Lovely, thank you very much, Rich, and thank you everybody for joining us tonight. So Addison's disease is one of my favourite diseases for a couple of reasons. One, because it doesn't affect the patient's life expectancy.

They can go on and live a normal life with this disease, and secondly, because it's called the Great Pretender because it can present in so many different ways, and that's what makes it interesting to us as nurses, both to try and figure out what's going on with these patients and also to nurse them afterwards. OK, so a brief introduction. So it was first described by Doctor Thomas Addison in 1849, and they came across it through tuberculosis of the adrenal glands in humans.

And he also first described pernicious anaemia in humans as well. So a little interesting fact, JFK was a sufferer of Addison's disease as well. And this disease is uncommon in dogs, but we do believe that it's under diagnosed, so it may actually be more common than we initially believe, and the condition is rare in cats.

OK, so we'll do a little bit of anatomy on the adrenal gland before we go on to the physiology. So it's called adrenal because of the close proximity to the kidneys. And it's they live cranial to the kidneys bilaterally, and they appear to be one structure, but they're actually two glands, one inside the other.

So you have the inner gland, which is made of the adrenal medulla and this is nervous tissue. And then we have the outer gland, which is the adrenal cortex, and this is made up of glandular endocrine tissue. So I like to think of the adrenal gland as a chocolate coated peanut.

So the, the peanut in the centre is the medulla with all that nervous tissue and then the, the chocolate around the outside, the capsule is the adrenal cortex, and that's a nice easy way of remembering which part is which. OK, so some physiology of the different layers. So the outer layer, the cortex is under the direct, the direction of ACTH and that's produced in the anterior pituitary gland.

So this is, this produces a couple of different hormones, and they're classified into three main groups which are glucocorticoids, mineralla corticoids, and sex hormones. So the main two that we're looking at today with Addison's disease are the glucocorticoids and the mineralla corticoids. And all of these are steroid hormones because the main chemical structure is cholesterol, which is also a steroid itself.

And the adrenal medulla. So this is made up of the nervous tissue, and two hormones are produced here, your adrenaline or noradrenaline, or if you're in America, epinephrine and norepinephrine. And this just controls the sympathetic nervous system, so it's in charge of our fight and flight.

It sends the glucose to those muscles so that we can run away from any danger and it just increases and controls our heart rate in these situations. OK, so physiology of the way this all works. So the negative feedback loop, we will have heard for many different diseases, especially endocrine conditions.

So the pituitary gland secretes ACTH into the bloodstream because it's a hormone. ACTH is then released to stimulate the adrenal glands to produce cortisol. Once the cortisol has been released in the adrenal glands and we've reached a normal level within the bloodstream, that negative feedback loop will be sent back to the pituitary gland to say, OK, our levels are now normal, stop producing ACTH.

However, if you have Addison's disease, the disease is in those adrenal glands, it causes destruction of the gland and they atrophy as well. So all of that ACTH will be produced by the pituitary gland. However, you won't get the stimulation and the release of the cortisol from those adrenals because they're diseased.

So you might have a normal or an elevated level of ACTH, whether that's from the normal ACTH produced from the animal or whether we've given synactin or a synthetic ACTH, but either way, it won't stimulate those adrenal glands because they are diseased and they've the destruction of those glands makes it impossible to produce any cortisol or produce a lower level. So let's talk firstly about glucocorticoids, which is one of the deficiencies that we'll see with Addison's disease. So the name comes from its effects that it has on the blood glucose levels.

So glucocorticoids, and they have a hypoglycemic effect. So this just causes the blood glucose to rise within the bloodstream. And it, it stimulates the liver to break down proteins and lipids so that they can be converted via gluconeogenesis, and it just converts them into glucose so that it can be used as energy by the body.

So the hormones, the different glucocorticoid hormones are cortisol, cortisone, and then corticosterone. They're the 3 different ones produced in the adrenal cortex. So what do glucocorticoids do to the body?

So they promote appetite, they affect the patient's mentation, and they affect your GI function as well. So you might see mild signs like vomiting, anorexia, a little bit of weight loss with a lack of glucocorticoids. It also maintains blood pressure.

And the most important one, it protects the body from stress. So we all know that when we're stressed or we're ill, we produce cortisone, we produce steroids, and we also produce glucose. Think of your cats with your stress hyperglycemia.

But in Addison's disease, the lack of cortisol may gives us an inability to be able to deal with those levels of stress. So the main thing the cortisol does, it just maintains the metabolism of glucose in the circulation to deal with stressful situations. And deficiencies can cause things like anorexia or an altered mentation and you might see a generalised weakness in these patients as well.

OK, so mineralla corticoids. So these regulate important electrolytes in the body. So mineral salts, mineralla corticoids, just think of that when you're thinking of mineral corticoids.

So the main one is aldosterone, and this controls sodium and potassium and along with hydrogen ions as well. So the target organ is the kidneys and it promotes the reabsorption of the sodium. Wherever your sodium goes, your water goes as well.

