Endo - Thyroid and Adrenal Glands + Hyperthyroidism and Adrenal Pathway Dysfunction



This on-demand teaching session will provide medical professionals with deep knowledge of the thyroid and adrenal glands, covering physiology, anatomy and pathology of each gland, as well as relevant clinical management. Anushka and Aan, the fourth-year medical student at UCL, will also discuss the HPT axis and the importance of iodide, provide practice questions, and discuss some relevant anatomy such as the left recurrent laryngeal nerve, all through an interactive lecture session. Join this session and other sessions in the series every Tuesday and Thursday at 7 pm to get some SPAs.
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Learning objectives

Learning objective 1: Understand the anatomy and physiology of the thyroid gland, to include physical structure, cells and components involved, and location of the gland in the body. Learning objective 2: Explain hormones involved in the thyroid hormone pathway, including trh, TSH, T3, T4, thyroglobulin, MIT, and DIT. Learning Objectives 3: Discuss the potential complications related to this area, which include impairments to the laryngeal nerve and parathyroid gland. Learning Objective 4: Relate thyroid physiology to the other endocrine axes in the body. Learning Objective 5: Answer practice questions related to the thyroid hormones and describe clinical scenarios in which thyroid hormones may be active.
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The following transcript was generated automatically from the content and has not been checked or corrected manually.

Hi guys. Um I hope you're all doing well. Let's get started while people uh be just kind of continue to trickle in. Uh My name is Anushka and I'm the preclinical lead for be a this year and welcome to the second lecture of our endocrinology series. So we have five lectures. So this will be the second one and we have three more and they are every Tuesday and Thursday at seven o'clock. And just to remind us to fill in the feedback at the end and make sure you join, join all the sessions because for those of you who join um majority of the sessions, um you will receive some unseen S PA S which will be good. So today presenting, we have aan who is 1/4 year medical student at UCL. So I will hand over to him to get started. Hi, guys. Hi, everybody. Um As I know, I said, my name is a, I'm 1/4 year medic at UCL. Uh I'm hoping you can see the slides and everything is all good. Um If there's any problems we can't see or hear me, just put it in the chat and I'll see what I can do. But yeah, as you can see, um we're gonna be talking about a couple of pretty important glands in the body today. So the thyroid and our adrenals. Um I think to my understanding, you guys have already had a lecture on the pituitary, which should have been on Tuesday. Um So this follows on quite nicely from that. So we're gonna very briefly touch upon a bit to do with the pituitary, but much more to do with these couple of glands here. Ok. So let's get started then. So a little bit before we jump into it. Uh, just a bit about me, as I say, I'm 1/4 em medic at UCL. Um, particularly fascinated by surgery. Er, I like orthopedics, sports surgery, the idea of, um, potentially a career in those. So those are the, those are where my interests lie. Um, last year I in, circulated externally, I was at Imperial just for a year, er, where I did the I BSC in management. So a bit unrelated to medicine and just in my spare time, er, I play a lot of sport, especially cricket. And, uh, I've also, I've learned some, a couple of musical instruments as well, so that's just a bit about me. Um, and without any further ado then let's get straight into it. So, as I said, thyroid and adrenals, we're gonna talk about both of these glands and we're first gonna begin with just talking about some physiology. So what is sort of how does the thyroid work when everything is going well as it should be normally in the body, then we're gonna talk about some pathology. So what happens when things go wrong? Um So talking about uh what happens when the thyroid is a bit too active when it's overactive? What happens when it's too underactive? It's not doing enough and likewise, same with adrenal. So we'll talk about what the adrenals normally do and what happens when uh something goes wrong as well. And we'll talk about um putting that into context as well. So we'll do some SBA little practice questions just to show you what it actually looks, uh what it actually looks like. Ok, so to begin with, then some thyroid physiology, let's get straight into it. So the thyroid then is uh a gland, of course, which is situated just in your neck. So it's just sort of lies over on top of your trachea. Um just sort of below the thyroid cartilage. And you can see that it's kind of shaped a bit like a butterfly. It's, it's separated uh into two lobes. So you've got your left and right lobe. Um And you can see it's connected there in the middle by a structure called the isthmus. Um So that's just sort of the, the broad overarching anatomy of the thyroid gland. And if you zoom in then um and you look at it on the cellular level, you can see you've got your cells arranged into some structures that we call follicles. Ok. So follicles are essentially made up of these sort of rings of cells and in the middle of those rings, uh we have this substance, this sort of gel like fluid that we call colloid. And then around the outside, we've got these er, cells that we call follicular cells. So as the name suggests, um, and then also just sort of scattered between them. We have our parafollicular cells as well. Ok. And we'll go, we'll go into now and just shortly, um, what each of those sort of components are responsible for? Ok. So just in terms of some relevant, maybe more clinical anatomy, we have our left recurrent laryngeal nerve which runs very, very close by to the thyroid and it actually supplies the vocal cords. So, because of that, um, it is very relevant because in some sort of, uh, some sort of intervention management where you might want to do surgery on the thyroid, you might wanna do a thyroidectomy and remove it altogether. That can be tricky in terms of that nerve cos if you do a bit of damage to that nerve, which runs very close, you might encounter some problems there, especially, um, with the, well, the vocal apparatus. Uh, and what's more, we've also got our parathyroid glands very closely embedded into the thyroid. Um, and we're not gonna touch upon those today. Um But it's just useful to know just some good anatomical knowledge. So, let's