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Chemical Pathology 1

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Summary

This medical teaching session is designed to provide an in-depth look at endocrine pathology and related disorders. It will cover the anatomy, physiology and histology of the thyroid, pituitary, adrenal and pancreas glands. It will also provide information about the external factors that regulate hormone secretion. Participants will gain a deeper understanding of issues such as thyroid peroxidase enzymes, thyroid stimulating hormone, hypothyroidism, hyperthyroidism and Goiter. It will also cover the effects of TSH on the menstrual cycle. Attendees will receive individualized attention, be able to ask questions and be given the knowledge and skills they need in order to succeed in their exams.

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Learning objectives

Learning objectives:

  1. Describe endocrine regulation in the body and its components
  2. Identify features of hypothyroidism and hyperthyroidism
  3. Explain the physiology of thyroid hormone production
  4. Describe why irregular menstrual periods can be seen in hyperthyroidism
  5. Recognize the causes of Goiter formation
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The following transcript was generated automatically from the content and has not been checked or corrected manually.

So far and today we'll be doing a chemical pathology and uh shortly a little outline content of the lecture because obviously it's quite a dense topic. And, um, yeah, let's take it away. You give it a go give a yard. I'll stop the recording. Okay. So, um, hi guys. I can't see exactly how many people are here, but I hope we've got a decent number. Uh So others as Kier introduced, I'm Jared, I am a foundation doctor at Guy's and ST Thomas's. I've completed two rotations. Now, I've completed uh transplant surgery at guys and I've just completed geriatrics at ST Thomas's. I'm moving on to general surgery. So I'll be giving a talk today on endocrine pathology. Um We'll be mainly focusing on the glands listed there, pituitary, thyroid, adrenals, pancreas, uh and then there'll be a small cell slide about poor Farias at the end, uh which I understand is important for you guys as well in terms of the metabolic disorders, there's a few others as well like the glycogen storage diseases, the fatty chain acid diseases, the amino acid key to acid uh to see diseases as well. I think these are less yield. So I haven't included them in this talks. I wanted to focus on the nitty gritty stuff, but please refer to the guide and you can email me if you have any questions on topics like that. I would say the main things to focus that the high yield things that are going to be asked in the exam is based around thyroid disorders, adrenal disorders and diabetes. Okay. So that's the focus where I really want you guys to pay attention. Okay. So I'm hoping that at this point, I think you've had a lecture on this topic, the guide has been distributed. So I'm hoping kind of the basics are already ingrained and implemented for you guys. And now it's about discussing the case, is having a think about the nitty gritty final details and making sure you're all set for the exam. Okay. So I very much want it to be as interactive as possible. I know that sometimes it's a bit scary to speak up in front of a lot of people. So please feel free to use the chat to uh type answers and type questions. We will have breaks in between each of kind of the gland topics to ask questions and answer them. But I do feel free to stop me at any point. I've got the chart on my phone as well here so I can answer things as we go along. Okay. So let's move on. So as I said. So we've got two sections, we'll have a break 10 minutes in between the two. The first section will focus on thyroid pathology and disorders and the next one will be pituitary pathology and disorders. And then moving on intersection to will be adrenals, diabetes and then short slide on porphyria is at the end. Okay. All right. So let's just briefly talk about an overview of the endocrine system and hormonal system. Okay. So it all regulates in kind of a negative feedback. Apart from there are two uh changes in that, which would be the oxytocin um system. And the other one's escaped my head at the minute where they're actually positive feedback systems. The other one, sorry being the menstrual cycle and the estrogen surge release there for ovulation. But the majority of hormones are controlled by negative feedback system. And that means it's very kind of easy once you understand the action of the hormone and what it does to understand the symptoms and presentation of disorders