Good evening and welcome to tonight's platinum webinar with James McCurr, who's going to be talking about feline primary hyper aldosterism, sorry. For those of you, thank you for tearing yourself away from this crucial match that is taking place, I believe, England versus Costa Rica. I'm sure many of you are, riveted by it, but, I promise that this is gonna be twice as exciting as any England friendly, so, I'm really looking forward to tonight.

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OK, so on to tonight's speaker. I'm delighted that, James, it's the first time he has done a webinar with us, so we, we've got a new one for you. James graduated from the University of Bristol in 2008 and took a position in a busy out of hours and referral practise the same year.

He gained a certificate in AVP small animal in 2012 and has just finished his second cert AVP certificate in veterinary Cardiology. James currently works at Vets Now Referrals in Manchester, dealing with the referral internal medicine, oncology and cardiology cases. His particular areas of interest are cardiorespiratory diseases and gastroenterology.

So without further ado, I'd like to hand over to James and please, as I say, as we're going through, put any questions you may have in the box. Thank you. Many thanks for the introduction there.

So I'm here today to talk to you through this session, about feline primary hyperaldotrinism or CO syndrome. Which have called in the title an emerging endocrinopathy, because I think as we go throughout this webinar, we'll start to appreciate that we really are seeing it more and more in general practise and becoming more familiar with how to diagnose and treat it. And I think we should be increasingly aware that this disorder is out there and that it should be on our radar for those geriatric cats that present to us in clinic.

So the aims of the lecture, ideally we'd like to be able to define feline hyper-aldostrianism. And we'd like to understand the causes as well. And that will cover a little bit of everyone's favourite subject, physiology, of aldosterone.

And also we will go onto the pathophysiology of how aldosterone, is elevated in this disorder. We'll be aware of the presenting signs by the end of today. And those, as I say, are quite important to be aware of because they can mimic several other diseases of older cats.

So we have to be quite clued in as to which cats that present to us, might have this disorder. We're then going to discuss which tests are available in general practise to diagnose feline hyperaldosterinism. Whether they're the in-house tests or the external ones, which ones we sort of recommend and what are some of the pitfalls of the other tests.

And then finally we're going to become familiar with the treatment options, and they primarily are based around either surgery, which is not going to be performed generally in, in first opinion practise, but we need to be aware that that option is out there and when to refer, but also medical therapy, which is certainly going to be the cornerstone of therapy, for most of your cases of COsyndrome. So hopefully we'll achieve all of those things by the end of this session. So I'll kick off with a little bit of an introduction and I'll start talking about the history of CO syndrome.

So primary hyperaldostrinism is a disorder of the adrenal cortex. You'll hear me saying that numerous times throughout the rest of this webinar. And ultimately that leads to excessive secretion of the mineral corticoid, aldosterone.

So this was first described in 1955 by Jerome Conn, who's pictured on the right-hand side here, smoking a pipe like any good medical professional of his era. And what he found in this very first case that he described in the literature was an aldosterone secreting adenoma in a 34-year-old woman with both hypertension and hypokalemia. So if there's only two words you can remember from this whole webinar, I think it should probably be those two hypertension, hypokalemia.

I'll repeat them, ad nauseam, I'm afraid. So this patient presented with a history of periodic cramps associated also, with occasional complete lower limb paralysis, which does sound really quite scary, and altogether not too dissimilar from what we see in our feline friends. Since then, it's been studied in quite a lot of depth in human medicine, and it's reported that about 6% of all human arterial hypertension cases are caused by COhn's syndrome, and as many as about 15% of therapy and responsive cases of hypertension in humans.

So in small animals, this disorder was first described in cats, and it is gonna be cats for the remainder of this lecture, and it was first described in 1983. And this case was a geriatric cat who presented with chronic weakness and depression, which I suppose the two clinical signs we see in pretty much all feline disorders, so not that specific. But upon further investigation, they found that this cat, also was profoundly hypokalemic.

And hypertensive as well. And because of those two findings, they did some further investigating and some novel testing for hormones, and detected increased serum aldosterone levels in this patient and marginally subnormal plasma renin activity as well. So a diagnosis of primary hyperaldotrinism was reached.

And the cat was successfully treated for 2.5 months with spironolactone. Ultimately, however, the cat developed renal failure, as we get on later into this, presentation, we'll see that's not an uncommon feature, and unfortunately it was eventually euthanized.

At necropsy, they identified a large adrenal cortical adenocarcinoma, so a functional malignancy of the adrenal cortex. And then this case was written up in the Journal of Small Animal practise, as you can see in this little image below. So, the reason why I wanted to talk about this today is because this is becoming recognised more commonly, and I would say it probably is out there a lot more than we think.

And whether that's because some of these geriatric cats are not presented to general practitioners because their owners just think some of these changes are normal, ageing changes of their otherwise healthy cat, or whether it's that we're seeing these patients and perhaps not picking it up. In every instance. We also refer to this disorder as KOhn syndrome, as the title suggests, but also sometimes we see it referred to as just primary aldostriism rather than hyper-aldostrimism, but essentially these terms are all interchangeable.

So a little bit about a nap and fizz. The adrenal gland is composed of the inner medulla and the outer cortex layers. And the cortex is made up of three layers, which are the zona glomerulosa, the zona fasciulata.