keep going then. So you hopefully should be familiar then with uh the general sort of hormonal axes that we tend to have in the body. This is no different than the thyroid. So we call it the HPT axis. Uh That's the hyperal thyroid axis and you can see this diagram simplifies it, sums it up pretty nicely. So we have a hypothalamus, of course, er, in the brain, which is sort of connected to our pituitary gland and the hypothalamus is gonna release what we call trh thyrotropin releasing hormone that is going to be released to the pituitary and the pituitary in response to that is going to release TSH. So, thyroid stimulating hormone into the circulation, ok, into the blood. So that circulation, once it's uh sort of traveling around the body eventually will reach the thyroid and that is gonna stimulate our thyroid to release the hormones that it normally produces into the circulation. And those hormones are T four and T three. As you can see there in the diagram, we're gonna talk a bit more about uh those uh shortly now as well. And then once T three and T four are in the bloodstream, they're obviously gonna be, er, running around the circulation, they're gonna reach their cells, er, the target cells and they're going to have their actions again, which we will discuss um fairly soon now as well. So, yeah, it's pretty similar to all the other hormonal axes that you will come across and let's delve a little bit deeper into it. OK. So let's talk about how it's made then. So how our thyroid hormones are actually how they, how they come about. So this is a very complicated diagram. OK. And just for the sake of uh sort of what you need to know at preclinical level, this is in quite a lot of detail. So I wouldn't expect you to, to memorize this ro learn this at all. Um I have summarized it quite nicely for you on the next slide, just sort of a very basic overview of it. Um But this the really important thing here that I want you to take away from the slide is the iodination. OK. So you will probably have come across er this idea that iodine or iodide is very important for the thyroid especially. And that's because iodine er pr er plays a pretty integral role in er the formation of the thyroid hormones. So that's all I really want you to take away from this. And ultimately, you're gonna end up with T three and T four, which are slightly different sort of versions. OK. Um of this similar hormone. So another couple of things to mention here is we've got T BG albumin and prealbumin and these are basically er kind of binding factors. OK? So T BG is thyroid binding globulin, otherwise known as thyroglobulin. And that typically is kind of like a precursor er protein and it binds to our, our thyroid hormones, albumin also does a similar job and we've also got er prealbumin. So the vast majority of that job is done by thyroglobulin. Now, for our hormones to work for T three T four to actually be able to carry out their action in the body, they need to be unbound. OK. So you can see that these proteins are what bind to them in the blood, but they need to be unbound to actually end up being active. So you can see T four, a very, very small proportion of it is actually unbound and therefore active and it has a half life of just over a week. You can see it on T three, which is the more active er version is again, is, is pretty low but it's a bit more er, but a bit higher proportion of it is unbound. So it's got a half life of just a couple of days. Now, let's have a look at a much more simplified version then of how thyroxine, how T three and T four are sort of produced. So first things first, then our follicular cells. So remember those are the follicular cells are the ones which are sort of surrounding the outside of those follicles, those circular follicles, they are gonna take iodine in from the blood stream and the iodine is absorbed through well through diet, through nutrition. Um that's gonna be observed by our follicular cells and they're gonna sort of initially begin by producing thyroglobulin. So that is like our precursor protein, you could say now it's taken up this iodine, it's made this thyroglobulin iodination of thyroglobulin. This is one of the most important parts of it. So iodine is gonna uh gonna be combined with our precursor thyroglobulin to form two things sort of in varying amounts. You've got MIT and dit. So monoiodotyrosine and di iodotyrosine as the name suggests, one of them has just got two iodides, one of them has just got one. OK. Now again, in varying proportions, you're gonna get MIT and dit combining together to form tri iodothyronine and Thyroxine, which is well, kind of like the, the technical terms for T three and T four. And you can see the numbers, they make a lot of sense because T three again, because we've got three iodide groups there and on T four, on thyroxine, you can probably guess there are four iodide groups there. So this has all sort of happened in our follicular cells, OK, around the outside of the follicle and those hormones, those T three T four, they're now gonna be stored then in our colloid. So the colloid, if you remember is the gel, like sort of um solution liquid, which is in the middle of our follicle. And that is just sort of a storage unit basically for our T three T four before they get, er, sent out into the blood stream. So, and they sort of remain there until it's time for them to be released. And that is where our axis, our H PT axis comes back into play. We've got stimulation of the thyroid then by TSH, er, remember which is released by the pituitary and once that TSH sort of hits the thyroid and acts on the receptors that it needs to, that is gonna stimulate the release of T three and T four from the colloid in those er, follicles into the systemic circulation. Er, a nice and simple. Now it's, it's reached the circulation. T three and T four are gonna circulate around in the bloodstream bound to those proteins that we talked about before, er, thyroglobulin. And of course our different versions of albumin and ultimately, it's going to, uh, it's gonna reach, of course, its target cells. So, thyroid hormones then are gonna reach their target cells. T three T four, they're gonna regulate them, the metabolism, energy production and we'll talk a little bit more now as well about what the actual specific actions are, what effects those hormones have. Ok. So I'm just gonna quickly check the chat to see if there's any questions at all. I think we're good for now. So we'll keep going. So let's talk about what they actually do then. So thyroid hormone actions, what do they do. So, the prime primary thing that I want you to