Hello, everyone. Welcome to this 3rd webinar, and we're going to discuss, a couple of unusual endocrine conditions, talk about how they're diagnosed and then particularly how they are managed. So this is the first one that we're gonna cover.
It'll be interesting to know whether you've seen this condition before. It's relatively uncommon. Feline hyper aldosterinism or often referred to as KO's syndrome.
But it is something that we definitely see in a referral environment, so those cases are presenting to a, a, a primary care practise, and then some of them, of course, diagnosed in primary care practise, but maybe the more complicated ones come, come to us. So it's definitely a condition that's that's out there. And in this condition, as the name suggests, there's an excess secretion of aldosterone.
So just to remind you about the what the aldosterone is and what it does, you'll remember, of course, that's produced by the cells in the zon the glomerullosa of the adrenal cortex, so that's the outer zone of the adrenal cortex. And it's regulated by two mechanisms. Well, to be honest, predominantly one mechanism, which is the Renin angiotensin aldosterone system.
There's a little bit of input from concentration of potassium ions, but most of the stimulation of aldosterone secretion is via the RAS system. And so you'll probably be able to recall the rare system because it comes activated in response to decrease in circulating blood volume and renal blood flow. In fact, more specifically a reduced delivery of sodium and chloride to the maculadensa, which is a region closely associated with the kidneys.
And that leads to then renin secretion. And renin via a number of intermediaries, results in the production of angiotensin 2, which then stimulates aldosterone again from the zonal glomerullosa, of the adrenal glands. So in here and then see there, schematically how renin acts on angiotensinogen, which then converts angiotensin one, into angiotensin 2.
And then it's angiotensin 2 that causes aldosterone secretion, and aldosterone has a direct effect on arteries and causes vasoconstriction. So that automatically, of course, increases blood pressure, but then it also acts in the kidney, and it does a number of things in the kidney. But it predominantly causes a, a reabsorption of sodium and also chloride irons and therefore water retention.
It causes excretion of, potassium and excretion of, hydrogen ions. So then that in itself restores circulating volume. So, what about in this prim in, primary hyperaldosterinism or KO syndrome.
So this excessive aldosterone production can be primary or it can be secondary and secondary hyperaldosteronism. It's basically, you know, the physiological response to stimulation, activation of RAS by low blood circulating blood volume, i hypertension, dehydration, you know, reduced renal perfusion by other mechanisms, potentially in reduced sodium going to the maculo denser, so sodium deficiency. So that's, you know, the natural physiological activation of, RAS.
But primary hyperaldosterism or, or CO syndrome is due to a neoplastic adrenal mass, usually unilateral, occasionally it's bilateral, and it's usually an adenoma or adenocarcinoma. Sometimes the term aden adenomatous hyperplasia is used. But, so you may see those terms used interchangeably.
Or in some cases it's actually from bilateral hyperplasia of the aldosterone secreting parts of the adrenal gland, so that zon the glomerulosa. And so these animals have got an inappropriate release of aldosterone, which is Independent of RAS. And yeah, a unilateral adrenal cortical neoplasia, either an adenoma or a carcinoma, are the more likely causes of primary hyperaldosterism.
It's all about the sigma. Well, we tend to see it in middle-aged or older cats, as you might imagine, it's, you know, a, a, a neoplastic condition. And the average age is about 11 years of age.
And we tend to also see cats with this bilateral adrenal hyperplasia, again in, in elderly cats and. It's maybe that's on the spectrum from, you know, hyperplasia to adenomatous hyperplasia to adenomas. And there's no clearly reported, gender or breed predispositions, and that's probably in part because it's not a particularly common disease, so we just don't have that, have that data.
So what about the clinical signs and when should you start to consider this condition in your, in the feline population that you see? Well, we normally see signs related to significantly low potassium. So hypokalemic myopathy.
Or due to hypertension, and that probably manifests more commonly by hypertensive, retinopathy. So sometimes these cases may present acutely blind or with a reduction in vision or maybe on clinical examination, you find evidence of, of hypertension. So yeah, the hypokalemic myopathy causes episodic or acute muscle weakness.
These cats have sometimes got an inability to, you know, to jump, to climb onto furniture. They can have a plantigrade hind limb stand, so the sort of thing that you see with a, with a diabetic neuropathy. Relatively commonly, as you'll be aware, in cats with hypokalemia, they get cervical ventral reflection, so they have the inability to raise their heads.
And then, but there's other manifestations of this hypokalemic myopathy, limb stiffness, dysphagia, collapse. In, I would say in, in more commonly in the few cases that I've seen that the, features are sort of episodic. But then, they definitely reports being relatively acute onset and, and quite severe in some cats.
