Episode 20 - Endocrinopathies II - Hyperadrenocorticism, 'the stuff you never really understood about cushings'

Episode 20 – Endocrinopathies II: Hyperadrenocorticism
The stuff you never really understood about Cushing's.

We've all learned that dogs with Cushing's drink more, wee more, eat everything in sight, and somehow still end up with a pot belly... but have you ever stopped to think about why?

In this episode, we're diving into all things hyperadrenocorticism and tackling the bits that often get glossed over. We chat through the physiology behind the disease, why these dogs present the way they do, how to make sense of the diagnostic work-up, and what treatment actually looks like in practice.

Along the way, we unravel some of the concepts that many of us memorised for exams and then quietly hoped we'd never have to explain again.

Whether you're a student trying to get your head around endocrinology, a new grad facing your first Cushing's case, or a seasoned vet looking for a refresher, this episode is packed with practical discussion, clinical reasoning, and plenty of "ah, that finally makes sense" moments.

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Transcript

SPEAKER_01 0:10

Hi everyone, welcome back to the Chatty Vets Podcast. I'm Brendan.

SPEAKER_00 0:13

I'm Charlotte. Thank you for tuning in. We're back again with our next bonus episode. We hope you enjoyed our last two-week takedown last week. And thank you again to our lovely guests that we had joining us.

SPEAKER_01 0:24

Yes, thank you. Today we're changing it up, going back to one of our clinical deep dive episodes. We are going to delve into our endocronopathy series, talking today about all things hypoodreno corticism, i.e. Cushing's disease.

SPEAKER_00 0:38

Just before we get started, we wanted to mention something really exciting that's coming up. So just in case you've not seen on our socials, we're actually about to start running our first CPD event, which is very exciting. So on Tuesday, the 21st of July, we're going to run our first online CPD event.

SPEAKER_01 0:55

Yeah. So if you're a new graduate vet or a final year vet student and are feeling a bit apprehensive about diving into practice, we've got you covered.

SPEAKER_00 1:04

Yeah, join us for our new grad consult survival day, where we'll be covering the common consultations you'll see in small animal practice and how to approach them, how to deal with tricky clients and generally how to ace being a GP vet. You've got all the skills. We just want to help you feel a little bit more confident before you take that leap into GP practice.

SPEAKER_01 1:23

So if you're interested, head to our social media for more info or go onto our website at chattyvets.com. We hope to see some of you there.

SPEAKER_00 1:31

And also remember, Brendan has been amazing and created CPD certificates that you can access on our website.

SPEAKER_01 1:38

Yes, I have actually been amazing. I was really proud of myself. It took him ages, so please use them. It did. It did. It's a whole weekend. If you you click on, you answer a few multiple choice questions, you can have as many tries as you like. And if you there's only like three or four, and then if you answer them correctly, it will literally email you a CPD certificate for that that podcast episode that you watched. So you get one hour of CPD. And obviously, you know, if you've listened to quite loads of episodes, you can give yourself get yourself a few of your CPD certificates.

SPEAKER_00 2:10

Yeah, because like we've said before, each podcast is actually CPD. So make sure you are claiming it and using the certificates as your as your evidence. So yeah, click on, but it will make Brendan very happy. Anyway, back to today's pod. So when we were planning these episodes, we had a bit of a chat, didn't we, Brendan? Because for Addison's and the Addisonian crisis, for DKAs, we thought there was so much to chat about. We'll be like, oh, we'll easily fit an hour's podcast discussing it. But when we got to Cushings, we were like, oh, is there really enough to say? You know, you see it's cushionoid and you give it some meds. But I think we've both been really surprised about how much there, how much there is about Cushings that we actually maybe didn't know beforehand.

SPEAKER_01 2:49

Right, I'm gonna say, if you if you listen to the thyroid episode and thought you were gonna get something similar with Cushings, you you are absolutely not going to. This is so different. What I realized, what I kind of I kind of, everyone vaguely thinks they know Cushings, but I think there's so many things that I learnt writing this about why things happen that I that I think this is a phenomenal subject to get into. Suddenly you'll understand so much more about steroids in general practice and why steroids have side effects they do have, how we treat low blood pressure, and so many other little funny aspects of that you you never really realize you didn't understand. Even DKA and the origins of that will kind of cover a lot of this within Cushings, because believe it or not, they're all connected with cortisol.

SPEAKER_00 3:34

Yeah, yeah. And I think we will be recapping some of the basics today. So to talk about, you know, exactly what is Cushing's disease and what eds do we use and how do we manage it, etc. Obviously, we're gonna speak about that, but um, I think we're gonna go through it from more of a pathophysiology background, which sounds really dull, but we promise you we'll keep it interesting. But I do have to admit, working a bit more in out of hours now than GP practice, this is definitely more Brendan's forte. So I will be, I will be asking you lots of questions as we go along, and I'll be as in the dark as anybody listening, probably. So, um, but we'll try and get through it together and hopefully we'll give you some really cool clinical nuggets that you can use in your day-to-day cases.

SPEAKER_01 4:12

No, it absolutely you know what? No, it's gonna, it's gonna affect everyone and even emergency because all the immunomodulation, the you know, the stress leukrograms, and there's so much there. So I think I think it's a real goodie, and this is a proper deep dive, but I think it's really clinically relevant. So Yeah, so let's get into it, yeah. Yeah, go for it. Let's start off with a quick reminder about what Cushing's disease is. Essentially, it is the body producing loads of cortisol all the time, whether that's because of a little paturatory tumour or an adrenal tumour. Um, and we'll get into this a little bit down the line. And all that steroid in the body has a multitude of effects, and now we know them. So, you know, pot belly, loss of muscle, panting, the immune system that's altered, hair loss, all these things. So we all know the Cushingoy dog. Typically, it's gonna be that um small, curly-coated kind of little white bichon frise or uh, you know, the uh border terrier or or one of these, typically. So, but what I wanted to do was talk about how does this actually happen? How does how does all this caution soul have all these what seem like diverse effects? So, and then and then once you understand that, you'll remember much more better all the kind of facets of cushions and you'll be able to diagnose them and manage them much better too. So, as so yeah, if you're looking at a Cushings dog, you you I find often the client's gonna come not well, they might come because of the hair loss, obviously. Usually it's symmetrical. You can um kind of slightly irritate the client by I find by where where the alopecia is, you can just pull the hair out around the alopecia and make it even bigger, and it just kind of falls out in your hand. Um but uh I I do that. So yeah, and obviously weight get weight gain, and the owner's battling away, reducing the food, but the weight keeps going up. The dermatological signs, the hair loss, I think it's a bit more later onset.

SPEAKER_00 6:01

I always remember being taught at uni there was four peas, I think it was. So you've got polyuria, polydipsia, polypha polyphagia, and pot belly. That's what I remember. So if you remember the four peas, then you can't really go too far along.

SPEAKER_01 6:14

Five P's, panting.

SPEAKER_00 6:16

Panting, yeah. Yeah. Maybe it was some peas. I just caught one.

SPEAKER_01 6:19

Pooing. I don't know, it's fading out. Okay.

SPEAKER_00 6:23

So basically, if you see any of them in a consort room, then cushions is definitely on my list. So yeah.

SPEAKER_01 6:28

And the most really important thing, they're well. That's so important. They're not unwell. Because if they're unwell, it's gonna really mess up your diagnostics, and we'll come to that later. But um, these are well dogs, they're drinking a lot, and that's really important that you don't just you know, I think I've touched on this before. You don't just go, are they drinking a lot? You you're finding out, do they now need an a wee in the middle of the night? Are they now weing in the house when they never used to? So are they are you suddenly finding you're filling refilling the water bowl unexpectedly? You know, so these, you know, you need to ask it in in different ways to get that information out of the client.