be aware of is it is very intricate. It's uh again, it's quite, quite detailed if you really go into it. But the most important thing is that they alter gene expression. OK. So essentially it is gonna, you know, overexpress some genes, underexpress some others. But the overall sort of cumulative result of the genes which get switched on and the ones get switched off are the fact that our basal metabolic rate of B MR is gonna increase. So essentially we're gonna have some slightly increased energy expenditure. Um and we'll, we'll go on to sort of talk about uh how that impacts the different, the different systems of the body. It's essential for fetal growth and development and it's obviously going to have a slightly increasing effect on our protein fat and carbohydrate metabolism. Ok. And you can see there in the diagram, what actual sort of clinical effect it shows when you apply that to all the different systems. So, um probably the ones which you'll be most aware of the heart. You can see it's gonna affect heart rate and function. Uh you know, the hormones will actually cause er tachycardia, it will, it will cause an increased heart rate. Uh lungs is gonna cause our breathing rate to go up as well and we'll talk more about this. We've got some nice s uh a nice couple of SBA S coming up which actually summarize it quite nicely as well. So that's just what the thyroid is like normally then that is how the thyroid, uh, well, what it does, that's where it is, the anatomy of it. What does it do? What's its job, er, what hormones does it make? How does it make those hormones and what do those hormones do? Now, we're gonna talk about what happens when there's something wrong. Ok. So thyroid is basically not doing its job properly. It might be doing too much, it might be releasing too many of those hormones might be releasing too little. So, let's get straight into it. So broadly speaking, you can classify er, the two different, basically pathologies of the thyroid, uh, into a couple of classes. So that's hyperthyroidism, um, which obviously means, er, thyroid is basically too overactive. And then we've also got hypothyroidism, which is an underactive thyroid. So, according to the effects, then of our hormones, when there are, when there is too much, uh, thyroxine, too much T three T four circulating in the blood having its effect. These are the typical sort of symptoms that you can expect to see. So on the left, you can see essentially hyperthyroidism in that we're gonna see an overly quick metabolism. We're gonna see an excessively high heart rate, increased appetite. Uh, we're gonna see, uh, very sort of elevated reflexes, bowel movements, sweating, increased body temperature. So you can see that we're, we're painting a picture here that, you know, the body's metabolic demands are much higher than they should be. Ok. So there's, there's a problem there. Likewise, on the other side, hypothyroidism, we have a, a sort of an excessively slow metabolism, you could say sweet. Uh, on the other hand, we're gonna see Bradycardia, we're gonna see decreased appetite, very slow reflexes, um, slow bowel movements, less sweating, colder body temperature and a sort of, er, more intolerant towards the cold. You can also see on the other side, some stuff that isn't mentioned on the first one is we've got weight loss versus weight gain for hypo and hypo. Uh, what else is not mentioned? So, diarrhea, of course, we would see in hyper because we get increased bowel movements, we get reduced bowel movements and hypothyroidism, er, because, er, we're getting constipation, we're getting slowing down of the smooth muscle. Um, but yeah, that's, those are sort of the general, the general signs that you would see in, in either of those cases. So the first thing then that we're gonna do before we go in to talk about either of them, we're gonna do, uh, an SBA. So this is our first question you can see. Uh, I'll give you just sort of a couple of minutes to have a read of this and we need to put in the chat. Um, what do you think is going on here? So maybe if you can maybe try and give uh a differential diagnoses or even if not, just, just let me know, just put it in the chart saying what you think might be going on here. OK. So I'll just give you a couple of minutes to do that. I'll just have a quick look at the chart as well. I'm just gonna have a little look at the chart. All right guys, we'll, we'll go through it then. So having a little look. So a 27 year old woman then presents to our GP with progressive tiredness since the birth of her daughter last year. It hasn't improved with, uh, with good sleeper. She's also reporting difficulty passing stools, feels weak, uh, some weight gain, she's been a vegetarian drinks. Very little alcohol, never smoked or taken drugs. Uh, mother was diagnosed with type two diabetes and notes that her periods have been heavier as well. So you notice on examination she has dry skin, eyelid, swelling and a goiter developing around her laryngeal region. Uh, her pulse is 55 and you know, she is shivering a little bit despite the room not being too cold. Ok. So let's have a look. I'm gonna point out now what, uh, sort of the telltale signs of what's going on here, but I hope you have been able to sort of deduce that regardless of what the cause might be. This is a case of hypothyroidism. Ok. So let's have a look, these red things that I've highlighted in um are sort of the, the key telltale signs. Ok. So we've got um progressive tiredness. So remember if our metabolic rate is lower, we're having a lower energy expenditure, we're gonna see these uh these patients being more tired, difficulty passing stool, you can tell she's constipated as well, which is another effect um of an underactive thyroid weakness, weight gain because of that reduced metabolism, heavier periods are also associated with it as well. Dry skin, eyelid swelling. A goiter is just sort of a swelling again, uh developing in, in the neck sort of region. Um and it can happen in both cases, it can happen, you can find a goiter both in cases of hypothyroidism as well as hyperthyroidism. Uh pulse is 55. So again, according to the normal range of heart rate, you can tell that she is brady cardi. So another key sign and she's also uh intolerant to the cold. You can see she's shivering even though the room uh is not actually very cold. So very, very typical case of hypothyroidism. So how does it come about? Let's talk about that. So, the most common cause of hypothyroidism is an autoimmune, one called hashimoto's thyroiditis. So, again, it's uh sort of a very generic autoimmune condition where you will have uh