And then, yeah, the systemic arterial hypertension, can lead to most commonly manifested by reduction in vision, so acute onset blindness, either as anterior chamber or possibly posterior chamber bleeding, or retinal bleeding and then retinal detachment and You know, that's the extreme and subclinical hypertension is, is relatively common, so they may not present with the extremes of hypertension. And those are just some examples, of course, of things you might see top left is obviously anterior chamber, bleeding, and you can probably make out as well there's something abnormal, you've not got the normal topeal reflection and so this cat may well I got some degree of retinal detachment or significant retinal detachment and then the photograph on the right, top right, you can see again, of course, bleeding around those small retinal blood vessels, arteries, and then of course bleeding in the sub-retinal layers then causes detachment, and if that retina stays detached for a period of time, it dies off. So, yeah, we talked about signalment, clinical signs that can be episodic, that can be, acute and severe in nature.
So what might you find on examination? Well, you know, exactly those, you may find evidence of hypertension or the ocular signs consistent with hypertension, or you may find that these cats have got degrees of hypokalemic myopathy. But, you know, not every cat is gonna present, at least with the extreme ends of those, those syndromes, and some cats have just got one abnormality, or have got a completely normal physical examination.
So they may not be weak, they may not have ventral cervical ventral flexion, they may have no evidence of, you know, intraocular or ocular bleeding. Other reported findings, if you look at sort of, you know, case series of these cats, a variety of different clinical signs. Some possibly relate to concurrent diseases because of course these cats generally are, are older cats and so they may well have concurrent conditions.
So PUPD is reported, weight loss, palpable abdominal masses. Polyphagia, heart murmur, regular cardiac rhythm. So, again, the sort of caveats are that these are an older population that may have concurrent conditions.
What about on the clinical pathology? Well, these cats have got a moderate to severe hypokalemia. And so again in the sort of studies of relatively small groups of cats with primary hyperaldosterinism.
The potassium is of mean or around 2.5 millimoles per litre, and the reference is around 4 to 5.5.
So, you know, significantly, significantly decrease, but of course that's a, that's a mean. So there's cats that have got lower potassium than that and some don't present with such a severely low potassium, . But these cats can have a normal potassium at the time of your, you know, examination and, and blood sampling, so it can be quite difficult to, difficult to pick up sometimes, you know, if they don't have any clinical signs and they've got a normal, normal potassium, you'd be really struggling.
And one thing that, you know, might help you to make a diagnosis if you don't have a high suspicion of this disease is, you know, there's lots of causes of hypokalemia and most of them respond quite well to medical management with potassium. Supplementation, but if you ever have a cat that, you know, you need to give particularly high amounts of potassium to get the potassium, you know, back towards the normal reference interval, that might prompt a suspicion of this, of this disease. So these are just to remind you some of the differentials of hypokalemia, so renal related causes, increased renal loss, so yeah, CKD, .
Tubular acidosis, we don't see very, very commonly.hyrogenic things like furosemide will be a very relatively common one. You know, post cats with postostop diuresis, that get massive caloresis, loss of potassium at the same time as loss of loss of fluids, diabetic ketoacidosis, and the occasionally with urinary acidifying diets, and of course hyperaldosteroneeurysm is on there.
So it might be increased renal loss, it may be increased intestinal loss, and that's probably again a very common site of, of loss as well as the kidneys, so due to vomiting or diarrhoea, or it may be because of decreased intake and, you know, many of our patients present with hypokalemia have probably got combinations of, you know, increased loss either from the kidneys or the GI tract and decreased intake as well. And occasionally you can see intercellular shifts. So, you know, a good example, of course, there is insulin, hence why we use insulin as a management strategy for cats and dogs that are hyperkalemic, because when we give them insulin, it forces the potassium intracellular.
What other things might be see on, on clinical pathology? They can have a mildly increased sodium sometimes. It may just, represent, hema concentration.
So you can see the sort of range there and just in one study, so it's, you know, only very, only very mild. They can have significantly elevated creatine kinase if they've got hyperkallimic myopathy. They either have it at presentation or they've suffered with it in the previous, you know, relatively short, short period of time.
So you know that, creatine kinase can go into the many, many thousands. I've seen a cat with creatine kinase in the tens, late tens of thousands with this condition. So it can go significantly elevated.
So, you know, very mild elevations are less consistent with this condition, but again, you may not be sampling them at the time they are symptomatic, so that's always worth bearing in mind because these signs, i.e., the aldosterone release, can be episodic.
These cases may also have evidence of, of renal disease, and that may be because they are older cats that have concurrent renal disease, or it may be a consequence of their, hyperalotonism and particularly the effects of, of high blood pressure on the kidneys, you can imagine is gonna cause some degree of renal damage. So what else, how else? So, you know, we've got, ideally we've got, you know, the low potassium will be a big marker to try and pick these cats up and maybe that's low potassium that doesn't respond very well to sort of standard supplementation.