SPEAKER_00 7:00

Yeah, definitely. Yeah. Okay, so I think we also know how these dogs are gonna present, and we all might have a suspicion they're cushing oid, but do we actually understand why they present like that sometimes? And a cortisol is definitely the thing that we need to dive into a little bit more here. And we think of it as a survival hormone, but you wanted to dive into this a little bit more, Brendan, didn't you? Because it's so interesting.

SPEAKER_01 7:22

It's it's unbelievably central to everything, and it's relevant to so many different conditions. So, yes, basically, cortisol is adrenaline is survival hormone number one. Yeah. Um, immediate danger, everyone knows this, don't they? Your blood pressure's up, your heart rate's faster, that's adrenaline. Um fight or flight. Fight or flight. But why we're all taught that? Because that's actually not as helpful. What's so important is cortisol's role. So cortisol is mostly there to ensure the brain has a good supply of glucose. Now, from that, so many things spring out. So, and there's so many adaptations because cortisol is also there for if you're starving, if you're bleeding, if you've you've had loads of trauma, and all of cortisol's effects will help you. We'll go through these one by one. Um, and I don't know, though I think a good place to start is you mentioned, Charlotte, one of the peas, polyphagia, eating lots. Now, that is a really easy one to explain. Because I don't know if you've ever asked yourself why do cushions, why do steroids make you eat?

SPEAKER_00 8:22

No. And to be honest, whenever I've explained whenever I've explained to myself why cushioning oid dogs are hungry, it's because I'm like, oh, they've got high levels of steroid, and that's where it left. That's where it's left.

SPEAKER_01 8:32

Yeah. Yeah. But if you think in an emergency you want to maximize your glucose to your brain, you've got to eat lots. And that's the easiest way. So essentially, cortisol makes you eat well to get the glucose in, let's feed your brain. So I know it sounds like ridiculous, but this is how, as we go through these, you'll see. Now, look, step number two is if you look, oftentimes in starvation or whatever, your cortisol's firing off, there is no food to eat. So, plan B. Plan B is the other thing that cortisol does so cleverly. It's gonna go, well, you can't eat, you're gonna eat yourself. And that's when you start.

SPEAKER_00 9:10

Cortisol is a cannibal.

SPEAKER_01 9:13

This is you're gonna break down your muscle. So, cushing's myopathy. You break down your muscle into, we know acids, they travel to the liver. Your liver turns them to glucose in that. I know don't turn off gluconiogenesis, is the word we use, but basically, you're getting protein, you're making sugar, and this gives you the second sign that that we were talking about loss of muscle. Um, and um, the other thing we do is we break down our fat, but that's a little bit more nuanced because we all know that steroids and cushions disease gives you a big pot belly. So you've got a lot of adipose fat there. Now, how how are these two things working? Well, both things are true. You break down your fat, so lipolysis, and you generate glycerol, which makes more glucose, so it's back to there feeding the brain with sugar, and you also release lots of these fatty acids. Now, fatty acids can get digested by lots of tissues around the body and used as an energy source. Now, the reason why that's helpful is you now can reserve the glucose for the organ that really needs it, which is the brain, because the brain can't use fatty acids, they don't cross into the brain. So you're now, if you can get your muscles and other tissues to use fatty acids instead, you're now preserving glucose for your brain. So you are breaking down fat, but the reason why you get the pot belly is once you break down all that fat, we're not actually generally in cushions anyway. There isn't actually an emergency. You're actually just having a normal life. So it's kind of like, well, what do we now do? So what you then do is you store it all up again. So we break down all that fat, make all these fatty acids, preparing for starvation and emergency, but then the meals around the corner, because you've got cushions, that's that um survival hormone's not going to turn off, and you then have to do something with all this energy you're creating, and you just store it all away as fat.

SPEAKER_00 11:02

And with the pot belly, because you get uh hepatomegaly in cushions really often, don't you? So generally, when you feel these guys on abdomenal papation, the cranial abdomen wise will just feel really firm and full, won't it? It's not uncomfortable, but when you get really good at feeling them, you're like, oh, that liver feels huge because you can just feel it all around the right hand side of the abdomen. And I guess that's why, isn't it? The liver's doing more in terms of gluconeogenesis, it's working more and you're you're storing up some of that fat. Are you? Is that why you're getting that hepatomegaly?

SPEAKER_01 11:30

A little bit, yeah. But and and yeah, you've you've kind of got it pretty much because all of that glucose production hasn't got anywhere to go because the patient's eating and doing normal things in a cushing oil dog, so it gets stored within the liver cells. So the liver cells get full of glycogen. And so they get packed so that when you do your ultrasound on your liver, you get all these little bright, flecky kind of patterns throughout the liver. And that is basically hepaticels swollen with glycogen, and that's this vacuola pattern that you get. So again, it's all it's all down to essentially eating yourself, but digesting muscle and fat, and then having to store all that stuff away in your liver and as fat in your body.

SPEAKER_00 12:08

We know that cushions and diabetes can be kind of intrinsically linked. We can see one and then the other. And I know that cushions tend to throw up insulin resistance, doesn't it? And that's why we end up tending to get an issue if you see that alongside diabetes. But why is that? Why are we getting the insulin resistance?

SPEAKER_01 12:24

So, what happens is this is another thing about making sure the brain has a supply of glucose because the brain is so needy, it can only have ketone bodies or glucose for energy. So we don't want the muscles to use glucose if we can help it. So, what happens is cortisol comes along and it essentially it kind of gives you insulin resistance in the muscles. Now, your muscles, the muscles need insulin to be able to use that glucose. And if the insulin isn't working, they have to turn to another energy source and they will use those fatty acids that are coming down from the breakdown of fat instead. And they're quite happy to do that. So as long as you can block the insulin, they will they will switch and use fatty acids, and then it's going to preserve glucose for the brain. So this is the reason why cortisol seems to have this, you know, seemingly it's hard to connect. Why does it cause insulin resistance? Well, that's why.

SPEAKER_00 13:16

Yeah. And that that makes so much sense when you're dealing with your diabetic patients that are also cushionoid because they're so difficult to stabilize, aren't they, until you get on top of the cushions? Because the insulin that you give just doesn't work or doesn't work anywhere near as well as it should do. So it just kind of really makes sense as to why that actually happens.

SPEAKER_01 13:32

Yeah, yeah. It's it's like this whole beautiful system has been created, but no one had told me this until I started reading up about it. And I thought, wow, this is it all makes sense. Um, then the the other thing, and this connects with emergency now, but cortisol is central to maintaining your blood pressure, which am I right? I hadn't I didn't know this at all. Did were you aware of this?

SPEAKER_00 13:54

Yeah, but I guess the only reason why is that, or one of the reasons why is if you think, so we'll do a podcast on sepsis at some point, but there is something called Circe or like corticosteroid-related insufficiency in sepsis. And basically that's when you get to a point where if you if you are in septic shock, then often you're in vasodilatory shock. So you you have a ridiculously low blood pressure because all your all your vessels are super dilated. What you do in those patients is yes, you volume resuscitate them, but often they need vasopressors, so something like noradrenaline to try and get that blood pressure up. But if they're on vasopressors, if they're on uh positive inotropes like pimabendan to help with cardiac contractility, so you're doing those two things to try and get that blood pressure up as much as you should do and maintain your cardiac output. If you're still then really super hypotensive, then often in sepstic patients, they basically don't have enough corticosteroids, so they are corticosteroid insufficient. So there's a type of steroid that you can give them, which does help as almost like a vasoconstrictor, if you like. So it helps them to really constrict those vessels down and maintain your blood pressure. So, but yeah, I know that's probably that's whirlwind, and we will explain it properly in later episodes. But um, yeah, it definitely has a massive role to play. Now, I'm not saying give every hypotensive patient steroids. That's not what we're saying, but um, it does, it definitely does have a role to play.

