Dr. Marnin Forman joined us and spoke about the latest approaches to adrenal disorders.
Dr. Forman, DVM, DACVIM (SAIM), is a world renown veterinary doctor, highly involved with academia, diagnostic tool development, and lecturing around the US.
Pet guardians and referring veterinarians alike count on Dr. Forman’s deep clinical expertise and incredible approachability. One of the most sought-after specialists in the area, and the head of the Internal Medicine Department at CUVS (Cornell University Veterinarian Specialists), Dr. Forman will always take time to intensively review every case, to patiently explain a complex diagnosis to a concerned owner, and to work closely with their primary care veterinarian.
Watch the webinar below (or read the transcript).
Webinar recorded on October 04, 2021
cushing, dog, disease, pet, test, addison, question, jeff, drug, steroids, treated, lucy, bit, peeing, blood sugar, problem, urinary tract infection, diabetes, low blood sugar, insulin
Dr. Jeff Feinman, Dr. Marnin Forman
Dr. Jeff Feinman 00:02
Welcome back everybody to the weekly Holistic Actions! webinars where we help you put all of the symptoms of your pets into context and interpret them holistically. I’m Dr. Jeff Feinman and Dr. Sara Fox Chapman is here. Today we have an esteemed presenter that I will introduce in a minute.
It’s just a super-duper honor for me to welcome a world-renowned internist and head of Internal Medicine at Cornell University Veterinary Specialists here in Stamford CT, Dr. Marnin Forman. Thank you, Dr. Forman for being here with us. Dr Forman graduated from Texas A&M vet school, did his internship at Animal Medical Center in New York, and got wooed over to UC Davis, the vet school to do a residency, and then a fellowship in internal medicine. So he is incredibly well versed in all of the best of one world. And we’re here to take the conventional piece (that Dr. Forman was trained in) and help put it into a holistic context. Because that’s what we always really want you guys to do is take all of the best information from the conventional world and then decide what to do, based on all the other information. So, Dr. Forman, thank you again for being here. Take it away.
Dr. Marnin Forman 01:58
Well, hello, everyone, I am so thrilled to be here. I was eager when Dr. Jeff approached me to talk to your group to do it. I always enjoy these sessions. I think Dr. Jeff kind of gave me a—I think I’m blushing with the intro. I think it’s a bit much, but thank you. I’m going to start by sharing my screen and hope this all goes okay. Dr. Jeff, the host disabled participant sharing screen, do I need to be given permission?
Dr. Jeff Feinman 02:35
You should be all set.
Dr. Marnin Forman 02:51
So, this talk, what I was telling Jeff before, it’s tricky for me, because I’ve given talks before to different groups of non-veterinary groups. And some of the talks have been on old dogs or cats, or there was this one men’s group that I remember giving a talk to. But this one was tricky, because it’s on a disease process. And to some degree, when we start getting into disease processes, the way that I was trained, a lot of it gets into discussions of hormones and jargon, and things of that sort.
I’m going to give this a try, and I’m very eager to hear you guys’ feedback at the end of the talk, or you can boo during it, if it’s really going bad. But to give me your feedback on how it goes. And the way that this is going to work is that there’s definitely a lot of these slides that are of a higher level, but it’s more just to give a taste of what is going on and then hopefully I’ll be able to explain it. And then if I run a stray and I’m doing a bad job explaining it, or you have more questions, that’s what the chat feature is for, and Jeff and others and Sarah, maybe too, are going to help me out from that point of view. So here’s my kind of cutesy: “Can I have a little sugar and a glass of water?” We’re going to talk about Cushing’s, Addison’s, and more.
Brief: Endocrine Overview
So, when we talk about endocrine disorders, it’s actually remarkable how complicated the body is and how many different, if you split them up into endocrine organs, there are. Some of them we think about all the time. Some of them we may not think of. The thyroid gland is one of those ones where people think about because of the frequency of thyroid problems in people, thyroid problems in cats and dogs. Then you have others like the adrenal gland, the pancreatic beta cells, so one part of the pancreas. The parathyroid gland, these little minutia glands that are right next to the thyroid, that are super important in controlling calcium and phosphorus, the pituitary gland inside the brain, and then the ovaries and testes, which in a lot of our patients, they are neutered, or spayed and they don’t have those, and that androgen gland is removed.
And these glands produce tons of hormones. We’re not going to get into the hormones, and this list isn’t even complete. It produces tons of hormones, but you can test for these hormones. And a lot of times we are testing for these hormones. And we’re testing for them, when we see certain collection of clinical signs that fit a pattern. So for a lot of the diseases that you’re seeing in blue on the right—doctors are trained to recognize patterns, and some of these diseases have really unique patterns that we see over and over again. And when we see that pattern, we start thinking about a disease.