And then the innermost layer, the zona reticularis, and it's the zona glomerulosa that we're gonna be most interested in, in with our COS patients because it's that layer that produces aldosterone. The fasciulata and reticularis layers are both responsible for producing glucocorticoids and sex hormones. And then the innermost layer, the medulla is responsible for the secretion of adrenaline and noradrenaline.

So I think zona glomerulosa and aldosterone pretty much for the rest of this talk. So the functions of aldosterone are due to its very strong mineralla corticoid activity. OK, so we're not talking about glucocorticoid activity, but mineral corticoid activity.

And what does that do? Well, it essentially maintains the extravascular volume and the systemic blood pressure via the maintenance of our sodium homeostasis. Aldosterone is also very important in the regulation of our potassium homeostasis, OK?

So the hormone itself acts in the distal convoluted tubule of the nephron. And it binds to a receptor there causing active sodium resorption and concurrent potassium excretion into the lumen of the nephron. So as a result of this, increased levels of aldosterone will cause an increase in the active reabsorption of sodium and therefore, water will passively follow that molecule into the bloodstream, and increase circulating blood volume.

So it's really, really important to be aware that sodium. Is the ion which is ultimately responsible for maintaining nor volemia in our patients, and any derangements of the concentration of sodium ions will cause derangements of circulating volume. And, you know, at the same time, any increase in the aldosterone will cause, a decrease in our circulating potassium concentrations when we get on to that.

A bit more later on. So, aldosterone production is quite tightly regulated by the Renin angiotensin aldosterone system or the RAR system. I'm sure we all remember being told something vaguely about that at vet school and have pretty much forgotten everything about it since because I don't know, it's something that we, we, we don't commonly have to delve into too much detail in general practise, but it's worth just recapping a couple of things for this lecture perhaps.

So how does the, the RAA system work? Well, essentially it's all kicked off with a decrease in renal perfusion pressure often caused by hypovolemia, and that's detected by the Barrow receptors in the afferent arterioles of the kidneys. We also get a decrease in the sodium delivery to the macular denser cells as well in the distal convoluted tubule, which stimulate activation of the RAS system.

And the first thing that happens is that renin is released from the juxtaglomerular apparatus of the kidneys. And then in the bloodstream, this converts angiotensinogen into angiotensin one. Angiotensin 1 is then converted by ACE, which is angiotensin converting enzyme in the lungs, into angiotensin 2.

Now angiotensin 2 is a very biologically active substrate and it causes increased sympathetic activity. It causes, increased tubular sodium resorption and potassium excretion itself to some degree. It's responsible for arterio or, vasoconstriction.

And it also helps stimulate ADH secretion as well from the pituitary gland, which can help, with water reabsorption. But ultimately, we're interested in antigentensin too because it stimulates release of aldosterone from the adrenal cortex, OK? Aldosterone may also be produced in the heart, the brain, and in the blood vessels themselves to, to a lower level.

And the heart actually specifically has its own renin angiotensin aldosterone system as well, which sometimes operates slightly independently of the systemic RAAS system. So what do we see with the pathophysiology of this disorder when things start going wrong? Well, the disorder is characterised by excessive autonomous secretion of mineral corticoids, so mainly aldosterone, that's pretty much what we're talking about.

And the levels of aldosterone being secreted are often more than 5 times that of the normal reference range. So what causes this huge increase in aldosterone secretion? Well, most commonly it's because of the functional neoplasm of the adrenal gland.

And very commonly it's a unilateral functional neoplasm. And when we look at these cases, roughly 50% of those, are adenomas, so they're benign, but functional, and the other 50% are adenocarcinomas, which are malignancies, and the adenocarcinomas, as well as causing hypersecretion of aldosterone, can cause invasion. Into the the greater vessels in in the abdomen, such as the caudal vena cava and also have the potential for metastatic spread.

But obviously both of these tumours as well will act as space occupying lesions in the abdomen. Very occasionally we will see, bilateral adrenal hyperplasia. And also occasionally we'll see idiopathic hydroaldostrianism where there is no evident enlargement of the atrial glands.

So the hallmarks of this disease really are systemic hypertension and hypokalemia, OK? So as I say, those really are things that are gonna have in the back of our minds, at at all times when we've got a patient in front of us and we're thinking, could this be cos. High prodosteroneism in these patients is associated generally with a low, circulating renin concentration.

And that's because of the negative feedback loop, that is established when you've got very high aldosterone concentrations, and lots of water and salt retention in the kidneys. It basically doesn't stimulate the macular densor cells. And the aferent arterioles of the kidney to release anywhere near as much renin, so that's part of the negative feedback loop, so we often see those low concentrations there.

What we see is that having a maintained and severe hypokalemia, we tend to develop neuromuscular weakness, and we will see that with, with lots of different disorders, as well that that precipitate hypokalemia. And we will also see maintained severe systemic hypertension, which will lead also to end organ damage. As I'm sure you're all aware, those organs that we're talking about are primarily the kidneys.

So you'll get a worsening of renal function with hypertension, the heart, so you will get, hypertrophy of the myocardium. The brain, putting you at increased risk of a cerebrovascular accident. And Yes, I've forgotten the 4th 1 there, the eyes, sorry, of course, we'll get onto that a little bit later on anyway, the ocular complications of that.

So which patients tend to develop cons. So generally they are the middle aged to older cats, OK, so our geriatrics. However, it has been reported in cats as young as 5 years of age as well.

