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Okay. Hi, guys. How many is that? You go on one of the six PM Siris co founders and I'm also the temporary and the crime need for this medical Syriza's Well, so they were going to be doing the first part of the sort of endocrine syriza's going to specifically focus on disease of the adrenal gland between the cortex and the medulla on. So in terms of just a little update, which I'm going to be posting on two d main page. So today I'm going to be covering adrenals. As I mentioned tomorrow, the stroke webinars been moved towards the end of the series and were given update about when that's gonna happen. So instead, we're going to be having electrolyte abnormalities Part two tomorrow on the 17th instead of acute. And so, instead of and the crying part to, we're going to be having acute medicine. Part two, which was the lecture that was postponed last week on the 23rd, will have the parathyroid and fired lecture which will be in the crime part, too. The stroke of will be given a new date, as I mentioned on for the next medical Siris. When I'm doing some more. And the crime stuff is when I'm going to cover diabetes in depth and as well as that disorders of the pituitary gland and sexual development disorders and no be post. Sit up on the six PM Siris main page and the medal event pages and will be updated by tonight. So just the liver about socials if you haven't joined already. So as you know, we've got instagram tissue on Facebook page. It's how we keep you up today about what serious is running, what the latest weapons they're going to be on two day to day basis and where we help you update you in terms of content on, uh, give you some questions to consolidate your learning. So please, if you haven't done already, so please support us by joining our social media pages. And of course, when I just give you a quick thank Utd mg you who have sponsored us, they were there since you started the six PM Siris and helped us get it off the ground. Once you complete your medical training and you become a foundation doctor, at least in the UK, you're going to need some sort of medical legal advice, indemnity insurance or other forms support which the end you can provide. So if you're interested in that, there's a cure code in the bottom right of the screen that you can follow to the link of the page and join. And if you drawing, you can also get a pocket prescriber book, some free flash cards to revive her, to revise for your learning and as well as it as a foundation program handbook as well. So, without further ado, let's get started. So Question Number 1 75 year old gentleman was admitted with recurrent Falls secondary to offer static or a postural hypertension. The consultant consider starting fludrocortisone for the patient. They proceed to ask you about the structure of the adrenal gland from which layer on mineralocorticoid is released. Okay, so the majority of you've answered it correctly. But as a little bit of the split of the answers, and many of you have attended, my lectures will know Dr talk this more trouble times. So the correct answer is the's Oh, no glomerulosa. So the cortex into free layers, which will have an image of on the next slide. But in terms of what's released sort of fasciculus releases quarter soul. A type of glucocorticoid. The's oh, never two Killers releases sex hormones such a testosterone or dihydroergotamine industrial own, also known as D. H E A. And the adrenal medulla releases catacholamines about that. I mean, for example, adrenaline, more drugs and dopamine. And it's his own, a grammar be low side that releases mineral a court court court. And by that I mainly mean older star own, which is, you know, implicated in salt regulation and fluid sort of regulation as well. So a little bit about the adrenal cortex, so adrenal meaning Sitting above the the sort of the kidney sitting with the renal kidneys. Eso the gland is split into the cortex, which is the outer layer on the medulla, which is the on the cortex, split into free, further lays and each release their own substances. It substances. So the way that you can remember that for the cortex, at least if you remember adrenal meaning, we know sitting above the renal gland, think of G fro like E. J. Fox. Remember Refrigeration rate and gee, a farm meaning glomerulosa for circulatory. Particular artists are particularly from outwards to inwards and then to remember what into the layer releases. Just remember the order that you spend your evening and normally So you start by a salty dinner. Then you go have dessert. Maybe should like he sex. So that's the way that I remember how things were released on what the order is in g f r. And then the order that you spend your evening. And so the zonegran you're below so releases all the steroid type of men around a quarter. CoId, which is, as I said, important for the regulation amount of salt you have in your body. Sodium potassium on by by that reasoning, also involved in sort of fluid, sort of fluid regulation mechanics, anybody, the physical lotta as I said, desert sugar. So glucocorticoids, mainly cortisol and then the reticularis, the last in a layer, releases small amount of sex hormones particularly relevant in ladies, because that's how they get the small amount of testosterone so DHEA on testosterone. So moving on to the next question, a 75 ruled gentleman was admitted with recurrent fall secondary. Off are static hypertension, as I mentioned, it's also known as postural hypertension. The consultant. Consider starting food a quarter. So for the patient, the consultant goes on to ask you which catecholamine is most abundantly produced in the adrenal gland, specifically the medulla where they come from. And let's put up the pole case. You've got a split. Make Mexico a split between two answers. Really adrenaline or drawn and D correct Answer is with the majority is you have onset. It is adrenaline, A so in terms of sort of catecholamine city adrenal medulla release is about 20% noradrenergic in about 1% dopamine and a CT colon seat. Acorns, not the type of catecholamine. Although it is another type of neuro transmitter. The most abundant produced is adrenaline at about 80%. So if you ever forget, just remember adrenals equals adrenaline because it's they just sound the closest together. That's the way that I remember Adrenals. Specifically, the medulla mostly releases adrenaline about 80% of the amount, so just a little bit about the production and its precursors. So the initial precursor is a none. The Centrum, you know, acid known. This tyrosine, which is a precursor to all Tacoma means and specifically, adrenaline order on dopamine is what we're talking about. But it's also, you know, implicated in the production of sort of fire old hormones. It's important towards the production of fire old hormones on It's also a tire seems also sort of implicated in type of sort of congenital disease that screen for called fetal thenar ketonuria. So in vino ketonuria, very simply, you're unable to restart Symbicort of a lack of a female and mean hydroxyzine hydroxyzine enzyme, which would which turns female alanine into tyrosine. And because that you get all those sorts of symptoms and features you get of that. So that's another important thing to remember about tyrosine. Now it's the next sort of precursor that's formed this dopa El Dopa, which is a type of levodopa. Which type of drug use in Parkinson's