So how does that link to what we’re going to talk about today? Thisis how we’re going to do it. For each case, there’s going to be two different cases, I’m going to present the case to almost like you were standing in a veterinary clinic and watching us work, where you would see a doctor talking to a doctor or maybe a doctor talking to a client. And then they collect information, and then they go with it, and they start to try to figure out what’s going on with the pet.
So we talked about signalment. This is how we describe a pet a dog or cat, their age, what their neuter status might be, their breed. And then kind of what we call a capsule history. It’s like the quick little elevator ride discussion on what’s wrong with your pet. Not like the full drawn out every last detail, but kind of like, “This is what I really am worried about with my pet, can you figure it out?” Then some quick little tests that we’re going to do. We’re going to do a physical exam, and then some tests, and then we’re going to dive into what we think might be going on at that point.
So, here’s Jessie, I will tell you all the pets, that’s actually their picture, but it’s not their name. So I’ve changed all their names to kind of protect the privacy of the pet owner. But these owners did give me permission to use cases.
So, this is Jesse, an eight-year-old Lab, and this owner came in and literally, I went into the record, and I tried to pull out exactly what the owner said to us, and this owner said, “I think my dog may have had a seizure. She’s never had a problem like this before. So, we did what we call a “Quick PE”, it’s like a quick exam. We’re looking at them, and we’re trying to figure out, can we look at that pet just with our eyes and figure out, did she have a seizure? Is she having a seizure now? Why did she have a seizure?
So, when we looked at her, and I will say this didn’t come in to see me, it came in to see another doctor. They took her temperature, it was normal, they checked her heart rate. And this is an eight-year-old lab and the rate is heart 120 Beats Per Minute, BPM, that’s kind of quick for a lab, they usually have slower heart rates than that. And then there is the respiratory rate, how fast they’re breathing. And this lab was breathing quite quickly as 60 breaths per minute. But not strikingly, it wasn’t having a hard time breathing, just quicker than normal.
Then we looked at the gums to see if the gums looked abnormal, and they were pink, just like they should be and they were moist, hydrated. Then we did what we call a CRT, a Capillary Refill Time. And it was just like we would expect, one and a half seconds. So when we looked at the pet, there’s really nothing striking on the exam and it wasn’t seizuring when we were seeing it.
So, this doctor decided to place a catheter and then did what we call Statlytes. Statlytes is a blood test. I’m putting up the blood tests now and they’re just a mixture of numbers. But what I will tell you is that there’s one number that really stands out and that’s that GLU, which is glucose. And a dog’s glucose should be definitely above 60. Really choosy, but between 80 and 120. So, that’s a really low glucose. And when you have glucose that low, a pet can have a seizure.
So, this doctor when they took this case, they were like, “All right, I have a good sense of what’s going on with this pet.” This happened in 2011. So admittedly, this was a little bit ago, but it’s still valid even now.
So marked hypoglycemia, marked really low blood sugar. Now as a doctor, we’re thinking: wait a second, what should I do? Should I recheck that blood sugar? Because maybe it’s just wrong, maybe the test is wrong. Should I get more in history from the owner, because maybe the owner will tell us that this pet is a diabetic is on insulin, and maybe got too much insulin by accident, or got insulin when the pet didn’t eat well. We could treat it for low blood sugar by giving it something IV; we have that IV catheter in place. Or maybe you could just give it a meal. Right after we eat, the blood sugar goes up really quite quickly.
We can give it steroids, which is a common treatment that we would use for low blood sugar. Or we can give it a drug called Glucagon. Considering the number of people in this audience, there is probably at least a couple of people that are diabetics, just statistically. And if you’re a diabetic, you know that glucagon is a rescue drug to increase your blood sugar.
But why did this dog have this? Well, there are a couple of things. So one is that it could have eaten something that causes blood sugar to drop. So Xylitol is known to do this. Xylitol is a sugar substitute. It’s in orbit gum, it’s actually in lots of other things now too. Xylitol can cause a really marked drop in blood sugar. Insulin can do this. But usually, the owners are going to give us a hint, they’re going to say “my dog’s a diabetic.” Every once in a while, weird things happen. Then there’s rare things like if you give too much aspirin to your pet can do it, or ethylene glycol antifreeze. These are uncommon.
Cancers can really do this. And when a cancer causes low blood sugar, they call that paraneoplastic. But then endocrine problems can do this: Addison’s disease, hypothyroidism occasionally can do it, or we even what they call hypopituitarism, so a problem like a dwarf. And then there’s other things that can do this too, like severe infections, or pancreatitis, or when you work a dog so hard, their blood sugar’s go down. And this is something that we don’t see here. When I was in Texas, every once in a while, you would see this, they would have these dogs that they just love to work and work and work and their blood sugars would get so low, and then they would get sick.