So if you have a decreased level of sodium, you will have a decreased level of water and your patient will be dehydrated. And it's an exchange of potassium, so we normally get rid of that potassium through the kidneys and the hydrogen ions are excreted alongside the potassium in the urine. So deficiencies will cause the opposite.

So the aldosterone promotes the reabsorption of sodium, the excretion of potassium. So if we don't have aldosterone, we will start to build our potassium because we're not excreting it, and we'll also start to lose our sodium instead of retaining it. So we'll get a hyperkalemia and a hyponatremia, and alongside that, we'll get dehydration and hypovolemia because we're losing our water along with our sodium.

So I'll just briefly talk about how aldosterone affects the blood pressure in these patients, and the main system is the RAS system. So RAS being renin, angiotensin, and aldosterone. So the cells are located within the kidneys and they're called juxtaglomerullar cells and the macular denta cells.

And these cells just constantly monitor blood pressure. So, They will detect any drops in blood flow, or if it's sluggish or they detect any hypo perfusion to these patients and to these kidneys, then this will respond by releasing wrenin. So what Renin does, it converts angiotensinogen into angiotensin one.

And then ACE, also known as angiotensin converting enzyme, converts angiotensin 1 into its active form so that it can start working on this patient's blood pressure, and that's called angiotensin 2. So this causes arterial constriction, and then it stimulates the release of aldosterone from the adrenal glands, the adrenal medulla. So aldosterone will then increase the sodium and water reabsorption back into the bloodstream and therefore that will increase our circulating blood volume because if we keep hold of that sodium, we will also retain that important water that we need as well.

And that will just help reperfuse these all of our tissues. And along with that arterial constriction from the angiotensinogen, then our blood pressure should rise because of this system. And that's just how the RAS system works.

So it releases renin, then angiotensin, and then aldosterone, and that's how the kidneys have a big effect on our blood pressure. OK, so there's a couple of different types of Addison's disease. Primary Addison's disease is the most common, and this is the bilateral destruction of the adrenal glands.

So we believe it's idiopathic because we don't actually, we don't know what's causing it, and the reason for that is, as I said earlier, these patients can live a long, happy life, and they can be diagnosed at the age of 4, for example, and then live until 12. So by the time we do a necropsy or a postmortem, all we can see is the destruction of all of the different layers of the adrenal cortex on histopathology, and that's because these patients have lived with this disease for so long, but then there's not really much for us to examine to see what the actual cause was. So we believe that it's immune-mediated, but it can also be seen with neoplasia or an iatrogenic cause, meaning that we cause it, i.e.

With drugs. So if you have a Cushing or your patient and you're given too much, or the likes of mitotane, which we don't use in this country anymore, but they use it still in America. And instead of blocking the synthesis of certain hormones within the body, like our trialistta does.

Mitohane actually destroys the adrenal glands so that it can't produce cortisone. This is a treatment that they use for Cushing's disease. However, if that patient's adrenal glands become too destroyed and it works a little bit too well, then they may start to become Addisonian, and that can be the cause of this as well.

And one of the most important things you need to remember is primary Addison's disease. There's a reduction in both glucocorticoids and mineralla corticoids. So all of those things we've discussed earlier, all the GI issues with the glucocorticoids and the mineralla corticoids with your electrolyte changes, you will see that in, you will see both of those in primary Addison's disease.

With the other types you might have an atypical Addison's disease, and this is only a lack in your glucocorticoids. So your mineralla corticoids will be totally normal in these patients. So if you run electrolytes, you may not see the typical hallmark signs of the, the sodium and the potassium.

So these patients don't have hypovolemia and their electrolyte disturbances or there aren't any, they're absolutely fine, and they might just get the signs that are associated with the lack of glucocorticoids, and that'll be your mild chronic GI signs. This is an important form of the disease to be aware of, even though it's less common, because you could see a patient just with mild GI signs and hypovolemia and totally miss that it's Addisonian. So it is an important thing to remember to test these patients for Addison's disease and not always believe that we're only looking for primary disease.

Because we may not see any alterations on our electrolytes with these patients. And finally we have a secondary Addison's disease, which is less common again, and it's just due to the reduction of ACTH secretion from the pituitary, and that's usually some kinds of cancer, neoplasia and or prolonged glucocorticoid supplementation. OK, so some pathophysiology.

So, in order for clinical signs to occur, we must lose 90% of our adrenal function. So that's a hell of a lot, and usually that's how much is already lost at the time of diagnosis, or they could have complete loss at the time of diagnosis, and this is all, this is quite common. So the loss of aldosterone leads to the renal loss of sodium and the retention of potassium.

So therefore your hypo hypokalemia and your hyponatremia are hallmark signs of this disease. However, it's not common, it's not present in every single one of them. So you can't rely on this totally.