But you're gonna want to try and determine, firstly, whether that patient, you know, has got, an adrenal mass, whether it could be bilateral, whether it could be hyperplasia, and importantly, whether that mass is. Especially if it's a carcinoma, whether it could have metastasized to distant sites. And so we're gonna be doing diagnostic, diagnostic imaging and the advantage is that, you know, if you diagnose a, you know, a unilateral.
Tumour, then it could be cured, surgically, but of course those that have got bilateral disease or metastatic disease or a tumour that's, you know, a unilateral tumour that's invasive and is not amenable to surgery, of course, need to be medically managed. These adrenal masses are not large, so you don't see them, you don't feel them on palpation, you don't see them during with radiography. If you do see a mass, and particularly if it's, calcified, it, it maybe is a bit more likely to be a, a carcinoma.
So we tend to just jump straight to abdominal ultrasonography and then occasionally on to advanced imaging, and it's usually CT over MRI because of course the speed is required to do advanced abdominal imaging and MRI is not usually fast enough for thoracic and abdominal imaging. Angie just images, so these can be of varying size. So the top one of course is an ultrasound image and the bottom one is a CT angiogram of a a mass that's associated with one of the, one of the kidneys.
So what are the sort of if, if you look back at cases that have been diagnosed with primary hyperaldosterism or other the sort of autographic changes that you find, well, yeah, adrenal masses, adrenal calcification, and then just changes in adrenal, ecogenicity. If you have a unilateral adrenal mass, the, contralateral gland can look normal or may sometimes be small, so it's not, possible to visualise it. I would say more commonly it's of a relatively normal normal size, but just like in hyperadrenal corticism, if you have a glucocorticoid secreting.
Adrenal tumour, the other gland tends to atrophy, but that doesn't always happen in dogs also with Cushing's Cushing's disease. So, you know, you're looking really for, you know, a mass, possibly for hyperplasia, but again, it's quite difficult, you know, reference ranges, as suggested here, have, have been established, but, you know, we're not looking at, at vast increases often in the size of the adrenal glands in some of these cats that have, primary, hyperaldosterism. And you know, finding an adrenal mass, if you're lucky enough to find a, an enlarged adrenal gland or a specific mass, of course, it's not, diagnostic for hyperaloaneurysms, so you need to think about whether those are non-functional masses, which are not uncommon in in cats and definitely not uncommon in in dogs.
Could it be a cortisol secreting tumour, i.e., is that cat got hyperadrenal corticism?
Could it be a phao, so adrenaline no adrenaline, medulary secreting tumour, or occasionally the adrenal cortex tumour secrete other things, so, you know, sex hormones, progesterone, and, and others sometimes. So, yeah, it may be that, you know, tumours or hyperplastic adrenal glands, you know, there may not be enough significant enough change in size of the adrenal gland or glands to be, to be picked up with our sort of conventional, imaging. And, you know, there are some reports that suggest that that is the case, in one case series.
Only have 11 cats, so, you know, you have to sort of. Take these low numbers with a pinch of salt, but in that study, and you know, we don't know lots about the quality of the imager, the quality of the imaging machine, etc. Etc.
And you know, who knows if a different diagnostic imager with a different machine looked at those cats, maybe they would have been able to find adrenal masses or abnormalities. The adrenal gland did all those cases, but at least in this one study with this one, you know, imaging centre. Those, those, changes weren't apparent.
So if you're suspicious of this disease, yes, if it's an adrenal mass there, great. But caveats are that it may not be an aldosterone secreting tumour, but if you have a patient that is, you know, hypokalemic and with clinical signs that we've already been through, and then you find a mass, it's likely that that. Is associated with your clinical, the animal's clinical signs.
But don't rule out this condition in patients that have normal potassium, that don't have clinical signs when you, when you see them, and also don't have a, a mass on, imaging, diagnostic imaging. So again, you know, very challenging to diagnose those sort of, sort of patients. So when should you sort of, you know, maybe screen for these patients, start looking for them, .
So yeah, again, particularly in a, in a cat that's hypokalemic, you know, and or hypertensive. When, or when you can find an adrenal, adrenal mass. And you know, an adrenal mass plus those other, you know, one or both of those clinical signs would be, you know, far more suggestive of this condition.
But again, having a normal serum potassium doesn't rule out this condition and. You know, release of aldosterone is episodic, so at the time you come to sample the patient, it may be clinically asymptomatic, and it also may have normal serum potassium. But again, you know, your, your history of these episodic signs, weakness and things, particularly, or signs of hypertension and then spotting potassium probably, you know, on one blood sample at one point, you know, are gonna be helpful in making a, making a diagnosis.
So you're gonna, you know, look for maybe more common causes of hypokalemia and hypertension. So, we've been through the other causes of hypokalemia, but, you know, particularly ask about intake and ask about increased loss, GI loss, but particularly assessed for any evidence of renal, renal disease, and then, you know, look for signs of other conditions causing hypertension and. You know, common conditions with the game B CKD, but also hyperthyroidism.