History and physical examination
What we decided to do was go back and talk to the owner a little bit more. And what she told me was that there was an acute onset of really marked weakness, and then the pet had a seizure. But in hindsight, she’s been weak for three weeks. And she had gone to her veterinarian initially two weeks ago, and said, “You know what, my dog’s rear legs are really weak.” And they did a testing for Lyme disease, ehrlichia, anaplasma, these different tick-borne diseases that can cause this and it was all negative.
And then this was a hint. The dog ate better than normal. It was super hungry. That was a hint for us on what this might be. So here we are in a physical exam. I think that the assistant got more tired than she did, but she was pretty tired. And this was a normally like a robust lab that could really go for long walks. She was just tired, and it was hard for her to get moving. And she was what we call a Dull Mentation.
So then we did some standard testing. And for the most part, it really didn’t help us. Her blood pressure was normal. Her red blood cells were normal. Some people in the audience might be thinking, “Well, maybe she’s anemic.” Her biochemical panel was normal, except for that low blood sugar. We checked it again, it was still low, and she had no evidence of an infection. So, we took a chest X ray, look totally normal. So at this point, I’m actually curious if anyone in the audience is willing to unmute themselves and say, “I think it’s x.” I will say it’s hard to unmute yourself, especially when there’s, I don’t know, 46 people I think I saw at one point, and who wants to, really? You probably don’t know each other, so I get that completely.
What I will tell you is that if someone came out and said, “I know what it is,” I’d be impressed, because I didn’t know what it was at this point. I had a better sense of what it wasn’t. I didn’t think it was anything that was given to the dog. It wasn’t insulin, it wasn’t Xylitol. This dog was an active dog, but it wasn’t a hunting dog. It wasn’t a sick dog like pancreatitis, and I could probably have even taken off some of these other diseases that we see with sickness. I was wondering about Addison’s disease.
So what can be done now? Well, we can do more testing. We could test for Addison’s disease. We could test for thyroid problems. Thyroid problems don’t usually cause low blood sugar, but they can. We can do an ultrasound to look in the belly, or we can look at the liver. Or we could look for a disease of the beta cells. So if you remember at that second slide, another one of those endocrine organs is the beta cells of the pancreas.
So how about Addison’s. So there are different types of Addison’s disease. There’s classic or what we call typical, and atypical. So typical is more common. The typical one is when they have a decrease of two hormones, cortisol and mineralocorticoid, the one that controls salt and sugar— salt and potassium. The atypical is when the sodium, the salt, and the potassium is normal, but they only have a deficiency in steroids, cortisol.
If you look at the studies, the atypical are more common in females. The atypicals are usually older diagnosis or really young. There are some things that kind of fit the pattern with this one. I will say that at 12, she’s a little bit too old, if that makes sense, for Addison’s disease, but I thought about it. And there’s different ways that you can test for Addison’s disease; you can do a quick test, or you can do a full test. The other ways you can test for Addison’s disease or some of these other things, is with imaging. And some of you probably have had imaging done of your pets or even of yourselves, you can have an ultrasound or a CT and there’s pluses and minuses for each one.
I hope I’m building up some suspense. This is not as good as Netflix, but I’m hoping that there’s some suspense in the audience, that you guys, in your mind, you’re saying, “I think it’s Addison’s,” or maybe you’re thinking, “I don’t think it’s Addison’s, even though this talk is on Addison’s, I think it’s going to be cancer or insulinoma.”
So, we did an ultrasound, and for the most part, it didn’t help us. We saw one enlarged lymph node. But if you look at the left side of the screen, the cortisol was 7. If it’s above 2, it rules out Addison’s disease. This dog didn’t have Addison’s. Then we did that insulin to glucose ratio, and that was the problem. This dog’s body was making way more insulin than it ever should. And it was because it had a cancer of its beta cells, the little tiny cells inside the pancreas and that’s what her problem was.
Medical Treatment choice
So how do we treat this? Well, there’s different ways you can treat it. But dietary therapy is really important. Which is another reason why I thought this was a good one to talk about. We can give high protein, a simple carbohydrate diet. Even though their blood sugar is low, we really don’t want to just give them sugars, because what happens is that the sugar will go up, it comes down, it goes up, it comes down.
If we can, we also don’t want to give it IV sugar—and some people are surprised by this, they’ll say, “Well, wait a second, my dog’s blood sugar is so low, you must want to give it IV sugar.” But the same thing happens, the sugar goes up, then that cancer of its pancreas reacts to it and releases even more insulin. There are medications that we can give. And again, as Dr. Jeff did the lead in, my approach is with, I was trained to give drugs like prednisone dioxide, I’m sure there’s other drugs that maybe Jeff, would want to speak about that he would consider.
