April 14, 2021 – Dr. Kelly Diehl talks about hyperthyroidism in cats with Dr. Ellen Behrend, the Joezy Griffin Endowed Professor and Alumni Professor at Auburn University. The two discuss what is known about the disease, methods to diagnose it and treatment options.
0:00:10.8 Dr. Kelly Diehl: Welcome to Fresh Scoop, Episode 31, hyperthyroidism in cats. And I'm your host, Dr. Kelly Diehl, Morris Animal Foundation's Senior Director of Science and Communication. And today we'll be talking with Dr. Ellen Behrend. Dr. Behrend is the Joezy Griffin Endowed Professor in the Department of Clinical Sciences at Auburn University, and she's an Auburn University alumni professor. Fresh Scoop is the monthly podcast of Morris Animal Foundation, one of the largest non-profit foundations in the world dedicated to funding studies to find solutions to serious health threats to animals. And in each episode, we'll feature a researcher or a staff member discussing their work in advancing animal health, and whether you are a practicing veterinarian, technician or student, or just an animal loving science geek, Fresh Scoop is the podcast for you.
0:01:08.8 DD: You can learn more about us at morrisanimalfoundation.org. So okay, on to today's show, and as I mentioned earlier, today we welcome Dr. Ellen Behrend. Dr. Behrend received her veterinary degree from the University of Pennsylvania. She has a Master's degree from Colorado State University where she also did her residency in small animal medicine, which is where we met, because we're resident mates. Ellen also has a PhD from Auburn University, both of her degrees are in biomedical sciences, but the focus of her PhD was Endocrinology, which is why she's here today. She is also a diplomate of the American College of Veterinary Internal Medicine. Dr. Behrend's areas of interest are small animal endocrinology with an emphasis on diagnostic testing and canine adrenal diseases. So Ellen, thanks for joining us today.
0:02:03.6 Dr. Ellen Behrend: Absolutely. Thanks for having me.
0:02:06.3 DD: Sure. And I always ask everybody this, before we get into your work, can you tell us a little bit about yourself personally, and what led you to become, first, a veterinarian and then to specialize in endocrinology?
0:02:18.7 DB: So first, I'm a cat person, even though my main focus for research is canine adrenal diseases, I'm a total cat person. Dogs are just easier... [laughter] I decided I was going to be a veterinarian when I was four, like a lot of people do. And I made a deal with a little boy who lived behind us, who was my age, that I would protect him from the neighborhood dogs, if he would protect me from the neighborhood bullies. And I don't really remember having any neighborhood bullies, but at that point, I came home and I told my mother I was going to be a vet, and that pretty much never changed. I was put on this planet, no doubt to be a small animal internist, that's what I really like. And I was in practice for two years, never learned to like surgery, hate it with passion. And endocrinology is just where my... I don't know, I just always found that the most interesting feedback loops really interest me and how the body knows all of the different hormone levels and regulates them, I just find fascinating. My brain kind of works in that same way, so I think it's a good fit.
0:03:42.6 DD: That sounds great. I think all of us, I'm glad to hear you had a neighborhood connection, that's how I got my cat, my first cat, which started me down the path of veterinary medicine, so hurray for neighborhoods who get us started on our careers. To start off with, since we're going to talk about hyperthyroidism, can you... I know this is a big ask, but can you talk a little bit about what exactly it means when we talk about feline hyperthyroidism?
0:04:12.8 DB: Well, one thing I want to emphasize is that it's a clinical problem, and I think that's true for a lot of endocrine diseases. Dogs and cats can test positive for different endocrine diseases, but really, the disease is defined not by a test result, it's defined by a clinical picture, and a high T4 by itself doesn't define hyperthyroidism. Hyperthyroidism is caused by excessive production and secretion of thyroid hormone from an abnormally functioning thyroid gland. And then the disease also is characterized by the clinical signs, which I think we're going to get back to later. But it starts in the thyroid gland with most typically a benign tumor, and then the excess thyroid hormone production causes a clinical picture of hyperthyroidism.