Be aware of it, but don't use it. It has its limitations that you need to be aware of. And because of those reasons and those changes that you can see in your electrolytes, you can do a sodium potassium ratio and you just divide your sodium value by your potassium value.

If you get a number of below 27, this is abnormal, below 24 is suggestive of Addison's disease, and below 21 is highly suggestive. So say in, as I've just mentioned, it does have its limitations, the sodium and potassium. So you will see a hyperkalemia in 85% of these patients.

So that is high, but it's not all of them. So you will have 15% out there with absolutely normal sodium and potassium, and they are still aersonian. So you can't use it to totally rule this out.

Sodium, 85 to 90% of them are hyponatremic, and 80% of cases have both. So not all cases will be bradycardic. So if you have So a little bit really about potassium.

So potassium is the main intracellular cation iron with 95% of it located within the cells. 60 to 75% of that volume is within the myocytes in the heart. So this does have really, it can have severe effects on your cardiac output.

So imbalances can affect the more excitable tissues, so that is organs like the heart, the muscles, or also the nerves as well. And if you have a serum potassium level, which is controlled by your aldosterone and you don't have that aldosterone, then you can start to see a rise in your potassium and you may start to become bradycardic once your potassium value goes over around 88 milli per litre. So bradycardia is abnormal if you have a patient who has lost a lot of sodium because they will have lost a lot of their fluid as well, and therefore they will be dehydrated and hypovolemic.

So in those cases, your heart is usually pumping faster, they're usually tachycardic because they have to work harder to perfuse those tissues. However, if you have a hyperkalemia of over 8, you might see a bradycardia, along with hypovolemia and dehydration in a collapsed patient, which should start ringing some alarm bells because this is highly abnormal. So this is common, however, tachycardia could still be present in that small percentage of these cases.

So not all patients read the textbooks before they come into our clinic. So just be aware of the limitations of the sodium and the potassium as well. So reduced extracellular fluid volume will cause the hypovolemia.

You'll see hypotension because of that low volume of fluids within the bloodstream. You'll get decreased renal perfusion, and you'll also get a decreased cardiac output as well. So you might see an asotemia in these patients, which just means an increase in their kidney values, i.e.

Your urea and creatinine. So usually this is a pre-renal azotemia, and that just means it's from something prior to the kidneys. So it's not actually kidney disease, it's caused from dehydration or hypo, some kind of hypo perfusion.

So the kidneys aren't being perfused with the blood that they should be and therefore the urea and the creatinine starts to build. Once these patients are reperfused and the dehydration and the hypovolemia is corrected, that azotemia should disappear. That's an important thing to to be aware of.

But it can also be difficult to differentiate. Are you actually dealing with an acute renal injury here? So they can present really sim in really similar ways.

So just be aware that. Although these patients might come in with a severe azotemia, we need to also think, could they be Addisonian, especially in your young asotemic patients. If they haven't had access to any toxins or anything suspicious, then definitely test for Addison's disease.

It's got to be high up there on the list. OK. So the signalment, so we tend to see this in patients between 4 and 6 years old, although it has been documented that you can see anything from 2 to 12, and it tends to be female neutered.

So the patients that have a decrease in both mineral corticoids and glucocorticoids tend to be the younger patients, and there's a fair few overrepresented breeds. So we have the standard poodle, the Nova Scotia duck tolling retriever, Portuguese water dog, the bearded collie, the Liamberger, the Great Dane, Rottweiler, soft coated Wheaton terrier, and the West Highland white terrier. And there was a study done in Sweden with 530 dogs, and all of those dogs, there weren't one Yorkshire terrier, which is quite interesting.

So they tend to be underrepresented. However, they do get Cushing's disease, so that's probably where those Yorkshire terriers are. And this disease in cats is very rare, and it doesn't carry any breed or sex relation in cats, and their average age is roughly around 6 years, but it is very, very rare.

So there haven't been many studies done on cats with Addison's disease. OK, so early stages of this disease, we tend to see very vague signs and they can have a very variable history. So This is called The Great Pretender because it just, nothing screams as the sons to you.

It comes in and it can present to so many different things. It could look like a gastrointestinal foreign body, it could be a renal patient. There could be many different things, but there might just be a couple of little, little signs that you can look out for that makes you think, actually, I'm gonna, I think this patient could be Addisonian, so let's run an ACTH stim.

So you might see some waxing and waning of weight loss, some gastrointestinal signs, your vomiting, your diarrhoea. It's less common to see PUPD but it has been reported in some cases and also abdominal pain. So if you have a patient with gastrointestinal haemorrhage, this needs to be high on your differential list as well, because along with Addison's disease, you get your severe hypovolemia and your dehydration.

This causes a really dehydrated gut. And this leaves these patients susceptible for gastrointestinal ulceration. So if you do have some GI haemorrhage, then just check if your patient is really dehydrated, then it could be caused from Addison's disease and the lack of those glucocorticoids.