And then there’s chemotherapy or things of that sort. You can do surgery to remove it, or you can just treat it with medicines and diet. And this is one of those weird cancers that sometimes even when we give it with diet and medicines, the MST, Median Survival Time, can sometimes be quite long. That Median Survival Time in one study was 196 days. But if you look at the range, the range went up to years.
So, for Jessie, the owners decided to not go to surgery. They initially were considering it, but they ultimately reelected not to. And we’ve treated Jessie and I think we…Actually, no, we’re not still treating Jessie considering how long ago I saw this pet. I don’t know how long she lived. She lived for quite some time with dietary therapy and low dose prednisone. One quick second, before I go on to the next one, I don’t know if I should open up for quick questions now, Jeff, or should I go right into my next one?
Dr. Jeff Feinman 22:48
Why don’t we go right into next one—unless you want to raise any other discussion?
Dr. Marnin Forman 22:55
Okay. So, I will say guys, I’m going to try to finish a little early to leave some time for any questions. I know we’re an hour slot, so from 8 to 9, I’ll try to stick to that as tightly as I can. I’m going to try to finish this next one Maybe around 8:45 or so, maybe a little bit earlier, then leave a little time for questions.
So here’s Lucy, and that’s Lucy’s picture. And she’s adorable little dachshund. I will say I’m a dachshund fan. I currently don’t have any dachshunds because my wife doesn’t want a dog right now, because we have children. I said, “They’re not interchangeable.” I used to own dachshunds and I have dachshunds and figurines and collections with my daughters. So, this is 12-year-old female dachshund and the owner came in and said, “My dog must have diabetes mellitus.”
So, there’s different types of diabetes. But most people when they use the word diabetes, they mean sugar diabetes, “She’s drinking so much.” So, the doctor took her in, did a quick look at her. And they said, “All right, her temperature is okay. It’s like the high-end of normal, 102.” Normal for dog is up to 102.5. Her heart rate for a dachshund is 90. And she was panting, panting, panting. So, 80 breaths per minute, but she was just panting, panting, panting. And she was quiet, but she was fine. Her capillary refill time was one second, totally fine.
They didn’t place an IV catheter. They’re like, “Okay, maybe she just has sugar diabetes.” So they did that same test that they did on the last pet, and here it is. So they did that. Now with a diabetic, we’d expect their blood sugar can be high. And oftentimes, when we diagnose diabetes in veterinary medicine, the blood sugars are significantly high, like 300, 400, sometimes 500. If you have a mildly elevated blood sugar, we sometimes don’t focus on that as much as they would with you and I, because dogs can be nervous at the time of their blood draw, I guess we can too. But her blood sugar was totally normal. And also other things were normal, her sodium was normal, or potassium was normal, all the quick tests were totally normal.
So what can be done quickly now? She has a normal blood glucose level, I thought she was a diabetic. And I will suggest that I’ve had a number of clients say to me, “I think my pet has x disease,” and they’re right. I’m curious if the veterinarians in the group have had that same experience. And sometimes the pet, I wouldn’t have thought of checking that pet for that disease, but the owner had a sense, and oftentimes they’re right.
In this case, at least initial testing doesn’t seem that way. I guess we could recheck the blood glucose just to make sure it’s real, that it’s not falsely low. We could get some more history. Would we give this pet insulin? Hmm. I don’t know if I want to give a pet insulin if their blood sugar was normal. We can measure an insulin level. We can measure at home urine glucose levels of blood.
History and Physical Exam
So, we talked with dad and they said that Lucy has been drinking a ton, peeing a ton, so polydipsia, polyuria. And waking up in the middle of the night to pee, what we call nocturia. And having urinary accidents, and it has been going on for months. She’s gaining weight, even though trying to diet her. So they’re giving her less calories, but she’s gaining weight. She’s panting, panting, panting, she’s weak and she’s losing hair. But she’s not vomiting or having diarrhea. And importantly, she’s not getting any medications that might cause this.
This is a picture of Lucy up here, and has a very particular type of hair loss that we look for in dogs that might have Cushing’s disease, right? It’s called truncal alopecia. So their trunk, their midsection, they start losing hair right there. And she had this very particular type of appearance. The picture down in the middle there is not Lucy. But they can also get other issues where they get stretching of their skin, which is called striae. Or they can get these weird bruising where the blood vessels of their skin kind of break open and they bleed a little tiny bit. So, to be honest, she really looks like a dog with Cushing’s disease. There are other things that we sometimes can pick up, their liver is feeling large. Or they can deposit fat right around their rump, their back ends.
