Veterinary Vertex
Veterinary Vertex is a weekly podcast that takes you behind the scenes of the clinical and research discoveries published in the Journal of the American Veterinary Medical Association (JAVMA) and the American Journal of Veterinary Research (AJVR). Tune in to learn about cutting-edge veterinary research and gain in-depth insights you won’t find anywhere else. Come away with knowledge you can put to use in your own practice – along with a healthy dose of inspiration to remind you what you love about veterinary medicine.
Veterinary Vertex
The Importance of Recognizing Concurrent CKD in Hyperthyroid Cats
Are you overlooking azotemia in hyperthyroid cats? Explore the intriguing world of feline hyperthyroidism with veterinary endocrinologist Mark Peterson, who sheds light on why some hyperthyroid cats developing azotemia post-radioiodine treatment face shorter survival times. We'll challenge previous assumptions and dive into new research involving over 1,000 cats, revealing insights that are crucial for making informed treatment decisions for these beloved pets. Uncover the complexities of diagnosing concurrent chronic kidney disease and the critical role of factors like increased blood flow, muscle mass loss, and subsequent treatment options, including medical and dietary therapies.
In our conversation, Mark also takes us on his personal journey into endocrinology and his impactful contributions to feline health over the past four decades. As we look to the future, we discuss the potential advancements in diagnosing and managing azotemia, including the promising but cautious role artificial intelligence might play in veterinary research. Join us for a captivating discussion on the challenges of recognizing hypothyroidism in cats and the ongoing efforts to improve survival rates through innovative treatments, all backed by Mark’s extensive experience and passion for unraveling the mysteries of hyperthyroidism in cats.
Open Access JAVMA article: https://doi.org/10.2460/javma.24.10.0653
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You are listening to Veterinary Vertex, a podcast of the AVMA Journals. In this episode, we chat about how hyperthyroid cats that develop azotemia following successful radioiodine treatment have shorter survival times compared to cats that remain non-azotemic, with our guest, Mark Peterson.
Lisa Fortier:Welcome to Veterinary Vertex. I'm Editor-in-Chief Lisa Fortier, and I'm joined by Associate Editor Sarah Wright. Today we have Mark joining us from Chile, Pennsylvania. Mark, thank you so much for taking time out of your day to be with us here today.
Mark Peterson:Thank you, Lisa and Sarah. It's really a pleasure to be here to talk to you today.
Sarah Wright:All right, let's dive right in. So, Mark, I found your article especially interesting because one of my cats, whenever we get our blood work done like semi-annually her thyroid is always kind of on the cusp of being hyperthyroid. and were like kind of just waiting until she goes over the edge so for my own knowledge, I found this very interesting. In your article discusses how hyperthyroid cats that develop azotemia following successful radioiodine treatment have shorter survival times compared to cats that remain non-azotemic. Please share with our listeners the background on this article.
Mark Peterson:So what we know is that multiple studies have shown that between 15 and 50 percent of hyperthyroid cats will have concurrent chronic kidney disease, or CKD. The problem with hyperthyroidism is it's more difficult to confirm or diagnose this concurrent CKD for a number of reasons. First of all, hyperthyroidism increases the blood flow from the heart, so it increases the blood flow to the kidneys, increases GFR or the pressure of the kidneys. That increased pressure and increased blood flow tends to lower the serum creatinine, serum BUN concentrations and you may have a cat with CKD. That we all think is very normal because when they're hyperthyroid the numbers tend to go down and look better. In addition, hyperthyroid cats commonly lose weight, including muscle mass. Creatinine is derived from muscle creatine, so as muscle mass goes down, serum creatinine will also fall. So again, if you have a cat with CKD or chronic kidney disease, it's very common, because of their muscle loss, to have a lowering in their serum creatinine concentrations. So this overall, it can be very difficult to know for sure if that hyperthyroid cat as CKD or not.
Mark Peterson:It's well known that hyperthyroid cats that are azotemic at diagnosis in other words, you have a hyperthyroid cat. The T4 is high, the creatinine is also high, as we define that greater than two. Those cats are well known to have a poorer prognosis. Generally, they survive with a median survival time of less than two years, which is not nearly as high as those without azotemia.