And mineralla corticoids. OK, so what clinical signs might we see with the Athertonian crisis? So you might have an acutely collapsed patient who was perfectly fine earlier.

You might have hypovolemia or hypovolemic shock, so all the signs that come along with that, such as your pale mucous membranes, your decreased capillary refill time, you might have, you're likely to have hypotension, weak femoral pulses, and you might see a profound weakness overall in these patients. They may even present moribund. So potential bradycardia with hypovolemia, and as I said earlier, that can be because of your hypovolemia because you've lost that sodium and that fluids.

So you will have your bradycardia because of the hyperkalemia. And we'll go into those signs a little bit more later on. And it's an important differential, it's important to differentiate between different diseases that can present with all of these signs.

So how do you know this is an Addisonian crisis? It could be an acute kidney injury, it could be a diabetic ketoacidosis. It could be a severe pancreatitis.

There's so many different things that this could be. The bradycardia is one way of trying to differentiate between the two. And Bradycardia is present in a lot of these cases, but again, just be aware that it doesn't rule it out if bradycardia is not present.

So if you do have a collapsed patient and their heart rate is reduced, that's where you need to start thinking actually we might have a anothersonian patient here. So there's a couple of other clinical signs that you might see, hypochloremia, hypophosphateemia, hypercalcemia, hypoalbuminemia. You might see a hypoglycemia.

So these glucocorticoids, as we mentioned earlier, have a natural hypoglycemic effect on the body. And when these are reduced, you might see a mild hypoglycemia. However, it is very mild, so it wouldn't be as low as the likes of a patient with an insulinoma.

And that's because there are other ways that the body will maintain that normal blood glucose level. Glucocorticoids do affect it, but they, they're not the main source of your blood glucose maintenance. That's all controlled by the pancreas and many other different things in the body.

So you will see just a mild one, so maybe 2.5, 3-ish, and anything around that figure in these patients, you could start to question Addison's disease. You might have a urinalysis of 10:07 or 10:30.

And also you might see a decrease or a lack of a stress leukogram. So what is a stress leukogram? So in these patients, in all of the patients in our hospital who are sick or stressed, and you run a haematology, you are likely to see a stress leukogram.

And that's because when we're stressed or we're ill, our body needs to cope with these situations, so we release cortisol. That causes a stress leukogram, which is an increase in our neutrophils and a decrease in our lymphocytes and our Einophils. So if you see these red marks on your haematology and you can see this neutrophilia, lymphoenia and einopenia on those that haematology results, you know, it's just a normal stress leukogram.

However, if you're at asonian, you can't release that cortisol, and you can't cope in these stressful situations, which is why you've collapsed. And therefore, you might have either a lack of a stress leukogram in a really sick patient, which is abnormal, or you might have a reverse of it. So instead of an increase in the neutrophils, you might have a a mild decrease.

Instead of a decrease in the lymphocytes or the sinophils, you might have a normal or an increased level. So that's a lot to try and remember. So the one that I'd like you to focus on is the Eoinophils.

So you will only have increased eosinophils if you have an allergy or if you have parasites. So if you have a normal, a really sick patient with a normal Eoinophil level and it's not decreased, but it might actually be increased instead, then that's one sign that you can start to look out for for other so in patients. So they will only be increased with parasites or allergies.

So if that is there, you need to question those two or Addison's disease. OK, and how do we diagnose Addison's disease? So an ACTH stimulation test is gold standard, and I'm sure we've all run millions of these in-house.

So first of all, we'll take a basal serum sample and then we'll administer some synthetic ACTH. So that being synactin or tetrachosectide, whichever you have in house, and this goes IV, we'll then take a post ACTH sample one hour later. Once we've administered this ACTH, the idea is that ACTH should stimulate the production of cortisol from those adrenal glands.

And then we should have an increased level after we've we've injected that ACTH. But in the Addisonian patient, those adrenal glands have atrophied and they've become destroyed. So we will have a low basal and we'll have a low post ACTH cortisol as well, because no stimulation has happened because of this destruction.

It's very important that we check that these patients have not been on any form of glucocorticoids. Have these patients been on steroids? Is it a chronic skin disease?

You know, there's many other conditions that cause us to have to administer the glucocorticoids or prednisolone to these patients, and that's One really important thing to check, have these patients been on those glucocorticoids, because this will suppress the release of cortisol as well from the adrenal glands. If they're receiving steroids, your ACTH won't do anything and therefore you might wrongly diagnose them as ass. If they have received any prednisolone or glucocorticoids, you need to wait 48 hours washout period.

The basal cortisone, so this is run quite commonly in practise, and an elevated basal cortisol will rule out Addison's disease because if your cortisol is increased, then you can't have Addison's. A low basal cortisol may be suggestive of Addison's disease, but again, this is another thing that has its limitations. So it could also be due to adrenal exhaustion.