So, what’s going on with Lucy? Well, to be fair, I really thought she had Cushing’s. But maybe she has diabetes, this is not apparent. But to be fair, we want to be careful whenever we’re diagnosing pets that we don’t have the blinders on. And we have to do this as doctors, just as you have to do it with your own pets, where you sometimes will Google a disease process and you’re like, “That’s it, that’s what my pet has.” But then once the testing comes out, you’re like, “Oh, my pet doesn’t have that.” It’s hard to kind of switch away from it. If you didn’t, at the beginning, keep an open mind.
So other things that can do this, thyroid problems can do this, liver disease, hypercalcemia, elevated calcium. Fluid accumulating in the belly can do this. And that’s actually one of the things that sometimes really fools us, is fluid accumulating in the belly. Infections can do us like pyelonephritis, a kidney infection. Or you can have a different type of diabetes called diabetes insipidus. So, this is water diabetes. This is when dogs or people are super-duper thirsty. And there’s different reasons why they get it, but they can’t concentrate their urine well, so they always are peeing. And because they’re off peeing, they always feel a little bit dehydrated, so they always want to drink. And then dogs sometimes when they get this, they drink so much that they rather drink than eat, and some of these pets will actually lose weight.
There’s a different disease called psychogenic polydipsia. This is when dogs drink more water than they should. And we say psychogenic from the point of view that it’s not due to a disease process, like we talked about above, but it’s something mentally that’s driving them. And sometimes this can be dogs that are really high energy that are given a high energy diet that aren’t exercised enough or something like that.
So, here’s Lucy. So, we did some testing. And a lot of our testing sure did look like Cushing’s disease.
We did some initial testing, she had mildly high blood pressure at 170. That’s actually relatively common in dogs with Cushing’s disease, they usually don’t get high high blood pressure, but it’s mildly high. They can have abnormalities on their complete blood count to CBC, where the lymphocytes are low, and the platelets are high, they can have a biochemical panel abnormalities. And here’s what’s interesting, when we sent out the biochemical panel for Lucy, her glucose was mildly elevated, but just mild, and she didn’t have any glucose in her urine, so we still didn’t think that she had diabetes.
She had elevated liver enzymes, she also had a urinary tract infection. And a lot of people are a little bit surprised by that when we diagnose a pet with Cushing’s disease, a lot of them have urinary tract infections. And they’ll be surprised, they’ll say, “Well, my pet didn’t show me signs of urinary tract infection.” And sometimes those signs are really obvious, like they’ll pee and it’ll smell bad or it will look bad or look abnormal. But sometimes it’s more subtle, like accidents in the house, or peeing in the middle of the night, things that Lucy was doing. To complicate it even more, dogs with Cushing’s disease sometimes won’t show evidence of a urinary tract infection, because the disease of Cushing’s disease is too much steroids, the body is making too much steroids and those steroids decrease the inflammation in the bladder, and kind of hide some of the signs of a urinary tract infection.
There are different ways of testing for Cushing’s disease. And I really didn’t want to get too down deep in the Cushing’s disease discussion. There are different ways of testing. All right, there’s a short test, and a long test. The short test is nice and easy and short, and that’s the one ultimate that was done in this case, ACTH stimulation test, and her test was consistent with Cushing’s. The long test has some benefits. And the one of the big benefits with the long test is that it can look for different types of Cushing’s disease.
Types of Cushing’s Disease
So big picture – there are different types of Cushing’s disease, there’s a brain type, and adrenal type, or a belly type. The brain type is usually due to regrowth inside the brain, deep, deep, deep inside the brain. What we’re looking at is a picture of a pet’s brain. He’s passed on, and this is a slice through his brain. And what we’re looking at is this dog had Cushing’s disease and he had pituitary-dependent hyperadrenocorticism due to a growth in the pituitary gland, and this dog had a big growth.
This is what we call a pituitary macro tumor or macro adenomas. Most pets don’t have a big growth like this; they have a tiny growth in their pituitary gland. You can see it if you do advanced imaging like a CT or an MRI. So, the most common type in small dogs is the pituitary-dependent and medium to large dogs, it’s about 50/50. About 50% of them will have the pituitary type, the brain type, the other 50% will have the adrenal type.
There are so many therapies for Cushing’s disease. There are therapies that have been looked at in the veterinary profession, there are tons of therapies that have been tried for dogs of Cushing’s disease. My training was at UC Davis, like Jeff said, and I trained with two doctors who have done a lot of the groundbreaking research on Cushing’s disease, although to be fair, was 20 years ago. And they looked at a lot of these different drugs. And what they found was that all of these drugs have pros and cons.
The drug that is used most commonly is at the bottom there, which is called Trilestane or Vetoryl. That is an FDA-approved drugs. So that drug has gone through FDA approval, and it has been shown to very effectively treat dogs of Cushing’s disease. But like, all of these treatments, they have pluses and minuses. I will say that with adrenal Cushing’s, one that I really didn’t focus on much at all, but that picture what you’re looking at here…Can you see my mouse? Great. So right here is a mass. So, what we’re looking at is we’re deep inside the belly of a dog. This metal thing right here is what the surgeons use to kind of open up the belly. And this is the mass and the surgeons are going to just about to remove it, and removing it cures Cushing’s disease. So it has a big advantage there. But it’s also a surgery.
