OK, so over for our speaker. So tonight we have Martha Cannon speaking on acromegaly in cats. Martha is a veterinary surgeon with a specialty in feline medicine and co-director of the Oxford Cat Clinic, a first opinion and referral cat only clinic in Oxford in England.

Martha combines her active involvement in feline referral medicine with a commitment to provide feline-focused continuing education for veterinary surgeons and nurses. Her lectures focus on providing up to-date information and practical approaches to diseases that are commonly encountered on a day to day basis in veterinary practise. She's also proud to be involved in developing and promoting the ISFM cat friendly clinic programme.

Which provides constructive advice on how to reduce the stress cats suffer when visiting the veterinary practise, making veterinary visits easier for cats and their owners as well as the veterinary professions who work with them. OK, over to you, Martha. OK, well, thank you very much, Sophie, for, for that introduction and, and welcome everyone to this evening's webinar.

And anyone who was listening along as Sophie was speaking, she mentioned that really what I like to do, what I, I kind of, I suppose, specialise in in terms of the, the teaching and the continuing education that I do, is to take common problems that you'll see in the clinic and try and, and keep us up to date with those and look at very practical ways of managing them. So given that is my interest and, and the, and the starting point, it might seem a little odd that tonight's subject is feline acromegaly. Because certainly if we go back 4 or 5 years, we would probably have said that acromegaly was quite a rare condition in cats, and we might have mentioned it in amongst some of the rare endocrine disorders of cats, but we possibly wouldn't have given it the the headline in a webinar all on its own.

But those of you who are logging in may well be logging in precisely because you are aware that it is starting to come to light that acromegaly, or more correctly, hypersomatotropism is rather, perhaps rather more common than we thought. So This is an area where new information is coming to light that is making us think again about this topic, and therefore, I think it it fully justifies a little bit of time and thought dedicated to the subject itself, as I say, of feline acromegaly. So what are we talking about when we think about feline acromegaly?

Acromegaly, as you'll know, is over-secretion of growth hormone. And there is a major difference actually between dogs and cats in terms of the cause of acromegaly that we see. .

Cats in this instance are not at all like dogs, as we know in so many areas of feline medicine, and as in quite a few areas, they are actually much more similar to humans than they are to dogs. So in cats and also in people, when we get over secretion of growth hormone, it is due to changes in the anterior pituitary. And in the majority of cats that have been studied or identified or investigated, whether the clinical cases or in more of a research area, it usually comes down to a benign, but tumour of the pituitary.

So benign adenoma of the pituitary gland, which is overseing growth hormone and is outwith the normal negative feedback mechanisms, which would normally obviously control and and stop excessive production. Unfortunately, cats with acromegaly nearly always turn out to have essentially a brain tumour, a benign tumour of the pituitary. And that is to say is very different to dogs.

In dogs, the growth hormone is actually usually secreted from mammary tissue. It can occur, just during diestras, but most commonly, it's going to occur in bitches that are being treated with progestogens. So obviously a very different scenario in dogs to cats, and even less common in dogs than cats, so really a very rare condition in the dog.

And that, I'm afraid is as much as I'm going to say about dogs because I'm a feline specialist. I don't know anything at all about acromegaly in dogs. It's many, many years since I have treated a dog for any condition, never mind acromegaly.

So I'm afraid I'm certainly not going to be able to help you out on that score. But what we're here to talk about, of course, is the, is the cat. So, what happens when there is too much growth hormone?

Of course, it got its name because it was recognised that too much growth hormone caused growth of the body and growth of the organs, but we now recognise that although growth hormone itself does have an effect in stimulating growth, actually, what it also does is to stimulate production of the the the chemical insulin-like growth factor one, so IGF one. That's synthesised and produced in the liver and released from the liver in response to stimulation from growth hormone. And the two together have a quite a powerful overall effect.

And they'd actually have a mixture of both anabolic and catabolic effects. But, obviously what we tend to think of and what we recognise most commonly in in clinical cases are the anabolic effects. So enhanced protein synthesis, enhanced bone growth, .

A degree of lipolysis, and of course, in particular in cats, we recognise that they develop a decreased sensitivity to insulin and generally will go on to develop diabetes. So those are the sort of classic things that we think about and if we think what the effects those would have on the body, again this is where we come to the sort of classic syndrome of acromegaly which is relatively common in people been recognised for for many, many years. It causes if, if it .

If it occurs in younger people before bone growth plates have fused, then it causes what's called gigantism, and there's an example here of two lads who are identical twins. One of them has the excess growth hormone, one does not, and obviously he has the longer, long bones, the, the larger bones of the cranium, and so on. You can see that it has quite a major effect on the, on the hands and the feet.

And so, people, even if they are affected after the long bones have closed, and they don't get the necessarily excessive development of height, they do still get very characteristic changes in facial features. And hands and feet, as well as unfortunately, other internal organ issues which will will come on to. So it does produce a very characteristic appearance in people and indeed in cats, it tends to produce a very characteristic change in their body.

Confirmation and in their appearance as well. And here's a cat that that exhibits many of the classic features that we would expect to see in a cat with acromegaly. So the first thing is that it is clearly a big cat.

It's it's a cat that is continuing to grow even into adult life and into later years. If I bring my pointer up, we tend to find that the face gets very broad. We get often quite a pronounced brow ridge.

They can look as if they're frowning a lot of the time. This cat is sticking his tongue out, and that may be just because he's feeling a bit gormless right now, but actually commonly it's because the tongue increases in size and ceases to fit comfortably within the mouth. And I think you can see in this cat that we've also got some changes in the modelling and the shape of the elbows, and indeed, he has the classic big paws that we expect to see in people in their hands, but also in cats when they have acromegaly.