medications is a replica of this, and it's a precursor to arrest the catacholamines, where they form adrenaline. About 20% noradrenergic 20 adrenal, about 80% noradrenergic, 20% and dopamine less than 1%. And just remember this so the medulla is mostly made up of the's types of salt call chromaffin cells, and just remember, adrenals equals adrenaline. That's the most abundant released catecholamine from the adrenal, medulla and the ovary guys. The questions will get more difficult as we come along guaranteed. So, um, a 70 year old lady presents you with palpitations and feeling generally normal. Well, she has a history of hypothyroidism and hypertension. She has newly been started on the second height. Anti hypertensive agent. What election? I'm the man. It she has most likely been caused. And let's bring up the pool. Okay, so majority of you answered correctly so you would have seen me talk a little bit about this in lectures that have done previously as well. So it's sort of a two step on. So one is known what some of the anti hypertensive guidelines are, and the second part is known what the electrolytes side effects of the anti hypertensive medication is. So the correct answer is what the majority of you answered. It's hyper convenient, so, and the answer of the medication that's newly been started as a second line would have been an ace inhibitor in someone about 55 years old. Um, took a little bit more about the guidelines in the next step, so usually a slip just don't cause other electrolyte abnormalities. However, calcium and magnesium derangements can also be associated palpitations, but no anything that sort of causes derangements and sodium. So if you remember that sodium is thesaurus of neuro symptom, electrolyte potassium is implicated in sort of palpitations, sort of heart. What mostly heart stuff and muscles. Calcium was also implicated in sort of heart issues and sort of muscle issues while and so can magnesium as well. So in terms of the hypertension guidelines to second line medications for someone above 55 years old who's not Africa? Rabin. The second line would be in a second Hepatitis A and a senator sort of indirectly causes inhibition of all the sterile police by inhibiting production of Renan. We'll talk a little bit more about the function of these hormones, and this is what can lead to a type of hyperkalemic other than the fact that it can possibly cause a naked eye as well. But that's more sort of significant in patients with bilateral renal artery stenosis. So anti hypertensive guidelines in the UK just bang this into you repeatedly. So if the less than 55 years old you typically start on a sin, Hibbitts or or on angiotensin receptor blocker because they send him a disk and sometimes cause coughs because of the build up a Brady Kenan eso if they have lots of coughing and ARB is on alternative to that if the intolerant of them in terms of if you're over 55 years old or Africa or a bee in, you tend to start calcium channel blockers first, and then second line would be to add both of them together. So this lady was over 55 years old. Nothing to say that she was Africa being probably on the calcium channel blocker initially. So she was then started on an ACE inhibitor, a zoo next therapy to help control her hypertension. Now, a little bit about the Renan angiotensin alone or with the star on system. You guys know that I'd like to talk about it quite a bit because relevant in a lot of sort of medic know how your medications work and disease is a swell. So the liver releases angiotensin it gyn he sort of the kidneys produce a hormone called Renan. We'll come back today, so it would be sort of a both it would still be added together will come back towards that. It was the question so angiotensin gyn gets cleaved and angiotensin one. Then what happens in the lungs is you have an enzyme called Ace. Ace is under tense of converting enzyme turns angiotensin one in today, more activated form, angiotensin. To do it binds to a whole bunch of receptors on stimulate all the star on release from the adrenal cortex. Specifically, the zonegran memory Losa acts on the posterior pituitary gland that stimulates the release of 88 or vasopressin, and then it also can lead to vasoconstriction more, more directly as well. And where a sin if it's active. By inhibiting this, a PSA enzyme, as I've mentioned on that sort of reduces the production of Andrew Tension to and thereby reduces to production of all the steroid, which can lead to the hyper convenience symptoms that we talked about, apart from it, possibly being able to cause of AKI as well and in terms of a Arby's. So a ARBs are angiotensin receptor blockers, so they act further downstream, so they stop angiotensin two from binding to it's receptors, which is why it doesn't cause that typical cough because it doesn't need to break up of Bradykinin because it doesn't inhibit aced because Aces. What stops the building of the ace enzyme is what stops the buildup of Brady Kenan. So a little bit more specifically about eight inhibitor ARB. He's on on sort of old Austro. So all the statins have mentioned is the mineralocorticoid meaning release from Zonegram or below. So where acts specifically sort of in the kidneys when you look at an afferent is the distal, convoluted she bills, because there is where you find these channels called epithelial sodium channels, and what these do is when they're activated, they re absorb more sodium from reading the sort of nephron cheap you. And in return, they release potassium. And all the stair own, as I said, is the whole month of interest acts interest side, any so enters the cell, and then it causes up regulation of these in actual Is there by course, and more sodium reabsorption and more potassium buddies, now a sandhill. But there's others mentioned inhibit angiotensin two, and by that effect, in directly sort of reduce the amount of all the stair own that you produce. Because angiotensin two stimulates all the star on release and because you have a lack of all the steroid, that means you have less sodium reabsorption and you hold on to more of your potassium and that that's potentially looking cause a hyperkalemic a a well as a naked eye as well. If it does cause an a k I. And that's the mechanism of that, and ARB is again similar. They also sort of indirectly inhibited release of all the star on a swell. So let's see a so question number four. A 70 year old gentleman presents with a new presentation of acute C CF. Likely secondary to skim a cart disease on discharge. He has been started on several medications, including ramipril by soporiferous. A. Might apply around aspirin. Type a grill on I pulled the statin. So how does a planner own work that's put up the pool that I could answer some questions? Okay, let's have a little look. So the majority of you've asked correctly. It is a competitive mineralocorticoid receptor binding. So in terms of inhibition, sort of direct inhibition of enact or video sodium channel synthesis. That's where millwright and that's another potassium, sparing your I think that's how many ride works. It doesn't reduce production quarters off drugs that can reduce the production quarter. So include things such as Keep the corners or we can talk a little bit more about that later on within the webinar in terms of sodium potassium chloride channel inhibition NK CC, which I've previously mentioned before. That's where Loop Diuretics act such as