So Lucy was started on Lysodren, and part of this was because this was so many years ago. Lysodren is a drug that is very effective. but again, has its pros and cons check. She did great on it. She was losing weight. She was drinking and peeing much less, she could hold her pee all night long. She was just a more happy go lucky dog. The one thing that the owner said is that she still eats like crazy. That’s the polyphagia. And I don’t know if that’s because she’s a dachshund and she just wanted to eat or whether a different reason. So that’s it. That’s a picture of my daughter many years ago. And I’m going to open up the field for questions or whatever Jeff feels is right next.
Dr. Jeff Feinman 37:40
That was amazing as always! If you could unshare your screen, that way, we can all come back together and answer any questions. So there was a lot of stuff in the chat. Anyone wants to unmute and ask
Dr. Marnin Forman 38:15
And I can try, if we want to kind of look through here and try to pick out some questions. I see a question about surgery. So the question is, “surgery is considered very risky, UF surgeons steered me away from it, but my friend’s dog just had it done. It was doing great.” Sao the question about surgery is that it has risks, there is no question about that. Surgeons that are really good at that type of surgery, they oftentimes will do well, but it is not without risks, and the risk goes up much higher if the mass is really big, or grown in the blood vessels. And a lot of owners, even if surgery is an option, they just choose that that’s not right for them. It’s okay. It’s not something that, even if we diagnose and adrenal mass, someone usually elect not to do surgery.
Dr. Jeff Feinman 39:21
There was a bunch of questions on prevention, do you have any thoughts on if Cushing’s can be prevented?
Dr. Marnin Forman 39:33
So, there are a couple of ways of looking at this. So, there’s type of Cushing’s disease, and I meant to circle back to this, and I didn’t. If a dog is getting steroids, and they’re getting a higher dose of steroids, they’re going to form signs like Cushing’s disease. It’s not what we term in dachshunds as Cushing’s, it’s not because of problem inside the body. It’s because we’re giving a drug that causing those same type of science.
So, reducing a drug, if you can, stopping that drug, if it’s safe to do so. The challenging thing is, at least for the patients that I see, we sometimes get into situations where we have to give them drugs and we feel like we have to give them drugs to control their disease, and then they develop side effects like Cushing’s disease. That’s one. There is some thoughts that Cushing’s disease might be genetic. And this is something that at Cornell at Cornell University we’re looking at, we have a very large genetic bank, that we’re trying to look at different diseases to try to determine if there’s a genetic mechanism for it.
Now, this is not something that’s going to happen today, tomorrow, 10 years from now, but the hope says is that at some point, we could identify if maybe certain breeds of dogs have genetic markers for Cushing’s disease. If a breeder elects, they will not breed that type. But that’s far down the line. What causes Cushing’s disease? The vast majority of the time, we don’t know. We think of it as a cancer, from the view that it is a proliferation of tissue, either of the pituitary gland or the adrenal gland. And really, the reason why we recognize it as syndrome, as Cushing syndrome, is because it makes this hormone, and that hormone causes plastic science.
Dr. Jeff Feinman 41:49
And there was a great question about using the urinary cortisol: creatinine ratio for screening Cushing’s.
Dr. Marnin Forman 42:07
So, it’s actually a very, very effective test for classic Cushing’s disease. For classic Cushing’s disease, this one test, which is called the Urine Cortisol Creatinine ratio, UCC—so what it is, is you collect a urine sample, ideally, when the pet is not stressed at all, maybe even at home. It’s better to do it that way, rather than to even bring him into a veterinary clinic, they get a little bit nervous on the ride, maybe they get a little bit nervous in the waiting room back when we used to have waiting room where clients would wait, and then they can falsely effect this test.
But the Urine Cortisol Creatinine ratio, if that test is negative, the likelihood of Christian sees is very low. But the drawback of that test is when it’s positive, it really doesn’t help us that much, because there’s so many other scenarios that can cause a positive Urine Cortisol Creatinine ratio, including just being super sick. If you have a pet that’s really sick, like vomiting, diarrhea, has diabetes, has pancreatitis, has liver problems, they can have a positive Urine Cortisol Creatinine ratio.