So this poor cat is really showing all of the classic features, you can see how broad he is around the shoulders. He's a big cat who's continuing to gain weight, not necessarily obese weight, but continuing to gain muscle mass, continuing to put down bone growth, which is slowly and progressively changing his appearance. And as we'll come on to later on, unfortunately, those changes are not limited to the bones and the, and the external confirmation.

They are also affecting the internal organs. So if we had been sitting together a few years ago and talking about acromegaly, I would have been saying to you that feline acromegaly is a rare condition, but still one that we have always needed to be aware of, because certainly still something that we see in general practise, but not a common problem. We would have said that cats with acromegaly have insulin resistant diabetes, and that is usually the, that was usually the the the the means by which we identified them.

So we would find that a cat was diabetic. We would find that it didn't respond to insulin the way we expected. We would start to look for reasons why the cat might not be responding as we would expect, and from that we would find that acromegaly was one of the potential conditions that we needed to look for, and that's usually how we then came across it.

But again, these cats classically will have uncontrolled diabetes, but they will continue to gain weight. So whereas many cats with poorly controlled diabetes have, have an increased appetite but weight loss, these cats will continue to gain weight over time. And progressively develop those classic facial and other feature changes and and and these pictures that I've put up here have come from a publication from Steve Neeson and his group at the Royal Vet College, really the same, the same cat before, and after the development of the disease, and, and it's quite striking the the difference in the facial confirmation in the before picture of a fairly normal looking cat.

And here the after picture with the big brow ridge and the widened muzzle. So that's where we thought we were. But as you perhaps know, and as I've always alluded to, we are now finding that actually, we've been wrong about that for some years, and this cat is sternly telling us, no, you need to rethink about acromegaly because actually feline acromegaly is common.

And you will perhaps be aware from some speakers that it is now thought to be the cause of diabetes in around 1 in 4 diabetic cats. Which is quite a staggering statistic. And you might hear that statistic and think, wow, really?

You might feel a bit the way this cat looks. Really, are 1 in 4 of the diabetic cats I see suffering from a brain tumour? Am I seeing 1 in 4 diabetic cats with insulin resistant diabetes and with those classic changes?

And like me, when I first came across these studies, I thought, well, this doesn't seem to fit with, with what I know, with what I see. So what's going on? Where is the, where is the mismatch?

What, what's, what's happening? And that's one of the things that I want to, try and, and, and shed some light on this evening. But before I move on to my next slide, I must say, this is, I'm being very unfair here because I've put up a very stern looking cat.

And as you will probably know, the, a lot of the recent research that has been done into this condition has come from the Royal Vet College. From a group that has previously been headed up by a chap called Steve Neeson, who is by no means a stern person. He's a very cheerful and very enthusiastic and, and very excellent clinician.

And so we should certainly give him full credit for the increased information we now have about this disease, but we should certainly also not brand him as a stern person who is going to beat us with a stick for not having known about this in the past. So let's give Steen and his group enough credit, because they certainly have spearheaded the research in the UK. But it's not just that group, it's not just the findings of one group in one centre in one country.

Other centres in other countries have also looked at this condition and have come up with really very similar results. So this here is the publication that came out of the Royal Vet College, which we will look at in a little more detail, published on PLOS One, so it's free to access for everybody. You don't need any subscription, you don't need any membership.

You can access that paper in full just by searching online. And then another recent publication over here published in JFMS, which if you are a member of the International Society of Feline Medicine, you will have full access to all back records online and indeed all new copies as they come out. So that's a huge resource that's freely available to all members of the International Society of Feline Medicine, where the practise members or individual.

And this publication, which came out in 2017, is from a different group, and they will Looking at the incidents of associated problems, concurrent problems in diabetic cats in Switzerland and in the Netherlands. And again, they found a very similar rates of acromegaly in that population of cats as the Royal Vet College group found in the UK cats and a Slightly different study, but a publication from America also again looking at IGF one in unstable diabetic cats again found similar, a similar amount in America. Although that study wasn't geared up to look primarily for, for, for, for, for acromegaly.

So, so we need to interpret that one with a little bit more caution. So we have, we have new evidence from several sources to suggest that this is a common problem and if we look a little bit more detail at the statistics from the Royal Vet College group working in London. It's a big study.

This is over 1200 diabetic cats that were included in this study. All had IGF-1 measured and in 26% of them, the IGF-1 was over 1000 nanograms per mL, which is generally taken to be the cutoff point for identifying acromegaly. Of those cats, 63 had further investigations to look into this to make sure that this was not an anomaly, to make sure that they weren't false positives.

And of those 63 cats that had further investigation by way of CT scan, MRI scan, or in some cases, I'm afraid, postmortem. 60 of those 63 cats were confirmed to have a pituitary lesion. So taking that information, I think we can draw two conclusions.

One is that IGF-1, 1 that goes over 1000 nanograms per mL. It is a very strong indicator that the cat is likely to be acromegala acromegalic, because 60 out of 63 cats that had that level of IGF-1 did prove to be acromegalic. So IGF-1 greater than 1000 has a 95% positive predictive value for the disease, which is a really very good result.

It tells us that this is a good screening test to use. If we factor that 95% positive predictive value back to the figure up here, where 26% of the cats had that level of IGF1, that would suggest that the incidence in UK diabetic cats is around 25%. We'll come back to that in a little bit more later on, but for the moment, just hold that, hold that number in your thoughts.