How else can you go on and try and, you know, ultimately confirm the condition well, you know, you're wanting to find an elevated plasma, aldosterone concentration. The problem is just finding high aldosterone doesn't differentiate cats that have got a physiological response, so, you know, activation of RAS from those that have the, the primary, primary disease. You know, and there's a lot of sort of, variation and crossover in, aldosterone between those different, different condi different conditions, so it's not that.
Cats with primary hyperaldostrianism can have a massively increased aldosterone, whereas those cats with secondary physiologically responsive, you know, the natural physiological response have got a, you know, sort of only a slightly increased aldosterone that's not the case. There's a lot of crossover, crossover between them. So just finding a high aldosterone on its own doesn't, you know, doesn't give you the diagnosis, but again, you know, having a cat with history of weakness and hypertension and finding hypoklemia on a blood sample, finding adrenal mass.
And if the patient looks like it's, you know, normovolemic, normohydrated, and you find an elevated plasma aldosterone, you know, that's gonna be nearly as good as you're gonna get to make a, make a diagnosis. So yeah, looking at the aldosterone in combination with the potassium to determine whether it's a, you know, appropriate or an inappropriate, response. So, you know, if you find a plasma aldosterone that's above the reference interval.
In a cat that's hypokalemic, you know, the, the natural response to hypo kalemia is, you know, not to, not to cause aldosterone secretion. We want to try and retain potassium and aldosterone causes an excretion of . Potassium.
So, in a patient that's hypokalemic, you know, we'd expect aldosterone to be, to be low. So if you're finding it's high, or even within the reference interval, so that would be inappropriate in a hypokalemic cat, you know, that can sort of, help you make the diagnosis. You know, or in a cat that's, you know, clearly not hypovolemic or is in fact volume overloaded, if you're finding an aldosterone, which is within the reference interval or particularly above, again, that helps you to make the diagnosis.
So, you know, it's important that we don't always rely on finding an aldosterone that's above the reference interval, because it may still be within the reference interval. It just might be inappropriate. That cat that's hypokallimic or volume overloaded, so, you know, don't just rely on finding an elevated, elevated result.
It's the same, to use another example. It's the same in cats and dogs with insulinomas. Often their insulin is within the reference interval, but it's inappropriate because they're significantly hypoglycemic at the time you take it.
And if they had a non-insulinoma cause of their hypoglycemia, like they've got a, you know, a big liver tumour or they were septic, or they've got Addison's, to give 3 examples, you would expect that insulin to be massively down. Unregulated. So those those dogs and cats with insulinomas that are hypoglycemic can have an inappropriate insulin, which is an insulin which which is within the reference interval, but it's inappropriate.
And other caveats are that, you know, high aldosterone has also been reported in cats with CK CKD as well. And the higher in the game, the sort of smaller numbers of cases, the higher aldosterone values tend to occur in cats with adrenal cortical tumour rather than hyperplasia. So what you really need to do then, you know, if you've got a case that's got high aldosterone and, you know, you're not sure about volume status and there's some uncertainty about how potassium plays in is really to measure renin, because that's gonna help you differentiate from, you know, a physiological aldosterone secretion because of raz activation.
Because in those patients, of course, if you've got high aldosterone, cause you've got RAS activation, you're also gonna have high renin, whereas in these patients with a primary hyperaldosteroneism, they're inappropriately secreting aldosterone. It's not under the control of RAS systems, so they'll have a normal or a reduced renin. The problem is it's it's not very many labs offer it, and it can be quite expensive and difficult to, to measure or to transport to the lab for measuring.
So that's, you know, in a, in an ideal world, but in practise, you know, we're gonna be looking for, clinical signs, you know, evidence of hypokalemia, maybe hypokalemia that's not responsive to standard therapy or, you know. Keeps returning, you know, plus or minus hypertension, on your Doppler blood pressure analysis for clinical signs of hypertension, and then, you know, ideally, but not always evidence of a, of a mass on diagnostic imaging. And I, I mentioned CT and MRI and, you know, there's no good studies to show that at least, you know, CT isn't is better in finding these masses than ultrasonography.
You can be lucky in one imaging modality over the other sometimes, so you may see them on CT and not on ultrasonography and, and vice versa. So we would always start with ultrasonography and occasionally go on to advanced imaging by way of CT if we're. I'm still really suspicious and we're struggling to identify a mass, particularly if that patient, you know, the owners of that patient may be interested in surgical management.
So, yeah, as I mentioned, you know, aldostro and ideally measuring with Renni is Renin is, the sort of diagnostic test, but it's not often, it's not often, done. So finding a, a, high aldosterone and a normal or a low renin, suggests primary hyperaldosteroneism. And yeah, it's, you know, renin's been measured in, in, in small numbers of, of cases.