Feruzzi myd on be Matter Night and a panel on the spironolactone or a type of potassium sparing spring your attic so they sound like all the steroid, and therefore they compete with all the stern to buy to the same receptor. That's why they're competitive mineralocorticoid receptor, binding drugs or mineral Oh, good receptor and, uh, antagonistic or the store on and tightness. However, you want to think about them so a little bit about the Nephron once again worth knowing the nephron and its parts because if you know the Net from and it's physiology of know whether sort of channels are and where and that sort of the they are the target of multiple drugs for lots of different reasons. That's why I quite like to know physiology. So when you look at the Nephron. You've got the proximal convoluted shooper, where the majority of absorption of Soviets takes place, such as sugars, bicarb, sodium, among other things. Then you've got the loop of Henle descending on ascending, and it's in the ascending loop of Henry, where you'll find these A K C C channels or simple. It is because they used the natural grading of one electrolyte and their energy to bring something else in the same direction with It s So that's the where Loop Diuretics act. And that's when they inhibit D's. And that's where the genetics can cause global electrolyte depletion, distal, convoluted sugars where you find in actuals. And, as I mentioned, that's the target of potassium, sparing diuretics and as well as that indirectly things like eight inhibitors and ARBs because of their sort of indirect inhibition of all the steroid release. It's also if I think sodium chloride channel, which is the which is type of Cymbalta. That's where fires I do retic act again important sort of part the anti evidence of guidelines type of diuretic and then within the collecting ducts of thie Nephron is where you can find Aquaporin V two channels and those channels are specifically meant for water reabsorption only, and it's the target of anti diuretic hormone as well as anti genetic hormone analog. Such a statin. A present now again, a little bit about the potassium, sparing diuretics so little bit more closely in terms of its mechanism. So, as I've mentioned, let's go back. So all the steroids, so a panorama spironolactone sound like all the steroid, the end of the same way. So therefore they sort of competitively buying to the same receptor a lot of stair on those there by sort of inhibiting its effect. So the competitively bind to the same sort of receptors the old standard inhibiting it and in terms of the mill a ride, it's inhibition. So it's another potassium sparing diuretic. But a little bit different terms of its mechanism of action in the directly inhibits the production of the E natural. So that's how they differ in terms of how they function, but sort of the same result in a sense. And Amiloride also tends to be used, I guess should be mentioned doesn't tend to be used on its own intensive using other things. So, for instance, a combination drug that you may have come across his co Miller fruits. So for a reason why being used directory with, um, in a ride and sometimes Comella. Right. So, um, you know, I could also be used in fires, antibiotics directly as well. Sort of combinations that it tends to be used rather than its own. Most plantar on and spironolactone tend to be used by themselves. Okay, so we're gonna have a little bit of a break, and then the more difficult questions they're gonna come up and diseases that you guys been waiting for. That a physiology stuff? There's anybody else. Have any more questions at this moment of time and I'm I'm going to fast guys, let me know. Okay. Okay. We'll give it a couple more seconds for anybody that wants to ask any burning questions, and then we'll move on. Okay. Gonna move straight onto the fifth question. And so an 18 year old lady who's a student presents the evening feeling faint on well and nosiest private share worsening symptoms of headache, neck stiffness and photophobia on Examination Airways. Patent entries clear bilaterally on. Be respectful. He's 21. Your sats 94% on their cardiovascularly wise. She's got BP of 70/30 so she's hypertensive and she's tachycardia with a Sinus tacky 110. In terms of GCS, it's 13 blood sugars of 3.4, so a bit on the lower side on dominant examination Abdomen is soft nontender. You also notes hyperpigmentation around the hands. What is the most likely cause of this or this lady's issues? So let's bring out the pool eight. So the majority answered correctly. The correct answer is Waterhouse, Friedrichs and Syndrome, so it took a little bit about the, um, the next light. So in terms of whites and the other answers, so in terms of steroid withdrawal, guess it can be a common cause of someone having interest in adrenal insufficiency and therefore adrenal shock. However, there's no history of taking steroids in this patient. TV is the most common cause of sort of Addison's worldwide, but there's no history to indicate it again. And also immune is the most common cause of sort of Addison's or Prime Addison's within the UK. But the history is suggestive of meningitis, which makes Waterhouse Free Jackson something that's a little bit more likely and something that's more to think about giving that sort of clinical presentation. So it's like that she has septicemia, although the rash hasn't developed yet, which could be causing bilateral adrenal hemorrhage, which in effect causes water hawks, Friedrichs and syndrome. So a little bit about water as frequent syndrome. So it's It's a rare, of course, of adrenal insufficiency, and it's It's a primary cause primary, meaning it affects the adrenal glands directly. And that's what Addison disease mean. Anything that's classified as Addison disease causes adrenal insufficiency through, uh, inadequate release of sort of hormones from the adrenal gland itself. It's adrenal gland itself that's been affected rather than a secondary cause, which is a for a mortar patootie in the hypothalamic access. So in more tax rejects and syndrome, you get this bilateral hemorrhage of your adrenal glands. That could be lots of different causes for it, but the most common thing is sort of a severe sepsis. It's particularly implicated with the cereal, meningitis and therefore meningitis and specifically meningea cockle septicemia and sort of when you have sepsis forever course, the gene or grant so are very vulnerable in terms of the skin here because of their sort of blood supply. And because of that sort of tension scheme er affecting your adrenal glands on top of someone say, having septic shock because of, you know, widening of the blood vessels and having leaky sort of capillary membranes causing sort of, you know, fluid extra base, a shinin a whole lot of other sort of done ship effects happen with sepsis. You also get this adrenal sock because of a lack of sort of quarter saw on mineralocorticoid, causing sort of avoiding depletion as well as that low BP because of lack of sympathetic activation. So off septic shock, you get adrenal structures. A double whammy and the way that you sort of also think about it is that if they're septic shock that's not responsive to sort of fluids. And vasopressin is, if appropriate, which would give him I see you. Then you also need to think quite heavily about adrenal adrenal shock, a z well, and that would mean that you need steroids so a little bit about adrenal