So that I think we would all agree is a very high number and a higher number than we probably would have predicted. And the vets who were submitting blood samples to this study were asked ahead of time whether they were suspicious that the cat they were treating had acromegaly. And what we see here is that actually a minority, only 24% of them, had a strong suspicion that the cat they were treating was acromegalic.

And in 15% of the cats, the vet ascribed that they had no suspicion of acromegaly. So these were, this was a study in which vets around the UK were simply asked to submit blood samples from diabetic cats. Whether insulin responsive or insulin resistant, it didn't matter, but just in diabetic cats across the board.

They got some free blood tests done to incentivize owners to allow the bloods to be taken and sent, and then the IGF one was measured. So 24% of the cases, there was a strong suspicion of acromegaly, but 15%, there was no suspicion. And again, looking at that in a little more detail, the reason why they usually had no suspicion was because many of the cats did not have that typical acromegalic appearance, which I've just been outlining to you.

So most affected cats looked really very normal to the vets who were treating them. And the diabetic stability of these cats was also very variable. So some cats, the samples were submitted early on in the course of their disease before they perhaps had had time for to, to, to, to establish full diabetic stability.

But whereas in the past we have thought of acromegaly is causing really very significant insulin resistance, what this study has shown us is that actually some cats with acromegaly, with a very high IGF one and with a pituitary lesion on advanced imaging. Actually can be stabilised on higher than average doses of insulin, but not the extreme doses of what we previously considered to be the true acromegalic. So some of these cats actually will be on 5 or 6 units of insulin, which is quite a lot.

But getting moderately good stability on that level, whereas in the past, we might have expected to need to use 2030, even a higher than that, units of insulin and still not get control. So we seem to be seeing a different population of cats here. We seem to be finding acromegaly in cats, but we might not previously have looked at.

Or tested for acromegaly because they didn't meet the criteria that we previously applied. So previously we would have said cats with acromegaly have insulin resistant diabetes, weight gain despite uncontrolled diabetes, and progressive changes in confirmation, typical of the disease. And I guess now we're moving to a situation where we say, well, yes, actually, acromegaly does describe that syndrome that is outlined here.

But what we are now recognising is perhaps a different population of cats that we perhaps should meet more accurately label as having hypersomattotropism. So an excessive growth hormone leading to an excess of IGF one. But those cats are, will not necessarily have developed the full syndrome, clinical syndrome of acromegaly, as we previously recognised it.

Perhaps because the more we look, the earlier we find it, and the earlier we find it, the less time they have had to develop these extremes. Or perhaps as we follow these cats and study them over time, we may find that there is a population of cats with hypersommatotropism that do not go on to develop the classic acromegalic syndrome. And so that may help to explain why we might look at our diabetic population in our clinics and think, well, I don't see 1 in 4 diabetic cats looking like a classic acromegalic.

And yet the studies would suggest that 1 in 4 of them are indeed suffering from hypersomattotropism. Now, this table is taken again from that publication from the Royal College Group, and as I say, you can go online and find it very easily and read the paper in detail. It's a very well written and very easily readable, publication, but I've just pulled out this just so that we can highlight, a couple of interesting factors.

So the first thing again is to remind ourselves that this was in veterinary terms, a big study. Over 1200 cats and 26% of them had the high IGF. You can see that this is a condition that mostly affects older cats, but actually, diabetes is a condition that mostly affects middle-aged to older cats.

And so, although there is a little bit of a tendency, for, for these, for the acromegalic cats to be A tiny bit on the younger side. I think it's probably not a huge difference. So we would still say that both diabetes and acromegaly are conditions that we more expect to see in older, more mature cats, but not in the very aged cat population, either.

So that, that, that mature adult age. We can also see if we go to the next column that male cats here, here, here this bottom darker grey row are the acromegalic cats and we can see that round about 3 quarters of them are male cats. And again, that, that's a significant, you know, that's a significant weighting.

But if we look at the non-acromegalic but diabetic cats, we recognise that again, diabetes in cats is more common in males. Cats. So perhaps we're just seeing the same the same thing reflected that diabetes is more common in male cats and therefore the study population would contain more male cats because the study population is a population of diabetic cats.

But nevertheless, we would say acromegaly more common in mature adult male cats. You can see that there was a tendency for the acromegalic cats to be a little bit heavier in their body weight, but again, not a dramatic change in fact between the two. And they did also tend to have a higher level of fructosamine, suggesting less well stabilised diabetes.

But note that the cats that were not acromegalic also had relatively high fructosamine, suggesting that at least a proportion of the cats in the study, and perhaps a reasonable proportion of them, were not well controlled diabetic cats. We also see that there was a significantly higher insulin dose being given to these acromegalic cats, but despite that high dose, they still were having these high fructosamine levels. So high levels of insulin, but still not well controlled diabetes.

And then again, this interesting last column about whether the clinicians suspected hypersommatotropism at the time they took the samples. We saw these figures earlier and we said that 24% of the the cases that proved to be acromegalic, the vets did have a high suspicion. Whereas in the non-acromegalic group, only 1% had a high suspicion for hypersommatotropism.

So we see that there is a difference between these two groups in terms of their appearance and their diabetic regulation, but we also see that there's a lot of the maybes in the middle in both groups. And I guess this is the moment to to say that we do need to be a little cautious when interpreting these kinds of studies, because there is no negative control group, and the, the study is not a controlled study. So in this particular example, the Royal Vet College were encouraging vets from all around the UK to send blood samples from diabetic cats.

But there was no requirement for vets to send blood samples from all the diabetic cats that they saw over a time period. And so it could well be, and these numbers here might imply that they were more likely to submit samples from cats that they were having difficulty stabilising and that they felt needed more information. And so this 1 in 4 number does still need to be interpreted with a little bit of caution, because the population that was being studied may have had a higher proportion of poorly regulated diabetic cats, rather than the well regulated diabetic cats.