SPEAKER_01 15:13

So, yeah, so all steroids are needed for the sympathetic nervous system to do its job and create vasculatone and support your blood pressure. And without the cortisol, your noradrenaline, which is being secreted from the nervous system and it's onto those blood vessels and it's trying to make them constrict and get your blood pressure up, that won't work without cortisol. Now, where this is relevant is your cushion's dog has loads of cortisol. Then the blood vessel is gonna get really super sensitive to all of that noradrenaline coming from the sympathetic nervous system, and you're gonna get hypertension. And this is why Cushing's dogs can have hypertension. But where it's also really relevant is Addisonian dogs are gonna have the opposite. Now, they haven't got the cortisol. Now you can release all that noradrenaline onto the blood vessels, you can release your adrenaline into your body to try and cause vasoconstriction. It's not gonna work because it needs cortisol. And that's why Addison's dogs have got these floppy blood vessels and hypotension as well. And there's multiple reasons, but that's another big one. So that's another thing where cortisol, yeah, is is really, really important for maintaining blood pressure.

SPEAKER_00 16:23

I don't know if many of you have seen the really nasty Edison crisis, but but often they need to be on your vasopresses as well until you've got on top of everything.

SPEAKER_01 16:30

The last bit about the blood pressure I'll go into is that it's not just the systemic circulation where it's supporting the high blood pressure. You're also getting high blood pressure in the kidneys as well. And this is leading you to your next thing that Cushingoid dogs have. That extra high blood pressure through the glomerulus leads to damage to the glomerulus, protein leakage into the urine, and now you're getting your urine-protein-cratene ratio going up because you're now getting protein in your urine, and that's all another function of this hypertension caused by too much cortisol.

SPEAKER_00 17:04

A little bit later we'll go on to how to diagnose cushions, but that that sort of leads on to one of the ways that you can do, because we obviously we can do a urine test to be checking for how much protein is in the urine as part of our diagnostic workups.

SPEAKER_01 17:14

How that connects to survival is obviously you want to maintain blood pressure when you're in a massive crisis in emergency. So it all connects back. And remember, I said right at the beginning, it's all about making sure the brain has glucose. Well, if you maintain your circulation, you maintain the blood perfusion of your brain and you maintain sugar going to your brain. So it's you know, it's all feeding that one thing.

SPEAKER_00 17:34

And so we've spoken about emergency ways that that cortisol can really help. But why do we get the hair coat changes and the skin changes? Like what why do we see those changes with Cushing's disease?

SPEAKER_01 17:46

Yeah, right. Um amazingly, again, it's connected because if you're in a massive emergency or starvation or long-term like chronic difficulties, you don't want to waste time with hair. Hair's just a fluffy per extra, you know, unnecessary thing. And you don't always want to put lots of effort into maintaining your skin either. So two things that happen with cortisol is the hair follicles stop doing their thing and so you're you're not producing your hair, the hair follicles kind of shut down. But the other thing is the skin isn't replenishing itself in the way that it normally does, so you thin your skin. And this is why when you're using topical steroids, you know they how they always say they thin your skin if you keep using too strong steroids too much. And that's why, because it's a considered like a bit of a luxury when you're in an emergency and you're gonna cut back on skin and hair production.

SPEAKER_00 18:38

I mean, it makes sense. I mean, you think of me last last month when I was revising for my sir, that was definitely me. No, no skincare, no hair care. Yeah, greasy and dirty and carrying on with revising. So, yes, it makes sense.

SPEAKER_01 18:50

Yeah, I remember my friend doing his A levels actually so when we were quite young as well. And he c he woke up before his A-level exams, and no, it was three or four weeks later, and there's a whole bunch of hair on his pillow, and he was absolutely horrified. But the stress of the uh of the A levels had made his hair fall out.

SPEAKER_00 19:07

Yeah, yeah.

SPEAKER_01 19:08

Yeah, so um, and and I never I knew everyone thinks stress makes hair fall out, but when you think of it in terms of energy conservation, it starts to all make sense.

SPEAKER_00 19:16

I feel yeah. Okay, so I think we've chatted a little bit about how and why these dogs might present the way that they do. And to be honest, even if at this point where your dog has walked into your consult room and you're still not actually sure that it is cushions, you might end up doing a routine blood test just to be like, oh, what changes have we got? Have we got any changes on hematology? Have we got any changes on biochemistry? Just to see if you can rule in or rule out some things. Um and one of the big things that we do see in these guys is that we often see a stress leukogram on their hematology. Stress leucogram, for anybody who's not quite sure what that means, basically is a change in your hematological parameters that is literally influenced by stress, so influenced by cortisol. So it can be for a number of different reasons. That can be physiological stress, but also with your Cushings patients, is because you've got too much cortisol. So generally, that's when you get a leukocytosis, normally, and that consists of normally an increase in your neutrophils and an increase in your monocytes. So you get a neutrophilia and a monocytosis, and really often that's paired with a decrease in earzinophils and a decrease in lymphocytes, so an earzinopenia and a lymphopenia as well. So normally you see the four of those together. So if you do see the four of those together, and usually they're quite mild changes, you're not talking about an absolutely massive neutrophilia, and that's probably something different. But if you're seeing really mild changes in those directions, then usually it's to do with stress. And Brendan, you've got a little funky acronym that you've got for this, haven't you?

SPEAKER_01 20:43

Yeah, I can't attribute this to someone, unfortunately, because I don't know who, but since I was a student, not much eats leopards. And it I still use it to this day, not much eats leopards. The first two go up, neutrophils and monocytes. The last two eats leopards, earcinophils and lymphocytes, and they go down. And just by the way, how many times for me I've gone and I've seen an Addisonian dog, I've gone onto the white blood cells, and you do see the earcyphils are up a little bit, or the lymphocytes are up a little bit, and the neutrophils are down. So you get the opposite. Now, I'm not saying every Addison's has the opposite, but I've definitely seen the opposite as well. So not much eats leopards. Yeah.

SPEAKER_00 21:23

Yeah, I think for me, you know, we see stress leucograms so often in unwell patients because their body is under physiological stress. That for me, actually, if you've got an Addison patient, a dog that comes in that is that sick, if you have an absence of a stress leucogram, that makes me think it's probably Addison's. So even before I checked my sodium and my potassium, if you've got an absence of this, that actually tells you a hell of a lot anyway. So when you're checking your hematology, be thinking, can I see one? And if I can't see one, is it normal that I'm that I can't see one? Because we see this really commonly.

SPEAKER_01 21:52

Yep. And if it just in case you were thinking that Brendan's gone off the track on his crazy notion that this is all about making Sure, that the brain gets glucose. I haven't, because this is also connected. Amazingly, another way of saving energy during a crisis is to calm down your rather sophisticated adaptive immunity. That's the immunity you get by your principally mediated by your lymphocytes. Also think eartcinophils, controlling parasites. You know, these are not the the these are things that we can calm down. We don't need to be doing them. We don't need to waste energy on them. What we do want to maintain, however, is the innate immunity. It's lower energy, it's easier to do, it's the neutrophils and monocytes just going around the place, eating things up. Really simple, low energy. Let's do that. Adaptive immunity involving antibodies, lymphocytes, lots of bone marrow, upregulation, and all of this. That's much, much more sophisticated, much more energy demanding. That can wait in an immediate survival sense. So this is the origin of what where the stress stress leukogram comes. So, yes, again, it's it's cortisol telling the body, let's focus on the basics, let's not try and be too fancy. We haven't got enough resources to do everything.

SPEAKER_00 23:08

Yeah, yeah, it makes sense.