insufficiency. Adrenal insufficiency sort of end all term of just a gene or glands not functioning properly, and it affecting all layers. So when you have primary sort of adrenal insufficiency that's known as Addison's disease on the most common cause in the UK, as I mentioned or two immune and we'll talk a little bit more about the antibody that's implicated in that and you're right in thinking that this is a woman, a young lady, so auto and it's the UK that it was referring to, So an autoimmune course is the most likely cause. But as I said, within a clinical context of her presented with meningitis and sort of shock, you got to think about Waterhouse Friedrichs, and that's why I needed to. And that sort of in yet infection is most common sort of second white, especially T B worldwide, then other process is not in any particular order Waterhouse, Friedrichs and syndrome, which tends to be rarer infiltrative processes. And by that I mean malignancy, hemochromatosis, amyloidosis, sarcoidosis. Anything because infiltration of any organ, such as the adrenal glands and sort of destructive normal structure, and thereby sort of inhibiting the normal function and release of normal hormones and then drugs such as, you know, particular anti fungals, which is through I've put in the little corner inhibition of steroid forming. See why people 50 enzymes taken him a cortisol release is well so in terms of secondary causes. Your thinking about decreased ACTH for adrenocortical drop in releasing hormone release from the anterior pituitary gland. It's most commonly due to steroids because of suppression of the sort of hate pH between access on it's withdrawal is followed by insufficiency. So if you know, giving someone, if someone say on steroids and they're not taking a normal steroids, they're gonna have insufficiency because their body is not gonna be producing its own natural mount of steroid. And also, when patients get really on well and they're on long term steroids, that's where they say when someone's on. Well, the second rules are to double their steroids because that's what you're supposed to do, because when you're on well, you could increase your cortisol production because your body is stressed. When someone's on well, long term steroids, you need to double the dosage of the steroids on. I do that whenever someone comes in very on, well, in the hospital. So, uh, did you do to do Let's move on to sort of the features of adrenal insufficiency. So, as I've said, we've talked about the layers of the adrenal cortex. And that's why I like to know about the physiology, because it's things the symptoms so well. So starting from sort of the the Zona for sick, your lot a. So there's only physical arteries glucocorticoids a quarter. So And when you have a lack of quarters or because of the adrenal insufficiency, you get these non specific symptoms of of feeling unwell. And you also get sort of hypotension because of sort of sympathetic are common question of it later because of sort of a lack of sympathetic activation, because what court so involved in in going also get hypoglycemia? Because course is important in sort of glucose metabolism as well. Mineralocorticoid so remember his own Remember Low. So releases mineralocorticoid mainly old, the steroid and the electrolyte abnormalities that you can see with in it because of the lack of all the sterile and therefore, the lack of inactivity Will Symphysis is hyponatremia because of increased sodium excretion and hyperkalemic because you're having potassium retention. But one thing to know in clinical practice rather than exam worlders in about sort of 25% of patients are roughly a quarter of patients. You won't see any like electrolyte abnormalities at all, and it can still have internal insufficiency. So that's something to know in clinical practice rather than example. And there's one more set of symptoms that will come on two later. So in terms of investigations and management, if there's a suspicion of index is high enough, take blood and just treat it, especially if you think they've come in in shock because of adrenal shock. Because adrenal shock or sort of an Addisonion crisis, which is what happened in this patient, can kill on Ben, you know, worry about investigations. They just take blood and treat immediately. And you can if you already taken blood, you can under random cortisol on instead of a nine AM cortisol and just a little bit about long snacks and test because this has been previously asked about. So I wouldn't worry much about long Senexon tests, but they're rarely used a lost 40 hours, and he's used to differentiate between primary and secondary causes of injury. No insufficiency. But again, it's It's a really sort of used test. So let's talk about the main investigations in someone with adrenal insufficiency, so you can either choose to do a random or nine AM quarters. All we've talked about quarter so in that it has this sort of, by model peak distribution, recent reports of half fashion. So the highest amounts in someone with normal circadian rhythm. So you know, normal body clock is that at nine AM, they release the most amount and your evening, you know, somewhere around nine PM six PM wherever you want to say they release the most mild cold sweat. Those times some sort of this by motor representation. Now you can do a random quarters are in that. If someone has a normal random cortisol, i e. Above 4 50. That that practically sort of fought for Paco, perhaps excluded renal insufficiency and the next very unlikely. So that's why I find a random cortisol easy to do, because if it's if it's normal level, that's already sort of answered your question. And if it hasn't, it doesn't mean that they that they have a dream insufficiency because you need to go into a short snack contest or a nine AM quarters or so Other tests that you can do is anti 21 hydroxylase antibodies that's implicated C antibody that's implicated in auto immune Addison's disease. So specifically, you know, if you're thinking of a not a mean cause these antibodies that you be looking for you can get CT adrenal is to see if they're sort of any sort of disruption of the normal sort of structure of the adrenal gland such infiltrative processes. And you can also add on the CT angiogram, adrenal or your teeth, look at the blood supply and see the blood supplies been affected as well. And MRI Head would be more looking at the sort of Patricia gland and secondary causes of adrenal insufficiency. So the general management principals are that in the acute sort of setting, you give 100 mg of IV hydrocortisone and continue that Q. D s until they sort of been sort of, uh, acute situations been managed on once the acute situations been dealt with, sort of the cause of it investigating the patient's well, if the new maintenance you'll give or or steroids, which could be something like prednisolone and then you can add on something like future quarters own a swell because, remember, the steroid has meant to replace the sort of glucocorticoid insufficiency and the food quarter. So it's specifically for the mineralocorticoid insufficiency and the reason why Well, you wouldn't need food court. So when you're giving someone hydrocortisone is because hydrocortisone has mineralocorticoid effects. All steroids have some sort of mineralocorticoid effects. The hydrocortisone. That's a strong mineralocorticoid effect, which is why you can give it on its own, because it has