But looking at the retrospective data, the median age is 13 years of presentation, and certainly my experience, the cons cases that I've had before have all been really quite geriatric cats. There tends to be no sex predilection in these cases, and there is also no specific breed that tends to be affected, although most cats that present are domestic short hairs, probably because most of the patients that we see in general are domestic shorthairs. So the clinical signs that we're looking for.

Well, as I've said, they're most commonly ass associated with muscular weakness due to the hypokalemia. And then the ocular signs most commonly associated with the hypertension. And that's particularly common in cats that, you know, cats get ocular complications much more frequently with maintained hypertension than dogs do, OK.

. We will show you a few pictures and talk about the specific signs in just a few slides. But the muscular weakness tends to develop at potassium levels below 2.5 millimo per litre.

And as I say, it tends to be when they're often quite significantly below those concentrations and generally quite chronically low as well. It's obviously quite common to see transient hypokalemia in cancer multiple disorders, such as patients with anorexia or those patients that are on diuretic therapy. You know, it's not that common to see such profound weakness with those cases.

However, our cos cats, they do get these signs, and the more subtle ones that might be hard to pick up on include, dysphagia and problems jumping up onto surfaces at home, which can sometimes be mistaken by owners for again, just the normal ageing process, or perhaps, osteoarthritis, which is also going to be very common in the geriatric cat population. You will occasionally see a fall in lameness due to profound muscular weakness of that limb. But generally one of the most common signs that certainly I've seen, in the cases.

In first opinion referral practise are cats that come in with a plan a great stance. So we've got a picture of that in the next slide, but that's essentially where a cat is. Ambulating slowly and weakly, and their metatarsal bones lay flat along the ground with the tarsus non-elevated.

It's quite easy to spot when you know what you're looking for. We will also see ventroflexion of the neck, so the head starts to drop in its normal position. And that's particularly profound in cats because they don't have a mal ligament which normally in dogs, for instance, would connect to the back of your skull to your thoracic vertebrae and help hold your head in the normal position of head carriage.

These signs can progress, and can be really quite profound, leading to flaccid paresis. So remember paresis means movement of the limb, but a weakness of that movement rather than paralysis, which is a lack of movement. And hyporeflexia as well, so that's a reduction in any of the skeletal muscle reflexes such as the patella or withdrawal.

It may even lead to difficulty with breathing as well, if the muscles of wrist respiration are severely affected. So on the top left here, we've got a picture of a cat with a classic planter grade stance. So as I say, it's very common in cons, but it doesn't equal cons.

The other main differential for a planter grade stance would be, a diabetic cat with a peripheral neuropathy, OK? So those two things flag in mind when you see cats coming into the consortium room walking like this. .

And then the picture to the bottom shows the progressive stages of muscular weakness, from just general weakness with ambulation to a low head carriage and then to flaccid paresis. And I certainly have seen a handful of cats that have presented at the clinic completely collapsed, unable to lift their heads off the consulting table because they are so profoundly weak. Moving on to the ocular signs, these are common, as I say, and present in approximately 50% of cases.

And sometimes, they are actually the sole reason that the patient is presented. For instance, the owner has noticed that their cat has, has become blind. So the ocular signs that we see, as I say, are secondary to the systemic hypertension and most commonly include transient anisocoria, so a temporary difference in the size of the pupils.

Madriasis, which is a dilation of the pupils, and that's often because of blindness. High femur, which is haemorrhage into the anterior chamber of the eye, associated with the rupture of an ocular blood vessel because of the maintained high pressure. And we may also see retinal detachment and or, intraocular haemorrhage.

So here are some nice images of these examples. See if I can get my mouse moving. So here we have some retinal haemorrhage, OK?

You'll sometimes see very dilated, distended and tortuous blood vessels. And with the retinal detachment, that can either be bullas, so you'll have small areas, dispersed throughout the retina that are just lifted like a little vesicle. Off the back of the eye, or you may have a complete retinal detachment and if you ever looked at the back of a patient's eyes, you've got that, you'll see the entire retina sort of billowing, in the fluid in the eye, almost like the sail of a sailboat.

The cat on the top right has bilateral myodriasis, and the cat on the bottom right has high femur or haemorrhage into the anterior chamber. So the signs may mimic several other disorders of geriatric cancers, as I've said, chronic kidney disease and diabetes can look very similar to these signs potentially. But the other things we'll also pick up are reduced bodily condition.

We will also, in some patients, and I've certainly never seen this myself, but we can, see palpable abdominal masses as well on physical examination. This is really quite rare because as I'll get on to a bit later on, the sizes of the abdominal masses are often not much larger than just a couple of centimetres, and obviously the adrenal glands are right up in the retroperitoneal space at the top of the abdomen and not the easiest things to feel. We may see a horrible disorder which is, skin hyper fragility, if we have combined hyperalostrinism and hyperprogesterism, and that's a really nasty presenting sign if you've ever seen it, whereby the skin literally fractures and tears as you're examining it because it's so thin because of excessive progesterone secretion, .

I always remember this from vet school because I remember the dermatologist saying every cat with the dermatopathy should have skin scrapes and plucks performed unless you think they've got skin hyperfragility because you will just tear through that animal's skin unfortunately. We also can see cardiac complications on physical examination, and they would generally include murmurs or arrhythmias. And as I said earlier, that's often because of, chronic hypertension leading to hypertrophy of the, myocardium.