sort of autoantibodies er to the thyroid gland itself. And if those antibodies are sort of attacking and causing damage to those cells of the thyroid, we're gonna get reduced production of these thyroid hormones. Ok. Uh, and ultimately that is what that is what's gonna manifest as all of those symptoms that we just spoke about. So, some other causes could be surgery. Um, er, sort of any surgery, really radioiodine therapy, radiation iodine deficiency and in sort of less developed countries that is the most common cause. Um, and then we've also got congenital causes. So, congenital hyperthyroidism again, just means of course, Children are born with that hypothyroidism. So, and then we can also sort of further divide hypothyroidism into primary versus secondary causes. So, primary hypothyroidism refers to essentially, we've got a thyroid insufficiency which originates in the thyroid itself. That's what we mean. When we say primary primary hypothyroidism, the thyroid itself is not working secondary. On the other hand, obviously, overall, it still manifests as hypothyroidism, but the cause is not necessarily to do with the thyroid itself. The cause is actually to do with something a bit more further upstream. So if you remember, think back to that H PT axis, we've got trh which is uh stimulating the pituitary to release TSH, which is then stimulating our thyroid. So there might be an issue a bit further upstream, which can cause uh sort of a secondary hyperthyroidism. So, again, just sort of very er quickly to go over. What does hypothyroidism look like? Uh dry, sort of hair, dry mucous membranes, uh cold intolerance, slow heartbeat, dry skin fatigue weight gain constipation. These are all sort of typical signs of uh underactive thyroid, of sort of reduced basal metabolic rate. Ok. Um What do we do then? So, if a patient comes in similar to um, this lady that we've hypothetically just seen, what are we gonna do? Uh, we, there's a couple of things that we need to do before we can obviously make a definite diagnosis and before we can go on to treat her. Ok. So at the bedside, of course, we're just gonna take her general observations as we have done. Um in that question itself, we know her, her heart rate, that sort of stuff, we can do a thyroid exam as well, sort of examine it, palpate it, you can feel the goiter swelling again that tells you that something is not right. Uh We can do some blood tests. So T FT S thyroid function tests. That's what that means. FBC S is a full blood count again, is always safe to do a full blood count when you're doing blood tests just to check for potentially, just to sort of rule out anything else that might be a problem, maybe if it's not the thyroid. And then thirdly, we can do some imaging as well. So we can have a look at some images of the thyroid to see if there's any kind of structural abnormalities. Ok. So how do we treat it then? So once we've sort of done the investigations, we need to, we know there's a problem with the thyroid or it could be a problem with the pituitary or whatever it may be. Um, how do we treat it? So, the first thing is we can replace T four. So, remember the sort of hallmark of hypothyroidism is that we are not getting enough thyroid hormones being released into the blood. So, we've got, uh, a nice replacement for T four, which is called levothyroxine. It's just a sort of synthetic replacement um which you just sort of administer to patients. And as you're doing this, you wanna monitor the TSH level because you wanna make sure that your TSH is sort of in, in a nice medium range. Thinking back to nice basic principles of homeostasis. You want it to be in an optimal range in terms of potential complications because you know, every treatment has potential side effects some minor complications, you might get some weight loss, some headache and in more serious cases, heart attack and some more chronic tachycardia. On the other hand, we've also got a combined replacement of not just T four but also T three complications of that. Uh As you can see some palpitations, tremor anxiety and this also does suppress TSH. OK. So again, thinking about that same negative feedback, the same basic principles. So we've got another question. Um Let's sort of uh oh, so this is actually the exact same one. So not to worry about that. Uh Never mind that question. So let's move straight on to talking about hyperthyroidism then. So how does this come about? How does the other hand happen? So, if there's too much of these thyroid hormones, too much T four, too much T three, essentially, uh this is gonna manifest as a few symptoms that we're gonna talk about in a minute as well. Ok. So again, it's all to do with negative feedback. If we have too much T four, too much T three negative feedback dictates that we should get a suppression of trh and TSH um as well. Ok. Now, whether or not that's actually the case, when we examine is gonna dictate what might be the cause of our hyperthyroidism. So, the most common cause of hyperthyroidism. So, an overactive thyroid is graves disease. Uh Graves disease again is also um an autoimmune disease as well. So you can see the trigger is unclear. It's not too well understood, but B cells are gonna produce antibodies against thyroid proteins. Ok. Um Essentially those autoantibodies bind to and they sort of do the job that TSH would have done. Um and it sort of is constantly stimulating your thyroid to keep releasing more and more and more T three T four into the blood. And that of course, is gonna give you those symptoms of hyperthyroidism. So some other causes toxic multinodular goiter is almost kind of uh a neoplastic kind of er, some small masses some small, small growths in the thyroid gland, er, which are pretty overactive and then a solitary toxic nodule would just be one such little mass or nodule um, as opposed to being multinodular. Ok. So these are probably the more common causes of hyperthyroidism. Ok. So, as you can see this is more to do with graves disease, these things, er, that you're going to have, er, and again, you're gonna get a goiter, as I said, you can have that in both hypo and hyper exophthalmos is bulging of the eyes and it is very, very characteristic of Graves disease. Um uh you must have come across this, if not, you definitely will. Uh that's exophthalmos and then pretibial mx edema. So this is growth of soft tissue on the shins. Um again associated with a similar thing. So this is what hyperthyroidism looks like. Um What do we get? We get weight loss. We've got this again, we've got this elevated metabolism. So you've got tachycardia, tachypnea, uh high BP hypertension. Um