sort of this sort of double function. And that's why you wouldn't get food or quarter song with it. So question five A. A. An 18 the same meeting old lady that were talking one time. Is that a vignette? In terms of history, you also know they've got hyperpigmentation around hands. What's caused the hyperpigmentation and let's bring up the pool. And then I could answer the question. Okay, so the majority of you have answered correctly. So it's increased adrenocortical trump in hormone release that causes sort of this typical hyperpigmentation that you can sometimes see in sort of someone with Addison's disease. Specifically, not eso in a dream insufficiency that's primary and secondary and secondary. You wouldn't see it. It's, um, primary adrenal insufficiency Addison's disease that you would see this hyperpigmentation because increased ACTH release so decreased quarters all leads to decrease inhibition of ADH I've mentioned previously, is not something to just remember because indicated SIADH 88 for anti diuretic hormones rates to fluid and sodium regulations, specifically the sort of re uptake of fluid for the Aquaporin V two channels within the collecting ducts of the nephron of the kidney on growth hormones implicated in acromegaly and gigantism and not really related to sort of hyper pigmentation. So with hyperpigmentation is have mentioned in Addison's because of the adrenal glands not producing enough quarter. So when you look at the access, the patootie grand and hyper fun, um, it's up a brigade, their production of CH and ACTH. And it's that increased amount of a CT hate that also sort of stimulates increased production of melanocytes stimulating hormone from the anterior pituitary gland, which is implicated in hyper pigmentation and therefore sort of mostly sun exposed areas such as the hand is where you tend to see hyperpigmentation, and therefore it is only really seen in primary adrenal insufficiency, a k Addison's disease, and not secondary because in secondary if you think about it perfusion grand or the high profile, Um, it's really CH and ACTH, and if any of those are effect that really don't really sussmann, you're not going to be releasing as much ACTH and therefore you know, could be releasing as much MSA age. So that's where know, in the the access to sort of hate the hyper for Lamictal, true traditional access, you know, comes into play. So the last set of symptoms that I've talked about specifically only seen in primary and that's what Permian Addison's disease is hyper pigmentation because increasing ct Adrian to increased melanocyte stimulating hormone production and already mentioned Patricia Access. But this is just visually so. Hypothalamus releases cortisol releasing hormone, which the anterior cruciate grands response to my recent adrenocortical trope in recent hormone ACTH. Destin acts on the adrenal cortex specifically, as we've mentioned the Zona for sick, your lotta on that produces quarter saw and then as a negative feedback loop perfect and a little bit about the anterior posterior pituitary gland city anterior pituitary gland releases six things that you need to remember what seven really ACTH involved in court saw production, M s H E stim like in my left melanocytes LH FSH, important in sort of a sex hormone production and sort of sexual development. And also the menstrual cycle. Prolactin, which has its own problems and functions growth hormone again involved. Quite important prior to growth plate closure. It's related to the you sort of growing somebody development and post sort of growth plate closure. If you have a disease that can lead to acromegaly TSH, thyroid stimulating hormone, you know observation. A fire with bland pursuit. Future releases 80 88 Okay, a vasopressin and oxytocin oxytocin, which is produced in the hypothalamus, particularly relevant in sort of pregnancy. And that policy feedback loop cycle when there's uterine contractions when you're giving birth. And it's the only really example of a positive feedback loop that you'll see in the body for oxytocin. If you just want to store that away in your heads on question five. Be so which of the steroids has the higher ist mineralocorticoid activity. Okay, so the majority of you also correctly the correct answer is hydro quarters own so just a little bit about sort of equivalency in terms of steroids. So when you compare all of these steroids that all compared to 5 mg of pregnant or prednisolone. Prednisone is the pro drug to Prednisolone, and it's thesaurus of liver that converts. So pro drug is an inactivated drug that when the body metabolizes, it becomes an activated drug. If that makes sense, so Nissan is an example of that, and it's just he sort of, as I mentioned, a pro drug to prednisolone. So it's 5 mg of prednisone is equal to 5 mg penicillin. Penicillin has median levels of mineralocorticoid activity, as I've mentioned, generally speaking generally from all, steroids don't have some mineralocorticoid function. Um, and that's just something to remember. Hydrocortisone 5 mg equal to 20 mg of hydrocortisone on hydrocortisone has a high mineralocorticoid activity. That's why it's a choice of steroids in sort of adrenal insufficiency. Addison's because it has a double whammy of acting as a glucocorticoid on a mineralocorticoid as well. Now methylprednisolone dexamethasone have a very low mineralocorticoid activity, so dexamethasone, your know, it's also used in sort of cerebral edema, and it's the choice of and sort of steroids because it doesn't cause increased fluid reabsorption you don't really want than someone who's got a swollen brain. For whatever reason, giving because of, say, mets and things. That's why it tends to be the choice of steroid for that. And it's also, you know, much. So 5 mg of penicillin is equal to 750 micrograms of dexamethasone is much more compact in terms of its strength compared to prednisolone as well on. Fludrocortisone has practically no group to court glucocorticoid activity. Very high mineralocorticoid activity, which is the items to be used in postural hypertension, also replaced some sort of be a replacement for someone who's not able to meet Mineralocorticoid, saying someone with long term and you know and sufficiency as well. And if you want to have a look at that, also may be enough for my skied insp age in terms of glucocorticoid therapy, and that's what you can find this information. So a question Number six A 40 or gentleman presented with recent 5 kg weight gain tiredness and feels or swelling building between your shoulder blades on examination. He is hypertensive, hasn't into scapula, fat pad and moon faces. He's well on himself. Otherwise, were initial investigation. Would you like to carry out to be knowledgeable? Uh, huh? Okay, so it has been upset. It's been a mixed set of answer. Sorry about that has been the mix it of on some of the majority of your answer correctly. It is the 1 mg overnight dexamethasone suppression test, although 24 urine a cortisol isn't wrong, and it's technically speaking the best test. But it's it's the most impractical, so both of them are really the right answer, to be honest. But in terms of what's easy to do, 1 mg overnight dexamethasone suppression test is a lot more easier to carry out in terms of patient compliance and sort of a few other things. So did you do to do? That's a military, So the dexamethasone suppression test in a normal patient will cause negative feedback. So if