Mark Peterson:But one study done about a decade ago and this was castrated with methimazole found that hyperthyroid cats seemed to be different. Those that developed azotemia after treatment with methimazole did not have a shorter survival time than those that didn't have azotemia. And, to be honest, this really didn't make any sense to me at all, because we know that you thyroid cats not cats, your regular cat with not a hyperthyroidism, that has even stage two to three early chronic kidney disease those cats have a shorter survival time. So it didn't make sense that hyperthyroid cats would be different just when they have hyperthyroidism. So and this wasn't my clinical impression either so in this study the goal really was to study a larger number of cats and in this study we studied over 1,000 cats followed from the time they were diagnosed to when they developed azotemia between 6 to 12 months until they died. So we looked at these cats over about a 10-year period to try to make sense of this and see what we found.
Sarah Wright:Yeah, super interesting study and, I think, very clinically applicable too. So what are some of the important take-home messages from this JAVMA article?
Mark Peterson:Well, my clinical impression was right, if you believe the study, because when we looked at our cats that developed CKD or developed azotemia, defined as a creatinine concentration greater than 2 at 6 to 12 months after radiolidon treatment, their survival time was one and a half years shorter than those cats that didn't become azotemic at that time. So survival time between the two groups was 4.3 years in the cats that didn't develop azotemia to 2.8 years in those that did so. This isn't to say that all cats that become azotemic after we treat them are going to die immediately and it's a terrible thing to necessarily treat them. They should be treated in some fashion. But it's important that the owners realize this and the veterinarians realize that their survival time will be shorter and that may influence how we manage these cats and how we treat them, what treatment we we choose. Maybe we don't want to treat all these cats with radio iodine. Maybe some of them should be treated medically or dietary wise or something else.
Lisa Fortier:Congratulations on a manuscript that's going to change clinical practice. Sometimes we do a lot of studies, but this one's really going to move the needle, so thank you for sharing it with us at JAVMA as well.
Mark Peterson:Well, thank you for accepting it.
Lisa Fortier:You're clearly a really good clinical educator. I'm an equine orthopedic surgeon, so the last time I thought about the neuroendocrine axis was a long time ago, and even I understand what you're talking about. What sparked your interest in endocrinology?
Mark Peterson:Well, you know, I went to school I graduated in 1976. And you know, in veterinary school I loved endocrinology. I liked diabetes and Cushing's in dogs, for instance. And so when I did an internship and then a residency at the Animal Medical Center in New York, and during my first year residency I got involved in a clinical research project with a physician studying canine Cushing's disease and that was very interesting and I for years I was probably one of the world's top investigators for canine Cushing's disease too.
Mark Peterson:But in 1979, we discovered our first hyperthyroid cat and I was lucky because of this relationship I had working with this physician on canine Cushing's disease. I was doing endocrine rounds with physicians at the New York Hospital Presbyterian in New York City. So when we first had this hyperthyroid cat, I went to one of the thyroidologists on rounds and I said we have this cat with hyperthyroidism. What do you think? What should I do? How should I work it up, what we should do? And they were extremely helpful and interested and I started a collaboration with these guys who were, you know, I couldn't have done what we've done with hyperthyroidism without them.
Mark Peterson:So that's after once we started hyperthyroidism, my interest in Cushing's went way down and hyperthyroidism went way up. Here's a new disease no one knew nothing about and we were seeing it. The first year we saw about 10 cats, and the next year we saw about 100 cats, and the year after that it just kept going up and up and up. So you know, right now it's the most common endocrine disease in cats and it's one of the most common diseases we see in older cats. Cats are older than 10 years of age. One in 10 of those cats will be hyperthyroid, so it's a very important disease.
Lisa Fortier:Fantastic, what a fabulous career. It's so great to be a veterinarian and contribute and collaborate with MDs and bring that one health approach. Yeah, move the needle on both sides, mark. Every time we do a study, like Sarah asked you earlier about what some of the most important findings are, but we're always surprised by something. If you're really thinking about the data, what surprised you from this article?