And So we have a study which really looks at that across the board, we have to just interpret this 1 in 4 number with a little bit of caution. But I think these numbers still tell us that this disease is more common than we thought. And the clinical signs that were shown by the cats with acromegaly are interesting.

So, yes, they had diabetes, and so they had polyuria, polydipsia, and polyphagia. And, and by definition in this study, they had diabetes because it was a study of diabetic cats. It's interesting to note that there have now been just a a sprinkling of case reports, 3 reported from the Royal Vet College of cats with acromegaly that were not diabetic.

So that does appear to be a rare situation, but it certainly can occur. And again, as long as we only look in the diabetic population, then of course, we will only find in the diabetic population. But we do tend to see unstable diabetes and affected cats, in this study anyway.

Their owners reported a level of polyphagia beyond the norm. So we expect diabetic cats to be hungry cats, but some of these cats were really extreme in their search for food, their desperation for food, and it was more common to have that extreme polyphagia in the acromegalic cats than in the non-acromegalic. And then in terms of the appearance, did these cats have the typical acromegalic appearance?

Well, a higher number of the acromegalic cats had the broad facial features than in the non-acromegalic group, around about 37% of the affected cats had that feature, and that did reach statistical significance between the two groups. But of course, it still tells us that a lot of the cats, even in the acromegalic group did not have that typical phenotype. Interestingly, the researchers also noted an increased reporting of respiratory stridor and snoring in the affected cats.

It didn't reach statistical significance, but it was a trend in that direction, and that probably relates to narrowing of the nasal canals of the nasal passages because of increased bone and soft tissue. And also elongation of the soft palate, again because of ongoing protein synthesis and tissue growth, causing that stridor and snoring. So just something to, to keep a watch out for.

But an important comment an important quote from the study, phenotypical abnormalities which form part of the clinical syndrome of Arogaly, including prognea inferior, which is protrusion of the mandible, weight gain, abdominal organomegaly, broadening of the pores and the face were present in only a minority of cases. So again, if we only look for acromegaly in these cats, we will miss it in a high proportion of affected cases. Over time and given enough time, we do expect to see those changes start to develop, but it is a very gradually progressive condition usually.

However, do be aware when you do see a cat with those acromegalic features of big head. Big jaw, big feet. The chances are that internally there is a lot going on as well.

So abdominal organomegaly in terms of enlarged liver, enlarged adrenals, enlarged pancreas. But quite significantly also cardiac hypertrophy, very common in cats with the phenotypical expression of acromegaly for them to have cardiac hypertrophy, which commonly will progress to cause congestive heart failure, and that can be a significant cause of mortality in these cats. Sadly, the changes in limb bone con confirmation can also lead to a significant polyarthropathy, so changes in the confirmation of the joints, and this can be a very painful condition.

So, although arthritis anyway is common in older cats, in this cohort of cats, they very commonly get a, a really, a really painful and unpleasant form of polyarthritis. And that's certainly something we need to be aware of when we think about treating and managing these cats. Chronic kidney disease tends to develop over time as well.

And again, that's common in older cats anyway, but in these cats, they very often demonstrate a thickening of the basement membrane within the glomerulus. So that leads onto a glomerulopathy, which obviously then contributes to progressive chronic kidney disease. So again, internal organs can be affected, and we do see a, a syndrome which involves more than just the insulin resistant diabetes, which tends to be the, the headline.

And the changes in body confirmation are more than just a change in appearance, they do have very significant clinical effects on the cat. And then sometimes, again, as things progress, we will also see cats that start to develop central nervous signs, and we sometimes find cats who appear for, for want of a better word, to be suffering from a headache. They can be quite mentally dull.

They can also start to develop, seizures and other issues as things get really more advanced. And that can be as a direct space occupying effect of the growing tumour in, in the pituitary and then obviously, coming out of the pituitary fossa and pushing up into the surrounding brain tissue. So it's a, it's a nasty condition.

It's not a benign condition. It does much more than just cause diabetes, even though the diabetes is very often the headline finding. So given all of that and given this new information, we now need to think what under what circumstances should we be testing for this disease?

Again, in the old days we would have said, well, we certainly want to test cats that have insulin resistant diabetes. We want to test cats who are gaining weight, not, not obese weight, but gaining muscle and bone mass despite unstable diabetes. And we want to test any cat that has both diabetes and conformational changes, facial and paws, and so on, changes that are consistent with acromegaly.

And that's not very controversial. That's what we've always done and what we've always thought, and it's certainly, that holds good today just as it always has. But now that we recognise that not all cats will have those confirmational changes, and now that we recognise how common it is, the question arises, should we widen the scope of screening?

Should we, in fact, be testing all diabetic cats? If truly 1 in 4 diabetic cats are going to prove to be positive, then actually, a screening test, which is relatively inexpensive in the grand scheme of things. That could be done at the same time as testing fructosamine and testing for kidneys and other organ, changes which you would want to do once you have identified diabetes.

Perhaps if 1 in 4 cats are truly affected, we should be screening at a very early stage. We'll come back to that just shortly, but again, it's an interesting thought. On the other hand, I must admit I personally tend to a school of thought that says, actually, I really only want to run laboratory tests where a positive finding will have a significant change in what I can do for the cat and how I will approach treatment.

And as we'll see when we come to the section of this webinar that looks at treatment, unfortunately, treatment options for cats with acromegaly are quite limited, and for many owners, specific treatment of acromegaly will not be something that they would or could take on. So you could argue that knowing that the cat has acromegaly may not change your approach to treatment. I would argue that it would help to inform the owner of what their expectations of treatment might be, because we would expect that the cat would need higher doses of insulin.