I mean, get enlargement of the thyroid is what produces that goiter swelling. And so it's kind of just the opposite really um of hypothyroidism. You see some extra sweating and that sort of stuff with this. These are specific to graves. So you can see there on the left that, that sort of bulging eye is what we call exophthalmos. But otherwise, um your sort of symptoms are exactly, as we just said, So you've got your goiter sweating, arrhythmia, tachycardia, nausea, diarrhea, uh, in females, of course, it can sort of impair menstruation, uh, and muscle weakness and tremor are also very common as well. Ok. So that more or less discusses sort of brings us to a close on both, uh, hyper and hypothyroidism. Um, before we move on to adrenal, then I'm just gonna have a quick look at the chart and just see if there's any questions. I think we're doing. Ok. So adrenal physiology then, so we're gonna talk now about very quickly, sort of what does, what do the adrenal glands do normally? How does it normally look? And then of course, similarly, we'll have a look at what is it, what sort of stuff is happening when it goes wrong? Ok. So I'm sorry that this image isn't. So it's a little bit blurry, but this is just to illustrate where the adrenal glands are. So, in terms of the anatomy of the adrenal gland, so we have our kidneys sort of in our, in our sides, in our flanks and the adrenals are basically these little triangular glands, they're sort of like little hats that the kidneys wear on either side bilaterally. Uh and that is where they live. Ok. That is where the adrenal glands are and they produce some very important hormones in the body. Ok. So just zooming in some more sort of specific anatomy. Then we can see, er, you've got uh you've got your adrenal medulla, which is the middle bit, sort of the innermost bit. And you've got your adrenal cortex and even then it can go sort of, you can be sort of further divided so you can sort of split then your cortex into your zona glomerulosa. So the sort of er the most out a bit next bit in is ozona fasciculata got ozona reticularis, which is starting to become part of the medulla and they all produce different hormones. So the gl- glomerulosa is gonna produce our mineralocorticoids. We're talking uh aldosterone here. Zona fasciculata is gonna give us our glucocorticoids. So that's our cortisol and our zona reticularis are gonna give us our androgens. Ok. So, adrenal feedback there. So this is just a different type of axis, but it's the same, it's the same concept. It's just different hormones. That's the only difference. So, similarly, again, our hypothalamus is going to release C Rh this time. So that's actually corticotropin releasing hormone that's gonna stimulate our pituitary to release uh our ACTH. And that ACTH er when it's, once it's in the bloodstream, once it reaches the adrenals, it's gonna stimulate our adrenal glands um to essentially kick out a load of these, these, well, more or less these steroid hormones uh into the bloodstream. Ok. So we're talking cortisol, uh predniSONE aldosterone and we'll talk about all of these to come as well. So, how are they made? What does it look. Like. So you can see cholesterol is sort of the main derivative that sort of will go on to become any of these things. But you can see it's a very, again nitty gritty pathway, but I would say sort of just know your different classes and only very broadly. Um Do you need to know specifically about how it's uh how it's made? So you can see our mineralocorticoid pathway is gonna end up uh making aldosterone or Glucocorticoid pathway. Generally, we will end up making cortisol and then we have our sex hormones, our androgens, you can see d hea and ultimately, we're not going to talk about that too much today as a topic for probably a different day, but we're gonna end up with testosterone and then estradiol or estrogen, they can sort of be converted peripherally between each other. Ok. So what do they do then? So again, there's a lot of information here, but we're just gonna focus on what each of the hormones do. So, mineral corticoid is like aldosterone, what do they do? So they regulate um our balance of electrolytes. So, salt and water in the blood. So the action of aldosterone is to essentially keep sort of uh keep sort of sodium and water, sort of absorb sodium and water. Uh and also sort of stimulate potassium secretion in the distal convoluted tubule in the kidney Glucocorticoid, Glucocorticoid, sorry, like our er cortisol. So this is essentially these suppress our immune responses and they have an impact on our carbohydrate metabolism. Uh We've also got, um we've got our catecholamines which are made in our adrenal medulla. So, epinephrine, norepinephrine, that is just adrenaline, just the American name for adrenaline. Um They do probably things that you have come across before. So they increase heart rate, increase respiratory rate, increase BP, they cause vasoconstriction, that sort of stuff. Ok. So that is what it normally looks like. That is generally what is expected from our adrenal glands. Now, let's talk about what happens when stuff goes wrong. Ok. Adrenal pathology. So let's talk about underactive adrenal glands to begin with. So largely, largely speaking, we can refer to this as Addison's disease. Ok. Addison's disease, adrenal insufficiency, they mean kind of the same thing. Ok. So underactive adrenal glands refer to when all those horm hormones we just spoke about um talking mainly sort of glucocorticoids, mineralocorticoids, androgens. Er, basically, when we're not getting enough of those being produced. Ok. So why does that happen? What causes that? So some of the most common causes of primary addisons. So remember, we can always uh sort of differentiate between primary and secondary primary means we're not getting enough of those hormones because there is an innate problem with the adrenal gland itself causes of secondary. On the other hand, secondary refers to we're not getting enough of those hormones, not necessarily because there's a problem with the adrenal gland, but maybe something further upstream where, you know, maybe we're getting too much ACTH being released because of a pituitary tumor, let's say. So, most common causes of primary problems with the adrenal itself, maybe autoimmune condition. And so autoimmune addisons is fairly common infection of the adrenal. Some people can just be more genetically susceptible to that um to that underactive uh adrenal gland as well cause of secondary as I said, uh pituitary tumor, which is just churning out ACTH is gonna constantly be stimulating the adrenals to just