you've got a normal access and you're giving someone, dexamethasone meant mimics sort of cortisol that would sort of inhibit thesaurus a C a C that would inhibit this sort of release of ACTH and thereby indirect so thereby directly causing sort of decrease of quarter. So levels and dexamethasone is used because it doesn't inhibit, so it doesn't interfere with sort of the measuring of quarter soul or it's your orginally metabolites. Sit outside. Dexamethasone is sort of the choice of test, because if you use another one, it can interfere with the levels of quarters or because they have to be structurally similar. Remember, it's act. It's a basement active mimic the function of quarters. Also, if it's something that structurally is similar, it may interfere with the test levels of it if that sort of makes sense. So in theory, when you've got a normal access, you should be able to suppress the cortisol levels by less than 50. If not should be considering Cushing's syndrome so and then about Cushing's syndrome. So it's excess glucocorticoid, which caused all those symptoms that will will talk about a little bit later in terms of causes, so common causes include exogenous sort of steroid usage. So patients, for instance, sort of steroid reliant asthmatics. You know, anybody that's got sort of a renal transplant will need steroids or any organ transport really will need steroids. Anyone sort of other autoimmune conditions that need long term suppression. So it tends to be anybody with long term steroid usage, for whatever reason on that tends to be the most common thing. If you're looking at endogenous reasons, they need to split them into something that's in the pain. Independent ACTH release I eat the adrenal glands sort of acting independent of how the home, no matter how much ACTH release independent of the access or secondary, which is still dependent on sort of a c t H religious. So in terms of primary sort of ACTH, independent and adrenal, either know my would be a common cause or internal malignancy, which tends to be rarer. Secondary causes sort of the most common endogenous cause off Cushing's syndrome is cautions disease gushing disease specifically reverse, too sort of a pituitary adenoma. It's releasing Access ACTH, and then you can also have ectopic release. Best example you can think of is small. Cell lung costs know most, which tend to release all sorts of funny things on. Does have mentioned costing syndrome is through quickly. Access exogenous tends to be the most common thing, and in regards to indigenous causes, remember Cushing's disease, which is disease in the truth. Your plan is more common than sort of other causes of an indigenous cause of cashing syndrome. Quite a mouthful. Sorry about that guys. So let's look what features investigations and management's in terms of chemical features. Remember, the sort of demonic Cushing's is the one that I always just used your medical school. C and get the central obesity. In the long term, it can lead to cataracts. Actually, two ulcers and sort of muscle loss can eat the skin thinning and strike a hypertension hyperglycemia. And also here, citizen, which is like when you get these Xs has, um, get immunosuppression because of it. You get a vascular necrosis of the femoral head. You get gynie issues. We had sort of the menstrual cycle. You can also get sleep apnea. So Cushing's is the new morning that I tended to use. And it's also very useful for someone unlock term steroids and sort of the effects of basically steroids in general. Exogenous steroids in general as well. Sometimes of investigations thesis of Prime It First and guests Gatien. The best one is 25 year course, tends to be sort of more difficult to do and a bit impractical, and then you can also do, um, 1 mg overnight dexamethasone suppression test, where you give a dexamethasone overnight and then the next morning on nine AM You measure their cortisol levels and they should be suppressed. We can, you know, the late nights live recorder so you can do one of these investigations to sort of at the end expiration. Second line thing you can use is a 40 hour dexamethasone suppression test, which, over the long term suppresses quarter saw in sort of. Cushing's disease cautions that he's being in the disease of protruding planned so it can help. Distinguish between course is off off endogenous sort of Cushing's syndrome in terms of sort of other investigations that you could. You could measure ACTH with some cortisol levels to also distinguish between primary and secondary causes. But just remember 25 year old quarters or 1 mg dexamethasone suppression test sort of as the best test to do so. Question Number seven, a 32 year old obese lady presented with uncontrolled I'll come back towards with that answer question towards the end, a k D, if that's all right. So a 32 year old obese lady presented with uncontrolled high BP despite do anti hypertensive therapy, she also states she has been getting headaches and palpitations occasionally have blood sugars aren't f, b, C and Artie. So for blood count and renal function has some unremarkable and therefore normal have BP. During this clinic is 160 over 100 40. What is the most likely diagnosis? And that's part of the pool. So the majority of you answered correctly, So correct answer is a pheochromocytoma. So in this lady, So this has happened before where it took a long while to diagnose somebody in the community before they had to come in for surgery because they were obese because it was for the other causes were of the hypertension. But it actually happened to be a few chromosome toma, not very often that you would see that. But so in terms of pheochromocytoma, it's a disease of the renal medulla majority of time. Whether you can have these weird ectopic topics sort of chromaffin cells because remember, the adrenal medulla is mainly made of chromaffin cells, and those are the ones that produce catacholamines are implicated in pheochromocytoma. You can have an ectopic release of it, which tends to be rarer, so I won't be focusing on that. But you want to think about is the young patients with episodic in episode of nature of these headaches. Uncontrolled hypertension, sweating, palpitations, episodic sort of episodes, As I said mentioned, need you point more towards a field chromosome? Toma, Now hyperaldosteronism is another common cause, but nothing in the vignettes suggested in terms of renal vascular cause of hypertension, it's comment. It is a common cause of secondary hypertension, but the patients very, very young and the blood pressure's also control uncontrolled despite medications Cushing's disease and also see other signs of symptoms. So I do agree this lady's obese blood sugars are normal and everything else is normal, which doesn't point towards it. Still, be investigating for all these things that said, to be honest, because the screening for these things cause secondary hypertension. If that makes sense in clinical practice, so and every time or about sort of pheochromocytoma is so Ah, come back was it was the end A and you are right It can do is, well, eso features of sort of a few comments or tell me again. It's a neoplasm of the chromaffin cells of the adrenal, with Dallas specifically the medulla releasing the catacholamines in terms ideology the majority are sporadic or random and as a 10% or 10% bilateral, 10% off a real familiar A a related sort of multiple endocrine neoplasia, which