and how to read hormonal assays as well when we think about this negative feedback system. So we have the triad here. We've got the tertiary center. I don't know if hopefully, you can see the cursor, we've got the try the triad here. The tertiary center being the hypothalamus, the secondary center being the pituitary and the primary center being the end organ. Okay. So our hypothalamus releases releasing hormones such as crh trh. And these will stimulate the pituitary gland to produce hormones such as A C T H and TSH. And then these will go on to stimulate our end organs which include adrenal glands and thyroid. Okay, after just two examples, and when people talk about disorders of the hormone, they will refer to primary secondary and tertiary. Okay. Primary refers to a disorder in the end organ. Secondary refers to a disorder in the pituitary and tertiary will refer to a hypothalamic disorder or even beyond two things like Kallmann syndrome where we actually have external factors such as kiss pectin, affecting the regulation system. Okay. And when we get secretion from the end organ, these will act in a homeostatic mechanism as all systems in the body do to reduce the secretion from the pituitary and the hypothalamus to ensure that the hormone range is tightly controlled within the blood. So we don't get too much hormone or too little hormone being secreted. As I briefly touched on, there are external factors which control this negative feedback system. And these will include things like his peptone. I mentioned other substances such as glucose, proteins, amino acids, lipids, fats in the blood stream, uh external body features. So temperature, climate, altitude, all these kind of things, okay. And that's the overall general picture of how hormone regulation is controlled in the body. Okay. So let's move on to the first gland. Now we've got thyroid, okay. So that's a nice picture of the thyroid. Let's talk very quickly about the anatomy and the physiology of the thyroid gland. So, can someone just right in the chat roughly where is the thyroid gland located in the body or if you want to speak up, uh, you're more than welcome to neck. Neck. Exactly where. So we've got the thyroid gland sitting just uh inferior to the larynx who got the isthmus crossing roughly between the first and tequila rings And we have the left and right lobes coming from the isthmus upwards towards the thyroid, the inferior border of the thyroid cartilage. Okay. We've got three arteries and three veins which form the vascular supply to the thyroid gland. The arteries being the superior inferior thyroid arteries and the thyroid. I'm a artery being the last one. And then we have the superior middle and inferior thyroid veins. An important an anatomical distinction as well to remember is that we have the four parathyroid glands which are on the posterior aspect of the thyroid. And this is important for when you think about your thyroidectomy is and stuff parathyroid will not be touched on much in this lecture. As I think you have another lecture about calcium regulations. So that will be discussed there in terms of the physiology. So let's first talk about the histology and then move on to the hypothalamic pituitary thyroid access. Okay. Some terms of histology here of the thyroid gland. You can see that we have the keloids So we've got the stroma here, the very light pink stuff. We've got the colloid here, the dark pink stuff. I iodine rich. And then on the side here, we've got these follicular cells, okay. And then you can see some cells kind of in between that being the parafollicular cells. Okay. So this is the histology of the thyroid gland in terms of how thyroxine, which is the hormone, the functional hormone is made. Um we have thyroglobulin secreted uh well produced in the follicular glands which is then moved into the colloid. In the colloid. We have oxidation and I A donation and coupling of the thyroid globe thyroglobulin molecules. And this will form T four which is essentially to thyroglobulin molecules coupled each containing to iodine molecules. And that's where the four comes from. So it's got four iodine molecules on it. This is then moved back into the follicular cell and then excreted into the bloodstream. Okay. And this process is stimulated by TSH, which is secreted by the pituitary gland, important enzymes to know is thyroid peroxidase enzyme which is important it for that oxidation and I donation process which happens in the colloid. Okay. We have the parafollicular cells which the creek calcitonin. Can somebody tell me in the chat what calcitonin does? I'll shout it out. Exactly. Yeah. That's right. It reduces calcium and it would and exactly. It regulates calcium absorption. So