Mark Peterson:I think the biggest thing that I mean. This happens every time I write an article like this where we're dealing with hyperthyroidism and kidney disease and that's how some of the cats that became azotemic I would never have thought they were. You know there's, sometimes there's. You know, if you have a cat hyperthyroid cat that's untreated and has a creatinine in the upper third of the reference interval or has a dilute specific gravity or has polyuria or polygipsia PUPD, you know you can suspect hypothyroidism. Some of these cats were not that old, they had none of this and they still went on to become azotemic.
Mark Peterson:So there's just not a perfect way to make the diagnosis until we treat them. It surprised me in this article, like it surprised me in the past. They're just not a good way. But that said, looking at serum creatinine, looking at BUN, looking at specific gravity just the things that all practitioners can do and should do that can be very, very helpful. And if you have a cat with a low specific gravity and the creatinine is approaching that two limit, you know you have to be very, very careful and those are the cats that we want to really monitor very carefully after treatment.
Sarah Wright:I think this episode is a good reminder to clinicians. Just to keep an open mind. Don't take things off your list too early. Always consider the whole clinical picture.
Mark Peterson:I agree.
Sarah Wright:So what are the next steps for research in this topic?
Mark Peterson:Well, we're doing some studies now, or really are done, that I'm writing up, where we're looking at not just euthyroid cats but we're looking at survival of cats with hypothyroidism, because hypothyroidism is relatively common after we treat with radioidine.
Mark Peterson:And that muddles the picture because some of that azotemia that can develop in hypothyroid cats can be pre-renal, because hypothyroid cats have an increased GFR, an increased renal blood flow. So once we treat those hypothyroid cats they fall, hopefully to normal. But hypothyroid cats it continues to fall so they can have a decreased renal blood flow and a decreased gfr. So that even makes the azotemia look worse than it really is because of the pre-renal component. So I don't, we're looking we. What we want to publish next is our findings, a long-term follow-up of those cats, how those cats can also become azotemic and how treatment with thyroid hormone replacement can help both their survival. And I think in large part because we're helping with the azotemia, because as we treat with, as we supplement those hypothyroid cats with LT4, thyroid hormone supplementation, the azotemia gets better and it seems like the progression of the CKD slows. But those you know, that's another paper.
Sarah Wright:Well, we look forward to hopefully receiving more manuscripts from you.
Mark Peterson:That's only, that's only the only job. That's the only place I want to go.
Sarah Wright:We're happy to hear that. So this is. The next question is something we've been asking a lot of our interviewees lately. Just with the rise of different emerging technologies and such, do you see a role for AI in this area of research?
Mark Peterson:definitely, definitely, because there may be something that I'm missing as a clinician that AI will help. You know some absurd little thing in the serum chemistry profile that I'm missing that could help us do it. So I think we should look at it, and I say that being someone who is kind of well, I was really very against AI, and now I've been using it more and you know, I'm I'm still, I'm always, I'm always frightened about the false facts that can spit back if you don't know what you're asking. Uh, but I've also found it to be very, very helpful for me in my work, so I'm excited to get more and more involved with AI.
Sarah Wright:Very cool and, for those of you just joining us, we're discussing how hyperthyroid cats that develop azotemia following successful radioiodine treatment have shorter survival times compared to cats that remain non-azotemic with our guest Mark.
Lisa Fortier:Mark, what I've really enjoyed hearing you say is how curious you've been able to maintain, since you got your veterinary degree and worked with the MDs, just like thinking, huh, that doesn't make sense. How come that is? And what about that? How did all that combined training help you keep that curiosity and then get across the finish line with all the many, many manuscripts you've written?
Mark Peterson:I mean, I've always asked. You know, when I was an intern, one of my staff members and I won't mention his name because he may be embarrassed by this but he told me once that I asked too many questions. And he told me once I better do a residency and go on, because maybe I should go to a vet school and be an academic, because all I did was ask questions. And I've always asked questions, I've always been curious.