it's all sort of subsets, which I'll mention another lecture and future 10% or extra adrenal. As I've mentioned, sort of ectopic. You notice paraganglioma hours and 10% are not associated hypertension, you know, also always get hypertension necessarily with it. So investigations include urinary in Sir Metanephrines and Metanephrines are basically the in active metabolites of catacholamines are released it within the year and basically another investigation that you can use abdominal CT and an MRI as well. So the management really is surgery. So in terms of what you need to do before anybody gets surgery, as you need to do alpha blockade, you need to block sort of alpha receptors, give all four receptor blocking medications first and then beat a blockade in a week of surgery. The reason you do dies because during the surgery you're going to be touching sort of this pheochromocytoma, and it's very sensitive touch. So you could imagine if you let me poke it is going to release all these catacholamines and cause a massive with the core catecholamine storm or adrenaline storm, whatever. And that can cause during surgery or hypertensive crisis Increased tachycardia, you know, BP, nothing. Because of all those sort of catacholamines. These outside blockade is very important prior to someone having surgery. And you broke alpha receptor first pyre to be the booking because if you broke a beater receptors first and give me two blockers first, that can lead to a hypertensive crisis because of alpha receptor over activity and compensation, which means you're gonna have lots of systemic vascular resistance and vasoconstriction causing super super high BP. And I can lead to a hypertensive crisis. So you always block your alpha receptors first. And then you Cosby two blockade on. Then they can go into surgery once they're adequately prepped. And as I've mentioned, you could remember that episodic nature of it, which is headaches, palpitations, sweating and sort of high. Potentially in 10% of patients you won't get hypertension is well, so just remember that last question and then on through all the questions that were asked before, So a 40 or gentleman presents to the medical unit with hypertension 161 120. Confirmed with ambulatory monitoring. He's normally fit in while his plasma Renan concentration is low. So was rendered months or low. One is the most likely diagnosis. Okay, as I've mentioned, guys is the last question. So let's share the results. So the correct answer is going to primary hyperaldosteronism. We'll talk a little bit about why so Gettleman sort of syndrome doesn't cause high BP on it. Sold. Wasting disease that's autosomal recessive on it causes high reading high old Austro level. So this patient has hypertension, which schedule is typically doesn't cause. It's also tends to be more in a young age, and it also causes high run in a month. This patient had a low reading amounts, which is why I mentioned specifically renal artery stenosis again common, but because of sort of because of reduced Reno profusion that's picked up by sort of the kidneys that would cause over activation of the men on drug testing all doctor on system. So you get increased Rendon release to try and improve grammarian filtration. So you've increased red and amounts of estrogen levels, so I hope that makes sense from that perspective and little's is a little syndrome is a disease of the back channels, so cause it's over expression of the Actonel's, which means increased sodium absorption on the increase potassium excretion on it. It can cause hypertension for sort of that method again, because it's kind of like, in a sense, it's kind of like an over activation of the rent and attentional dust around system, although it's in the end, effect in that course is increased in AC up regulation and because that increased in a couple of regulation and increased sort of re absorption of sodium and potassium, it will cause low Renan and lower dose trauma. And it tends to be congenital one and also tends to be rare. But it can be a cause of hypertension. Um, in patients is well and something to think about in younger patients. So high progesterone is, um, tends to cause hypertension with metabolic alkalosis would abnormally high plasma austral levels hands primary hyperaldosteronism, which suppresses Renan levels, causing low Renan levels which which this patient had so in terms of features, investigations and management. So in terms of primary hyperaldosteronism, it's commonly caused by adrenal hyperplasia. Although it can effect one adrenal gland but tends to be rarer. Or it could be secondary, which is the most common cause. The secondary hyper August run is, um, which tends to be most communicable by renal vascular disease, a k a. The most common thing being renal artery stenosis or more downstream nephrosclerosis. Seaga increased sort of in Actos as mentioned, which caused increased certainly absorption and potassium excretion via the kidneys and what the integrated cells will do, which is another type of salad and additional conflict. You bruise because you get increased so potassium excretion. They will try to preserve potassium by exchanging potassium for hydrogen ion. See good hygiene. I on excretion on also, because you get decreased potassium amounts because of the increased in act regulation, you get a shifting of hydron. I'll interestingly. So that's how it leads to a metabolic alkalosis sort of two methods. One is increased hydron I on excretion. The second one is increased hygiene. I own interesting the shifting which leads to a metabolic alkalosis, and with primary hyperaldosteronism, you'll see a massively increased almost there own amount, so hyper sort of plasma or lost urine concentration. But you see a low Renan, a problem around in Congress or a low blow. Plasma ran concentration because of its suppression and with secondary, because for whatever reason, your kidneys are trying to improve your memory or filtration. Usually you'll get a high reading amount as a result of because then is being released in response to that low grammarian filtration. For whatever reason, and because of that, that would be to downstream effects of high plasma or disturbing concentration hype. Hypokalemia is always present, but you know, especially sort of when it's early on. In terms of management, If someone has a unilateral adrenal hyperplasia, it tends to be an adrenalectomy, specifically laproscopic. It is bilateral, your give mineral oh sort of competitive receptor binding drugs such a spring real active and Penarol, which compete with all the steroid and thereby inhibit its function and beaches. Just remember hypertension, hyper clean, you and metabolic alkalosis. Oof. Quite powerful. So let me postop the feedback thing first, and then we can go back for some of those questions that you guys will most likely have on. Here is the feedback. You are code guys, but let me just postop the actual feedback link. Ondas Usual. I'll be posting up the slides and the video tomorrow. Does anybody have any questions? I imagine there are lots of questions. No, no problem at all. No problem. It'll quite like under crime. Because electron well, it forms. A part of it is well, which will be covering tomorrow. As I mentioned the second half of it in terms of potassium, calcium and sort of magnesium. But I think Endo kind is a specialty. Just, uh, well, I don't want to be under chronic. I think it's a fantastic specialty