it reduces the serum calcium by binding to osteo class and preventing bone breakdown and bone resort in which the crete's calcium good, fine and just a bit about free thyroxine. So free thyroxine refers to T four. And then how this accident, the end organ is D I Adonis enzymes, which I'm sure you've heard of. And these convert the T four into T three which then acted an intranuclear receptor and regulates basil metabolic rate. It increases the metabolic rate and it potentiates the response of our catacholamines, which increase includes nor adrenaline and adrenaline. Okay. So can somebody just shout out or list if we've got too much of this thyroxine hormone circulating in the body? What kind of features are we gonna get? What are we going to see weight loss palpitations? Um He intolerance. Yeah. Exactly. Good. Yeah. Sweating. Good. So, and as you can see, so uh you've talked about in the process of increasing metabolic rate and you've also talked about effects of nor adrenaline and adrenaline on your body. Okay. Good. So let's move on to that now. So on the left, we've got features of hypothyroidism. So we get hair loss reduced. This is all to do with reduced metabolic rate, affecting cognitive processing, reduction in heart rate, fatigue, sensitivity to the cold weight gain, puffiness. So we've got lot, we've got reduced breakdown of our proteins causing an oncotic pressure and increase of fluid into the intravascular spaces causing weight gain. Let's touch on menstrual periods there. So this diagram isn't actually very clear on that. It just says in regular menstrual periods. And I mean, it isn't fully specific which one you see in which hyper and hyper thyroidism in hypothyroidism, we tend to see heavy periods and in hyperthyroidism, we tend to see oligomenorrhea. So very irregular and light periods. Does anybody know why that is the case? So, thyroid, the thyroxine hormone has anti estrogen effects. Okay. So if we've got excess thyroxine circulating the bloodstream, we will not be able to get that follicular maturation and the surge of LH as well, which corresponds to rises in the estrogen that cause um ovulation and follicular maturation. So that's why we get oligomenorrhea in hyperthyroidism and it's the reverse in hypothyroidism, we get excess estrogen, um stimulating progesterone, increasing the amount of endometrium, um high um growth in the uterus and then heavy painful periods. Okay. Um Goi to is an interesting one. What causes the thyroid gland to increase in size? What causes what causes a goiter? Is it in response to the thyroxine? Is it in response to the TSH? Is it in response to trh? So it's the, it's the TSH, the thyroid stimulating hormone that causes Yeah, exactly. As um John put in the chart, it's TSH or T S like h like stimulation. And this is why a goiter can be a feature of both hyper and hypothyroidism hyper if you've got a tertiary or a secondary hyperthyroidism where you're getting excess TSH being secreted, that will cause a goiter unequally in hypothyroidism. If you've got a primary hypothyroidism where the issue is with the gland, if we remember our feet, negative feedback cycle will get increased trh, an increased TSH release and that increase in TSH release will cause a going to uh to form good. Now, just some features for you to have a look at. Does anybody know what's on the top left there? And what that feature is specific of it? Pretibial edema. It is pretibial myxedema. Good. What disease is that quite specific for hypothyroidism? Not quite hypothyroidism. So I think you're thinking of myxomatous changes. So graves. Yeah, somebody has written in the chat. Yeah. Pretibial mix edema is very associated with graves. And so it's interesting because obviously we do quite often associate myxedema coma with hypothyroid, uh an excessive state of hypothyroidism, but it is actually a bit of a masson. Um er, because the mix it mix, it matters, changes are actually quite loose. They're not very sensitive. You can see them in both changes and you see them all across all four limbs. Whereas with specifically the myxomatous changes, you see here on the anterior tibia that is very specific for graves' disease. So it's important not to get those two things mixed up. What's on the right hand side there on the top, right. What does that look like? Those eyes look normal or not look a bit scary to me? If anything extra ophthalmoscope good. So she probably does have except Alma's. We can't truly tell that unless we look from the lateral side and we can be happy that the eye is bulging out of the orbit. But very likely that she has got that there are two things that I can definitely see. Um on there one is lid retraction. So I don't know if you can appreciate, but