Cushing’s Disease – Treatment

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Cushing’s disease is a disease where the body produces too much of the natural steroid hormone called cortisol. When we test for this disease, we will often use an eight hour low dose dexamethasone suppression test, potentially a one hour ACTH stimulation test and an abdominal ultrasound to look at the adrenal glands and measure their size. In our final episode of the series on Cushing’s disease, we talk about treatment options, including a medication called trilostane that inhibits the enzyme to produce cortisol within the adrenal glands or an alternative medication like mitotane. The ACTH stimulation test is used to monitor the medication safely. Remember, this disease requires a lot of diligence and a lot of close monitoring with your veterinarian. We will work with you to make sure that your pet is getting the dosage of medication that is just right to control the clinical signs at home. 85 to 95% of dogs will do great with just a single medication. Listen to this week’s episode for discussion of treatment options.

Welcome back!

[00:01:05] Dr. Lancellotti: Welcome everyone to today’s episode of Your Vet Wants You to Know. I’m very excited to continue our three part series on Cushing’s disease. The episode today is going to focus on treatment of Cushing’s disease and with me again for this series is Dr. Amy Oberstadt. She is a board certified small animal internal medicine specialist who has lived and practiced across the United States and is currently practicing in Texas, but has spent the last five years in Michigan, including doing a residency at Michigan State University. She is highly skilled in managing endocrine diseases and she has a soft spot for geriatric cats. Dr. Oberstadt. Thank you so much for joining us again.

[00:01:54]Dr. Oberstadt: Welcome to episode three, everyone. Today we are continuing our talk about a common hormonal disease in dogs called Cushing’s disease. Because pets with Cushing’s disease are often treated by both dermatologists, like Dr. Lancellotti, and internists, like myself, we thought it would be interesting to talk about the disease from our different perspectives. 

[00:02:14] In the first episode, we talked about how Cushing’s disease is the result of an overproduction of the body’s natural steroid hormone called cortisol. The most common clinical signs of the disease in dogs are increased thirst, urination, hunger, panting, and infections of the skin, ears and urinary tract. These pets are slowing down and their muscles are weakening so they get a pot-bellied appearance. Because cortisol affects many body systems, dogs can have a wide range of clinical signs. 

[00:02:45] In the last episode, we talked about the most common tests to look at Cushing’s disease, including the eight hour low dose dexamethasone suppression test and the one hour ACTH stimulation test, which are blood tests that look at cortisol production. An abdominal ultrasound can also be used to look at the adrenal glands and measure their size. If our suspicion of Cushing’s disease is low and we just want to rule it out as a possibility, a less expensive urine screening tests can be used. If it’s negative, we can say that the dog doesn’t have Cushing’s disease, but if it’s positive, we need to do more tests, back to those first two we talked about, before we can diagnose the disease definitively. Once Cushing’s disease has been diagnosed, the next conversation to have is about treatment options, which we’ll talk about today. 

Common Treatments - Trilostane (Vetoryl®)

[00:03:34] Dr. Lancellotti: That’s great. I’m sure our listeners have been really anxious to hear what their options are if their pet does get diagnosed with Cushing’s disease. We’ve been following my dog, Russell Sprout and his journey with Cushing’s. He is the Your Vet Wants You to Know mascot. He started getting frequent ear infections about a year ago, despite his environmental allergies being well controlled. He was having some urinary accidents in the house at the same time. When I did some blood work on him, it showed an increase in his liver enzymes. So I performed that eight hour low-dose dexamethasone suppression test and confirmed that he had the pituitary form of Cushing’s disease that we talked about in the last episode. About 80% of dogs with Cushing’s disease have a problem with their pituitary gland and these pets respond really well to medication that we use to decrease the production of cortisol in their body. So that’s what we did with Russell. I’ve had to play around a little bit with his dosing and I’ll talk about that more throughout the episode, but before I do, Dr. Oberstadt, can you talk to the listeners a little bit about the common treatments that are available for these pets?

[00:04:38] Dr. Oberstadt: Once we’ve confirmed our suspicion of Cushing’s disease, the primary treatment choice that I reached for is a medication called Trilostane. Trilostane works by inhibiting the enzyme that produces cortisol within the adrenal glands. This decreases cortisol throughout the body and reduces the clinical signs at home. 85 to 95% of pets will return to feeling normal. 

[00:05:03]Dr. Lancellotti: Trilostane is also my treatment of choice. That medication will decrease the production of cortisol, like you said, and it helps to kind of pump the brakes on that overproduction that’s occurring. So we do need to watch closely to make sure the medication is not over suppressing the production of cortisol. If that happens, then the pet isn’t getting enough cortisol that they need for the body’s normal functions. We can start to see some things like decreased appetite, vomiting, or diarrhea. I always recommend to pet owners, when they’re giving this medication to give it immediately after the animal eats in the morning and the evening, mostly so I’m sure that the pet has a good appetite before they get their medication. 