0:05:19.0 DD: Okay, that's a good thing. And we'll talk about that a little bit, because I think that is something, at least in practice, those of us in practice, and I get this question from clients a lot, they see a blood work result with a value that's elevated, so we'll hit that a little bit more, but before we do the clinical signs, I'm going to ask you to take a step back and say, do you know how common... I mean, does anybody know how common this disease is in cats? I think we hear it is the most common, or one of the most common endocrine diseases, but do you know? Does anybody know?
0:05:52.4 DB: Yeah. I think that's a really good question, and there's more and more papers coming out about it, and it does vary depending on where you live. It's more common in urban areas than it is in rural areas. I think we see it more commonly in certain countries as compared to others, like Mark Peterson, the guru of feline hyperthyroidism, estimates that 10% of older cats in the United States are hyperthyroid, which is a lot of cats. There was one paper that just came out recently saying that in Dublin, Ireland, it's 21%, which is really, really high, but usually the estimates are anyway in the different papers, in the different locations, are anywhere from 5% to 20% or so of older cats.
0:06:48.7 DD: Okay. And are these clinically hyperthyroid, Ellen, or just cats that have elevated...
0:06:55.0 DB: These are clinically hyperthyroid cats, I believe.
0:07:00.0 DD: So the number of cats that could have a little tweak in their T4 could even be higher, maybe?
0:07:04.6 DB: For sure.
0:07:07.2 DD: Okay, because I, having had a cat...
0:07:07.7 DB: A number of cats that have thyroid nodules, probably in some studies is way higher, and those cats are probably on their way to becoming hyperthyroid.
0:07:19.3 DD: Okay. We may come back to that, but let's move to the clinical signs. I think we have a variety of people who listen, a lot of vets and vet students, but for the people who may not know or they don't have a cat, what are the clinical signs that we associate with this most commonly?
0:07:36.4 DB: Yeah. And that's changed over time. I think it's really, really interesting that the first hyperthyroid cat ever was reported 40 years ago, and we've gone from, "Wow, this cat's hyperthyroid and it deserves the case report to... " 10% or so of older cats are hyperthyroid, it's increased hugely over time, and the classic picture of the hyperthyroid cat... When you and I were going to vet school, was pretty dramatic. These days, it's really pretty subtle because we know how common it is now, and it's really high on our radar screen. So the number one clinical sign is weight loss, and that can be in the face of a normal to increased appetite, usually it's a normal appetite at least to start with, so the cats just losing weight for no apparent reason.
0:08:27.6 DB: And that's in like 90% of hyperthyroid cats. The increased appetite is a lot less common, probably down around 50% to 60%, so at first cats are just losing weight with nothing else going on. The other thing that owners often will notice over time is some kind of gastrointestinal sign, whether that's vomiting and/or diarrhea. And then less common things are hyperactivity, which when a 16-year-old cat or whatever it is, starts becoming more active, that is weird, and that can be noticed by the owners. And then less commonly, we can also see things like PU/PD or some people just say the cat's not necessarily having diarrhea, but they're like pooping all the time, and that's probably because they're eating more.
0:09:25.3 DD: Okay. Can we take a slight dive because my big heavy cat came in here. We used to talk about apathetic hyperthyroids [chuckle] or hyperthyroid cats, remember a long time ago? And now I'm going to date myself. So do you see sometimes hyperthyroid cats that fall into that category, or is that just like... Where do we get that?
0:09:50.8 DB: Yeah. So apathetic hyperthyroidism means that they have all the same clinical signs, except their appetite is decreased, which is, as I said... Increased appetite is the classic for hyperthyroidism. And apathetic hyperthyroidism was never really well explained why some cats would have a decreased appetite and, like really old papers say it's 25% of hyperthyroid cats, then it was 10% of hyperthyroid cats, right now, I think it's a little bit controversial as to whether or not it really exists. Some people say that it truly is a form of hyperthyroidism by itself. What other people say and what I believe is that it's always a combination of diseases, that if a truly hyperthyroid cat has a decreased appetite, it's got some other disease besides the hyperthyroidism that is decreasing the appetite.