And that's because having hypertension significantly increases the afterload on the heart, i.e., it increases the pressure within the system that the heart is having to pump into, and therefore to maintain, those pressures, the heart has to hypertrophy, in order to do that.

So that's why a lot of these cats have concurrent heart problems, or it may just be that they have another cardiomyopathy as a concurrent problem because they're they're geriatric. So how are we going to measure the patient's blood pressures? I know this might be teaching Grandma to suck eggs, but we always, are worth going over some of these points.

So we tend to use indirect blood pressure, estimation in practise, and I think the systolic blood pressure is parti particularly the most important thing to look at, rather than the, the mean and the diastolic. We tend to say normal feline systolic blood pressures are up to 150 millimetres of mercury, certainly when you're taking into account the white coat effect, which is, Certainly able to increase the cat's blood pressure by 10 to 30 millimetres of mercury. And we would class hypertension as mild when it's 150 to 160, moderate when 160 to 180, and severe when we're over 180.

In my experience, most of the COSATs do have severe hypertension, and certainly severe hypertension, you know, is the level at which we start to see these, end organs being damaged. You know, it's very uncommon to get ocular changes, you know, cardiac changes with mild or really even with moderate hypertension, though. When we're investigating these guys, we're going to look at performing a minimum database.

And this kind of applies to just most of our geriatric cats that present at the clinic as unwell, and I think these should commonly include a complete urinalysis taken by a cystocentesis rather than free catch where possible. Obviously, we're gonna pay particular attention to the patient's sodium and potassium concentrations. We're also going to check out the urea and creatinine to assess for any evidence of azoenium.

We're going to check glucose levels. Potentially fructosamine levels, calcium levels as well, obviously they can cause abnormalities of neuromuscular function. Phosphate levels and thyroxine, which I think is very sensible to check in any cat really with an illness that's over about 7 years of age.

So the specific things that we're going to be looking for, hypokalemia, I've said I'd say that quite a few times through this lecture, so that's gonna often be quite moderate to severe and it's present in almost all cases. However, the potassium concentrations may be just within, the normal range in the early stages of disease. Sodium concentrations are generally normal or they may be slightly increased.

And we may even perform a creatinine kinase, it's available on most external blood profiles that we run, and we may see that that's really quite markedly increased, in patients with a very severe hypokalemic, myopathy. Do obviously bear in mind as well, the creatine kinase will be elevated in, in any cap that you've done jugular vein puncture on if you've, you know, accidentally caused a little bit of trauma, to some of the skeletal muscles there as well, so we always have to bear, that in mind. And as I said a little bit earlier on, we need to also be quite aware of the other causes of hypokalemia in our geriatric cats because there really are quite a few of them.

So I said we're going to look at the renal values. And that's gonna be very important because CO syndrome, as I've said, can either precipitate or worsen a chronic renal problem primarily due to the sustained hypertension. We may also, as I say, have a geriatric cat that, has concurrent, chronic kidney disease just because of, of age or perhaps, previous pyelonephritis or renal arthiasis, which are also quite common in geriatric cats as well.

So an azotemia in combination with inappropriately concentrated urine is how we diagnose renal insufficiency. And that's why we should really always be running a urinalysis with our biochemistry. So it can give us a bit more information when we're interpreting azotemia, to be sure that it's not pre-renal.

So it's common in, in coms cats, and actually it's present in about 50% of these coms cats, and as I said earlier, was present in that very first case that was diagnosed as well, back in '83. So proteinuria is also quite common, and that's often present because of, high aldosterone levels, because of hypertension, and also quite commonly because of the, renal insufficiency as well. So we can assess for that on a, dipstick, on a, urinalysis, but it's quite a crude method of assessment.

So we'll often send off a urine protein creatinine ratio to get a much more accurate assessment of protein in your ear. Hyperphosphateemia or hypophosphatetemia may also be seen in KOs cats, and hyperphosphateemia is obviously particularly common in cats that have the chronic kidney disease as well, and in itself, is its own sort of kettle of fish, with respect to secondary renal hyperparathyroidism, and obviously that in itself will, require some ongoing monitoring and therapy as well. Hyperglycemia can be seen occasionally, and that will be seen in patients that have elevated progesterone levels and, and can be diabetic because progesterone antagonises, the effects of insulin.

So we've looked at the presenting signs of these animals, the physical examination, and generally some very common routine tests that we're going to do to screen for the disease and to exclude others. So now we're going to get into the nitty gritty, how do we actually make the diagnosis of COS itself? Well, That is with specific hormone testing, and the first one I'm gonna talk to you about is the aldosterone to plasma aldosterone to Renin plasma ratio, I should say, my apologies.

So that's what we call the gold standard test for this disorder. And what we tend to see are increased ratios in primary hyperaldotrinism. So our aldosterone levels are very high because of hypersecretion from the adrenal gland.

And the renin level is low because of the effects of that negative feedback. So we tend to see, as I say, high aldosterone to renin plasma ratios. However, with bilateral hyperplasia, which I did mention earlier is quite uncommon, the renin activity may actually be just within or just above the normal reference range.

The aldosterone concentrations tend to be the highest in patients with adrenal neoplasia, and as I say, most of the patients that we're gonna see with, with COs have adrenal neoplasia, so that's helpful, in, in aiding in the diagnosis. An aldostri concentrations can be mildly raised or even within reference range with nodular hyperplasia. So if they are within re reference range, but we're suspecting KO syndrome.