So, one, D zero is a typical Cushing’s disease considered here as a differential? So I mentioned that with Cushing’s disease, you have two types, you have a brain type and a belly type, pituitary-dependent adrenal-dependent, but that’s a little bit of a misnomer. There’s even a different kind of spectrum to look at. You have classic Cushing’s disease, or atypical Cushing’s disease. So classic Cushing’s disease is an excess of one hormone, cortisol. Atypical Cushing’s disease is an excess of many different hormones, potentially, including something called 17-hydroxyprogesterone, or other types of hormones like it. That tests a typical Cushing’s disease.
There’s only one lab that usually does most of that, so people know it as the University of Tennessee test. Some people might be familiar with that. With that test, classically, we only look for atypical Cushing’s if the pet doesn’t have typical Cushing’s. So we start the process by looking for typical, either with the one hour test or the eight hour test. And then if we still think it’s Cushing’s, even though the one-hour test or the eight-hour test is negative, then we might look for the atypical. I think is a comment: “My dog was on Trilostane, it made him so sick so I decided not to give it to him anymore. We’ll try something more holistic natural,” and if anyone wants to jump out.
Dr. Jeff Feinman 45:29
I’ll actually jump in there because of lifestyle, homeopathy and other changes that can affect the underlying cause for Cushing’s in the first place, can be real effective in some pets but it depends on the full context of the situation: if it’s an adrenal tumor, probably not as much (effectiveness) as if it’s pituitary-dependent Cushing’s, but that’s a good place to consider a complementary or integrative therapies and that is when drugs like Trilostane and are causing the problem, or triggering a problem, (the drugs are often not actually causing the problem).
Dr. Marnin Forman 46:28
The other thing about Cushing’s disease is that Cushing’s disease is one of those conditions that’s very chronic, these pets usually don’t get Cushing’s disease quickly. And in some dogs who have Cushing’s disease, they really don’t have bad signs. Some do, but some of them, it’s more of a kind of people are wanting to know kind of what’s causing the problem. But once they hit that point of knowing what it is, they debate, do I want to try something that is like Trilostane or one of the other dogs, or potentially something like Dr. Jeff is mentioning, like a homeopathic approach?
And the nice thing about Cushing’s disease is that it’s not something that typically, if it’s not treated in either approach, very aggressively, the pets will go on and be very sick. There are exceptions. Some dogs, they have severe signs of Cushing’s disease like Lucy, you know, sometimes it just drives them crazy, all the drinking and peeing and the hair loss and things like that. And sometimes those infections like that urinary tract infection can cause bigger issues, either recurrent infections or maybe the kidney infection.
Dr. Jeff Feinman 47:47
So, you’re saying in your experience that most of the dogs look great or manageable, Cushing’s will go on to progress to more severe disease or that they can have severe consequences like thrombi or…
Dr. Marnin Forman 48:08
So yeah, so left un… I don’t want to say left untreated. Classically, if you look at the vast majority of dogs have Cushing’s disease, their signs will get worse. It doesn’t get worse, usually overnight or quickly, but it’ll slowly get worse. But the complication rates like urinary tract infections, or you mentioned blood clots, thrombi. Those aren’t common, but some of those complications are really severe if they happen. And the one that you just mentioned, blood clots or thrombi, these dogs, we believe have higher rates of thromboembolic disease, blood clots to their lungs, or blood clots to the brain causing a stroke or blood clots to their legs. These are not super common by any means. But if they happen, it can cause very severe signs, rarely death. So, it’s one of those statistic scenario of it’s an uncommon risk, but if it happens to your dog, especially if it’s a severe complication, it’s a big deal.
Dr. Jeff Feinman 49:24
Great, so yeah, that’s great, great rule for everyone. You know, it’s all a risk benefit ratio, no matter what you decide to do, knowing what the risks are, like somebody asked about not giving conventional meds to an addisonian. And that’s way more risky than doing the same for Cushingoids, for the most part. Yeah.
Dr. Marnin Forman 49:50
So yeah, that’s a really good example. So Addison’s disease—and it might be even be good to draw a direct line between the two. So Addison’s disease is literally the opposite of Cushing’s disease. So, Cushing’s disease, too much cortisol; Addison’s disease, too little, and left untreated, it is fatal. Early on when they were discovering Addison’s disease, everyone died from Addison’s disease, and then they discovered steroids and they started to survive. And so what I would suggest with Addison’s disease is don’t stop therapy with steroids if your pet’s well controlled. If by chance your pet has Addison’s disease and showing side effects from the steroids, like drinking a lot or peeing a lot, that’s often just a dose issue where you just have to modify the dose.
Dr. Jeff Feinman 50:47
Great question about use of ketoconazole for Cushing’s.
Dr. Marnin Forman 50:54
So ketoconazole was looked at back in—I want to say it was like the 1990s or so. And the dose of ketoconazole that they would need to control Cushing’s disease usually cause an upset stomach. You can control it with ketoconazole. But you had to give it a good amount. And usually, those pets have upset stomach. And with the development of the newer drugs, in particular trilostane, I haven’t treated a dog with ketoconazole or even heard of a dog treated in years and years. Probably over 15 years. The person who asked that, is their dog being treated with ketoconazole?