SPEAKER_01 23:09

Okay, so the main things we get are skin infections. You get demodicosis, and I don't know, I always see it on the pause. Maybe I've had it periocular as well. And then urine infection. So we'll come, but we'll come back into that because that's a little bit of a nuanced one as well. So these are the ones we see. Funnily enough, this is not like your chemotherapy patient with marked neutropenia, immune suppression, pyrexia. They get these kind of quite kind of low-level kind of problems. Um, and this it does rather spring from everything we've talked about. Because if you think about demodex, it lives down the hair follicles. Now our hair follicles are, they're on like they're on downregulate. They're just these empty little shells and all the immune surveillance is gone, they're not doing anything active, and it's like, ah, demodex might, I'm gonna live down there. It's kind of like it's uninhabited. Easy, easy place to dwell. So demodex comes in, skin infections coming in as well because of the downregulated immune system, but also the thinning skin. So you, you know, you've got also that that kind of factor. And um, the urine infection, we're gonna come back into these dogs drinking a lot, weing a lot, but it's diluting the urine, you've got less immune surveillance going on, we've got more skin infection, maybe for ascending bugs, bacteria, and yeast to kind of go up. So we've got this increased pathogens in the urine as well. So, yeah, so to help you remember anyway, so you've got the skin infections, the demodex, and the potential urinary tract infection.

SPEAKER_00 24:33

And I guess it's worth saying here as well is because you can sometimes get your cushions and your diabetes hand in hand, is it's always worth checking if if you are getting UTIs, double check whether you have any glucose in your urine as well, because you could be getting a UTI because you've got concurrent diabetes rather than because of the cushions on its own anyway. So they can be a little bit intrinsically linked like that, can't they?

SPEAKER_01 24:52

That's such a good point.

SPEAKER_00 24:54

And then one of the things that I maybe realised more recently in my career is the importance of using anti-clotting drugs on these guys as well, sometimes in terms of our management. And we'll get onto the drugs that we might use a bit later. But I know that obviously cushions, like you said before, can lead to protein losing nephropathy. So you can get to a point where you're getting lots of protein urea, and sometimes that can put them into a hypercoagulable state, can't it? But why is that? Why are we seeing that with cortisol with an increase in cortisol?

SPEAKER_01 25:24

Yeah, and again, it just is so obvious when you think about it, because in our ancestral kind of uh life, if we were under massive threat, then we presumably would be at risk of bleeding, trauma. So suddenly cortisol is really helpful because it's gonna increase the production of several clotting factors. It's increasing your blood pressure, which is potentially gonna be more damaging to blood vessel walls. So, yes, it's great that we're getting all this extra clotting ability, but when it's there for months and months, this is also gonna make you more prone to having a blood clot. Um, and with protein-losing nephropathy, when you're losing protein through your kidneys, you're also potentially gonna lose antithrombin three. So you're that also makes you more likely to clot two, because that's normally there hanging around stopping you clotting unnecessarily.

SPEAKER_00 26:14

Going back to, so when we said, okay, these patients are gonna present, maybe you'll be like, Oh, is it cushions? Is it's not, you might run a full blood panel, so you might do a CBC, full hematology, and uh a biochemistry, maybe a chem 17, for example. So if we're talking more about our biochemistry now, what else are we likely to see on there if we have a cushing or a dog? You know, I know that we've said that it can affect the liver. Are we gonna see any changes to liver parameters? Are we gonna see any changes to fats or to proteins, or what generally are we gonna look for on our biochemistry?

SPEAKER_01 26:44

Yeah, so we're breaking down our fats. So, and because we're not utilizing all that energy in the cushion stock, we then have to repackage the fat up that we've broken down really carefully and produced all this, all these lovely things to produce energy from, repackage them up and send them back into fat stores. So in the blood, we're gonna see that fat. So we're gonna see it as both as cholesterol, so high raised cholesterol on our biochem, and the sample's gonna be really fatty, which is your hyper-triglyceridemia. And it can interfere with your biochemical analysis. So, and I think this is really noticeable, isn't it? In a lot of endocrine cases where you get this really fatty sample when it settles out. The one, the obviously the one we're all looking for, the really high ALKP, high alkaline phosphatase. That one is a really weird one because you think, well, you've got epacomegalages, all the all the liver cells are all swollen with glycogen. Maybe that's contributing a little bit to this raised ALKP, but actually most of it is this weird thing that only, well, as far as I'm aware, only dogs do. Dogs upregulate, start making more alkaline phosphatase in the presence of cortisol. But it's a purely dog thing. Cats, humans don't do it. I don't think horses do it either. And I don't think anyone's quite worked out why.

SPEAKER_00 28:03

Yeah, the thing that makes that interesting is that you don't normally expect the ALT to be elevated, do you? So I think yes, it it there the liver is involved in all the ways that we've been speaking about, but the reason it is a bit strange that you get this massively, and sometimes they can be like in the thousands high ALKP, can't they? They can be massive, the sort of level that you're seeing, but your ALT is normal. And if you scan them, generally they don't look like they're in cholestasis, that their gallbladder looks okay. So you're like, well, it's probably just because of the cushions. But yeah, it is a really strange one because you look and you think, oh god, and you have to rule out, you know, is the is the biodact going to become obstructed? Is there a horrible issue with the liver? But the ALT is always fine, normally, anyway.

SPEAKER_01 28:42

Yeah, so do you know one thing I learned last year? I did read from someone reputable because I used to think if the ALKP was normal, that wasn't going to be Cushings, it was a rule out. But I did read, one specialist said that it can still happen. Not every dog has this canine thing where they get more alk foss because of steroids. So um just bear that in mind because obviously, then for me, all these years, I never tested them if they didn't, if the ALKP wasn't up. I mean, I think they're rare, but um it have it on your mind.

SPEAKER_00 29:13

Yeah, I think where I'd take that is that if, for example, I had a dog that I was pretty convinced was Cushingoid and its ALKP was normal. Again, we will talk about exactly how to diagnose cushions in terms of the definitive test that you want to do, but I'd maybe go for testing to rule it out rather than to rule it in. So I might go like a cheaper urine test rather than your full-on blood test, which we'll get to in a minute. So yeah, it just makes it a bit different in terms of how you might do the work up. It doesn't mean that you necessarily wouldn't do work up for cushions just because that ALKP is normal.

SPEAKER_01 29:42

Yeah, just much lower on your list, I suppose. But um, yeah, so this kind of takes us a little bit through. We've talked a bit about the loss of muscle, the big liver and the fat, into this is one of the reasons why you have panting as a really common sign with steroids. Oh, do you know what? This isn't 100% true, because as I think about it, so you you've got the increased metabolic activity, you're breaking down your fat and your your uh muscle, you're doing a lot of energy-demanding processes, that heat production is making you hotter. Um, and you're also you've got all this better insulation around with all the extra fat, so you're panting to cool down. But the panting I notice, you'll get it on day one when you give an animal high dose steroids as well, won't you?

SPEAKER_00 30:24

Yeah, but I think I mean if I'm using high dose steroids if I'm doing it in emergency work, there's not many cases that I'd use it for. But if I do, then I might be like, oh, it's probably on methadone or something as well, in which case I'm probably panting for multiple reasons or because it's got some horrendous metabolic acidosis and it's trying to blow off on its CO2. Um, yeah, it's yeah, I think I've I've never really thought about attributing it to the steroid as such, but yeah, I guess it it could be. So because we do see the panting so much in your cushion roy dogs.

SPEAKER_01 30:52

Yeah, well, you know, it's it's us older vets that reach for predicolone more than you guys. So we're we're used to the clients going talking about the panting. We have we've I've kind of skirted around the one of the biggest things, which is the PUPD. So why do steroids make you drink a lot or we a lot, or you know, which one are they making you do?

SPEAKER_00 31:10

I think it's one of those things that we everyone learn at vet school, but whenever we talk about the RAS system or ADH or vasopressin or anything, everyone just goes, ah, like and it was always something that we learn, and then everybody chose to forget really, really quickly, or I did anyway.