release these hormones. Similarly, hyperal tumor and there's also suddenly stopping long term steroid use. So, steroids are essentially they're good replacements for those hormones. Uh Cortisol, aldosterone, et cetera. And if you've got someone who's taking that medication for a long, long time, their adrenal sort of switches off because the hormones are being rela er, sorry, they're being replaced, er, so consistently that the adrenal is kind of like, ok, I don't really need to make it anymore. So I'm gonna stop making them. And therefore, if you were to stop the medication, suddenly it takes a while for the adrenal gland to sort of pick up again and say, oh, actually, I need to um I need to now continue making so it can cause a secondary hypoadrenalism or adrenal insufficiency. So, what does it look like though? So how do we sort of see this in patients? So, Addison's disease or insufficiency, you can see we might have low BP because we're not getting uh cortisol or adrenaline. Uh some weight loss, weakness, nausea, diarrhea, vomiting, some again, general gastrointestinal irritation, uh vitiligo hyperpigmentation, some skin changes are not uncommon. Uh And you can see that in cases of adrenal crisis. So when things are very, very dire uh fever, syncope or fainting, convulsions or sort of seizures, hypoglycemia, hyponatremia. So some severe electrolyte imbalance and as we've already said, vomiting and diarrhea. So if we investigate, then uh we can see here essentially once we've done our clinical assessment, which is what I just spoke about those symptoms that you see in patients. That's how they present to you er, clinically once you've done that, what are you gonna do to further investigate? So, first things first, we're gonna do some nice routine blood tests. So in addition to a full blood count as normal, we wanna measure the levels of cortisol levels of ACTH in the blood, the levels of sodium and potassium as well. Just to get an idea of the electrolyte balance, we wanna conduct an ACTH stimulation test. So that is basically you administer some ACTH into the blood and you see whether the adrenals respond to that. So what you'd normally expect if you put ACTH into the blood, you'd expect your adrenals to sort of be stimulated by it and to have more of these steroid hormones be produced in response. And then you can measure that if you do it and there's no response, there's no, er, extra release of steroids, uh, of any adrenal hormones. You can tell there's something wrong there, there's some sort of adrenal insufficiency. Thirdly, uh, you can measure for whether there's antibodies to your adrenals. So you can see if there's an autoimmune condition. Potentially. Here, we can do some imaging CT MRI to again, look if there's structural abnormalities, maybe one of the, maybe the adrenal glands are sort of structurally underdeveloped. That could be why. Er, and then also we've got our C Rh stim stimulation test. So this uh can t help tell us if the insufficiency is actually in the pituitary? Cos remember it's all sort of this one big stream. So if you introduce some new C Rh, you would expect that to stimulate the pituitary to release ACTH. And if you were to do that and you saw no increase in ACTH, you might then deduce that there's some sort of pituitary insufficiency. Those are just some of the investigations that you may do in that case. So here's a sort of um slightly a slightly more detailed diagram illustrating some of the investigations you don't need to, er, obviously wrote, learn memorize all of it, but just know the details. Um, know the sort of broad, speaking, broad, broad details, that's all you really need. Um But yeah, it's everything that we've already just sort of discussed. So adrenal insufficiency once you've sort of deduced us that you need to exclude uh some other causes. You know, whether it's sort of recent uh steroid use, which is what I was talking about when I mentioned suddenly stopping exogenous steroids, um measure your ACTH. So if you've got an underactive adrenal, but you've got high ACTH, what that means is, you've got your adrenal gland, which is, you know, it's not working properly, it's not releasing adrenal hormones, but you've got a really high ACTH, which means negative feedback is telling the pituitary to release more ACTH because it's trying to stimulate your adrenal to release those hormones. This is suggesting that the pituitary is fine because it's trying to get the adrenal to work. But the adrenal itself, there's some sort of insufficiency there. On the other hand, if you've got low or normal ACTH, that tells us that there's probably a problem with our pituitary because if there's low adrenals, low adrenal hormones, sorry. And that's sort of, that's the case you would expect ACTH to be high in response to that because you want your pituitary to be stimulating your adrenals to release more uh of those hormones to get them to normal levels. So, if ACTH is not elevated to try and get that to happen, you're thinking there's a problem there. Ok. Underactive adrenal glands. How do we treat it then? So what do you do? There's only so much you can do really. So and quite a big part of it is formed by replacement of your uh of those hormones that you've lost effectively. So, glucocorticoid replacement, we're talking about the synthetic supplements of steroids, um called hydrocortisone or predniSONE, methylprednisone, prednisoLONE. These are all very typical glucocorticoids, steroid hormone replacements. We've also got mineralocorticoid replacement. Uh So in order to basically replace aldosterone, fludrocortisone is quite a good one for that, quite common. Uh we can have electrolyte supplements. So remember if we've got um basically not enough of our uh not enough of our sort of aldosterone, our mineralocorticoid, then we're not getting appropriate balancing of our electrolytes. OK. So talking sodium potassium and so as a result of that, we're going to need uh some supplements to balance out those electrolytes. Regular monitoring, of course, is very important. You wanna make sure that everything is brought back to optimal range. You also don't wanna take it the other way and get too high in certain levels. And lastly, if there are sort of tumors, uh essentially maybe addressing the tumor separately. So that's trying to um I don't know we do it through chemotherapy, radiation surgery, whatever the method might be. OK. So we've got another question here. Um Again, I'll give just a couple of minutes uh for you guys to have a read of that and then we'll go through it together. OK? So just a couple of minutes to have a reader and have