Then a less than 50% reduction in the aldosterone to renin ratio after suppression of fludrocortisone over 4 days can help us differentiate primary hyperaldostertrinism from normal cats. So essentially, What we're doing there is, is giving them, an exogenous mineralla corticoid flu cortisone and seeing if there is a normal negative feedback loop. You know, if it was, in a healthy animal, you would get a significant drop in that ratio, whereas you don't in cats, with, with COhn syndrome.

I must mention that that test, you know, that dynamic test is, is quite, uncommonly performed, so don't worry too much about that. So we've said, we're going to measure the aldosterone and the Renin concentrations. Well, there is a slight caveat to that, and that is because Renin activity is difficult to assess in general practise.

And that's because for a few reasons. One, there are, wide ranges in, in the normal reference range for Renin between different labs. The sample is hard to handle because it requires centrifugation and immediate freezing, so that's not always logistically that easy.

But also very few labs perform the plasma renin test, so you'd have to contact your external lab and just ask whether or not they perform it and if not, who they send it to and therefore what the turnaround is going to be. But also we often need 4 mLs of blood for for measuring that. Renin concentration, which again is a lot of blood that we're gonna be taking from a geriatric cat which may have concurrent chronic kidney disease and therefore may have concurrent anaemia of renal disease, for instance.

So many general practitioners will assess the plasma aldosterone activity alone, as it is much more accessible, OK? So aldosterone levels that are within or above reference range are inappropriate in the face of hypokalemia or hypernatremia. So that's the way we tend to make the diagnosis in general practise, hypokalemia cap with the suspicion of coms, we send off the aldosterone assay and it comes back as high, normal or increased bingo.

We can also perform the urinary aldosterone to creatinine ratio. Because they're easy to obtain in general practise and generally are representative of plasma aldosterone concentrations. And this test can also be combined with suppression induced by fludrocortisone acetate as well.

Fludrocortisone will cause a significant decrease in the aldosterone to creatinine ratio in healthy cats, but not in those with primary hyperaldosterinism, because, as I say, of that, normal and maintained negative feedback loop in healthy cats. So onto imaging So we Decided that this cat's likely to have COs syndrome that's in front of us, but what we don't know at this point is the cause of the COs syndrome and therefore what the treatment options are. So we use imaging to check whether adrenal changes are present and whether they are unilateral or bilateral.

We use it to screen for metastatic spread as well because obviously having metastatic spread at the time of diagnosis significantly worsens the prognosis and really does alter the treatment options. And as I say, we use imaging to help guide our choice of therapy. So the changes that we tend to see on ultrasound will include calcifications of the diseased gland.

And that's particularly common, you know, in the, neoplastic forms of the disease. As I say, we will often get masses as well, as a course, and we'll get abnormal ecogenicity often of one or both adrenal glands. However, it's worth being aware that the glands may appear normal in some cats with cos, just as in some dogs with bilateral adrenal disease.

Adrenal disease, sorry, because of, pituitary dependent hyperadrenal corticism, having normal sized adrenal glands does not exclude an adrenal disorder, OK? It's also worth bearing in mind that the adrenal glands could also be bilaterally enlarged with non-adrenal disease in cats, for instance, hyperthyroidism. It doesn't tend to be the most dramatic, bilateral enlargement, but certainly, detectable enlargement of the adrenal glands.

So conversely, enlarged adrenal glands don't always mean primary adrenal disease again and that's seen in dogs as well. So, abdominal ultrasound can readily be used in general practise to image the feline adrenal glands. They're certainly harder than dogs to locate because of their size, but they are measurable with the majority of practise ultrasound machines, and they're located next to each, kidney, as you would expect.

In referral practise we are sometimes using CT and or MRI as a more sensitive method of assessing the adrenal size and certainly for also screening for metastatic spread as well. So normal sizes really vary depending on what study you read, but looking at retrospective studies of imaging the adrenal glands, I would say that normal would be a width of the adrenal gland of less than 4.8.

Millimetre and a length of less than 12.5 millimetres. But as I say, there is quite a large range of variation from from one individual to the next.

Generally, adrenal tumours will range in size from 9 millimetres to about 30 millimetres. So as you can see, 9 millimetres is almost within the normal reference range, in some patients. As I said, we're gonna screen for metastatic disease with imaging, and we're gonna also look, as I said a little bit earlier, at the major structures in the abdomen, in the area of our adrenal glands, such as the corral vena cava for evidence of invasion into those structures by a malignant neoplasm.

Other causes of abnormal adrenal glands will include cortisol or progesterone, secreting adrenal masses, pheochromocytomas, which are incredibly rare in cats and more more prevalent in dogs, and also non-functional adrenal masses as well, or as we sometimes refer to them as the incidental oma. So here's an image of an ultrasound of a cat's adrenal gland and it is enlarged, but actually the the length is only slightly above reference range. And this is a cat that actually has bilaterally enlarged adrenal glands because of non-adrenal illness, and this cat was a hyperthyroid cat, OK?

So these are both CT images with contrast enhancement. Thrill So we're getting now onto a little bit of what the treatment options are for these guys. And as I say, this is something that's certainly worth knowing about in a bit of detail, because from the offset we need to have this conversation with our owners to help set them off down the right path and to manage expectations as well.