SPEAKER_01 31:27

I'm impressed that you were taught it, because I mean obviously it's decades ago, but I didn't get taught this. I don't well, at least maybe I did switch off. Um, so this is what you were taught, yeah, that cortisol suppresses ADH or vasopressin or whatever Americans might call it. Um, see, I never knew that at all. So just for people who don't immediately know what ADH does, ADH is antidiuretic hormone, and it comes out the brain, it goes over to the kidneys, and it opens up little connections between the collecting tubules into the connecting connect collecting tubules of the kidneys, and it allows the body to withdraw water from the urine into the body again. And when you don't have ADH, you have, or vasopressin, you have this condition called diabetes insipidus. And that's either caused by a lack of ADH coming out of your brain or your kidneys not responding to ADH in the right way. And but that's diabetes incipitous, and you weelots because you're now no longer grabbing that water out and backing, holding it back into your body. So, cortisol, why on earth? It took me ages to puzzle this out. Why on earth would it antagonize ADH? Why is it, why are they acting against each other? And Joe, do you know, I don't know if you know this, Charlotte, this is where it fits in with blood pressure again. So we talked about adrenaline being released to improve your blood pressure, to constrict your blood vessels, and noradrenaline coming out of the sympathetic nervous system and going onto the blood vessels and constricting it. The other drug that's used in emergency medicine, vasopressid or ADH, ADH has that role too. So in an emergency, you spike ADH. And ADH actually has that constricting effect on blood pressure too. And the other thing it does is it grabs the fluid from that you were gonna wee away and holds it in your body, which is a pretty useful thing to do if you're about to bleed all over the place.

SPEAKER_00 33:26

Yeah, so in emergency medicine, people might use vasopressin, they don't use it very often because it's mega expensive from what I remember. Um, but yeah, so it it is used in that respect because you want to hold on to your water and everything that the blood is carrying and get it to where it needs to be, get it to your brain, get it to your heart. So yeah, and that's why you get that constriction with it too.

SPEAKER_01 33:46

So, right now, let me remind myself what the because I did eventually puzzle this out. It took me a while. So, right, why cortisol kicks in now is it's a little bit like you need to counteract, you need to counteract this because if you have got loads of adrenaline and noradrenaline like pumping through your body, all your vessels are constricting, you're holding on to every drop of water and not weing anything out, you could go dangerously into too high blood pressure. And where cortisol is coming is it's like the physiological break. It's kind of like, hang on a bit, this is going too far. We now need to just hold back on holding all this water in, or you're gonna get too hypertensive, and we need to do some weeing out and get our water balance about right. So it's kind of like it's the it's the it's the balancing, balancing with the ADH effect, is where it's coming from.

SPEAKER_00 34:35

So And it is, it is such a fine balance, isn't it? Because when you think about that Circe in sepsis, we're using it basically to help maintain our blood pressure. So to basically do the opposite of what we're saying right now. So it it it just shows that it's not cool to zone and nothing else acting. It's everything within the body is in such an intricate balance, isn't it? And it's when you get one of those things that's not quite regulated the way that it should do, that that's when everything goes of its pot. So it's yeah, it's really interesting.

SPEAKER_01 35:00

Yeah, exactly. Understanding how this whole system is put together really helps you understand what these diseases are and what our drugs are doing, don't they? Um this is why I I was just blown away by this topic. So um, so yeah, so one of the hallmarks of cushions, and it's really you must have this to investigate cushions. You must have PUPD. Is if you do not have PUPD, do not start looking for Cushings because Cushings is not a disease to be looking for unless you've got your ducks lined up. And uh, I really want to hear the owner kind of commenting that the dog's emptying the water bowl unexpectedly or weeing in four in the morning or whatever. Um, and yeah, this is all because of that ADH antagonism. Okay, the and so the very last bit here is Addison's, which is going to be the flip of this. One of the now, look, I think most of us think Addison's dogs get low sodium because of the aldosterone deficiency, but atypical Addison's can also get low sodium, and it's because of this same problem. So when you don't have the cortisol, you don't antagonize the ADH, you with you start retaining lots of water in your body and you dilute your blood. So now you're just diluting your blood, so your sodium's dropping lower because you're bringing bringing in free water into your blood. So that's a part of the reason why why Addison's dogs have low sodium because of the lack of ADH controls.

SPEAKER_00 36:20

And for anybody who's like, oh God, well, they haven't really covered Addison's, we are going to be doing a whole episode on Addison, so that is to come as well. So um, you can hear Brendan getting more excited about another topic then as well. So yeah, but we'll talk through it all in more detail. But we're hopefully going to go through acid-based disturbances first because that'll make Addison's make a bit more sense. So that will be coming later in the year. So look forward to that.

SPEAKER_01 36:41

Right, we better get on to testing. So we've got our dog that's classic cushions, and we know why. So we've got two tests, haven't we? Does every vet have their favourite test?

SPEAKER_00 36:51

I feel I have never done the low-dose dex test. I've never done it. Yeah, I just don't I don't do it. I think for me, for me, I do the ones that I want to rule out cushions, I do your urine protein creatinine ratio. That's the one that I'll do because it's lower cost than if I'm just ruling it out. If I'm ruling it in because I'm thinking it's really, really likely it's cushions, I'll go straight for ACTH STIM.

SPEAKER_01 37:13

I think you represent most vets. I really do. However, right, this is one of these silly anecdotal things, but because the first two or three ACTH STIM tests I did, I think they all had like borderline results or something. And I ended up then having to go to the client, say, Oh, actually, can I have the dog in for another eight hours, do another really expensive blood test, and uh then we will find out if we have got cushions. Uh I think it turned me off. Now I could have been unlucky, but I just found that the low-dose DEX was helping me because if it told me I didn't have cushions, it was really good. And I just trusted it. I just trusted it. It just and it gave me a little bit more info as well, because it can help you differentiate between pituitary and adrenal. Yeah. But I found the ATH wasn't always have you not had like it just it's a little bit unreliable, the ATH STIM.

SPEAKER_00 38:00

I mean, to be honest, it again, there's not been that many. I don't I can think maybe actually, there's probably only been one patient that I've actually fully diagnosed with cushions, to be fair. I think the rest like I've always tested for it if I've been worried that it is, but not normally it's not come back as positive. And the only one that I actually did test uh did do that came back as Cushingoid was one that was already struggling with diabetic management anyway. And that case didn't end up that well, I don't think, for various other reasons. But yeah, so I mean, and that's the other thing to remember as well, is that not only are we trying to work out whether something is cushing oids, but we're trying to work out why it's cushingoid in terms of what part of the body is going wrong. And that all comes back to that HPA axis, doesn't it?

SPEAKER_01 38:40

Yeah, should we explain how these tests work? Because I think it does help you get your head around it. Because this is kind of going into what you said, because the hypothalamus secretes CRH, corticosteroid releasing hormone, or something like that, and it goes into the pituitary, the pituitary then releases ACTH, and the ACTH goes to the adrenal cortex and tells it to make cortisol. Um, and then the cortisol would feed back into the brain and kind of go, when you've got lots of cortisol, it'll kind of go, right, stop your stop your production of everything now. You need to calm back down. So that's like your kind of classic kind of feedback loop. So when you give a patient low dose dexamethasone, um, that's like you're feeding back and you're saying, right, hypothalamus and protuptland, stop making all your stuff. We don't want to make any more cortisol. And what's meant to happen is your cortisol level drops for over eight hours, which is why you're meant to get two normal cortisol levels or two low cortisol levels on the subsequent the four hour and the eight hour. And why in cushionoid dogs, you will escape the negative feedback. So the dexamethone isn't as strong. It doesn't, it it uh isn't either isn't able to stop that pituitary from secreting ACTH, and so the pituitary will carry on releasing ACTH and the adrenal glands will make cortisol, or if you've got an adrenal tumour, it's that's just it's not going to feed back onto that at all. It's just gonna crack on, keep making cortisol, which is why an adrenal tumor tumour will typically give you your four-hour cortisol and your eight-hour cortisol as high, because there's no it's just making its own cortisol, it doesn't care about dexamethasone. Whereas the pituitary ones will often have some suppression because the pituitary is responding to cortisol, but it's not the normal kind of response, and it and it will by eight hours they will escape and start making HTH, and then you've got your cortisol.