Dr. Jeff Feinman 51:39
Dunno. I’m held up here. Do you want to come on the chat if your dog is being treated? Other great questions. What is your opinion about steroid eyedrops and systemic effects of steroids?
Dr. Marnin Forman 52:00
So, as a general comment, there is not a lot of systemic effects from it, but there is some, right, so there is some absorption. The absorption is probably higher when there’s really bad eye problems. So if the cornea is very abnormal, and there’s a lot of blood vessels, you can absorb more of those steroids if the steroids are given more frequently, but they have done studies that suggest they do effect the adrenal glands.
Dr. Jeff Feinman 52:30
Awesome! And question about the Alk Phos (SAP) numbers about where to begin to worry versus treating lifestyle and I guess, its right now SAP is at 203, the ALP is at 203. Does the numbers of the alkaline phosphatase affect your treatment decisions.
Dr. Marnin Forman 53:03
Not typically. By all means, if they’re really elevated, I’ll pay a lot more attention to it. So if the Alk Phos is over 2000 or 3000, like really, really high Alk Phos. But for the most part, when looking at liver enzymes, I’m just looking at the underlying cause and then treating that cause. So if the underlying cause of elevation on alkaline phosphatase is a gallbladder problem or Cushing’s disease or a liver cancer, right, to treat that cause versus just treating the number.
Dr. Jeff Feinman 53:43
And on surface total, and the key question, is there any lab, do you know only run SAP iso enzymes anymore?
Dr. Marnin Forman 53:54
Have you asked me this question before? I think I went down that rabbit hole before, and I want to say when I went down this rabbit hole last time, I thought it was Texas A&M, the GI lab.
Dr. Jeff Feinman 54:13
The reason I asked everyone is just because Dr. Forman mentioned Alk Phos and liver problem possibility in liver isn’t the only source for SAP ALP and isoenzymes, just to key in on where was coming from. And we have a few minutes left a lot of questions. Someone asked: “How does phenobarbital affect a dog with Cushing’s?”
Dr. Marnin Forman 54:51
So phenobarbital is tricky because some of the signs of a pet getting phenobarbital will overlap with signs of Cushing’s disease, it causes them to drink a lot, pee a lot, they gain weight. They can also have elevated liver enzymes. It affects the metabolism of drugs, the phenobarbital. So it makes it trickier to figure out if a pet has Cushing’s disease. But from a testing point of view, you can still go through testing for Cushing’s disease.
Dr. Jeff Feinman 55:29
And follow up on the ketoconazole question to confirm that the pup is not being treated currently with ketoconazole but she was wondering about, you know, a drug that would allow less monitoring than the Vetoryl.
Dr. Marnin Forman 55:45
I got it. So the ketoconazole, they still monitor those pets, if I remember correctly, the same pattern as Lysodren. So it was still a pretty frequent monitoring. If I was looking for a drug that was less than Lysodren (did you say less monitoring than for Lysodren?)
Dr. Jeff Feinman 56:15
I think the question was about Vetoryl.
Dr. Marnin Forman 56:17
You can try low dose Lysodren, it depends on the case and how bad the Cushing’s disease is, but if you’re going with low dose Lysodren, you could probably get away with less monitoring. I don’t know if we’re coming to an end.
Dr. Jeff Feinman 56:47
We are. There are lots of things in the chat like a question about a central resource for vets that aren’t familiar with Cushing’s.
Dr. Marnin Forman 57:16
Like a textbook? The one that I think is fantastic is by Nelson and Feldman. The endocrinology textbook um, I don’t have it.
Dr. Jeff Feinman 57:35
Who you knew (The UC Davis endocrinologists).
Dr. Marnin Forman 57:38
But yes, I know I’m a little bit homegrown there, but I think that that’s a fantastic, fantastic reference
Dr. Jeff Feinman 57:48
And I think her question was about just state of the art treatments, see that they keep that updated and…
Dr. Marnin Forman 57:57
Yeah, yeah, they’ve actually…I think they’re rolling out another one soon even, so yeah.
Dr. Jeff Feinman 58:06
More thank you’s, and “that was awesome”s. You’re getting a lot lots of bravos and we hope to see you in 2022. Next week, is our member Q&A. So if you have any Cushing’s, Addison’s or any endocrine questions, because you know, October is our endocrine month, bring them for next week and then the week after will be pancreas stuff with— but actually, no, sorry, the week after that is glyphosate and Dr. Forman, we didn’t even get talked about endocrine disruptors in the environment, like Roundup and other potential toxins. So, thank you again, and we’ll see y’all soon. Bye. Thank you.