So if you have a really sick patient, they're really sick, they're really stressed, they're in the hospital, they may have used up all of their cortisol. And therefore in these patients, you could take that basal cortisol and it's low. So you, you might think, OK, we now have a patient that we need to run an ACTH stimulation testing because it has a low basal cortisol, but it could just be from the adrenal exhaustion.

So that's why it's really important that we are following up these low basal cortisoles with ACTH stimulation tests, and we shouldn't be running them on their own. Sometimes vets will run them as a precaution just to rule out. If you have any inkling that this patient is Adisonian, just skip straight to the ACTH stimulation test if you can, because one, it could end up costing the client more, especially if you're running the vets are running basal cortisol on many of these patients just to rule out, but you can't necessarily.

Just ignore a low basal cortisol, so therefore you may end up having to run ACTH stimulation tests on many different patients that you don't think are Addisonian. And also it may just delay the diagnosis. If you think this patient has Addison's disease, you need to just run that ACTH so that you can start treating these patients.

OK, so first of all, how do we treat Addison's disease? So our main thing is fluid therapy. So we need to get rapid fluid restoration into these patients, and that should be high up on our priority list.

It should be our most important priority. So we need to correct this hypotension. We need to reperfuse these patients and correct that hypovolemia so that they can start perfusing their tissues again.

So they will have a decrease in perfusion to their kidneys, to their heart, to many different organs in the body. And death from Addison's disease results from the hypovolemia and the increased vascular permeability and the shock, not from the reduction in all of the other the steroids. So the one thing that will save this animal's life is the rapid fluid therapy.

So we need to correct that hypotension, correct the hypovolemia and the electrolyte imbalances, and also the metabolic disturbances if we have an aidedemia going on. And ideally stabilise them for 1 to 2 hours before administering any glucocorticoids. That won't be the life saving drug, it will be the fluid therapy.

OK, so how do we treat the hypovolemia to start with? So an Addisonian crisis is life threatening and it's an emergency that requires the intensive care ward. So treating hypokalemia will increase the renal secretion of potassium and it promotes movement of the electrolytes into the cells.

So potassium is, once we give fluid therapy, that promotes renal diuresis and that's when we will stimulate the kidneys to start losing this potassium again. Sodium chloride should be used. If you read a textbook, it will say sodium chloride, 0.9%, and this should be administered IV.

However, Hartman's contains potassium, which is why we say to avoid it in these patients. Hetman's contains such a small amount of potassium that it is not significant enough to ever change a patient's potassium value. And also it does contain some buffers.

So if you have an acidosis present, your hormones might actually be a better choice. Sodium Chloride is actually pretty acidic. I can't remember the exact figure, but off the top of my head I think it's around 5.6, so that's pretty acidic to be given to an already acidotic patient.

And the other reason why they say to give sodium chloride is because it will correct that hyponatremia and the hypochloremia, but we need to weigh up what is more important, the aci acidosis in this patient or the hyponatremia. So hyponatremia will still correct with Hartmann's disease, perfectly fine, sorry, with Hartmann's solution, . But also if that asidedemia is present, then we, we kind of need those buffers to be helping us along and get that acidic level down from the bloodstream.

OK, so we need to be administering ideally 10 mL per kg bolus to these patients. So if you read the textbooks, it might say a shock rate is 30 to 90 mL per kilo. However, we wouldn't just administer this total volume, we need to be administering them in, say, say a 10 or 20 mL per kilo bolus to start with, reassess, check those peripheral pulses, check that femoral pulse, check how this patient seems to be coping after that bolus, and do we need another one.

So you can carry on giving boluss up to this shock rate rather than administering it all at once, because some might need 50 mL per kilo and might not need the full 90 mLs. So it's important that we're reassessing our hydration status after each bolus. If you have a large patient, you might want a second IV catheter in there so that we can get it in a little bit faster.

Once we're happy with the perfusion of our patients and we're checking blood pressure, we're checking those the heart rate, the respiratory rate, and the peripheral pulse quality, then we can start with a 4 to 6 mL per kilo bolus per hour, 4 to 6 mL per kg per hour depending on how the patient is responding to those fluid therapies. OK, so we mentioned earlier that potassium will have some effect on cardiac muscle and the cardiac the myocytes. So an increased potassium will slow cardiac conduction and the excitability.

So therefore, you might see a bradycardia with potassium over 8 millimoles per litre. You also might see some changes on your ECG caused by this. So the most typical one being tall peaked T waves.

So as you can see here, you've got your P wave, the really small one, really tall, narrow, your QRS, and then that really big one is your T, which is usually similar size to your P wave. So that's really big. So.

For this to be from potassium or hyperkalemia, it needs to be ideally around 3/4 the height of the QRS. Some of our ECG machines, especially the ones that we use for monitoring during an anaesthetic, can sometimes give what is what looks like a tall P wave, put the tall T wave. However, just check, is it actually about 3/4 of the, the height of this QRS because that's what it would need to be in order for it to be caused by our potassium.