We would be concerned that the cat might go on to develop some of those changes that we've described in terms of organomegaly, polyarthritis, congestive heart failure, kidney disease, and so on. But at the moment, we don't know that for sure. We don't know whether all of these cats with And classical acromegaly will go on to have those problems, and we do know that some of them will have their their diabetes relatively well controlled on high, but not extreme doses of insulin.

So I think this is certainly an area where we will find out more as time goes on, as we're able to follow some of these cats that are identified relatively early, as we're able to see how their disease progresses and how it affects their quality of life longer term. Then obviously we will get a much better understanding of what we should be doing for these cats. So deciding which cats to test has become something of a conundrum.

If we decide that we do want to test, then IGF one is certainly currently the only test that is commercially available to us, certainly in the UK and I believe in America and I would guess elsewhere too. And we've seen already that it is quite a reliable test. So if we take a cutoff of greater than 1000 nanograms per mL, it will give us a 95% positive predictive value.

The other side of the coin is a 91% negative predictive value for cats that do not have IGF1 greater than 1000. And those are good numbers for a screening test. We can't expect a screening test to be 100% accurate on both positive and negative predictive values.

But it does mean that when we do the test, we do need to be able to interpret the results and to consider exactly what they mean. So we need to be aware that certainly false negative results can occur. So you could have a cat that does have acromegaly but has an IGF 1 less than 1000.

That is most likely to occur early in the course of disease. As the pituitary tumour grows, as more growth hormone is produced, so more IGF one is produced and the level tends to rise over the months and years. So if you catch it very early, it may not have elevated above that cutoff level.

It can also be an issue if we are testing diabetic cats very early in, in our treatment protocol, because, rather ironically, lack of insulin will actually prevent production and release of IGF1 from the liver. So until we start insulin treatment, some cats will not be able to express the increase in IGF one in response to the excess growth hormone levels, bearing in mind that we're testing, if you like, one place removed from the primary issue, which is the elevated growth hormone. So if we are routinely going to screen all our diabetic cats, rather than only the ones that are showing insulin resistance, then we do need to start insulin treatment before we do the IGF one test and screen, probably a few weeks down the line.

How many weeks? Hard to say. I don't certainly don't, not a Whether anyone's actually studied that, but the general advice is around about 4 to 6 weeks after starting insulin therapy, if you are going to screen all diabetic cats.

Now, clearly, in that time, some cats will have already started to stabilise very nicely, and you may then feel that there is no need to screen for hypersommatotropism. But if if you do want to be on the lookout for it, just, just hold back until the cat has had a chance to benefit from the exogenous insulin that you are encouraging owners to give. And then the other side of the coin, why might we get false positive results?

They can occur. There's at least one study that seemed to suggest that possibly IGF 1 may increase over time in diabetic cats being treated with insulin, whether they are acromegalic or not. So there was a tendency for even the well stabilised cat.

To have an increase in IGF-1 over time. It doesn't seem to often go above that cutoff of 1000. So again, if we are applying that cut off quite quite rigorously, then probably it doesn't much matter how long the cat has been on insulin.

If you get a level over 1000, it is likely that the cat does indeed have hypersommatotropism. But just some caveats in how we interpret IGF one. So if we find that the level is very high and we want to confirm the diagnosis, then it is a question of arranging advanced imaging of the pituitary, whether that's by CT scan or MRI scan to identify the enlarged pituitary and or the actual tumour within the pituitary.

And certainly, if you and the Owner between you are considering what I would call specific treatment of the acromegaly, I would strongly recommend that you do, that you do do that imaging to confirm that the IGF one result is is is a true reflection of acromegaly. So that brings us to what our treatment options are in terms of specific treatment. If we think about the human situation, three main ways that we can treat, surgical removal of the pituitary tumour.

Medical treatment through a range of options and radiotherapy of the pituitary as well. And those are all treatments that are routinely offered to, to people. I think most people probably do start with medical treatment and or surgery, but radiotherapy is a widely used option.

If we think about the situation in the cat, well, we do still have those three options. But unfortunately, as you'll probably be aware, they, none of them provide at the moment anyway, a perfect and widely available option. So let's just look at them in a little more detail.

Medical management in people, 3 types of treatment that's available, the somatostatin analogues, octreotide and lanreotide are the most commonly used, and then there is this newer drug, peryotide, which can be used for people who don't respond so well to octreotide and lanreotide. Cabergoline is a good choice for people with with acromegaly. And just recently, a growth hormone receptor antagonist has become available called PEG Visoman, and that, in the UK anyway, is now, approved by NICE, the organisation that approves treatments to be prescribed on the NHS, but only in people who have failed treatment by other means.

So that's kind of held back as the, the, the sort of last resort treatment. So I was interested to know whether there was any value of Peg Visserman in, in cats. And largely that is of interest because unfortunately, these other options are really less effective.

So Oreotide and lanreotide are not effective in cats because of a difference in receptors. Similarly, cabergeline, which is commonly used in people, is not effective in cats. The serriotide, we'll come on to, it does have some value, but it is an extremely expensive treatment option.

So I was interested to know whether the peg vitamin might be useful. Did a little, pub med search looking as you can see for any papers that mentioned peg Viciment for use in cats and for felines, and you can see that unfortunately, not a single published study or published report of its use in cats yet. I'm sure they will come.

