, C., Perez-Alenza, M.D. Evaluation of 2 Trilostane Protocols for the Treatment of Canine Pituitary-Dependent Hyperadrenocorticism: Twice Daily versus Once Daily. J Vet Intern Med 2013;27:1478-1485 
  2. Behrend, E.N.e.a., Diagnosis of Spontaneous Canine Hyperadrenocorticism : 2012 ACVIM Consensus Statement (Small Animal). J Vet Intern Med, 2013(27): p. 1292-1304. 
  3. Bruyette, D. Canine Pituitary Dependent Hyperadrenocorticism Series. 2016. Today’s Veterinary Practice. March/April. 30-38 
  4. Gallagher, A. Hyperadrenocorticism in Dogs. Clinician’s Brief. 2014. Nov. 59-63 
  5. Hoffman, J. M., et al. “Canine Hyperadrenocorticism Associations with Signalment, Selected Comorbidities and Mortality within North American Veterinary Teaching Hospitals.” JOURNAL OF SMALL ANIMAL PRACTICE, vol. 59, no. 11, pp. 681–690. 
  6. Midence, J.N. Cortisol Concentrations in Well-Regulated Dogs with Hyperadrenocorticism Treated with Trilostane. J Vet Intern Med 2015;29:1529-1533 
  7. Nagata, N., Kojima, K., and Yuki, M., Comparison of Survival Times for Dogs with Pituitary-Dependent Hyperadrenocorticism in a Primary-Care Hospital: Treated with Trilostane versus Untreated. J Vet Intern Med, 2017. 31: p. 22-28. 
  8. Reine, N.J. Medical Management of Pituitary-Dependent Hyperadrenocortism: Mitotane vs Trilostane. Topics in Compan An Med (2012) 25-30 
  9. Scott-Moncrieff, J.C. A Compass for Cushing’s: Demystifying Canine Hyperadrenocorticism. 2016. Clinical Brief. 1-12

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