[00:05:48] Dr. Oberstadt: That’s great. Making sure that they have a good appetite is an awesome way to feel confident about your pet each day before giving their daily medications. Trilostane does require close monitoring at home and with your veterinarian. Think of Goldilocks and the three bears. She had to try porridge that was too hot, then too cold and then finally got it exactly right. With Cushing’s disease we need to make sure that the dosage is just right. At first, I see pets back frequently. The monitoring test that’s most commonly used is the one hour ACTH stimulation test that is also used for diagnosis. Some patients can be rechecked a little less frequently, but most will need their first ACTH stimulation test and a check of their electrolytes in about two to four weeks after starting medication, and then again, every two to four weeks until they’re well-controlled. Once we have things at a place where we are happy with how they’re doing, we move out to a less frequent monitoring schedule. More like every three months, then every six months as a long-term protocol. Some pets can be maintained with once daily dosing, but many do require twice a day.

[00:07:07] I also watch for general wellness lab work as these tend to be senior pets and they can develop other diseases. So routine blood and urine testing remains really important for them. Some pets can also have a high blood pressure from their Cushing’s disease. So this can be monitored as part of those screening and wellness checks at the same time.

[00:07:28] Dr. Lancellotti: I monitor very similarly, really watching closely in the beginning as we start our treatment, because I want to see how that pet responds as we decrease their cortisol levels. Then as the pet is better controlled, eventually I’ll space out the testing to every six months for maintenance. I do want to mention that when we’re starting treatment for Cushing’s disease, it’s not an emergency. This is a quality of life disease generally. So it’s okay. If the medication needs to be shipped to you or ordered in so that your pet can have the correct starting dose. 

[00:08:03]Dr. Oberstadt: Yeah, it can take a little while for us to get the correct dose because the specific dosage for each patient has to be very carefully calculated. 

Alternative Treatment - Mitotane (Lysodren®)

[00:08:14]Dr. Lancellotti: So we’ve talked about both of us using trilostane as our treatment of choice for Cushing’s disease. But what other medications might pet owners hear about? 

[00:08:23] Dr. Oberstadt: The most common medication you’ll hear about as an alternative option is one that’s called mitotane. Mitotane is another medication that also works by inhibiting the production of cortisol. It’s an older medication and it can be used in certain cases, but, for the most part, it has largely been replaced by trilostane. Are there ever situations in dermatology where you would reach for something other than medications?

[00:08:53]Dr. Lancellotti:  If I’m concerned that something might be wrong with an adrenal gland, I will sometimes recommend an abdominal ultrasound. Like we talked about before, most of the patients have a problem with their pituitary gland, but if they’re not quite responding to medications and maybe we haven’t previously figured out if it’s coming from the pituitary gland or the adrenal gland, then I’m going to send them to an internal medicine specialist for that abdominal ultrasound.

[00:09:21] Dr. Oberstadt: Yeah, this is the classic situation where both of us really need to work together to make a diagnosis and help these patients. Remember 20% of Cushing’s cases come directly from the adrenal glands. So an ultrasound and additional testing may be recommended. If one adrenal gland is larger than the other. These cases can still be treated with the exact same medications, trilostane or in rare cases mitotane, but in very infrequent cases, I become even more worried, where there’s a severely enlarged adrenal gland. Those cases can actually end up having cancerous tissue within the adrenal glands. We will sometimes recommend continued monitoring with ultrasound or even make a choice together with our pet owners to pursue surgical removal of that gland. So there are some more dramatic situations, but that is where your family veterinarian, dermatologist, and internist are here to help you. 

Troubleshooting Treatment

[00:10:23] Dr. Lancellotti: So Dr. Oberstadt, what happens if these medications aren’t working the way that they’re supposed to? 

[00:10:31] Dr. Oberstadt: Well, going back to our Goldilocks story, we know that these medications require some finesse and so the first thing to do is if you think something is wrong, contacting your primary care veterinarian or the prescribing veterinarian for the medication that you’re using is a great place to start. The first places we look for when we’re troubleshooting these medications and how your pet is doing is first of all, is the pet receiving the medication as prescribed? Some pets are really difficult to give capsules to, and the most accessible form of this medication comes in capsules. The second thing we look for is, is anything else interfering? Diseases like diabetes mellitus, pancreatitis, and urinary or skin infections can make it harder to control Cushing’s disease. This all sounds a little overwhelming, but remember, 85 to 95% of patients do really well with medications alone. We are getting better and better in treating this disease. If pets truly don’t respond and we’ve done all the troubleshooting to help them, we can even look into newer options such as radiation therapy of the pituitary gland or even removal of the pituitary gland. These newer options are not readily available and are often restricted to academic or certain specialty veterinary hospitals. Thankfully pet owners have their pet’s specialty team to help decide if any of these will be required.