And these were cases that had histological evidence of primary hypo aldosterinism due to, due to tumours and, you know, it may be the way sampling's been done, timing of sampling, all sorts of things. So you can see it's, was actually within the reference into pulling, you know, more than, well, half those cases, so. Again, it's maybe it isn't a gold standard and we very rarely do it because of the challenges we already talked about in analysing it and cost and it's reliability.
In humans, they do, yeah, do ratios of aldosterone to renin, but they have other methods to try and diagnose these, these patients with this condition. OK, so what about treatment if you have made a diagnosis of this? Uncommon, but again, we, you know, we do see numbers of these, these cats, so look out for them, they'll be coming through your practises.
How would you, how do we manage them? Well, it's medical management or surgical surgical management, and this was a cat with a small-ish adrenal tumour that had primary hyper aldosteronism. So the sort of initial treatment, you know, you're not going to necessarily do surgery straight away, and the initial treatment is gonna be sort of medical because you want to control the, hypokalemia and, and manage the hypertension.
These are of course not good candidates for anaesthesia if they're significantly, hypertensive or they've got significant hypokalemia, so. Potassium supplementation, might be required intravenously in the hospitalisation in those more severely affected cases, or oral supplementation with, you know, quite a bioavailable potassium like potassium gluconate at moderately high doses, orally a couple of times, a couple of times a day. But you, as I alluded to earlier, you can often, struggle to to normalise, serum potassium concentrations.
But you can, improve serum potassium enough that hopefully you normalise clinical signs, or at least there's a big improvement in clinical signs. So again, going back to the sort of diagnosis, if you've got a patient that you're struggling to normalise potassium with your standard sort of oral or IV treatments, again, think about this, this condition. What other medical management then, so Spranolactone is, is the sort of drug that we use.
So you'll remember it's, you know, commonly used as a diuretic, but the reason it's used as a diuretic, it's an aldosterone antagonist. So it then results in potassium retention and, and sodium and water excretion, and the sort of standard, standard doses often starting maybe the lower end, but it may depend on what size, medication and the size, size of the cats. .
You might need to use potassium gluconate in combination with this aldosterone antagonist ranolactone, when, you know, you've got refractory hypokalemia. Other drugs you're gonna be using are, amlodipine, so you'll remember that amlodipine is a calcium antagonist. It acts in the, in the periphery really, rather than the heart.
So it acts then as an arterial vasodilator, so of course, decreasing blood pressure. And the sort of standard dose is about 0.625 milligrammes per cat once a day.
And you know, using the sort of standard doses or increasing to 1.25 mg per gig per day, many cats become nor intensive, but you do sometimes need to titrate up the dose and if you've still got then got refractory, . Hypertension, you could add in another drug like an ACE inhibitor, which are, you know, OK, anti-hypertensives in cats are no way as good as amlodipine tends to be.
So, you know, potassium supplementation, IV orally, spriolactone, there's aldosterone antagonist, if they're hypertensive using amlodipine. And, you know, there isn't a sort of one rule fits, fits all for these cases, so you're gonna have to titrate the doses of drugs based on the potassium, and also on the other the blood pressure. And you're gonna monitor these patients.
From the electrolytes, i.e., you know, predominantly potassium, and their blood pressure every sort of 557 days.
And as I say, although you may not be looking to normalise them, particularly the potassium, it would be nice to, it would be nice to try and normalise the blood pressure. If you're not able to normalise potassium, hopefully you've increased it to such a level that you've got control of, of clinical signs, . But you know, maintaining a normal blood pressure is quite important because we know that not only does hypertension cause the retinal and ocular damage that we've talked about, but it also potentially causes CNS damage, renal damage and other end organ damage.
So that's a particularly critical one to try and get really on top of the hypertension, which can be very significant in these cats with primary hyperaldosterinism. What about surgery? Well, I mean, surgery can be curative in these cats, and there's a great treatment option, but you have to have the, you know, the right patients, I, you know, you're only gonna be managing these patients, as we've alluded to earlier, we've got a unilateral, adrenal disease.
And no evidence of, of, of metastatic disease and, as we said, you need to correct the hyperkalemia and try and get that hypertension under control, preoperatively. There is quite a high perioperative, mortality, but again, there's, you know, relatively few, cases reported in the literature. So, you know, we have to sometimes take these, figures with a bit of a pinch of salt.
So, you know, again, it can be, can be curative and these patients then don't need any further medical management. So it should definitely be an option, in the, in these cats. They've got unilateral disease and no evidence of metastatic disease.
Yeah, what's the sort of prognosis? Well, these are generally older cats anyway, so we're not expecting them to live, you know, 10 years or more. So the survival time that's been reported in smaller numbers of cats that have had medical management with potassium supplementation, aldosterone antagonistronolactone.