So, the first treatment option that we have available to us is surgery. So patients with unilateral masses without evidence of metastatic spread. Are excellent candidates for surgery.

And the surgery itself is certainly complicated, it's very technical and should generally be performed by a specialist in soft tissue surgery, and they can be performed, and most commonly are performed, at laparotomy at open abdomen surgery, but I am aware of certain places, whether it's in cats or not, or whether it's just dogs, but there are certain places that will, perform laparoscopic, adrenalectomy as well, which obviously significantly reduces the morbidity for our patients. So the beauty really of surgery is that it will be curative for adenomas. So if we remove that neoplastic functional tissue, we're going to remove the hypersecretion of the aldosterone, you know, and cure those patients.

It will also be curative for some of the adenocarcinomas as well. If they haven't metastasized, you know, at the time of surgery and the surgery, you know, achieves complete excision and cure, in these patients really. Is the resolution of clinical signs and the cessation of medical therapy in many cases.

Now, obviously we have to stabilise our patients, to get them to the point whereby they are safe to be anaesthetized, and we'll cover that in the, the medical therapy. In just a couple of slides, but as I say, we have to really bear in mind, what the consequences of being hypokalemic, being underweight, of having concurrent cardiac issues, and having hypertension and what that might mean. For our, you know, anaesthetic risk and an ASA grade, so we always try and stabilise our patients, prior to surgery for that reason.

Post-surgical survival times, have of many years have been reported, so patients, you know, can do really, really well following surgery. Just as dogs that have unilateral, adrenal adenomas and, and Cushing's disease, you know, can do very, very well for many years post-surgery. So it really should be the treatment of choice for those cats, you know, that we can stabilise in medical therapy and the owners are willing to undergo referral to a specialist and and pay for the, for the treatment.

However, there are downsides to surgery and we have to always be aware of those. So the main downsides are that the surgical complications, you know, can be really quite severe if we could get them. So the main one that springs to mind is, is thrombosis.

And that can be fatal in a significant percentage of patients unfortunately, and it's also something that is noted in dogs undergoing adrenalectomy, and we often, we'll pre-treat these guys with, with anti-platelet drugs to try and reduce that risk, but it is unfortunately, something that is seen, immediately following surgery. We also see bleeding being reported, as well as a complication and sepsis as well in cancers. We also have to remember that whenever we are handling the adrenal gland at surgery.

It will cause stimulation of it, and because of the medulla's ability to reduce produce sorry catecholamines, we can get significant fluctuations in, Adrenaline and noradrenaline concentrations intraoperatively with handling of the adrenal gland, and as you can imagine, that in itself has profound cardiovascular effects on our patients that are already anaesthetized. So surgery is also going to be very expensive, and it is not going to be very readily available as well. There only very few centres that will perform the surgery, and certainly, knowing a few soft tissue surgeons myself, they often become very, very shy when I mention the possibility of an adrenalectomy on a patient.

It's certainly not something that I think a lot of surgeons are chomping at the bit to do. So I would recommend definitely, getting in touch with, Tertiary referral centres and just having a conversation with them about their experiences with performing the surgery before making a referral. So if we're not going to treat these patients surgically, we're going to treat them medically and certainly drug therapy is the most commonly selected treatment option, probably because we're looking at a population of cats that are quite geriatric and may not be covered by good insurance, or the owners may worry about how much they put a cat through at that age, when they may only have a few years left in them anyway.

So it is the treatment of choice as well, I must mention in cases of benign hyperplasia or in cases of idiopathic hyperaldostriinism instead of surgery. So the therapeutic aims are normalisation of blood pressure and normalisation of potassium concentration with a reduction in the aldosterone level. And we tend to achieve this with a combination of spironolactone, potassium supplementation and anti-hypertensive therapy.

And with medical treatment, the good news is that survival times can vary, but it can vary from months to years. And certainly in my experience, I've had some cats that have lived, several years on chronic oral therapy. In the more severe or unstable patients, hospitalisation and more intensive therapy and monitoring may be required, and I have seen a few of these patients over the years.

And in these guys, potassium supplementation will be given orally as well, but certainly intravenously, in the initial stages via CRI in the form of potassium chloride. So we always need to bear in mind that we don't exceed 0.5 millimo per kilogramme per hour when we're supplementing potassium because of the cardiac complications that it will cause.

And hospitalisation periods on, potassium CRI and other supportive therapy which may even include assisted enteral feeding, via the use of feeding tubes if our patients are, too poorly to eat for themselves. The hospital. Periods can be several days, you know, depending on the severity of clinical signs, and I've certainly had patients that have been hospitalised for, for over a week actually, before their potassium levels are, normalised and are well enough to go home.

It just shows how absolutely severe, you know, the whole body potassium depletion is in these patients. So with regards to the specific medications. Spironolactone is really gonna be the cornerstone of therapy, OK, this is our go to medication for treating this disorder, and it's an aldosterone receptor antagonist which acts on the distal convoluted tubule.

So it promotes potassium retention and sodium excretion. So that's gonna bring our potassium levels back up. And it's also gonna chuck excess sodium, sorry, out of the bloodstream and take water with it to help reduce the hypertension.

The dose ranges are those that are reported in the formulary of 2 to 4 milligrammes per kilogramme orally once or twice daily. And we tend to just titrate the dose to effect in these patients starting at the lower end of the reference at the lower end of the dose range. Side effects of spironolactone are quite rare as you're probably all aware, but they do include anorexia, diarrhoea, and emesis, which all will potentially further worsen potassium levels, so you have to just be aware of them.