a look at what you think is going on. Ok. So let's uh let's begin, just sort of going through it then, shall we? So, um we've got a 38 year old lady who presents to the clinic with lethargy, fatigue and weight loss. She mentioned she's been feeling very faint recently and has been experiencing nausea and diarrhea in addition to some abdominal pain. So that initial bit is not very specific. There's not much we can do with that, but it's painting a little picture here. So you desire to investigate further. She's found to be hypoglycemic, hyponatremic and hyperkalemic. Ok. So low sodium, low glucose and high potassium investigating further, you also find that she is hypotensive. She has a low BP 97/68 and further blood tests are gonna show her to have elevated ACTH with reduced levels of cortisol and Aldo aldosterone. What are the differential diagnoses? Now? Um, what they should be really, I hope you've been able to deduce from this that uh we've actually got uh well as we've just discussed um quite extensively, an underactive adrenal pair of adrenal glands. Um and this is why, so those sort of bold, bold uh symptoms paint the picture for you. So, lethargy, fatigue and weight loss, uh typically associated with a lack of those er, steroid hormones, feeling very faint as well, nausea, diarrhea, and abdominal pain. So, further investigations then hypoglycemic. So, remember low cortisol, um is basically gonna mean that we don't have much glucose being in, released into the blood hyponatremia and hyperkalemia are both sort of very classical indications that aldosterone is either not working or we don't have enough of it. Ok. Um Upon further investigation, you find she's hypotensive. So again, we, we don't have uh enough adrenaline being released. So, you know, there's no increase in BP, so it's gonna stay pretty low. She has elevated ACTH is going to tell us that there's no problem. Therefore, uh with our pituitary. So that's doing its job and the re reduced levels of cortisol and aldosterone. And they tell us that we do have um an adrenal insufficiency, but it is a primary adrenal insufficiency. So to then further deduce why uh what the actual cause is, you know, whether it's autoimmune or infectious that we'd have to do even further investigations. So, the last thing that we need to discuss then today is the last thing um which is the opposite then of an underactive adrenal. So, overactive adrenal glands. Er this is where we are gonna introduce this idea of Cushing's as well. So, how does it come about overactive adrenal glands? So, adrenal tumors um which could be overproducing our hormones. So, in the adrenal gland itself, if you got a cancerous tumor, um which is just mass producing these hormones that could cau cause our overactive adrenal gland. Cushing's uh Cushing's is specifically related to cortisol. Ok. Uh Primary aldosteronism is specifically related to aldosterone excess of that. A pheochromocytoma is a specific adrenal tumor only of the adrenal medulla. And remember which hormones are produced by the adrenal medulla. It's our sort of catecholamine. There's our adrenaline noradrenaline. Ok. That is specifically, he's got a special name. Pheochromocytoma. Cah or congenital adrenal hyperplasia is a genetic condition. It's congenital. Uh and there's a couple of important enzymes which are faulty in this condition. And this basically sort of d disrupts again, the balance of some of these hormones that get produced and we get overproduction of certain hormones and underproduction of others exogenous steroid medication. So, if you've got someone that's taking long term steroids and you know, they might be uh taking it for too long or their doses are incorrect, we can get some overactive adrenal response to that and chronic stress as well. So, remember cortisol, of course, is sometimes known as our stress hormone in response to chronic stress, chronic stressful environments. We can get this, you know, chronically, uh elevated cortisol, which is again, um evidence of an overactive adrenal gland. So what does it look like then when patients come and present them uh with an overactive adrenal gland, uh this is what it looks like. So this is of Cushing's Syndrome, which is specifically talking about cortisol. So, very typically, we have these classical features which are a very red and round face. We've also got um a sort of uh a little, a little hump on the back of the neck, which is fat, it's a fatty deposit. We've also got uh, truncal adiposity, which just means uh, quite a lot of fat around the belly region. And you can see, we've also got purple stria, which is kind of like stretching of the skin and bruising. Um, otherwise we've got hypertension, cortisol will do that, stress hormone, uh, muscle wasting osteoporosis. So overall, you can see, er, not great, not so much fun. So what do you do? Then how do you examine this further? So you've had a patient come in and uh they sort of present with some of those signs to make an actual diagnosis, you need to look a bit further. So the first thing we wanna do is again, measure the levels of these hormones or glucocorticoids, mi corticoids, catecholamines. Uh We wanna look specifically what is high, what is normal, what is low. And if we've got elevated levels of all of these, we can begin to deduce that, you know, we might have a pair of adrenal glands here which are doing way too much. So overactive, you also wanna measure ACTH cos remember if ACTH is uh elevated as well, then we might have a problem upstream. Cos remember if we've got really high levels of cortisol of aldosterone, then ACTH should be low in response to that because we've got such an excess of those hormones that the pituitary doesn't wanna be stimulating the adrenal to make any anymore. So we should have low ACTH. Therefore, if we measure it and it happens to be high, we can deduce that there might be a pituitary problem there. Uh where, you know, we might have a pituitary tumor which is just releasing, releasing, releasing ACTH. Ok. So if we have that suspicion of a tumor, we might do some further testing, we might do some imaging. So CT or MRI uh some imaging for those tumors. And then later, we of course, can do something about it, but we need to find it first. Genetic screening in advance, er, of some sort of antenatal screening er to check for cah cos remember it's congenital Children are born with it, unfortunately. And um of course, you otherwise wouldn't really know until they're born. Um congenital adrenal hyperplasia to check for that in advance. But we've also got the nice famous dexamethasone suppression test. So, dexamethasone is a