Finding Russell Sprout's Just Right Dose

[00:12:02]Dr. Oberstadt: So, Dr. Lancellotti, knowing all this information about treatment, how has your experience been with Russell Sprout’s treatment? 

[00:12:09]Dr. Lancellotti: Well, Russell, as with everything else that we’ve done with him, has not been an easy dog and actually I would prefer some of my Cushing’s patients that I have at the hospital compared to Russell in his management of Cushing’s disease, because he’s been a challenge for me, even though he is my own personal pet and I am a specialist highly trained in treating this disease. So when I first started Russell on trilostane, he’s a really small dog, so I started at five milligrams once a day because that’s the smallest size that the capsules come in and we weren’t fully getting control of his disease, still having those ear infections, still having some urinary accidents. So I increased his dose to 10 milligrams once a day, mostly to make our lives easier by trying to give the medication once a day, instead of giving five milligrams twice a day. As I’ve talked about before on the show, Russell also has allergies and now ear infections from Cushing’s disease, so he has to get his allergy shot, frequent medicated baths. He has to get medicated mousse to his paws. He has to get frequent ear cleanings. Anything that I can do to cut back on how many things my husband and I have to do with him is really helpful because he is as feisty as he is scraggly. I thought, Hey, let’s bump up his dose, but try and keep it at once daily. Well, just a couple of days after starting his new dose, his stool became pretty loose. There was no vomiting or loss of appetite. So we took a couple of days break from the medication and his stool improved pretty quickly. I restarted the original five milligrams once a day. After I knew that he was tolerating that dose, I increased to five milligrams twice a day instead of 10 milligrams once a day and he’s had no issues. Actually, since we first started talking about this episode, we’ve already increased his dose again, from five milligrams twice a day to 10 milligrams in the morning, five milligrams in the evening. Like you were talking about with Goldilocks and the three bears. It is a lot of, well, this is too hot. This is too cold. We’re still trying to find what’s just right for Russell. 

[00:14:17]Dr. Oberstadt: It’s great to hear that you guys have been moving towards your personal, just right. He absolutely illustrates that this is a complicated disease it’s great that you guys have been able to make such tremendous progress with him. Just out of curiosity, how is he feeling with his trilostane at a better dose now? 

[00:14:39] Dr. Lancellotti: Oh my gosh. Russell is full of energy. This kid could run around the house with his tennis ball all day long. My daughter actually has a bouncy house that has been a lifesaver for us during the past year, since we’ve been staying at home and quarantining and the two of them go on that bouncy house for hours. It is ridiculous. He is energetic, he is happy. We’re dealing with less ear infections, and we’re dealing with less urinary accidents in the house. It has truly made a difference. We’re still waiting for those liver enzymes to come down on his blood work, which is one of the reasons why I bumped up his dosing again. Overall I’ve seen a dramatic improvement in him, so I’m very happy that we got the diagnosis and we got him started with treatment.

[00:15:28] Dr. Oberstadt: I think he’s a, a really wonderful illustration of how, if we’re diligent with our care, with our patients, with Cushing’s disease, we can have these tremendous, tremendous outcomes where they just feel so much better. It almost seems like they go back to feeling like they’re three or four years younger.

[00:15:46]Dr. Lancellotti: Yeah, it’s really rewarding to see these pets start to get that energy back again and have that pep in their step that they’ve lost because of this overproduction and cortisol. So it truly is a quality of life disease where you can make these pets feel so much better and it’s something that the pet owners notice very quickly once we find that just right dosing for them. Dr. Oberstadt, why don’t you kind of wrap everything up that we’ve talked about over these past three episodes for the pet owners who have been listening along with us. 