0:10:49.7 DD: Okay. And remind me to ask, I think I have that later, but let's get into diagnosis because I think you and I came up in the era of accelerating tests, and I even... Talking about Dr. Peterson, when I did my internship at AMC, we were starting to do there T3 suppression tests and all this stuff, so tell us what we have available now as tools to diagnose hyperthyroidism and your best pathway to making that diagnosis?
0:11:26.3 DB: Well, as the saying goes, ask another endocrinologist, you're going to get another answer. [laughter] And you asked me, so I'm going to tell you what I do. So actually, I think hyperthyroidism is one of the easier endocrine diseases to diagnose, certainly way easier than Cushing's disease in dogs, or hypothyroidism in dogs. And honestly, a T4 by itself is going to give you the diagnosis the majority of the time. Again, as long as you have clinical signs. If you don't have clinical signs, then an elevated T4 deserves some attention, but an elevated T4 by itself is not a reason to treat. So T4 now is included in a lot of geriatric profiles of blood that’s sent to Antech or Idexx or places like that.
0:12:21.2 DB: And sometimes T4 comes back elevated and the owners haven't really noticed anything. It may be that it's elevated and that's just normal for that cat, because some cats just normally have a T4 that's above the reference range, or it may be early hyperthyroidism and they haven't noticed any clinical signs. So that's a cat that I'm going to start having the owner weigh like every two to four weeks and monitoring for weight loss and things like that. But if you have all the clinical signs and T4 is certainly significantly elevated, and significantly, that's in the eye of the beholder, so if the high-end of the reference range is four, and it's 4.1, you might want to do a little bit more testing, but if all of the clinical signs are there and it's 4.5 or above, that cat's hyperthyroid. The problem is, is that in the early phases or in cats that have one disease like renal failure or diabetes and they also have hyperthyroidism, T4 could still be in the upper half of the reference range at times.
0:13:33.4 DB: So the way that I look at T4 is if it's elevated and you have clinical signs, it's pretty much diagnostic. If it's in the lower half of the reference range or below, you ruled out hyperthyroidism. But that upper half of the reference range is a gray zone, and then you need to go on and do another test. What the next test to do is where I think the controversy comes in. Mark Peterson likes to do the TSH, this is like... I think it takes a lot of guts to disagree with Mark Peterson when it comes to anything having to do with hyperthyroidism, but this is probably the one place that I do disagree with Mark, and I like to do the free T4 by equilibrium dialysis instead. I think that's more helpful in this situation. I think the TSH does help, but I think the free T4, in my opinion, is a little bit better to help ferret out those more difficult cases.
0:14:39.6 DB: Thyroid scanning, radionuclide scanning, a technetium scan is considered to be the gold standard test for diagnosing hyperthyroidism, and in some cases, that becomes necessary to help confirm the diagnosis in really difficult to figure out cases, but I think those are really pretty uncommon. There's other reasons to do scans where we sometimes do them, but to need a scan to make the diagnosis, I think is pretty uncommon, although that is a possibility. I can't remember the last time I did a T3-suppression test. Never say never, but I know... Once we realized that the free T4 by dialysis is such a good test, which was what, 15-20 years ago, I haven't done a T3 suppression test since.
0:15:32.2 DD: Yeah, I think you're right, I think when that came about... Yeah, late '90s, 2000. I don't think I ever did one in practice because they're not that easy, I probably did one...
0:15:41.4 DB: Yeah, they're not that easy.
0:15:42.5 DD: I think I probably...
0:15:44.6 DB: I mean, I did a few at some point, it could still be done if you have a really difficult case to figure out, and a thyroid scan is not available, a T3 suppression test is still a fair option. But as you said, it's not that easy. You have to get seven pills into a cat over three days, which... Right. We all know how that is.