Lisa Fortier:Did anybody call you Horshack? Do you remember Horshack?
Mark Peterson:No, but they probably should have. So for me, the clinical, I mean I love, really, I love taking care of hyperthyroid cats. I really I love cats, right. So that's fun for me. But it's the clinical research and learning and trying to get to the next stage to help them. I mean, when we discovered this disease in the late 70s, we knew nothing. We knew nothing. We thought it was a rare disease that was going to go away pretty soon and it's becoming a worldwide epidemic, you know. So there's so much more to learn. I thought my goal in my career was to try to figure out the cause and and make the disease go away, and that hasn't happened. In that regard, I failed, but I also have a lot of other people helping me now, so hopefully we will figure this out. But it's, it's been fun, it's been. I've been doing this for 45 years, doing the clinical research on these cats, and it's don't know why I find it fun, but I do, I really do. I love what I do.
Lisa Fortier:What's your gut instinct as to the cause? I've been thinking about that this whole time.
Mark Peterson:I don't think it's one thing First of all, it's older age. When we first, when, when the median, when we, when we first I wrote our first paper, uh, the in these cats and the average age has always been about 12 years, about age the 12 years at that time was was an old cat. We used to say look at this cat, he's 12 years and he's hyperthyroid. And people would come in and say that's really an old cat. Are you sure you want to treat that old cat? Well now, 12 years is not old, that's middle age.
Mark Peterson:So we did a study and between 1983 and 1993 at the Animal Medical Center, the reviewer made us do this work. We did our whole hospital population. You know, in the Animal Medical Center at that time we saw about 100,000 pets a year. So we had a lot of cats to look at. The average age of our hospital population in that 10-year period went up by four years. That's how much we've advanced veterinary medicine. And that was in the 80s. That's continued to happen.
Mark Peterson:So what's causing it? Part of it is, I think cats could have always had this first of all, but they just never live long enough, just like you and I never used to get heart attacks because we would die or be eaten by a lion in our family. Right now, we live longer, so we can die of some of these other diseases. That's one thing, but I don't think that's all um. There's stuff in the, in the, you know, in in the 70s that's when cat food was still starting to come out um, all these synthetic compounds, the plasticizers, the bpa, all these chemicals that are now so ambiguous. They were that they were, just they weren't there before.
Mark Peterson:And we've shown that some of these um flame retardants that tend to accumulate in dust. We've done some studies, one of which we put a collar around the cat's neck and we did control cats and hyperthyroid cats, and the hyperthyroid cats had significantly higher flame retardants exposure than the other cats. So I think it's a combination between their age, their genetics. Obviously there's something in genetics because some breeds are less likely to get hyperthyroid than others, notably like the Siamese and other Oriental breeds. So age, genetics, environment with the chemicals in the environment and probably die. You know, we've heard a lot about these highly processed compounds in food that are bad for us. What about cat food? The same thing is probably true there.
Mark Peterson:People really haven't looked at it.
Lisa Fortier:Well, thank you for sharing your insight.
Sarah Wright:So, Mark, this next set of questions is going to be very important for our listeners, and the first one is dealing with the veterinarian's perspective. What is one piece of information the veterinarian should know about hyperthyroid cats that develop azotemia following successful radioiodine treatment?
Mark Peterson:Well, you know, as I said before, if you have a hyperthyroid cat that's already azotemic, that cat has a. Fairly the prognosis is not very good. If we treat them they generally live less than two years. So the prognosis isn't great. But as long as they're not azotemic prior to treatment, as long as that creatinine especially if the creatinine is less than 1.5 or less than 1.8, kind of in the mid to low range and then they do become azotemic, this unmasking of the azotemic chronic kidney disease isn't necessarily a death sentence. Some of those cats live a long time. The median survival was 2.8 years, so almost three years in these cats. So they can still live a long time. So why is it important to know this? It's important to know it because we want to pick it up as soon as we can so we can start to manage it. So if they have chronic kidney disease we may want to start them and die. There's other drugs to maybe help kidney function improve, so at least stabilize it. But again, the important thing is that we can't predict very well, at least right now, and that's what AI may help. But AI or not, I still think there's going to be cases that we're going to be surprised that this cat became azotamic, but he did so. Now we have to deal with it. So close monitoring, early identification, is really important for that veterinarian to know.