I'm sure people will be looking at it because it is an area of, of, of, of interest, and it is, it would be fantastic if we could find a medical treatment that was effective. Suffice to say, at the moment, we cannot recommend peg Viciment until or unless we get a little more information. So if we go back to our list, if pegviciant is not an option, cabergoline, octreotide, lanreotide are not effective, that just brings us back to peryriotide.

Which, as I say, does have potential value in cats. It has been looked at in some small studies. Again, if you do a search, there are only 3 publications that mention it, and the third one is actually not talking about its use in cats with acromegaly.

So if we're thinking about this population of cats, just the two studies, again, both out of the Royal Veterinary College, from the group there. Looking in the earlier study from 2015, looking at the use of a short acting in a short acting injectable form of percireotide. Cats need to be treated twice daily.

And this study reported 12 cats that were treated twice daily for 3 days, so very short study. But in all the cats, IGF-1 was reduced, and in all cats, even within that 3 days, their insulin dose was reduced. So in terms of its effect against the growth hormone and the IGF-1, it certainly does seem to be a potentially effective treatment, at least in those 12 cats.

The problem is it does need twice daily injection, and all the studies that have used preciotide or the centres that have used it. Warn us that this is an incredibly expensive drug, which is just not going to be practical for lifelong twice daily use. So the search is still on for something more practical, something more affordable.

And again, this is now quite a recent study. Just published, towards, back in, in 2017, and this one looked at 14 cats using a long acting injectable form of perciriotide. So a monthly injection rather than twice daily, which obviously would have be attractive for owners.

8 cats completed the trial. Again, IGF-1 was reduced and insulin dose was reduced in those 8 cats, and 3 of them went into long-term diabetic remission after about 3 months, which is quite an amazing finding for a medical treatment of acromegaly, and it does, you know, it does bear further investigation. There were some adverse effects, 11 cats, so quite a lot of the cats developed diarrhoea.

5 cats actually had hypoglycemic episodes, presumably because they became more sensitive to insulin, but it was difficult to adjust their insulin appropriately. And 2 cats actually had an increase in polyphagia. So there were some adverse effects, but there certainly were some positives too.

So specific medical treatment at the moment, perciotide is our only option, and at the moment, it is not a practical option for most of us because of the cost involved. Other options, surgery and radiotherapy that are used in people can certainly be used in cats. And I guess radiotherapy has been conventionally used worldwide and is probably, the, the modality of treatment that we have most experience with, most widely available, although still obviously not available to all cats and all owners in all countries.

And conventional radiotherapy, which tends to be what we use in the veterinary world, is partially effective in most cases. It doesn't tend to bring IGF one right down to normal, but it does improve glycemic control in most cats, and it does reduce the actual tumour size. So it is shrinking the tumour itself and having a direct effect on the tumour.

As well as, as, as, as reducing the amount of IGF one. So it it does have benefit. Unfortunately, the degree of benefit is unpredictable.

Not all cats gain the same level of benefit as the others, and again, this is not expecting to produce diabetic remission or cure. But it is a, a, a fairly available treatment. Interestingly, a new publication just out in 2018, so just come out this year was is looking at a different way of doing radiotherapy, the way that it is widely done in people, and this is stereotactic radiotherapy where the radiotherapy beam is more directly, aimed at the area of interest, but from different angles so that it minimises the damage to surrounding tissues, allowing higher doses to be delivered.

And in this study anyway, that did seem to produce a much improved response. So I've highlighted the results section at the bottom of the 41 cats for which insulin dosage information was available. 95% of them experienced a decrease in insulin dose, and 32% of them achieved diabetic remission.

And then remission was permanent in 62% of those cats. So that that is a much better response than we would see with conventional radiotherapy and actually approaches the type of response that we appear to be getting with perciriotide, although again, clearly we need to be very careful about extrapolating from to small studies, the serious study and and this stereotactic radiotherapy study. But nevertheless, it does, it does show that there is value here and that there is the potential to actually have a major effect on the tumour itself and of the consequences that it causes.

And then that brings us around to the 3rd treatment option, the surgical option, which is, obviously quite a, a, a dramatic concept to actually go in and remove either the tumour from the pituitary gland, which is what is usually done with people, or in cats, go in and remove the whole pituitary gland. But this is an option which is now more widely studied or, or more widely used, and we do have some publications showing that it can have significant benefit for, for, for cats for whom it is an appropriate treatment. And again, in the UK this has been spearheaded at the Royal Veterinary College at their diabetic remission and acromega acromegaly Group.

And what they have been able to share with us is that, that since 2012, they've now treated more than 40 cats by doing hypophasectomy, so removal of the pituitary gland. They see a good response rate, 85% of cats in diabetic remission within one month. Relatively high mortality rate.

This is a form of brain surgery. It's a major surgery, and Perry and postoperative mortality is reported to be around 10%, although less in more recent years as the team have obviously got more experience of handling the cats and the anaesthetics and the post-op care and so on. So a perian postoperative mortality rate of just under 10%.

Which owners, of course, need to be aware of, but given the very limited options for alternative therapies that are as effective as this, for many owners, they will feel that is an acceptable mortality rate. What they do need to be aware of is that this, this treatment removes the entire pituitary. So it isn't specific to the growth hormone producing tumour and cats after treatment do need lifelong supplementation with L thyroxine and with cortisol.

Immediately after surgery, they also need treatment with DDAVP and some of them. Need permanent treatment with DDAVP others, that's a more temporary treatment requirement in the immediate post-op phase. But that's a long term dosing commitment.

It's a long term cost commitment that owners do need to be aware of. And of course, those cats need monitoring and managing lifelong with those supplements to make sure that appropriate amounts are being given. So it's, it's certainly not for the faint hearted.