0:16:08.5 DD: Right. I just wondered if it was still even a thing or... I'm just dating myself, but... So I'm going to put you on the spot with a question that will always plague me, and it plagued me even with my own cat, is the elderly cat that is losing some weight but has GI signs, as a gastroenterologist, I'm looking at it. I've got a very high normal or maybe a little bit above the reference range, asking for a friend, but actually it was my cat had a mildly elevated free T4. So I'm going to pick your brain a little bit on the comorbidities and sifting it out, and I think the hardest for me personally was sifting out hyperthyroidism, GI disease, maybe both, maybe one or the other. Do you have any pearls of wisdom on that, because it bamboozled me in practice.
0:17:02.5 DB: That's where I really like the combination of the T4 and the free T4. An elevated free T4 by itself, I don't like to do free T4 by itself for diagnosing hyperthyroidism, about 20% of sick cats, or cats that have some kind of other disease, IBD, whatever, have an elevated free T4. So if you're using the free T4 by itself, you have a one in five chance of misdiagnosing a cat as hyperthyroid. So that's why I like to use the combination, and if the T4 is in the upper half of the reference range or above, in combination with the free T4 that's above normal, I think that's a hyperthyroid cat, especially if you can feel a thyroid nodule and how often you can feel a thyroid nodule, I think it really depends obviously on the person. I've seen estimates that you should be able to feel a thyroid nodule in 95% of hyperthyroid cats. To be quite honest, I'm not that good. I don't feel, even in cats that I know are hyperthyroid based on thyroid scans or whatever the case may be, I don't always feel the nodule, they can be absolutely tiny. But if you have a complete clinical picture and the T4 and the free T4 are both saying this is consistent with hyperthyroidism, I would go with it as a diagnosis.
0:18:35.0 DD: Yeah, that's a tough one, I think. My cat had a normal total T4. So the situation you mentioned, and which we are now joined by my one cat, and if I put her up, she's definitely not hyperthyroid. But anyway, thanks for taking that dive because I think that presents a diagnostic dilemma and it actually bears into my next question, which is treatment for cats with hyperthyroidism, and why don't we talk about just the hyperthyroid cat with no comorbidities on this, because it gets complicated if they have comorbidities.
0:19:14.1 DB: Yeah, it does get complicated. So there's four options: Radioactive iodine, medical therapy with methimazole or Tapazole, surgery, and the y/d diet from Hill's. Surgery, I think... I was, again, dating ourselves, in vet school, radioactive iodine was not very available at all, and surgery was the only option for curing a cat. And we did thyroid... Well, not we, we, not me, did thyroidectomies all the time, and they've now really gotten a bad rap, and I don't think surgery deserves such a bad rap. I think it is a very fair option for people who I-131 is not available and want to cure their cat because they don't want to treat their cat every day. In general, I think that I-131 is the treatment of choice. But that is going to depend on the availability, the cat, the cost over time for a cat that's on methimazole for a while, and especially with the monitoring that goes on at the beginning, especially for the side effects, probably the owner is going to spend just as much money, if not more, with medical therapy as compared to I-131, but I-131 can be a big chunk of money up front, which not all owners can afford and I totally get that. And it's not always the best for every cat.
0:20:55.4 DB: I mean, one of my own personal cats who's no longer with us, he had renal issues and he had IBD and he was 16 and he became hyperthyroid, and he was easy to pill, so I gave him methimazole. So it does depend on the situation, but in general, my order of preference for treating would be I-131, if you really want to cure the cat and I-131 is not an option, then surgery is a consideration, then medical therapy, and diet's my last choice.
0:21:30.5 DD: Okay, and I'm going to flip-flop one of the questions I was going to ask, but how do you tell people to time it, what's your process as far as doing medical therapy or just going right to... First of all, do you guys do a lot of thyroidectomies at Auburn? I mean, are you doing them?
0:21:58.1 DB: No. No. because we have I-131, and given the choice, they're pretty comparable in price. I-131 may be cheaper, actually, I'm not sure about that, but they're pretty comparable. And given a choice between I-131 and surgery, I would always do I-131, because there's no anesthesia and if the cat has any ectopic tissue that is contributing to the hyperthyroidism, you're not going to get that with surgery, I-131 is going to kill off any hyper-functional tissue anywhere. So that's always going to be my first go-to, but the times that we do do surgery are if we're concerned that it's a thyroid carcinoma.