SPEAKER_00 40:28

Oh, okay. So when you send this test off to the lab, so say if you were, I don't know, sending it to IDEX or whoever, and then your your response came back in your thing. Do you know, like when you're if you get like a hyperthyroid or whatever and it will have your your normal marker and then it says over this would be suspicious of this, over this would be suspicious of this. Do you get after your low dose DEX tests, you get a result that says if it's between this level and this cell for would be worried more about pituitary, this level and this level would be more about adrenal. Is that how it will come back?

SPEAKER_01 40:56

I think so, but it's not quite as easy as that because look, this is where you need to know a little bit about which ones get which, I suppose. But because most dogs get the pituitary form, even though adrenals are much more likely to just crack on and you give you high cortisol at both both times four and eight hours, because a few of the pituitary also do that, when you get one that escapes and gives you high cortisol at four and eight, it's 50-50. It could be adrenal, it could be pituitary. But then you need to look into context. If it's particularly the large breed dog, not your classic kind of cushionoid bichon fries or or or whatever, and small breed dog, if it's your large breed dog and you then get this high levels of cortisol at four and eight hours, I think you should be thinking a little bit more, this could be adrenal. And the adrenal ones, the relevance of that is they're not going to respond as well to your medicine, medical management. So you're gonna start losing your client. Clients gonna be going, oh, it's not working that well, or you'll get an okay month and then a bad month. So um it can be quite useful to have an idea if they're adrenal, because at that point, imaging's on the cards and surgery if you've got the right owner, is a possibility. And you can also talk them through that medical management might not go quite so well, but you can give it a crack.

SPEAKER_00 42:10

Yeah.

SPEAKER_01 42:10

But you might have lower expectations.

SPEAKER_00 42:12

Yeah. And if we circle back to imaging in a minute, so how we've just spoken through how your low-dose DEX test works, when we're then talking about our ACTH stimulation test, in a way it's almost working, but in the opposite way to what a low-dose text test low-dose DEX test would do, isn't it?

SPEAKER_01 42:28

Yeah, I'm not as good on this. Now, yeah, so you're giving them ACTH, and I assume with cushions, you're gonna have a bigger impact and it's gonna go crazy. So your cortisol's gonna go sky high, really, really loads. But thing is, I I do think quite a few cushioning dogs just don't do that. But I think what the ACTH STIM test is really good at is telling you, are my adrenal glands functioning at all? I think it's it's good in that context. So your Adasonian is spot on and it's not gonna fail. If you've suppressed your adrenal glands or they've got nothing, no cortisol to give, your ACTH DIM is gonna be great. Have you got any active adrenal gland? But this idea that cushimoid dogs go and you give them ACTH STIM and they pump out ex loads of extra cortisol. Well, it does happen, but it's not a million, it's not totally reliable. When it does happen and you get a really good response to ACTH STIM, then it is it is accurate. That patient is is cushimoid. So that's the good part of that test. So don't get me wrong, it's got value.

SPEAKER_00 43:27

Okay. Yeah, so I think basically how it would normally work is that if you had a normal healthy patient, then your cortisol will still rise, but it will rise to a moderate, so to a normal level, like you're expecting a normal body response. So it's not that you're not expecting a rise at all, but you're expecting a normal rise in sort of conjunction with how much ACTH you've given. Whereas in Cushing's disease, because you've already got that high level of cortisol anyway, and you're basically expecting that massive exaggerated response. So it spikes to an abnormally high level after the injection. injection rather than just rising slightly. So it's not the rise, it's the degree of the rise that you're looking at. And then obviously if you're looking on the flip side of that, if you were looking at Addison's, you won't get any response to that really. So the cortisol will stay low and it won't come up after the injection, which tells you that your adrenals aren't working properly. So it's more about the level of the rise of cortisol rather than the actual rise itself, isn't it?

SPEAKER_01 44:23

Yeah, like a yeah big exaggerated response. But this I was chatting to Avet the other last week actually and um she was saying how she always uses urine cortisol creatinine ratio. And I thought this is a really clever this isn't about the medicine here. This is about the client I think. You can manage the client really well because if you've got a urine test where basically the urine cortisol creatinine ratio is just giving you an idea of your average cortisol over a period of time by looking at the cortisol level in the urine. And we know that this is a test that is a really good rule in. All cushing oid dogs are going to have a raised urine cortisol creatinine ratio. The only problem is lots of other dogs will too. But if it is normal that dog does not have cushions. And that can be really helpful for a client because some of these cases the dog is quite well and you you have to bring the client with you. And if you can do a non-invasive test where it's just a urine test and it comes up positive, I think it's then really easy to say to your client well look this dog might have cushions because this test came back like this. It may not but I think it's good evidence to say how about we do a blood test to to find out for sure.

SPEAKER_00 45:31

I just think it's a yeah do you think I think that can work for a client urine Yeah and I actually just realized I think when I was speaking about urine tests earlier I meant urine cortisol creatinine. I think I might have said urine protein creatinine at some point but I mean cortisol creatinine and I actually use UTCR quite a lot to be fair because I find to be honest like an ACTH STEM is quite expensive. Like to get the ACTH injectable is quite spinny. And a lot of people because especially because they're well it can sometimes be quite a battle to get clients to want to test for cushions because they're like well so they sort of don't really want to be spending 300 350 quid on a test if they're like they're not really sick. Whereas if you can say okay well we can send a quick urine sample off to the lab which isn't invasive. And if it comes back as positive like you say I'd say it's probably quite likely to be cushions but we just need to double check. Whereas if it comes back negative I can say great they've avoided that really expensive blood test because if it's negative like you say I use it as a rule out. So if I it's quite good for those cases where you're like should I be worried about cushions? Should I not be because if it comes back as negative you can be like great I've saved them an ACTH stim. Whereas if you're really if you really think it is cushions, it wouldn't be my first go-to because if it comes back positive you're still going to have to do your ACTH STIM or your low dose DEX anyway.