If not, it's likely to just be our machine, but check it along with heart rate, you would see a bradycardia with these patients, and you might see widening and flattened QRS's. They could have decreased P wave, you might have missing pee waves, or they might be wide and flat. It can eventually lead to atrial standstill, ventricular fibrillation, and even cardiac arrest.

You might see some wide and bizarre complexes, your VPCs. So this really is a life threatening emergency if we have a really severe hypokalemia above 8. Because it will cause those that bradycardia, if you listen with your stethoscope, you might hear some Brady dysrhythmias.

And you will also see that on your ECG machine if you have one of those available. But you, you can listen to it with your your stethoscope and you will pick up on that, the bradycardia and the the Bradysrhythmias as well. OK, so how do we treat hyperkalemia that's associated with Addison's disease?

So first of all, fluid therapy. So we need to administer that fluid therapy to try and promote renal diuresis and excretion of this potassium. That's the quickest way of getting it down.

So, We need to think of the cause. So what's causing this hyperkalemia? So it's caused by a reduced mineral or corticoid, i.e.

Aldosterone, causing the potassium retention in the kidneys. Increasing secretion of sodium leads to the dehydration and the hypovolemia. And you need to administer fluid therapy and also steroids as well.

However, it's important to stress that the fluid therapy will be the life-saving drug and about 1 to 2 hours later is when you can administer your steroids. So you need glucocorticoids. Dexamethasone is one glucocorticoid that you can administer and it will not affect your ACTH.

So I mentioned earlier to do an ACTH, you need to make sure these patients haven't received any any steroids given by us. Dexamethasone, you can administer and it won't alter your ACTH results for these patients. However, there's no rush to be administering this dexamethasone.

So you have 1 to 2 hours of fluid therapy to get that ACTH stimulation test done, and then you can administer the dexamethasone if you are sure that this is an Addisonian patient. Mineralla corticoids, we have hydrocortisone, which is a human drug. This can be administered prior to the ACTH as well, but again, there shouldn't be any reason to, as long as you're reperfusing this patient, you can be saving its life without having these on board necessarily in the 1st 2 hours.

And please notice that Zycortal is not on this page. That is not an emergency drug. Once you give that drug, it lasts 25 days.

You need to be sure that this patient is Addisonian before you go given that drug and therefore, even though it is a mineralla corticoid and we use it for treatment, that's only once we have the diagnosis. OK, so treatment of hyperkalemia. There's a couple of different ways.

If your fluid therapy hasn't made enough difference, then you can use neutral soluble insulin IV. And this just increases the potassium uptake in the cells. So if you're given insulin, The potassium and glucose are co-transporters.

So once you've administered the insulin, both electrolytes will enter the cell. So insulin promotes the movement of electrolytes intracellularly, and therefore your glucose will move intracellularly too. And therefore the glucose will need to be stim to be supplemented in order to prevent a hypoglycemia happening.

So you can use a 50% dextrose to make up the 50% dextrose, the glucose solutions, to make a 5% solution, you just put 100 mLs of this, the 50% extras per litre of fluids, and that will make a 5% solution and you can just give that as a CRI alongside the IV soluble insulin. You should monitor the ECG closely and don't use potassium containing fluids. So there's no reason why you would spike any bags with potassium, but just as a note on there, because this is quite common in your patients with GI disease that we would spike their bags with potassium.

But hopefully in these patients, even if their potassium is normal, we wouldn't use potassium containing fluids, which we might do with other GI signs. What is the GI patients, and most patients stabilise over 12 to 72 hours. So to treat the cardiotoxic effects of hyperkalemia, so if the patient is showing signs of severe cardiotoxicity, i.e.

They have severe bradycardia or brady dysrhythmias, then you can administer calcium gluconate. And the calcium allows the cells to repolarize and improve conduction of the myocytes. So you can give 1 milligramme per kilo diluted in water for injection.

This can be administered slowly IV. This will treat the cardiotoxic side effects and it will stabilise those myocytes, but this will not affect your potassium value. So your patient will still be hypothalemic, even if you've given calcium gluconate.

It only stabilises the myocyte. It does not affect your potassium value. This should be given slowly and it should be given while your patient is ideally linked up to an ECG or be auscultating the heart as an absolute minimum because it can affect the heart.

OK, so supplementation of glucocorticoids dexamethasone, 0.5 to 1 mg per kg IV initially, then you can repeat it 12 hours later with 0.05 to 0.1 milligramme per kilo until the patient is well enough to be switched over to oral medication.

So you need to also correct the acidosis with fluid therapy, but sometimes if the, if the acidosis is severe enough that it's not correcting with those fluids, you can administer sodium bicarb. And this is just for prolonged acidosis, but you do need to be aware of the effects that can be caused by administering sodium bicarbs such as cerebral edoema is one of the potential fatal complications. So hypoglycemia should be treated with an IV bolus or a CRI and it's usually mild or asymptomatic if you, if you do have a hypoglycemia caused by this.