0:22:46.7 DD: Okay, alright, that makes sense. And then do you have... Do you do a lot of pre-treatment of cats first? Sometimes we would do that, kind of watch their kidneys, right, that was a thing. Well, we'll try methimazole first, right, see if it blows their kidneys out of the water, and I think that's fallen apart, right?
0:23:08.8 DB: That's... Yeah, the only... So, yeah, that's totally fallen out of favor now. So for a while... So it was probably mid-90s maybe, when we recognized that treating hyperthyroidism unmasks azotemia in about 25% of cats, maybe, something along those lines. One-fifth to one-third, depending on the study. Somewhere in there. So that a fair number of cats when you treat their hyperthyroidism, azotemia is unmasked. So the thought process was that before you unmasked severe renal failure, that you should do a methimazole trial and make sure the cat can handle being cured, basically. Well, we now know that if a cat is not azotemic when you make the diagnosis of hyperthyroidism, again, they may be azotemic once you treat it, but it's going to be a mild azotemia. And a cat is much better off living with mild azotemia, and a cat, you know, can live with mild azotemia for years, they're better off living with mild azotemia than they are living with hyperthyroidism. So treat the hyperthyroidism and then deal with the azotemia with diet, all that regular kind of stuff.
0:24:44.2 DB: The only time I would consider doing a methimazole trial now is if the cat is azotemic already when I diagnose hyperthyroidism. Because then when you treat the hyperthyroidism, the creatinine could shoot up to five, six, seven, it can become really sick with their azotemia, and in those situations, surgery or I-131 is not a good option. If they're already azotemic and treating their hyperthyroidism, fixing their hyperthyroidism is going to make them have severe renal failure then in those cases, I recommend medical therapy, doing a balancing act between controlling the thyroid hormone as much as possible and keeping their kidneys happy. The other time that I would do methimazole before any other therapy is with surgery, and I'd probably treat them for about two weeks to make them better surgical candidates, but you don't need to treat them before you do I-131, as long as they're not azotemic when you make the diagnosis.
0:25:56.4 DD: Okay, so circling back to another question, which is the causes, which I think we've come... Like all the stuff has been talked about causing hyperthyroidism. As you mentioned, it was a disease, was it always there? We just didn't know about it. Or is it... Right, so what are the thoughts on causes?
0:26:23.6 DB: There's lots of thoughts, I guess, is the bottom line. And part of that is because it's not one thing, it's multifactorial, for sure. So trying to find one thing is impossible, so there are some genetic causes, there are some papers out there that suggest there may be some TSH receptor mutations, and that's very common in people with the human counterpart of feline hyperthyroidism. There are some thoughts that it relates to diet in some ways, potentially iodine deficiencies, and then there's also thoughts about environmental factors, and the most interesting research that's come out lately from cats in this country and cats in Sweden, are exposure to PBDEs, which is... I can never remember... Polybrominated diphenyl ethers, and those are flame retardants, so they're present in children's pajamas, I think, but certainly in furniture and carpet and things like that, as flame retardants and cats are exposed to those. And there's some very interesting data that they may contribute to the development of hyperthyroidism as well.
0:27:43.6 DD: Okay, cool. Yeah, that's I think really, really interesting. It'll be interesting to see what happens. It'll be interesting to see what happens with all the fires we have, and cats exposed to that kind of stuff. So, as we wind down a bit, what is a major misperception? We just talked about the evolution of treatment and diagnostics for hyperthyroidism, so I think there's stuff that's been disproven or just shown that it's not effective, but what are you encountering now that you have to counsel veterinarians and owners about?