Cushing's Disease Overview

[00:16:20] Dr. Oberstadt: So to recap what we’ve been talking about over the last three episodes, we have covered a common hormonal disease of dogs called Cushing’s disease. Cushing’s disease is a disease where the body produces too much of the natural steroid hormone called cortisol. Most of the time, this was a problem with the pituitary gland in the brain. That covers about 80% of cases in about 20% of cases, the problem is with the adrenal gland itself. So when we’re testing for this disease, we will often use an eight hour low dose dexamethasone suppression test, potentially a one hour ACTH stimulation test and an abdominal ultrasound to look at the adrenal glands and measure their size. In our final episode, we’ve talked about treatment options for Cushing’s disease. We typically reach for a medication called trilostane that inhibits the enzyme to produce cortisol within the adrenal glands. Every once in a while, we’ll need to use an alternative medication like mitotane. The medication is one that is typically given twice a day, although sometimes it can be given once a day, and we use the ACTH stimulation test to monitor. Remember, this disease requires a lot of diligence and a lot of close monitoring with your veterinarian. We will work with you to make sure that your pet is getting the dosage of medication that’s just right to control the clinical signs at home. 85 to 95% of dogs will do great with just a single medication.  We see tremendous, tremendous success, but it takes a lot of diligent care and a lot of patients for us to get there. It’s one of the most rewarding diseases that Dr.Lancellotti and myself are able to treat. Even Russell Sprout has shown us that you can make these dogs feel so much better if you work together with your veterinary team. 

[00:18:15]Dr. Lancellotti: I hope people feel more confident after listening to today’s episode and the rest of the episodes in this series. and If they have further questions, they feel comfortable going and talking to their veterinarian about what’s going on with their pet. Thank you so much, Dr. Oberstadt. 

[00:18:30] Dr. Oberstadt: Thank you, Dr. Lancellotti. 

[00:18:32] Dr. Lancellotti: So I would encourage you, if you are concerned about Cushing’s disease in your pet, or if your family veterinarian has talked to you about their concerns for Cushing’s disease have that discussion about what the next step is. Make sure that you are having open communication so that you can work towards finding the best treatment plan for your individual animal. Many family veterinarians are very comfortable managing pets with Cushing’s disease, but the links to the American College of Veterinary Internal Medicine and the American College of Veterinary Dermatology are available on our website, so that you can find an internal medicine specialist or a dermatologist near you, if you would like to consult with a specialist. You can also view the references for today’s show and the show notes and see pictures of pets with Cushing’s disease. I would encourage you to join the Facebook group and tell us about your pet with Cushing’s disease, talk to other pet owners who are experiencing the same thing that you are.  If you found value in today’s episode, please subscribe so that you don’t miss future episodes of Your Vet Wants You to Know and leave us a rating so that other pet owners can find us and get the benefit as well. 

[00:19:47] Dr. Lancellotti: I’d like to finish each episode with a short segment that I call “Scratching the Itch.” It highlights something, either a human interest story, a product or a website that either provides relief or just makes you feel good. Hence, scratching the itch. Dr. Oberstadt, you’ve been really wonderful with providing us with “Scratching the Itch” segments over the last couple episodes. Do you have one more “Scratching the Itch” to share with our listeners today? 

[00:20:16]Dr. Oberstadt: So for my final “Scratching the Itch” with you, I’d like to share an app that you can get on your smartphone.  This app is called Storyteller and it’s by a very talented artist by the name of Morgan Harper Nichols and Morgan Harper Nichols is a poet and artist who has put together a meditative type app that has daily affirmations and uplifting words. It’s actually one of the only paid apps I have on my phone. I’ve completely cleared out my phone of anything that doesn’t bring me a lot of value through the day and this app is one that has a wonderful way of just giving you two to five minutes each day to start off with a really positive note. As you mentioned with Russell Sprout and your daughter spending time on your bounce house with all of the quarantine and things like that, as my family has been in a similar situation, I find that having some positivity to be able to wake up to on my phone every day has been a really uplifting thing. So I would highly recommend the Storyteller app by the poet Morgan Harper Nichols. 

[00:21:28] Dr. Lancellotti: This is beautiful.

[00:21:29]Dr. Oberstadt: I think I’ve sent you guys pictures from this actually. 

[00:21:32] Dr. Lancellotti: I know you have, I know you’ve sent us some pictures from this and sometimes I get those and I’m like, “Oh, I really needed that right now.” It just makes you feel okay in this time that is very tumultuous and uncertain. It’s nice to just have an affirmation and a moment to just be okay. 

[00:21:52]Dr. Oberstadt: I agree. And it’s one that I turned to daily, so I very, very much wanted to share it with all of our listeners and I certainly appreciate being able to do our three part series together. This has been a wonderful experience. 

[00:22:08] Dr. Lancellotti: I’m so happy to have you on here. I really hope that people are getting the information and feeling more comfortable about this entire process, because it really is overwhelming, even for me as a specialist and having studied this for many years. Having a pet with Cushing’s disease is very different than just treating a pet with Cushing’s disease. So I understand what people are going through and I hope that they found value in our conversations and that they feel comfortable talking to their veterinarian about what’s going on with their pet, so that they can have success in the treatment. So thank you very much, Dr. Oberstadt for all of your time and wisdom. 

[00:22:50] Dr. Oberstadt: Thank you so much for having me. 

[00:22:53] Dr. Lancellotti: 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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