And when I say a hypoglycemia, I mean caused by the Addison's disease, not caused by the the injection of insulin. You always need to supplement the the glucose alongside the supplementation of insulin. OK, and Zycotal.

So this is our mineralla corticoid. So let's just go back. So the glucocorticoid is your dexamethasone or your prednisolone.

This one is your mineralla corticoid. So this does not contain any glucocorticoid at all. So its real name is Desoxycorticosterone pivolate, and it's an injectable suspension.

So it's given initially as 2.2 milligrammes per kilo, so of course, and it lasts about 25 days. However, it has been known to last around 30 days in some patients.

So When you're administering this, gently mix the bottle and just check that it's fully mixed before you administer it because it separates really quickly. Even just drawing up this solution into a syringe, if you put it down and wait for a minute, it will be separated before you administer it to the patient. So we may need to make sure that we've mixed this bottle properly before we're taking our injection out.

Check electrolytes, 10 days post first injection and then at day 25. And dispose of the vial 120 days after the first puncture or on the 4th puncture, roughly. Most patients only require 1.5 milligramme per kilo long term, and dose interval can be increased to 30 days.

So the aim is you can use the sodium potassium ratio like we mentioned earlier. So ideally you want of between 27 and 32 because anything under 27 is abnormal and suggestive of Addison's disease. We're treating these patients so that they are not Addisonian and therefore we want it to be over 27.

If it does increase over 32, it's unlikely to cause a problem. And glucocorticoids. So this is necessary to give alongside Zycotal.

So Zycotal is a new drug for everybody. It's only been around for 1 year, 2 years, and we're all still Starting to learn how this drug works. But one of the most common things that we see in our practise is Addisonian patients who have just been put on Zycortal and the vet hasn't realised that they need glucocorticoids alongside.

This has absolutely no glucocorticoid property and therefore they must stay on steroids for the rest of their lives alongside this injection. It's not there to replace the steroids. So prednisolone, 0.2 milligramme per kg per day, and then it can be reduced to the lowest effective dose.

So we have seen doses as low as 0.05 milligramme per kilo. And remember to advise on our steroid side effects to our owners.

Quite often this can be one of the, the more the things that an owner will come in and say, actually, I can't cope with the increased there that we endured in the night when they didn't used to do that. The soil in their beds, they go into the toilet in the house, and I can't actually cope. So we need to make sure we're advising on these steroid side effects to give the owners a realistic expectation.

And the prednisolone dose should be doubled or tripled at times of stress. So if our patients are going into kennels, going on holiday, moving house, then they need to, they, we will get stressed during those situations and our body will naturally produce that cortisol. These guys can't produce any increased level other than what we're supplementing them with, so we need to double that dose or triple the dose.

And that could be for any time that you would deem as stressful for these situations for these patients. So the prognosis of most patients will show a dramatic improvement within 24 to 48 hours of the start of treatment. And ideally you'd like to move from IV oral drugs, gradually switched over to oral, sorry, IV drugs switch over to oral, ideally 2 to 4 days after the initial treatment.

And those that don't transition smoothly, and they carry on having imbalances in their electrolytes, you can start to suspect, have they got any other secondary issues alongside this Addison's disease. So that could be a second endocrinopathy. Or it could be something caused by that severe hypo perfusion that was caused by that lack of aldosterone.

So if you have hypoperfusion and that blood is not being perfused to those tissues and to those organs, that blood delivers oxygen, so you will have a hypoxia to a lot of different organs as well. So all of those hypoperfused organs will also be hypoxic. And that can affect some of the most, the organs that have the highest metabolic rates, such as your kidneys, so it can cause a real severe kidney damage or an acute kidney injury or pancreatitis.

So those patients who don't switch over to oral meds and their electrolytes don't seem to be balancing out and correcting like they should, that's when you can start to think, do we have a second disease going on here? And is it? Caused by the hyper perfusion or do we just have a second endocrinopathy?

So home monitoring, so ask our owners to keep home records. So this is the most accurate way of monitoring our patients. So if we just rely on what our owner says, how's the patient doing at home?

Oh, they're absolutely fine, oh, they had this episode. We're going to look at potential missing information. So if they can record how the patient looks and feels at home, then that's the most accurate way of us knowing whether this patient seems to be on the right dose of Zycortal and prednisolone, and it just helps us to prevent missing information from those owners.

So the prognosis for this disease is generally excellent, and they live a normal life expectancy. So this is why it's one of my favourite diseases because it doesn't affect. The patient's long term life expectancy, as long as you have good owner compliance, they're aware of the side effects of the steroids, the therapy, and the monitoring long term for the rest of this patient's life.

It's a nice, easy disease to treat and it's a really nice disease to have. If my own dog needed a disease, it would be Addison's disease because it doesn't shorten their life expectancy. Thank you very much.