SPEAKER_01 46:46

So yeah definitely well should we use this moment to go into endogenous ACTH because I've done this test three times and I refuse to ever do it again because I've literally never heard of this. Oh I think you know you used to have to send it to Cambridge specialist labs. I don't know what they're called now but um you do have to send it to uh look you have to go through so many hoops to do it because I think I remember like the I gave the nurses the instructions and they were cooling the centrifuge and you have to put it into ice straight away. It's one of these you've got to do everything right you've got to get a courier you've got to get to the lab quickly enough. So it's it's a real faff to bother her. And they say I've I've gone to all the trouble of doing it three times and every case had an intermediate gray zone answer. So the idea of endogenous HTH is exactly that. It's measuring your ACTH level that you're naturally making from your pituitary gland. And obviously well kind of obviously if you have a pituitary dependent cushions you're going to make loads of ACTH that should be high. If you have an adrenal tumor you're going to be producing loads of cortisol which is going to shut down your ACTH stimulation from your pituitary and you're going to have low HTH. So it kind of makes sense. This should be a great test but I say the three I've done all were in the grey zone and I think it's just you've gone to all that trouble you've cost the owner a load of money and you know further on and I think yeah if it was a bit more if it was more frequently helpful great but yeah that's why I'm a bit on more people would be doing it if it was super useful wouldn't they so it's um yeah it's something to bear in mind but not necessarily the thing that you'd reach for first. So yeah so yeah this this brings us on to so this is all about differentiating have you got the pituitary or the adrenal form and then the other big way we do this is abdominal ultrasound or for a lot of people because adrenal glands are so damn scary for ultrasound very difficult. CT. It's like oh why do we just see do a CT? It's so much easier. So yeah the this is kind of springing up and I hadn't really kind of got my head around what I would do in the modern era with uh these Cushings patients now whether you would so I I don't know my my take on it is if it's a small breed dog and I've let's I don't know it's 13 years old the owner's unlikely to be going crazy with surgery and and epic things I might just go look it's probably a peturatory tumor especially if I've got suppression of four hours on my low dose DEX and it's escaped to eight hours so that's not normally what an adrenal tumor would do I might just go look 80 80 85% this is going to be pituitary let's treat it as that we'll come back to this if I've got it wrong but it's that's a reasonable approach I think um because it's really important to remember um when you do do your scan these adrenals can have such variable appearances and it doesn't 100% help you tell whether whether it's cushions or adrenal tumour they're they're much more complicated to I to interpret.

SPEAKER_00 49:41

I think as well it it comes down to how much people want to spend the money as well doesn't it? Because you might actually be saying in some cases well we know it's cushions we don't quite know whether it's pituitary or adrenal but if you don't want to do any more work up at this point then let's try some medication see how we respond. Because ultimately if they're responding really well to medication like does it massively matter? Because you're making them feel better and you're treating some of the symptoms so like does it massively matter whereas yeah I think if we wanted to go that horrible gold standard term then yeah imaging to work out exactly which one it is is is ideal. Um to be honest is I'm not going to be scanning them because I wouldn't be able to tell you if I'm seeing an adrenal tumor or not I'm not good enough. But um yeah I think that people that are great at scanning then it seems like the most sensible first step doesn't it I I yeah I totally like what you're saying.

SPEAKER_01 50:30

I I think that's true. And I think my when I'm reading through this myself for this episode I thought look if maybe if I get a large breed dog, I do my low dose DEX and the cortisol's high at four hours and eight hours, so it's just not responding to DEX suppression at all, maybe I'm gonna have a good chat with my owner and say look this is a bit suspicious we've got an adrenal tumor this might not go that well what do you want to do? You know, because if it is an adrenal tumor would you do surgery you know um so um and then look at the insurance part and look at how much their funds are and ask them if they want to have a referral ultrasound or a CT. And then that's how my probable take on how to do it, I think, which I think fits with how you would go about it too, doesn't it really?

SPEAKER_00 51:10

Yeah yeah and I think you've also uh so I know we were going to speak about in the pod sort of potentially if you were wanting to sort of teach yourself how to be looking for these on ultrasound exactly where you'd look but I think maybe we because Brendan always does these amazing blog posts after each podcast so that maybe we'll go into a bit more detail on the blog post rather than sort of talking through it blindly and taking ages to chat through how you do it. Because some people are probably just going to go yeah we're never going to do that ever. But if you are interested then have a little look at that blog because I think it's definitely something that you can try and learn how to do. I personally am not very good at it but I think you're much better than I am.

SPEAKER_01 51:46

Yeah it yeah you well no I'm I'm not very that good but the left one is more doable because it's kind of sitting in a nice position because the right one is tucked up under the ribcage a little bit. I think you need to sedate your patient and just give yourself loads of time.

SPEAKER_00 51:59

Okay so we've chatted a little bit through sort of how these dogs are going to present how we can work them up in terms of blood tests the testing that we want to do to try and diagnose and then maybe touch on imaging. So maybe we need to think about how we're actually going to treat these guys. So if we're thinking about medical management, I mean there is sort of one drug really that is our mainstay of treatment isn't there?

SPEAKER_01 52:20

I think there is trilostain yeah now well there is now it used to be mitatane which actually was wonderful drug to use but yeah so now it's trilostain. Um I thought this was twice a day. I think when I was reading up about this people do do it once a day as well. But um yeah and so then then you get into the monitoring um and how you monitor them as well because obviously if you go too hard with your trilostain dose then they're gonna go Adison and that is a crisis. So it's really important not to go too heavy with the dose. So build up to it.

SPEAKER_00 52:51

Even just looking at like one of the common data sheets now for one of the particular brands that we might use, I think they generally say that the starting dose is normally about two mig per gig and this one particularly says give it once daily with food. And to be honest they normally say in terms of monitoring so this data sheet basically says you should take biochemistry including lights and an ACTH stimulation test pre-treatment and then at 10 days four weeks 12 weeks and then every three months following initial diagnosis and after each dose adjustment. But the tricky thing is there's quite a lot of testing and a lot of money for people to do so it's gonna depend on you know if you've got an aggressive dog, you're not gonna be having them in for an ACTH SIM every few weeks are you? Or if it like if you can't get blood off it or if they've got no money or so I think yes you your data sheet gives you the most ideal and it's going to give you the best monitoring ideally but nothing is perfect is it so yeah I think the main thing is check your data sheet to see exactly what it suggests for the particular drug that or particular brand that you're using.

SPEAKER_01 53:55

But I think there is a little bit of give and take with this isn't there yeah that's that's good that you found you that you saw that actually yeah I I feel like as well I think no you know when we have those synacthan shortages and then the labs were kind of like look you don't need the synacthin just do a quartzold before the next trilistane's due and I feel like they kind of let the genie out of the bottle then because I do think that is a pretty valid way of monitoring these as well. And I don't think you need the ACTH STIM to monitor them. There's one one trick I have which if you have a one dog household um and I do this for my diabetics too get them to measure the water intake before treatment over 24 hours a couple of times a week and then whilst you're treating and it's a really nice way of seeing the water intake going down. And just make sure they do it and they measure it and they write it down and that you want to see it because you tell them that and then they come in with their bit of paper and they've written it all down. So you know you've kind of you've got them on you know and I think it's it's motivating for them too because when they start seeing it coming down they're like oh yeah it is working. Yeah yeah that's a really easy one uh measure water intake yeah and then maybe these just pre-dose cortisols rather than if you did want to save the owner some money and and they do seem pretty helpful in helping you decide and then obviously you just you've got to have those um symptoms of Addison's in your head at all times. Yeah yeah which you will you will know very well.

SPEAKER_00 55:19

And I guess in terms of um when to monitor because that's always another question isn't it is of when do you when do you take these tests in relation to drug dosing. I mean this particular data sheet for example again check the data sheet for the drug that you're using but this one suggests trying to get owners to dose them in the morning because then if they dose them in the morning then you can do bloods four to six hours after administration of the last dose so that probably makes the most sense whereas obviously if they were giving it at 8 pm at night then you don't really have an option unless you want to do it an hour of hours so which most people don't yeah so I'd say you know that would probably make sense.

SPEAKER_01 55:56

So yeah that's true. Yeah that's true unless you're doing your pre-trinostane cortisol but even then it might still work. I haven't even over all these years I don't feel I've done that many Cushingoid dogs maybe one every two or three years.

SPEAKER_00 56:09

Yeah again it's kind of like you know when we were talking about hypothyroidism how like that school it gets like oh this is really common you'll see it all the time and I think we do see Cushingoid dogs but I think we don't see as many as I expected to see. Yeah.