Potassium supplementation, may only be necessary during the initial stages of therapy, and once we achieve normal potassium levels, we can often, take patients off of the oral potassium supplementation and just, maintain them on spironol lactone. But some of the patients who have very chronic or refractory, disease. You know, may need, to stay on long-term potassium supplementation.

For individual dose ranges, I would basically go off what what your product says and what's in the formulary, and we just titrate, you know, the dose to effects basically in these patients. So muscular weakness can take weeks to fully resolve. And medical management is less likely to be a successful long term as surgical management, OK.

But certainly, you know, a lot of cats, who come into the clinic are not going to be ideal candidates for surgery because of, you know, various factors I've already mentioned, so I think, you know, you're not doing any disjustice to these patients by putting them on medical therapy long term. The hypertension itself, as I say, will improve as we lower. The amount of sodium reabsorption that we have in the kidneys, but we can also control hypertension with anti-hypertensive medications.

And as again, you'll all be very familiar with using, the first choice in cats is amlodipine, at an initial dose of 0.1 gig daily. The therapy should be maintained, at, sorry, the the therapy should be aimed at maintaining, systolic blood pressures of definitely less than 160.

And I think with newer and newer guidelines, we're saying ideally less than 140 millimetres of mercury. So titrate dose is to effect, but make sure we're leaving, enough time for changes in our, medical therapy to have their effects before we recheck their, systolic blood pressures. And monitoring of these patients.

So my recommendations tend to be the, that we monitor systolic blood pressure about once weekly, and alter the dosages, once a week with the aim of normal tension, as I say, below 160 millilitres of mercury. The serum biochemistry should be monitored weekly, with the aim, ideally of normalising potassium concentrations. Long term in our stable patients, I think 3 monthly rechecks are appropriate, absolutely.

But we need to be aware that over the course of the disease, as a functional adrenal, mass grows, the amount of aldosterone it secretes may also increase over time. So we do see in some patients that the dosages of medications need to be slowly up titrated. Over time to maintain good control of the disorder.

And as I said a little bit earlier. Survival times in patients that are medically managed will range from several months to several years. Brill, so I hope that was informative and useful to everybody and you know, I do wonder how many of these cats you guys have seen before and successfully treated, and whether or not you think potentially you know the back of this lecture, we may be picking up some more of these patients in future, and they certainly are very, very rewarding to treat in my experience, when you have that cat that's presented as an emergency that's, Geriatric and acutely collapsed, and you instantly think, oh God, this is not going to end well, because it often doesn't, given the types of disorders they have, and then actually you end up diagnosing them with cos and saying to the owners, you know what, with a bit of medical therapy at home, your cat could probably do really quite well, for several months and years, you know, and, and achieve a normal life expectancy on therapy.

So it's certainly, One of the more, in my opinion, interesting and rewarding disorders to treat. So thanks very much for listening, and I believe we are open to a few questions. Yes, thank you very much for that, James, much appreciated.

We've had some great, we've had a few questions, but also, great to see some really fantastic feedback, people saying well presented and practical, great talk, fantastic talk, so much great content. Thank you, very useful in thought. Webinar sounds like we'll be having you back definitely James from that feedback so just as a snapchat anyway.

OK, that's good to hear. So please do, post any questions. Obviously there's been some really good, practical tips and advice there.

It'd be also great to hear of any, . Cases that you've had yourselves, that you've taken a similar line or how if you've found that certain things happen, it's always good to share that information because I'm sure the people have been in a similar situation. So, first of all, we've got a question for you, Greg.

Greg says he has the cat with the potassium of 2.6 and a T4 of 90. Bun slash 38.

I'm not sure what that stands for, sorry, it's a shorthand. What was that, sorry? It says bun BUN slash C R E A.

Suggestive of iris stage 3 with presenting signs of hypothermia. Yeah, and hypertension and and and sorry, and retinal detachment. He doesn't have a blood pressure measuring kit.

The cat is 18 years old, so what would you suggest the treatment should be, as he does not want any more investigations? I assume cons and started, the laminozole, is it, and coming up. Would you add in any of the meds?

Limazole Cainox, OK. Well, potassium supplementation is, is always gonna help, so that is good. We definitely want to, improve that thyroid level, absolutely in this cat.

And there's a bit of a, a discussion that we often have, and it's a bit of a misnomer really that the better we treat hyperthyroidism. The more we decrease gomelar filtration rate, GFR, therefore, the more we, the, the less we perfuse our kidneys and potentially the worse our kidney, values can get. Now, that is true, but at the same token, having a cat with a total T4 of 90 will significantly increase your blood pressure, and that will certainly worsen renal function.

And actually we should always be treating our, hyperthyroid cats, even if they have concurrent kidney disease. And to be honest, there probably will be mild increases in our BUN and creatinine on hyperthyroid treatment. But as long as they're not shooting up, you know, immediately after starting therapy, by maintaining normal thyroid concentrations, we're actually gonna significantly improve renal function in the longer term.

So certainly if that cat's not majorly clinical, you know, with its disease. I would, yeah, definitely treat the, the, the, the, hyperthyroidism. With regards to the hypertension, I think you've got very clear signs of hypertension in that patient and, you know, that cat's blood pressure has got to be at least over 180 millimetres of mercury, could be way higher than that.