That's great. Thank you very much Sophie, and a ringing endorsement there of Addison's disease, wants to pick one to have. Yeah, it'd definitely be Addison's.

As I said at the beginning, we do have some time for questions. I know there's a couple coming already, but please do, post any questions you have in the Q&A box, and we will, ask them to Sophie shortly. Also, just a reminder, you should have pop up at the end of the webinar, a feedback survey.

It'll only take you a couple of minutes to complete, but please do because it helps us provide valuable feedback for the speaker, but also helps us determine our programme for the forthcoming year as well. So, on to the questions. I don't know whether you can actually answer this one, Sophie, but it's why is there Greg's first question was, why is there a shortage shortage of cinnati and again.

Yeah, is, is it, is it, is it just a production issue, do you know, or, and do you know if there's a time frame that it will become more widely available again in the UK? As far as I know, it's a worldwide thing. Europe seem to be absolutely fine with their levels of obscen acting.

I know America have a shortage along with us. I think it's just a shortage in production. With regards to when it's coming back, I don't know.

If you are in practise and you ever have no synactin in, the one thing that you can do for these patients is you could take a basal cortisol in the serum gel tube and then you take an EDTA tube alongside. If you spin down and separate the plasma from the EDTA you can send that off to measure ACTH levels in the plasma. So if you do have, if you come across a situation where you don't have any synactin, then that's one way of getting around and kind of doing an ACTH stimulation without the synactin.

Ideally you should still be doing an ACTH and not using. Instead, but if you are in that situation, then then that's one alternative that you can use. Well, yeah, hopefully it's back in soon, but I don't know how, how soon that will be.

How pros, and you're such a pro. I was gonna ask you that as a follow up question. If you don't have any, or you got a shortage of it in practise, is there any alternatives, and you answered it straight away, so fantastic, thank you.

Got a further question from Greg. He's saying, if BP is very low in a collapsed dog, what would you do if you can't get an IV catheter in? See, ideally you do need an IV catheter in these patients.

There's not much you can do with a hypotensive patient other than restore the fluid volume. So I would say just carry on trying the different peripheral vessels if you can. Maybe see sometimes just getting a new pair of eyes, getting a different nurse or a different vet to try and have a go at a different leg, but I would say just try your best, try and get an IV casted into these patients because really there's not much that you can do for.

Hypotensive and dehydration, especially if they, if they are collapsed, you can't offer food or water. So ideally IV access is really the only way that we can reperfuse these patients quick enough to prevent any levels of hyper perfusion that's gonna go on to an ongoing problems such as your hypoxia to different organs, your pancreatitis, your kidneys. So yeah, it's just kind of keep on trying really, maybe get a second pair of eyes sometimes that just helps having another person there to try a different vein and also with your You can try a couple of times in your, your cephalic vein.

Sopini is also really good, but you can also go dorsal pedal. So just on the, just kind of if you have the paw in your hand, just at the very front as the vessel branches off kind of coming from the toes up towards the front of the the carpal, the torsal joint, then there's those vessels there are quite nice, the dorsal pedal. Rather than going in that big bouncy sofina, you can try the dorsal pedal first.

When you are trying to get an IV of these, they do feel a little bit thicker and a little bit tougher to advance off, but just as long as you've still got blood there, keep on trying. But there's many different vessels that we can try, but we just need to keep on trying to make sure that we're getting these fluids on board as quick as we can. Even so fluids, I wouldn't recommend it.

I don't think they make any difference whatsoever. So an IV access is the most important thing really. Fantastic, thank you, and a few good tips there to try getting that access for yourselves.

. It'd be great to hear you, it's, it's still a bit of time there with the questions coming in, but hopefully, you know, you have enjoyed tonight's webinar. I'm sure you have. I'm sure you're busy jotting lots of notes down and useful tips that you can take back into practise and put into place when you require them.

If there is anything else, obviously you can, you know, email us and we can contact, Sophie at a later date if something suddenly springs to mind. I'm sure, Sophie wouldn't mind just dropping you a line, at some point, Sophie, just keep you on your toes. I am happy to give out my email address as well if anybody does have any questions, they can just email webinar vets and I'm happy for them to.

Take my email and they can send me them as and when they might come up. Fantastic, thank you very much for that. All our webinars are up, the recordings are available 24 hours after they've been broadcast.

So if you do want to revisit tonight's webinar, then you're more than welcome to. So give it 24 hours and it'll be available on our website, which you can access by just logging in and looking for Sophie's, presentation in the that in our online library there. But if there's no other questions, I'll, we'll leave it there.

I'll leave me to thank Lewis for being on hand to answer any, technical queries we've had tonight and setting, Sophie up initially. Thank you to yourselves for attending and obviously last but not least, thank you also to Sophie, for putting on such a fantastic presentation this evening. And obviously thank you to our ongoing sponsors, Tails.com and JHP recruitment for their continued support.

So, thank you very much and good night. Good night, Sophie. Thank you very much.

Bye.