Am amlodipine, you know, they can survive for, for several years and I'm sure there's cats out there that have lived for much longer than that. And yeah, in some cases, the, well, both the hypokalemia and also particularly the hypertension can become refractory to, to medical management, no matter how much amlodipine or ACE inhibitors combinations of you give, these cats can still be hypertensive and you struggle to get on top of their potassium levels as well. But if you have a cat that's got a unilateral tumour and there's no evidence of metastatic disease, and it's completely excised, you know, they can live for significant, significant amounts of time.
And again, caveats with these figures are, these are cats that are, that are older and so have probably got concurrent conditions as well, so. Bear that in mind when you're, when you're looking at survival figures, you know, periods, and sometimes these studies are quite old and things changes in the management and new drugs come along and things you should really interrogate the studies that provide these survival, survival figures. So yeah, look out, look out for that condition, primary hyperaldosterinism or COhn's syndrome.
It's, you know, middle aged to older cats. They may have acute onsets and severe, they may have milder and episodic signs, particularly like muscle weakness, and they went through the various signs of muscle weakness. You know, or they may be ones that present to you as hypertensive and you can't find another cause of hypertension.
It'd be nice if they all had significantly low potassium on serum biochemistry, but they don't at the time you sample them, just like they may not necessarily all be hypertensive at the time you sample them because the aldosterone is secreted episodically from, most commonly a unilateral adrenal tumour, either adenoma or a carcinoma, but occasionally it can be bilateral tumour and sometimes it can be bilateral hyperplasia. So we talked about the, the diagnosis, which can be quite challenging, particularly finding an adrenal mass, and then we talked about measuring aldosterone, which should be done, ideally with Renin, but Brennan's challenging and doesn't always give us the, the answer. So good clinical examination just to make sure as best we can.
This patient shouldn't have activation of RAS, so, we sort of talked through one or two scenarios that would help us really make a diagnosis of this condition and then treatment, of course, surgical or using potassium supplementation, Spranolactone, and managing the hypertension. I wanna, move on to next discussing diabetes insippidus. It's not a very common cause of polyurea and polydipsia, not at least in its sort of, you know, extreme forms, but we definitely see cases that are diagnosed with central or nephrogenic diabetes incipidus.
As an absolute thing. So yeah, ADH or vasopressin is the hormone that we're, we're talking about, and that's released from the, posterior pituitary. And there's a variety of things that lead to its secretion.
So, you know, the end result of its secretion is that it increases renal absorption of water. So the things that cause it to be secreted are things like, you know, reduced circulating volume, decreased cardiac output picked up by Barrow receptors, increased plasma osmolarity. Yeah, decreased blood volume, and there's some other things like, like pain as well.
And it, it travels in the circulation. And it gets to the kidney and particularly in the, the collecting duct. And it causes insertion of these things called aquaporins, which are also known as water channels in the apical membrane.
So you'll of course remember that in the kidney you have a concentrating gradient and that's predominantly made up of, you know, higher levels of urea and and sodium within the medullary interstitium. And so as you, as water passes down that tubule from the cortex, sorry, from the glomerulus downwards towards the collecting duct, you know, you get increasing concentration of that gradient that allows water to be removed from the lumen of the tubu and passed back into the bloodstream by the vasoreta. And so when ADH is released, as I say, it's one of these receptors on the basal membrane.
Of the collecting duct cells, the principal cells in the collecting duct and causes these water channels, aquaporins to be inserted in the apical membrane that then allows water to pass from inside the tubule across the apical membrane, inside the cell, and out and again, you know, back into the systemic circulation. So that's how and where ADH or or vasopressin as it's often caused is, is working. So diabetes is, is, Diabetes Incipius, sorry, is either of two types.
It's either central diabetes incipidus or it's nephrogenic diabetes Incipidus. And in central diabetes incipidus, we've got a partial or a total failure to synthesise or release antidiuretic hormone vasopressin. And there's a number of causes in dogs and cats that we go on to diagnose with this condition.
There's a number of postulated causes, but many times either we don't go on to do diagnostics, particularly looking for, you know, advanced imaging, looking for some of these things within the brain, we decide it's, you know, i idiopathic or of unknown cause. So, neoplastic disease, either primary or metastatic, you know, trauma or infection, inflammatory, developmental disease, structural disease, which is gonna be affecting the posterior pituitary's ability to produce ADH. Nephrogenic diabetes incipidus, there's sort of two types, I guess, of nephrogenic diabetes incipidus.
There's primary nephrogenic diabetes incipidus, which is where the kidney isn't able to respond to antidiuretic hormone. Either has no response or only has a partial response to antidiuretic hormone. So, primary nephrogenic diabetes and sympathis is quite uncommon.