to know about. But yeah, as I've mentioned next Medical Siris, well, specifically, focus on diabetes alone, which is just massive subject of itself. Just insulins alone is a massive subject by itself and as well is that the protruding and more specifically and as well as that sex, sexual development. Almost, you know, different diseases that are related to that. Um and that's post up than that. I possibly I did possible. Think fine. Oh, I have a little look at that little Do you know which which lecture? That was specifically because usually the certificate you should be able to get it immediately following completion off the feedback if that makes sense on the slides you posted the next day. So you have have a metal account and make sure you clip catch up content. And if you haven't made a metal account year, you can follow thiopental sort of metal page. You can find it on the Facebook event page on that you can click towards there, and that's what you'll find the content posted as well. Does anybody have any other questions? It doesn't seem like there's many questions, actually, yeah, we can go food, uh, number for So the question that somebody asked is, Why are reading Level's high or low for some conditions? So let's focus on primary and secondary help high pollen dust realism first, and I'll try and draw you. Let's go box in a diagram from before, So let's go back to this slide and we'll talk a little bit about this. So I think we'll talk about it specifically in the context of primary and secondary hyper Hold off Strong is, um so let's talk about primary hyperaldosteronism first. So for whatever reason, so say that adrenal hyperplasia. We're looking at the adrenal gland. There's a work when I move my mouth. By the way, can you see what I'm sort of circulating? Thank you. So when you look at the adrenal gland in primary hyperaldosteronism, it means affecting the adrenal gland. Say, there's hyperplasia, for whatever reason, because it's hyperplasia. It's gonna up regulate and increases production of all the stair on now because you get lots of all the steroid and it's downstream effects, you know, because of the fluid mechanics increased sort of sort of fluid retention because, remember, oldest their own acts on the Actonel's. So all the stone cause increased upregulation of sodium channels. You get increased sodium the absorption, and because of that, remember where sodium wherever sodium goes, water will follow. You have increased water retention, which is why drugs like fludrocortisone, a used because often start of hypertension. You're concerned that they don't have enough intravascular volume, and because you have the increased intravascular voiding your your granny. Lessels, which reactive pressure will notice that increased pressure and because of that increased pressure, it reduces the amount of Renan that you need to produce because it's already saying that, you know, there's so much older starting around you're holding onto enough fluid. Why do we need so much running? So because of that, you'll get decreased amounts of Renan. Now, even when you get decreased amount of renting because Theodore anal glands are acting independently and primary hyperaldosteronism they're still gonna continue producing. Although Stromberg Arliss of how much reading you produce some primary hyperaldosteronism. You get high ultrasound because acting independent me and a decreased Renan because your body sensing increased pressure and freed retention so saying we don't need this much women. But your adrenal glands don't care because they got hyperplasia and it can continue producing all the stone. Does that make sense number, uh, for I don't have sorry from butchering your name, so it's probably high. Progesterone is my hope. That makes sense now in secondary, which tends to be the most common thing. Remember, the whole point of your body having the rain in Andrew Testosterone system is related to sort of BP and body profusion and organ profusion and keeping your mean or two your pressure a certain level, remember? So if someone has a low BP, the initial immediate response is gonna be rated across and baroreceptor but the long term response is going to be the brain and angiotensin auto strong sort of system. Now, when someone has secondary, hyper or just run is, um I could give you a good example renal artery stenosis. So let me draw the venous artery. Just assume example, which can be very It's not gonna be the best drawer and guys, but sorry. So let's get a pen. So we have the renal sort of the sort of the kidney here, and let's draw out the sort of renal artery which is gonna be represented in bread. So stenosis meaning, you know, sort of constriction or smalling sort of, you know, a smaller area of a true because of choose becoming getting a stricture. So say, if you've got renal artery stenosis, I eat. There's decreased profusion to your kidneys because they're blocked up and I'll try and draw that. So think of that as sort of. Let me draw black habit. Got black pen. Let's get black out. So because of stenosis, the area of your sort of renal artery has been produced, and you get decreased profusion to your kidneys. Now, remember, I talked about those granular cells that that are reactive to pressure within the sort of grim, every less so they pick up pressure within the sort of Reno arterials. If that makes sense because you get renal artery stenosis, you get decreased sort of supply and profusion towards your glomerulus, which means you're gonna Maybe your filtration will decrease your body picks that up. There's decreased pressure that it senses because there's decrease pressure. You get Renan release readiness have mentioned, has all these downstream effect, which eventually causes angiotensin increase. That, and that leads to increased all the steroid production from your zonegran very low PSA. So that's where you get in sort of renal artery stenosis. Decrease profusion need to increase training concentration and thereby causing increased all the stair own production, which is a natural response to try and improve profusion of your kidneys and thereby increasing the, um, infiltration. And that's technique that is, technically speaking, The mechanism sort of most sort of things that cause secondary hyper old Austrian is, um, the most commonly implicated thing being renal artery stenosis or renal vascular disease. Does that make sense number for So yeah, that's why I know in the physiology of things. And again it's it's just a feedback loop. It's all you're thinking about the feedback loop percent mental things. Either something's acting independently or will follow the natural physiological feedback loop. For whatever reason, does anybody have any other questions? Okay, um, I will leave it at that. Thanks a lot for joining me, guys. As I said, please join me tomorrow or or be covering electrolyte abnormalities part too. We can focus a bit more other electrolyte derangements much potassium, calcium and magnesium. And please, with these fell up, remember to fill out the thing back up to our post updated sort of timetable on schedule for this Medical Siris tonight as well. So you guys will know what's happened tomorrow. But as I've mentioned some baby stroke, it's gonna be electrolyte abnormalities part, too. And I hope you guys have enjoyed it, and it's made sense. Endocrine is a big, big topic, but we'll get for it by it s so I will see you guys tomorrow and take a