It's certainly not going to be for every cat and every owner, but if it is available in a surgical centre near you, it is certainly, at the moment, a valid treatment option and more likely to be truly effective at dealing with the tumour. The diabetes than the other options of medical treatment or radiotherapy at current, with currently available medications and currently available approaches to radiotherapy. But all of this, we hope will be a changing field as time goes on.

So those are the specific treatment options, but I, we have to recognise that for many owners and many cats, going for radiotherapy, going for surgical removal of the pituitary gland is just not going to be an option. And if truly 1 in 4 of diabetic cats have this disease, we are not going to be in a position to apply those specific treatment options to anything like all of those cats. So for those that we cannot offer those specific treatments, I'm afraid it does boil down to supportive treatment aimed at controlling the clinical signs.

And achieving as good a quality of life as we can for these cats for as long as we can, recognising that generally this is a slowly progressive disease, but that it is progressive. Of course, we need to try and manage the diabetes. To do that, we're gonna need to use the lowest possible carbohydrate diet that we can.

We know this is going to be an insulin resistance problem. We need to give ourselves the best possible chance of getting response to insulin and so the lowest possible carbohydrate diet in the UK. That would be diets like Thrive and Cannagan which are pretty much carbohydrate free.

They're wet foods, they're balanced diets for long-term use, and as I say, in the case of thrive and Cannagan, they're pretty much carbohydrate free. In the prescription diet ranges, we have Purina DM and Hills MD, which are low carbohydrate diets. Again, the wet foods will always be lower in carbohydrate than dry foods, so aim for wet foods across the board and picking as lower carbohydrate diet as you can.

But we obviously will need insulin. And again, in these cats, we are aiming to control the clinical signs, not necessarily to completely control the diabetes to within the normal glycemic range that we would hope for in a non-acromegalic cat. So we're looking to control the clinical signs to an acceptable level, and I think we do need to be cautious here to consider what is acceptable to the cat.

As well as what is acceptable to the owner. The owner may feel that if they can reasonably keep up with the cat's hunger, and the cat is not peeing outside the litter tray and they can keep the water bottles topped up, they may feel that is adequate. But think of the cat who is permanently thirsty, permanently hungry, and living with that level of discomfort, anxiety, distress at constantly trying to get access to food and water.

And I think we do have to keep in mind that for some cats that will actually be too much of an impact on their quality of life. And sadly for these cats, euthanasia usually is going to be where we end up at some stage and counselling owners to be aware of the quality of life indicators for their cats is a terribly important part of the management of this treatment of this disease. So insulin aiming to control the clinical signs, some cats do stabilise well, at least initially, at least in the early stages of the disease, but they will tend to be on higher than average doses.

And of course, some cats do not stabilise at all and end up on 2025, 30 units of insulin twice daily and still have extreme polydipsia, polyuria, polyphagia. So we tend to use a long acting insulin in the background, given 2 or even 3 times daily. And then usually these cats also need a top up with soluble insulin, given around the time of feeding, which obviously is a big difference to a normal diabetic cat.

So be prepared to use more insulin than you expect, but we do need to then monitor very carefully. Because ironically, some of these cats will at times develop an unexpected degree of insulin sensitivity, and those that are on these very, very high doses of insulin are at risk of hypoglycemia. When they hit one of these unexpected incident sensitive periods.

So home monitoring, I would say, is really essential for these cats. We cannot rely on fructosamine, we cannot rely on clinical signs because those, the, the changes can happen so very quickly. So they will be on very high doses of insulin, but again, using doses to try and control clinical signs, not expecting to eliminate clinical signs.

And then very importantly, we need to remember that there is more to this disease than just the diabetes and the changes in external confirmation. Looking out for and managing joint pain, I think, is vital for these cats. They can develop this very painful polyarthropathy, and we must manage that with non-steroidals and with joint nutraceuticals and other, other analgesics as, as needed.

We need to manage congestive heart failure if and when it occurs. So monitoring through heart scanning is certainly a useful way to, to, to, to monitor these cats over time and stepping in with diuresis when we need to. And again, chronic kidney disease, managing that as best we can in a scenario where the diabetes that the cat suffers means we need a high protein, low carbohydrate diet, so minimising our ability to use dietary management, but phosphate binders, ACE inhibitors or angiotensin receptive blockers, potassium.

Supplements, monitoring blood pressure, all the usual things that you would do for a cat with chronic kidney disease will need to be done for these cats as they move into the more advanced stages of their disease. And again, always keeping an eye on the quality of life to make sure that we are not exceeding what is what is fair for the cat to cope with. Because it's really not a benign disease.

Early on, yes, it can be well managed. Yes, it is a slowly progressive disease, but absolutely it is, you know, it is a nasty condition which has multiple effects on multiple organs and progressively over time. Which is rather a sad note on which to end.

But that is the, the reality of the situation until or unless we get better and more available ways to specifically treat the pituitary tumour, if we are if we're relying on supportive treatment, unfortunately, the disease will ultimately, catch up with us. And as I say, euthanasia is usually the end point for, for these cats. OK, so just briefly, I'm sorry, I've run over time a little bit, but just the key points.

So we're talking about overproduction of growth hormone from a pituitary adenoma, which may affect up to 25% of diabetic cats, although as we've seen that the, the population in these studies may be a little biassed, so perhaps it's not quite as high as that, but nevertheless, it is clearly a common condition and much more common than we previously recognised. Mature adult male cats are overrepresented. Most cases will have insulin resistant diabetes, but many will not have confirmational changes, at least at the time of diagnosis, although we expect and predict that they will start to occur later in the disease as time goes on.