0:28:22.5 DB: I think there's still some misperception about how treatable it is, I think people hear the fact that it's going to unmask renal failure in 25%, 30% in cats, and that scares them from treating, and as I said before, cats are much better off mildly azotemic than having untreated hyperthyroidism. I think in the last five to 10 years, maybe, we're now really starting to understand the significance of causing hypothyroidism, we used to think it was pretty uncommon with I-131 like a much older paper says 2% of cats become clinically hypothyroid after I-131 we're now realizing that the incidents of hypothyroidism with I-131 is much higher than we used to think. And even with treatment with like methimazole or surgery, hypothyroidism is a big deal, and it's bad for the kidneys and it limits life if a cat is hypothyroid and azotemic together that's a bad combination. So people need to really be aware about monitoring hypothyroidism and doing something, either lowering the dose of Methimazole of the cats on that or putting your cat on thyroid replacement if it became hypothyroid after surgery or I-131.
0:29:54.0 DD: Okay, that's good to know. Yeah, I think it's important for people to realize like you're not done. Right? Like get your iodine.
0:30:02.4 DB: They tend to revert.
0:30:04.0 DD: And then you... I think it's easy when people have methimazole, they kind of go, "Oh, I got to go check this," but I think a lot of people just sort of scamper off and don't watch, and so that's a good reminder that we need to be...
0:30:15.4 DB: Hyperthyroidism, I-131 is very, very effective. So I think just scampering off into the sunset is common, they're like, "Yeah, 98% chance my cat's going to be fixed, and if there aren't any clinical signs, then we're good." but that's not true anymore, we now know that hypothyroidism is absolutely something you need to pay attention to.
0:30:38.9 DD: Okay, so just to end with, Ellen, what do you think is the take-home message for our listeners, which are again, veterinarians and owners, and vet students and vet techs?
0:30:50.0 DB: I think just what we just said, it's very treatable, it's curable if the owners can afford surgery or I-131, and that it is something that is very common. You really need to be paying attention to it, but it's very fixable and very, very treatable, so it is something... The median survival of cats with I-131 and... Excuse me, with hyperthyroidism is about... Is at least two years, and some studies say even longer than that, and remember these are older cats. The median age of cats getting hyperthyroidism is 13 and they don't usually die of their hyperthyroidism if the hyperthyroidism is treated. So it's a very treatable, very controllable disease.
0:31:39.0 DD: Okay, yeah, that's good to know, because I think sometimes it seems daunting and it's nice to hear, like we do have a pretty good grip on methodology on how to treat these guys I think, yeah, the comorbidities are scary, but can you... I know this is not exactly the question I want to end on but what's the effect of treating hyperthyroidism, you and I know this on comorbidities? You should probably treat it. Right?
0:32:08.2 DB: You should probably treat it. I don't think there's much effect other than the kidneys, I don't think there's much effect of treating hyperthyroidism on the comorbidities, it's not going to make IBD worse, it's not going to make arthritis worse, it's not going to make other things worse, and it potentially could help. If a cat has heart disease, being hyperthyroid would be a bad thing. So other than the kidneys, it's not going to make anything worse, and again, if they're not azotemic when you make the diagnosis of hyperthyroidism, the renal failure, to me, is just not that big a deal. They're mildly azotemic and they can live that way for years.
0:32:52.1 DD: Right. So Ellen, thanks so much for joining me today. This is so much fun. It's great seeing you, and we'll look forward to... I know you're retiring.
0:33:02.8 DB: From Auburn University, not veterinary medicine, but I'm retiring from the university.
0:33:08.7 DD: Right, so we look forward to what your next big adventure is, and thanks again for coming and talking to us about this topic, so that does it for this episode of Fresh Scoop. Once again thanks to Dr. Ellen Behrend for joining us, and we'll be back with another episode next month that we hope you'll find just as informative. As we know the science of animal health is ever-changing and veterinarians need cutting-edge research information to give their patients the best possible care. And that's why we're here, and if you liked today's episode, we'd sure appreciate it if you could take a moment to rate us since that will help others find our podcast. And of course, to learn more about Morris Animal Foundation's work, again, go to morrisanimalfoundation.org, and there you'll see just how we bridge science and resources to advance the health of animals and you can also follow us on Facebook, Twitter, and Instagram. I'm Dr. Kelly Diehl and we'll talk soon.