So I don't think you can do any harm by starting on anti-hypertensive therapy within, you know, the dose ranges. I think the chances of making a cat hypotensive with, anti-hypertensive therapy is very, very low. And often I find the problem is more that no matter how much we treat these cats with really advanced hypertension, we often can't quite get their blood pressure down to where we want it.

So I think there'd be nothing wrong with starting anti-hypertensive therapy, as long as you've made the owners aware that we can't monitor the blood pressure long term to be sure we're achieving, the levels that we want, but I don't think you can do any harm. I suppose the other thing to do would just be, maybe contact . Another, you know, drugs company such as one of those drugs companies that sells lots of cardiac medications to clinics and say, hey, I'm buying a lot of your cardiac meds here, could you give me, a Doppler, you know, blood pressure monitor so that I can monitor some of these patients long term for free?

That's something that I've certainly heard of other clinics doing. So, I hope that answers his question. I'm sure, yeah, that was great, thanks, James.

So, for the feedback, I think it might be something with James, so I'll just anytime I speak and then I'll mute him so I'll answer the question and that should, solve that issue. So hopefully that's answered your question, Greg. Christiane has asked in cats pre-treated with spirone lactone, how long should the medication be stopped for measurement of aldosterone concentration?

I. So, we, we would, I, I'm not quite sure of the . The reason for the question, as to is he's, I'm not sure if he's saying a patient that's been on spironolactone for whatever reason, and then we want to check, their aldosterone levels, you know, how long do we have to stop them before checking them.

That sounds, yeah, maybe if somebody's put this patient on spironolactone presumptively without doing the blood tests. Honestly, I wouldn't be able to say. I would probably think, you've got a high index of suspicion.

You know, stopping that medication for 2 to 4 weeks, but actually I wouldn't know the answer to that question I I'm afraid. No problem. The follow up to that was also, have you seen skin lesions as a side effect of, spiral oxagone?

I haven't seen many myself, no, but I'm aware that they are seen sometimes in practise. It's something that I suppose is quite infrequently prescribed for cats. You know, in general, spronolactone tends to be used primarily in dogs as part of quad therapy for congestive heart failure.

You know, in cats, we do use it for congestive heart failure. Primarily to reduce, hypokalemia associated with loop diuretics and to help reduce what we think will be ongoing myocardial fibrosis and congestive heart failure. But otherwise we don't use it very often, so that's probably why I've not myself seen, any cutaneous reactions.

No. No problem. Thank you.

We've got a question from, Ian. Great presentation. One comment, Renin activity assays went off market over last year, but we've just validated a new assay with Cambridge Specialist Labs.

They don't need 4 mL of blood. And then he follows up with, has anyone tried to use trilosta in these cats, was reported in German cases of human hyperalderism. Ah, OK, interesting.

I wasn't aware of that, so that's good to know. Yeah, I mean, to be honest. All the cases that I've diagnosed, I've just used, you know, the aldosterone and assay itself in combination, with the, the clinical picture and, and I'm happy that that is diagnostic, but now they've got the red in as well.

OK, brilliant, that's good. Otherwise, with regards to trial saying, as far as I'm aware, I've not read any of those papers, so I'd be really reticent to sort of comment on it, really, if I'm honest, and yeah, I think we've got to be very careful about what drugs we use, when we're looking at. Suppressing enzymes in the adrenal gland, because we have to be aware that there are, even though the renin angiotensin system, you know, could be summarised quite nicely on a simple diagram, there is actually a lot more to it that we're not aware of and by blocking different parts of different enzymes and different parts of that, we can actually up regulate other pathways without being aware of it.

So, it's not something that I've actually heard of, no. No problem. Greg has come back with a follow up, saying, would it be worth starting Semintra?

And then he's followed up with what's better, increasing plasma potassium, er is its spironolactone or Cainox? I'll get that one right before we finish. Take a run up to it next time, yeah, and certainly the spironolactone is much more effective than the potassium supplementation for for various reasons, really, and partly the potassium's not amazingly well absorbed, it's given orally, .

So yeah, I'd definitely say that spironolactone is the cornerstone of therapy and all patients should go on that, and I only tend to use the Camiox or Tila, whichever potassium supplement you want, to use in the initial stages of therapy. And the other part of the question, I couldn't remember, increasing plasma potassium. Oh, is it we start in er Semintra?

Yeah, I mean, essentially I, I tend to go for, you know, just, just the use of, the, the, the, the spironolactone and the potassium supplementation, and I wouldn't wouldn't use cementra no. OK, no problem. So I'll just meet you there.

It looks like that's all the questions we've had in. So, you know, it's Testament who benefit, so it's fantastic. So, you know, I'm sure we'll have you back, James.

It's, you know, people have found it very useful. The webinar will be available on our website within the next 48 hours. So if you wish to go over the webinar again, you can just log in within the next 48 hours and access the, webinar and then re-watch it, just to consolidate any of the points that James has made throughout that, period.

All it leads me to do is to say, thank you very much to my colleagues, Anna and Catherine, who have been on hand sorting out any issues you may have had. And then thank you to James also, for this fantastic presentation. And we look forward to seeing you at a future webinar.

Thank you very much, Jenna. Good night. Thank you very much for having me.

Take care, everybody. Bye bye.