It's maybe more commonly patients that have got congenital disease, so they've got lack of those V2 receptors, or they've got abnormal receptors or they've got problems with acroporins, those those water channels. But you can see a sort of primary nephrogenic, it's probably only partial primary nephrogenic diabetes and syphis in patients with, you know, renal disease, if there's fibrosis, if there's calcification of their kidneys, that can affect the ability for anti-diuretic hormone to work. The most common cause of nephrogenic diabetes incipidus is a secondary nephrogenic cause.
So that's where you've got something that's interfering with the action of ADH. ADH is being produced, it could work in the kidneys, but you've got something that's antagonising it or interfering with it. And you know, relatively common causes are things like hypercalcemia.
Inflammatory cytokines, toxic cytokines, steroids, either endogenous, in the case of, hyperadrenal corticism or exogenous steroids. And in these conditions, these patients, you know, are, you'll recognise, of course, these patients are polyurec and polydipsy and they, they drink more because they're unable to maintain water. So they've got a primary polyureic because their anti-diuretic hormone, vasopressin is getting antagonised by the high calcium or the inflammatory cytokines, or the steroids, and so they can't insert those aquaporins and then try and retain tubular fluids.
So, you know, secondary nephrogenic causes are quite, quite common. What we're really talking about here is the primary nephrogenic cause for patients with central diabetes incipidus. And yeah, well, there are clinical signs of diabetescipida, so it should be on your list of causes of polyurea and polydipsia in both dogs and cats, but it should be quite low on your list.
Things that might increase my suspicion of this condition are pretty severe, polyrhea and polydipsia. So these animals can be drinking hundreds of litres of water per day, and sometimes they are just not even then able to retain retain enough water. And so they become dehydrated, they get weight loss, they develop CNS signs.
In part they develop the weight loss because they're probably also anorexic because their stomachs are full of water all the time. You know, they may have a severe polyurea and they're, you know, urinating or urinating at night or they're incontinence. It can be acute onset, so patients with, trauma, to their CNS or to their brain or posterior pituitary, maybe more accurately, or the hypothalamus, of course.
That can cause relatively acute, acute onset, you know, infarctions, bleeding, . Could be, could be other causes of relatively acute onset, very severe PUPD would raise my suspicion of them having diabetes incipidus. What about the what might you find on laboratory, laboratory testing, well, their urine specific gravity, this is another giveaway, it's often very, very significantly low.
So it's usually in the 1. You know, 001 to sort of 1.005.
If you're investigating a PUPD dog or cat and it's got You know, you're in specific gravity that's 1.0, 10 and more than that, then, you know, it won't have diabetes incipidus or at least it, you know, it will possibly have some partial form, but definitely won't have complete absence of ADH or inability to, to respond. We don't tend to measure, urine osmolarity, but if you were to, that's also, also low, just like we don't routinely measures plasma osmolarity, but that would be extremely high, you know, they're sort of, you know, deficient of circulating water.
So history of significant PUPD producing very, dilute urine, urine with a really low USSG. And ultimately the diagnosis is via the water deprivation test, but if you've ever done that before, you'll remember it's quite challenging, it's time consuming, it can be costly and it, it can be dangerous as well. So sometimes we trial treat them with synthetic ADH or desmopressin.
But the water deprivation test can, we do occasionally perform it, and it can be, can be useful. So yeah, have a look in in texts, there's something like the BSAVA endocrinology manual is a good source, the BSAVA guide to procedures in small Animal practise, subtle plug for that, book that I co-authored has got details of the water deprivation test in there. And as I say, we can also consider it a desmopressin trial.
So this is where we give synthetic ADH and assess the response. And we normally give it into the conjunctiva and we give it a few days to a week or so to work to see what the response is. The problem is there are issues with that trial in that patients that have other causes of PUPD can, of course, respond to, to desmopressin.
But it's often done in preference to a water deprivation test. But the critical thing about water deprivation tests or a desmopressin synthetic ADH trial for that matter, is that you must rule out the vast majority of causes of, of PUPD before you do a water deprivation test. So you should really only be left with patients that you're suspicious of got either psychogenic polydipsia or diabetescipidus, either central or nephrogenic.
So yeah, make sure you rule out other causes, you know, more common causes of PUPD renal disease and hyperadrenal corticism and hypoadrenal corticism, hypercalcemia, liver failure, and others. Before you do a water deprivation test, because otherwise it's challenging to interpret, and, you know, you can do a lot of harm by starving the patient that's hypercalcemic with water or of course starving the patient with renal disease or that's got hypoadrenal corticism, of course. So it is a test then to differentiate diabetes Incipidus from psychogenic polydipsia, that, that's, that's why we do it and.
This sort of gives you a tabulated, and again this is taken from textbooks, this gives you sort of tab tabulated results. So ultimately what we're doing is we're sort of starving these patients of water and then measuring their urine specific gravity. You know, a normal healthy patient, of course, when you start to starve it of water should produce ADH vasopressin and concentrate its it's tubular fluid.