IGF one is currently the diagnostic test of choice and a cutoff of 1000 nanograms per mL is highly suggestive of hypersommatotropism. Specific treatment options are surgery or radiotherapy if those are available to you. And surgery and stereotactic radiotherapy do appear to have potential, or would we do indeed have potential to produce diabetic remission.

Medical options at the moment are not all that practical, but we hope that in the future, other medical options may become available that are more affordable and potentially more effective. But for many cats at the moment anyway, once we know that we're dealing with this disease, it is about supportive treatment to maintain good quality of life, which if we catch it early, we can often do for many years, but ultimately, The progression of the pituitary mass will lead to damaging, damaging disease, diabetes, yes, but also heart disease, polyarthropathy, kidney disease, and ultimately neurological signs from the enlarging mass. OK.

So, a bit of an overview, a bit of a review of where we're at with this disease. A lot of questions that we hope will become more answerable as time goes on, but I am very happy to take any questions that people may have at this stage. OK, thank you Martha, that was brilliant.

We do have a couple of questions through already. While we're just waiting to see if any more come through, I just like to remind our listeners to fill in the feedback form at the end. It should be opening your browser once you close the webinar, so just fill that in and we can give you feedback to Martha.

OK, so Anne says, I have a diabetic cat who is acromegalic. Loads of photos of him. Would you like those pictures?

I would love those pictures. Thank you very much, especially, especially if the owners have any in their archive of the cat before it was acromegalic and sometimes owners can go back. Over the, you know, over the years on their, on their iPhones or their tablets or even in their photo albums and find pictures of the cat in its youth, and, and that can highlight to them just how the changes have occurred, because the changes occur so slowly that often owners are, are not very aware of them.

So that's always interesting, but I would love to have those if you wouldn't mind sharing them with me. Brilliant. And maybe if you put your email address in the chat box, I'll make a note of it and we can send it over to Martha.

And Jill has said which volume of JSMF because it was too small to read. Oh, sorry, 45 slides in. Yeah, OK, I'm gonna have to go back to the slide.

I think that's the easiest way for me to get to it. And when we get to it, I will be able to tell you. So, there we are.

So the, as I say, the, the study from the Royal Vet College is free, free to access on plus one. The original article in JFMS, it is volume 19. Issue number 8 pages 888 to 896.

But if you have access, if you're a member of the ISFM and you have access to the online resource, then if you just put in IGF1 or Acromegaly, then, or any of those authors' names, but if you just do a search for, for IGF one, you'll find that, that. That publication pops up very easily. So it's a it's a fantastic resource to have access to is the full, the full history, you know, the full gamut of all JFMS is ever published is available to you online to easily search and and download and and and print whatever articles you're interested in.

Brilliant. And one has written wonderful talk, roughly how much is the IGF one test and does it have to be a starved sample? So roughly how much is the IGF one test?

Obviously it's going to depend where you are off the top of my head, and I am, I'm afraid, guessing a little bit here, but I would say it's probably of the order of 20 to 30 UK pounds, that sort of amount. Maybe even a shade less than that, but it is, I, I, I, in my head, it's, it's sort of similar to fructosamine, that, that kind of, of cost. And no, it doesn't need to be a fasted sample.

And it's a very stable. I say that's why we use IGF one and why that's the one that's commercially available, because it is very. Stable, growth hormone can be measured, but it's more difficult to measure and the levels change quite dramatically hour by hour through the day, whereas IGF one is a nice stable level, so it doesn't really matter when you take the sample, you, you get a, a, a reliable results.

Lovely. And two questions from Ashraf. How do you manage fluctuations in insulin resistance when using high insulin dose and how how good are blood glucose cars?

I think if the owner is able to do the blood glucose curves at home, then they certainly are, are reliable and, and useful. But I think that the, the key is really that, that the owners do need to be, obviously watching the cat carefully for clinical signs, but really, ideally testing the cat most days to make sure that the blood glucose level is as high as they would expect it to be. I don't think it's practical to check every time they give insulin, especially if they're using soluble insulin through the day as well.

But it is a significant problem. Most cats, as long as we're on moderate doses of insulin in the sort of 5, 1015 range, do cope well, but we just do need to be aware and owners need to be aware as much as anything else, to test if the cat looks as if it might be hypoglycemic, so if it looks a bit vague, if it looks a bit weak, if it's vocalising abnormally. They need to test and they need to have glucose, oral glucose standing by to treat the cat straight away if there is any inkling that the cat is becoming hypoglycemic.

OK, and Carmen has said thank you for a great webinar. And is the IGF one blood test available at most labs? Yes, certainly in the UK, the majority of the external labs can, can run it.

I guess some of them may outsource it, so you send them the sample, they may possibly send the sample on elsewhere, but, it, it is, it is now a widely available test. Yeah. OK, and Anne has written the IGF1 test is closer to 60 UK pounds even to staff animals.

Apparently it's a little higher than we thought. Hm, may depend a little bit which lab you're using, but so it might be worth shopping around a bit, but if, if that's what it is, that's what it is. Fab and Anne has said, once I give you my email address, which I've got here, I'll have it sent over to you.

She will send you a link to a Dropbox account so you have access to all of those cats. Thank you very much, Anne. That's much appreciated.

Lovely. And just a couple more just saying thank you very much for a great talk. Oh, very good.

Well, I hope it's been useful, yeah. Lovely. And on that note, I'd just like to thank our listeners for their time tonight for logging on and thank you very much, Martha, for your time and enjoy the rest of your evening.

Oh, very welcome. Thank you everybody for your attendance and have a nice evening. Thank you, bye.

Thanks. Bye bye.