steroid. Um and essentially you give sort of um you administer some low dose dexamethasone and essentially, if you have given dexamethasone, uh you've increased the levels of these steroid hormones in the blood. The response to that from the body should be a r er, sorry, a reduced amount of cortisol being released because um you've increased it artificially, the amount of steroid hormone in the blood cortisol should go down uh in response to that. So, if you do this test and cortisol, the release of it does not go down then again, you can deduce that we might have a, a case of an overactive adrenal gland. Ok. So how do we treat it then? So we've got, um, if you've got an adrenal tumor, if you've got a pituitary tumor, again, do exactly what you need to do to treat those tumors. So it could be a surgical resection, removal, radiation, chemotherapy, whatever it may be, adrenalectomy. So, just removing the adrenal gland altogether. So again, it might be because there's just tumors all over it and you can't really get rid of just one. So you might just have to get rid of everything aldosterone receptor antagonist to sort of oppose the excess of aldosterone and spironolactone. Er is quite a good one for that. So, uh quite kind of like coexisting er with our overactive adrenal, we might also have hypertension because remember if we've got excess cortisol and adrenaline, we're gonna have that er, vasoconstriction, we're gonna get that hypertension. And so you need to address that hypertension, which coexists by itself as well. So you're gonna have anti hypertensives uh to be able to do that. It could be beta blockers, ace inhibitors, that sort of stuff, hormone replacement again in cah. So again, I told you that in cah, you have some hormones which are high, some which are low. Um and the ones which are low, of course, you need to replenish those to make sure they are normal and then six because of course, chronic stress is, uh, in fact, quite an important, er, sort of risk factor for cushing's or excess cortisol. It's important to manage that stress as well in terms of kind of like a modifiable lifestyle factor. So, our last question then that we're going to do, I'm gonna give you again a couple more minutes to have a little look at this. Um, and we will do this last question and we'll wrap up um with that. OK. So I'll give you a few minutes uh just to have a reader and of course, just to have a think about what you reckon is going on. All right then. So let's have a little look, um, little look through this, let's go through it. Uh And then we can wrap up as well. So then you are the F one working in a GP practice. You've got a 46 year old lady here who's presenting them to the GP um with a history as you can see of hypertension and she's gonna present as you can see with an increasing amount of fat developing around her abdominal area as well as some blurred vision as well. So that's an interesting one upon closer inspection. Uh We're able to see some purple striae. You also note that she has a very round face and a small hump on the back of her neck. So further investigation shows her to have a BP of 100 and 43/94 as well as elevated blood cortisol levels. Her cortisol levels do not decrease as well. Uh In response er sorry to a low dose dexamethasone test. An MRI head shows a small mass in the pituitary gland. So this is a very, very typical case, as you can see of something that we just spoke about is a pituitary tumor and the pituitary tumor is gonna be constantly secreting uh ACTH which is constantly stimulating our adrenal gland to produce so much of these hormones. So what we would describe this as is we'd say this is a se a case of secondary overactive adrenal. OK. Or a case of secondary cushing's, we would say so, what is it that sort of, what's the telltale sign? What is it that actually gives it away here? You can see um these bolden symptoms here again. So we've got a history of hypertension. If someone's got Cushing's excess cortisol, we're gonna get that elevated BP. Uh I told you about truncal adiposity. So that's uh fat developing around the abdominal area. Now, blurred vision is an interesting one. Now, blurred vision. The reason that she is having blurred vision here is in the brain where the pituitary is very, very close to it is what we call the optic chiasm and the optic chiasm um is essentially is quite an important landmark in the visual pathway er from the retina through back to the occipital lobe, er, where vision er, is of course processed. Um, now, the optic chiasm is a quite an important landmark there on the way and if there is a pituitary tumor and remember they're very, very close to each other, if there's a growth, a mass in the pituitary, that mass can press on the optic chiasm and that as a result is gonna cause some visual symptoms. So that's why uh she's having some blurred vision as well. Uh Purple stria I said of course, is associated with that, that sort of trunk or adiposity. Again, she has a very round moon face, which is again, is our sort of characteristic classical finding in Cushing's er, and a small er, sort of er neck hump um on the back of her neck, which is, again, is a little deposit of fat, um which again, is very classical in hypercortisolemia. Uh So, of course, she's had a history of hypertension but she presents again uh hypertensive as well, 1 43/94 as well as, as you can see blatantly now, elevated blood cortisol. So her cortisol levels do not decrease in response to low dose dexamethasone. So again, this is telling us that we've got uh definitely you got something wrong. There's a case here of um of Cushing's or overactive adrenals and the MRI head. Um It really sort of seals the deal then it shows uh that there's a small mass within our pituitary gland. Ok. Er, so, yeah. And then obviously that is a, again, er, again where we would target the treatment in this case. Cos that is the co, that is sort of the main cause of why our adrenal gland is producing so many steroid hormones. Um And ultimately, of course, it's that tumor there, which is causing it. So we need to resect that tumor, that tumor has to go. Er, so that could be done, er, sort of, er, surgically there's a variety of different techniques that could be used for that. Um And so therefore, those are where we would have to target our um our, our efforts so that more or less brings us to the end of what we've got now. Um So I would like to thank you guys for listening. Um Thank you guys for listening to this lecture then and if anyone has any questions at all, please do, let me know um put something in the chat and we can, uh we can, we can discuss them.