Mark Peterson:You can't treat with radiowire, dine and forget the cat saying well, he's got to be cured.
Mark Peterson:Now we have to look. We want to monitor for three reasons. We want to monitor for three reasons. We want to monitor after radiowire, as I tell my owners and veterinarians we want to make sure the T4 falls to normal, the thyroid levels fall to normal. We want to make sure that the creatinine and BUN stay normal and don't start to go up, because if they start to go up we have to address that. And then, as I alluded to earlier, we also want to make sure they're not becoming hypothyroid. So, to do that we always, for the first year after we treat, we always do a serum T4 and a serum thyroid stimulating hormone concentration. Because a high TSH or thyroid stimulating hormone concentration is the best and easiest way we can identify hypothyroidism. And if those cats become hypothyroid then we want to start treatment and that's going to help the hypothyroidism. It's always also going to help progression of their azotemia, if they have it.
Sarah Wright:Very well said. So you kind of answered this already a little bit. But what's one thing clients should know about this? If you could boil it down to like one important take-home that clients should consider.
Mark Peterson:Well, first of all, remember they have to be in charge it's kind of like of your own health or your mother's health and so forth. So this is if their cat has been treated with radioiodine, they need to know that their veterinarian may be a very good veterinarian, but this could all slip through the tracks. So they have to remember that it's their responsibility to go in, make the appointments for modulatory, make sure the right tests are done, make sure that thyroid function's looked at, including the TSH, as we just talked about, make sure that renal function is addressed and looked at. And you know, in my practice, all the cats that we treat, we encourage the veterinarians to send me the results and I will gladly interpret them and help them and advise them as we go along. They're not my—I consider them—they're patient, but I still would like to be involved and probably know a little bit more about this than many of them do. So I like to still be involved and help however I can.
Lisa Fortier:That's very generous of you. I've super enjoyed talking to you and remembering some of these things and just learning how you've moved the needle so much throughout your career, and thank you again for sharing your information with JAVMA.
Mark Peterson:Thank you for having me.
Lisa Fortier:As we wind down, we like to ask a little more of a personal question, and I'm going to guess yours is going to be about a bird, given your background. What's your favorite animal fact?
Mark Peterson:Well, it's about cats, of course.
Lisa Fortier:Oh, of course, silly Lisa.
Mark Peterson:So one thing that I like to tell people is the way. It's not widely known that cats and the way they communicate with us, their owners, is different than the way they communicate with other cats. When cats communicate with other cats, they do it through their body language, their scent, they may have vocal cues, but they don't normally meow at other cats, where my cats have always meowed and screamed and demanded stuff. And this is something the cats have learned in their interaction with humans. So, the way they address us and speak to us is learn from us. It's not normally how they would work with other cats. They don't need to, they can. They have their own, their own ways to do it through their scent and body language and so forth. So I again, like I, I just really I love working with the cats. That's been, that's been that I, I just that's been made my career and finding this disease early on and spending my life doing this has been very much fun. I've really enjoyed my career.
Lisa Fortier:That's awesome. Well, we compliment each other well, because I'm deathly afraid of mean cats and it's one of the reasons I went into equine. So they're all yours, buddy.
Mark Peterson:Okay, well, you know something I've had a few mean horses, and I'm glad that someone's there to take care of the horses too.
Sarah Wright:Look at that, it goes both ways. Yes, well, thank you so much, Mark. Really appreciate you being here today and just sharing your enthusiasm for this research with us.
Mark Peterson:You're welcome. Thank you very much again for having me.
Sarah Wright:And to our listeners. You can read Mark's article in JAVMA. I'm Sarah Wright with Lisa Fortier. Be on the lookout for next week's episode and don't forget to leave us a rating and review on Apple Podcasts or whatever platform you listen to.