It's urine, i.e. Retain retain water, and that's sort of what happens in a patient with psychogenic polydipsia.
So these, these patients have got psychogenic, psychological, whatever you want to call it, cause of their polydipsia, which can be very significant. Sometimes you change their environment like you put them into a veterinary veterinary hospital and they, they're drinking massively reduced, so that can be diagnostic in itself. .
But what happens when you do the water deprivation test in these dogs and cats is that after you've starve them of water, they're able to relatively quickly, concentrate their tubular fluid and produce urine that's above, you know, 1020, 10 or 10:30. But in patients with diabetes incipidus, either central or nephrogenic, when you starve them of water, even though they're clinically dehydrated and they're losing body weight, and they are unable to significantly concentrate their urine. And then we differentiate Central from nephrogenic diabetes Incipidus by then injecting, synthetic ADH, desmopressin, and patients with central diabetes Incipidus that aren't producing ADH are gonna be able to respond to that ADH.
Their kidneys are working fine. So after we inject ADH, their urine specific gravity normally rapidly increases to, you know, 1015 or often in reality, well above. Whereas these dogs and cats with their primary nephrogenic, so either they've been born with, you know, .
Receptors for ADH that don't work in their kidneys or they've got problems with those aquaporins or other reasons, you know, you give them ADH and it doesn't make much difference to their urine specific gravity. It might change it a bit if they've still got some receptors that are working or some aquaporins, but you're definitely not gonna get significant increase in urine specific gravity. So that's a diagnostic, yeah, there's, you know, the, there's sort of protocols in textbooks.
You also tend to do what we call a sort of modified water deprivation test. That's when we gradually reduce their, water intake in the home environment for usually 3 days before they, before they come in. So patients with central diabetes and scipidus if that's what you diagnose, so these patients are not producing ADH or not producing enough ADH, you know, it, it's.
You know, it's doesn't necessarily harm them to have this condition, but really critically, you must not strict access to water, so they only need to be able to cope with this very significant increase in PUPD and noctura and incontinence and things. But they do respond, or they can respond very well to synthetic ADH desmopressin. And it's a sterile solution that's either given intravenously and we do that when we're doing the water deprivation test or the second part of it, or the solution for home use, which is, Intra-nasal, but to be honest, we often use that intranasal solution in cats and dogs into the conjunctiva, or if they will tolerate it into the nose, but more commonly into the conjunctiva and there's standard doses, it's quite a small amount, you know, we're using one to sort of 4 drops maximum 1 to 3 times a day, and it makes a vast difference they're drinking.
They go from drinking hundreds of millilitres per kilogramme per day to drinking normal amounts within. You know, hours after starting the first doses and subsequent doses of synthetic ADH, I wouldn't use the tablets, they're quite unreliable, get the, get the drops that you can then use nasally or in conjunctially. Some people also use, dietary, dietary restriction, changes to the diet, particularly sodium restriction, but they're not gonna work alone and, .
Probably not probably not required in most, in most patients unless you're really struggling with synthetic ADH treatment. So yeah, that's, central diabetes incipidus. So, nephrogenic is luckily quite uncommon.
There isn't an easy solution for treating nephrogenic diabetes incipidus. You know, you can't sort of give them a, you know, replacement, receptors in their kidneys or aquaporins and things, so, . You know, they can sometimes respond to some excess Desmopressin, but often they've got circulating amounts of excess Desmopressin already, so there aren't any good, good management options for those guys, but they, central diabetes Eyfidus, as I say, they respond, pretty well usually to Desmopressin.
So yeah, I hope you found that useful. Just time to go through sort of a couple of, couple of the more unusual conditions. So yeah, we started with primary hyperaldosterinism or, or CO syndrome and talked through that.
Main signs were hypokalemic myopathy or hypertension manifesting as retinal bleeding, retinal detachment. Anterior or posterior chamber bleeding. These cats might not always, these older cats might not always have reduced potassium when you do your testing because their signs can be episodic and hence their release of excess aldosterone can also be episodic.
We move on to do diagnostic imaging, but we may now always find an abnormality there, and then probably do some measurements of aldosterone. And again, you know, people have previously measured renin, but it doesn't always, doesn't always help. So we have to look at a number of things in combination and also rule out other more common causes of, of hypokalemia and hypertension.
And then yeah, we finished by talking about diabetes and cipidus, which is either central, not producing ADH or enough of it, or nephrogenic, not able to respond to that ADH, but we said the caveat was the secondary nephrogenic, which is a very common cause of PUPD. Patients with hyperkalemia or exogenous or endogenous steroids or bacterial toxins that impede . AD ADH working.
And then we went through, briefly touched on the water deprivation test or a trial of Desma Preston, and yeah, finished by talking about the treatment of, central diabetes incipidus. So, yeah, I hope you found that useful. I look forward to seeing you in the, next webinar.
Thanks very much.