SPEAKER_01 56:25

But the dog population's changing too I mean I think less westies more Frenchies more pugs I don't know I wonder if if that's an element of it's actually is getting less common. Yeah yeah but um yeah I think the the the water intake goes down the fat the the loss the improvement to the pot belly and and the the hair is obviously going to take one to two months uh you know that's when we more one to three months kind of level but the the water intake usually goes down fairly quickly um yeah there we are and then Addison symptoms I always really drill into owners look out for these four symptoms and as I tell them often you'll get all four but any of these be on high alert and it's not eating oh I say inappetence they always go what? And I go not eating not eating vomiting diarrhea and lethargy those are the four and have that drilled into your own head as well you know because they are absolutely never forget when you've got a cushion oy patient that you're looking out for those symptoms because if you do not want to miss if they're going Adasonian.

SPEAKER_00 57:27

Yeah exactly and just if in doubt tell them to stop the trilysane and get the dog rechecked if in doubt. So don't tell them to keep giving it because it will be a lot worse if you do.

SPEAKER_01 57:37

Oh totally great advice yeah yeah and then while you're waiting for your blood then um yeah you might you could even start wanting bit of predus physiological dose yeah if you're uh if you're really suspicious.

SPEAKER_00 57:48

Yeah yeah the the one question I always have though with these is because so many people come in and you think it's cushimoid but the owners are like well the dog's fine don't really want to go through all this testing what's the point or it's like a really old dog and they think oh it doesn't really matter that they're we in a lot don't really mind and you think well how do I explain to you that this probably isn't great for your dog to be living with ridiculously high levels of steroid all the time so I mean what would you be most worried about if an owner is not wanting to treat these patients?

SPEAKER_01 58:18

You know what they never they don't have to do they I suppose I always start off with the premise that look it's that they don't have to I and then from that also I I tend to focus on loss of house training. You know I think that's the biggest issue. I think that's very universal. And I I generally say things like I do this with hypothyroid cats as well say do you know what they're actually not much fun to live with. You know trying to put it from the owner's point of view you know it's actually quite hard for them and it's quite hard for you because now they're drinking endlessly they're kneeling to wee all the time they're weighing in your house they're panting really loudly you you know you were enjoying your dog walks and now they can't go very far. Do you know it's actually better for both of you to get the treatment done. I don't know that's how probably and I think same for hypothyroid cats they're a pain to live with how many old really old cats that are possibly hypothyroid and the owners are like oh I don't want to don't want to stress her out you're like you know it's not it's not fun living with a hypothyroid cat. Well really often prior to treatment you'll do your urine test and you'll get bacteria in the urine in cushing socks. Now you don't often get lower urinary tract signs. So there is a bit of a question mark about whether you're going to reach for antibiotics or not when you haven't got lower urinary signs. Let's say you don't have blood in the urine, you might have protein but without an active like white blood cells in there without signs of low urinary tract disease, should you treat the bacteria in the urine is is the issue.

SPEAKER_00 59:38

I know Yeah and are you basing the decision to treat on culture or are you basing it on microscopy or what are you saying what are you talking about when you're talking about bacteria?

SPEAKER_01 59:47

I think nowadays I don't know if I'd be rushing to culture in the way that I used to I think if there's no lower urinary symptoms and the sediment didn't have white blood cells in even if I had bacteria and nowadays you know we do you've got those lovely um machines that would automatically tell you about all the bacteria in there yeah I I I think I'd be inclined to hold off I don't know yeah what would you do?

SPEAKER_00 1:00:15

Yeah I mean maybe it is if they've got no lower urinary signs I'd check there's no glucose in it so you've not got anything like concurrent diabetes going on or anything. But if you've got not an active sediment and such like you say like there's no white blood cells in there, then maybe you do just say to the owner, keep them informed and say look there is a bit of bacteria in here but there's not really symptoms for us to be treating at the moment. So let's just keep an eye on it. Maybe you start on the medication like you start on trilastane and then a couple of weeks later you reassess the urine and obviously you just mentioned to them if they start to develop any straining or whatever in the meantime then you reassess it sooner. But yeah maybe that is the way to go if we're trying to be really careful.

SPEAKER_01 1:00:53

Yeah and then if you might also get if the if the urinating in the house has just gone up a massive level and they're now doing it endlessly okay that could be your signal to go do you know what those bacteria in the urine maybe we will treat them with a short course of antibiotic. Yeah yeah so um yeah that's another one blood pressure keep an eye on that but hopefully that will come normal once you treat the cushions.

SPEAKER_00 1:01:15

Yeah always check blood pressure yes that's your favourite you were saying you were going in to say something about um how you might use anti-hrombotics in these is that right were you yeah about so yeah so sometimes you can do so it's quite important in your protein losing cases if you have like a massive protein losing nephropathy or protein losing enteropathy but there's an argument that potentially we could be using these in our AHDS or HGE type cases as well and because generally when you have a protein losing issue you do go into a hypercoagulable state. So using clopidogrel is probably not a bad idea but again it's very case dependent um I wouldn't be using anti-thrombotics lightly think about it um and if your dog's clinically well then it's maybe it's just a discussion you have with the owners because obviously once that protein urea urea comes down then obviously I wouldn't be keeping the dog on a clopidogrel anymore. So very case dependent use it sort of assess the patient and have a discussion with the owners and talk about it with your team etc to decide whether you're going to use it don't blanket use it for every case but it's something to consider. So yeah.

SPEAKER_01 1:02:24

When you say that the way I I can always remember this because I had a greyhound come into me it had a massively painful acute onset pain in its back leg, one back leg and we were like oh my God is it a bone tumor that's fractured pathological fracture or whatever X-rayed it completely normal and we worked out because its paw was cold it was a blood clot to its back leg. And then obviously from that we were like oh grikey it's got a blood clot that takes you to protein losing nephropathy and cushions mostly I think so then uh we did a it had grammar nephritis which I think is quite common in greyhounds protein losing nephropathy and uh yeah loss of anti-thrombin three so it's got a blood clot and it's like wow when you have that you never forget yeah exactly and like you can see it in your IMHA cases your I mean there's so many different cases where you might be considering anti-thrombotics so yeah bear it in mind have a discussion with the owner but yeah it's definitely something I'd consider so yeah why in your IMHA cases then?

SPEAKER_00 1:03:20

So in your IMHA they they generally just are in a hypercoagulable state but definitely definitely don't use it if you've got any evidence of Evans. So if you've got Evans syndrome and you've got a low platelet count don't use it. But if your platelet count is normal if your platelet count is normal then generally yeah IMHA cases should get clipidogrel. I think we're actually at roundup time. So we've we've covered all things Cushing's disease today and we hope you found this really useful and fingers crossed we've been able to add some new little nuggets you can add to help your clinical management of these cases.

SPEAKER_01 1:03:50

Yep hopefully you enjoyed it I certainly enjoyed reading up about it. I was super nerd I loved it. Anyway please get in contact with any comments or suggestions you have for us and topics you'd like us to cover next that really does feed into exactly what we end up doing on the show. So contact us via our website the WhatsApp number or just via our social channels.

SPEAKER_00 1:04:12

Yeah thanks again for listening to the Chatty Vets podcast and we look forward to seeing you next Sunday for our next two week takedown episode where we'll be covering everything from medications to reduce regurgitation in BOAS patients, bleeding bitch phase and we also have another very special guest on the show.

SPEAKER_01 1:04:27

Yes we do keep an eye on our socials next week and we will reveal it then. Until then it's bye from me and bye from me take care this podcast is intended for licensed veterinary professionals and is provided for educational discussion purposes only. Whilst it is publicly accessible it is not intended as advice for pet owners.

SPEAKER_00 1:04:59

The views shared are based on our own clinical experience and interpretation and do not replace individual clinical judgment. We accept no responsibility for decisions made based on this content and all cases should be assessed on an individual basis.

SPEAKER_01 1:05:10

Any references to medications, treatments or products are made for educational discussion only and are not intended to promote or advertise veterinary medicines to the general public. Veterinary medicine should only be used under the direction of a prescribing veteran surgeon and in accordance with the UK veteran medicine regulations.