if you can think about your own eyes, if you go and stare at yourself in the mirror or the camera, you can't see as much of your sclera as you can in her eyes. And that's because her lids eyelids are attracted backwards. Similarly, she also has conjunctival swelling, which is why she's got the hyperemia in the conjunctival vessels, which is particularly noted on the left, her right eye where were staring at on the left there and she also has eyelid swelling as well. And these are all features of um graves eye disease, okay, ocular involvement of graves disease, okay. And there's different severity ease. It can range from simple soft tissue involvement and lead retraction and lidl lidl ag like this patient has all the way up to Corneille involvement and sight loss. Okay. It's graded in six different cat degrees. Okay. Now, what kind of scan is showing on the bottom there? Is it Radio I D radioiodine? Exactly technetium scan good. So this is important. Again, if you've got a goiter, you can do a diagnosis using the scan to see on a neck lump, you can use the diagnosis this to find out what kind of um lump you're dealing with. Okay. Um This is to do with the idea being taken up by the thyroid gland into those keloids and you can see the activity of the thigh, the um colloid and follicular cells in the thyroid. So, in Graves disease where we've got a diffuse growth of the thyroid gland from that TSH antibody stimulating that receptor. We get a diffuse increase in activity and uptake of the iodine. And that's why all of the iodine is taken up symmetrically in Graves disease in a toxic multinodular goiter. The areas where you've got the increased functional nodules, you'll see increased uptake of the iodine here. And I'm similarly for a toxic adenoma where you've got a specific functioning tumor of the thyroid, you'll see an uptake here. Good. So I probably should have asked you before. But what are, so we've got here, some of the causes of hyperthyroidism and hypothyroidism. So let's start with hyperthyroidism, consumed. I kind of already touched on it. What is Grave's disease? There's a clue there with autoimmune or two antibodies, the TSH receptors. Exactly good. Yeah. So we get auto antibodies to the TSH receptor. We get those antibodies stimulating the TSH receptor like TSH normally does. Therefore, we get an increase in our thyroxine release production and release from the gland we also get our goiter because the goiter thinks it's being stimulated by TSH and we get the negative feedback. So we see a reduction in trh and TSH. But despite the reduction in trh and TSH, these antibodies continue to circulate, continue to stimulate the gland and continue to see secrete our thyroxine causing hypothyroidism. We also get the antibodies depositing in soft tissue behind the eyes which causes the uh I feature as I mentioned before in Graves disease, Dick Ravens, some uh diet is. What is that? So again, a bit of a clue, this could probably go into both categories of hyper and hypothyroidism. It starts as a hyperthyroidism picture. Any takers, you get information of the thyroid and the leakage of the hormones. Have you made good? So you've got some sort of stimulus. It could be an infection, it could be surgery, it could be a prolonged admission in I T U for example, and you get, as you say, an inflammation and a breakdown of the thyroid gland which causes a surge release of the hormones causing a hyperthyroidism picture. Eventually, when those hormones are depleted and your thyroid is recovering, it will not be able to catch up and make the, the hormone as well as it was before. And that's why we can then in the latter stages start to see a hypothyroid picture, but good knowledge. Yeah. What's the cause of the information? So it can be a range of things. It can be. If somebody is unwell from an infection, it can be a chronic kind of malignant kind of picture. It could be if someone's had a prolonged admission on I T U in their strain on the metabolic processes of the body. Again, a kind of inflam inflammation kind of picture. It can be any, any kind of acute insult such as surgery as well, that would cause an acute inflammation, inflammatory response of the body could lead to an ultimate breakdown of the thyroid gland. Some people are more susceptible to it than others. We don't have clear kind of identifiable cause as to who is more susceptible or not just the patient category that are at risk of it. Does that make sense? Yeah, thanks. So um I tried to break these down to got autoimmune effective and inflammatory. We've got um tumor's. So we've mentioned are multi nodular goiters, uh functional adenomas. We've got drug in juice. So, amiodarone, amiodarone is highly rich in iodine, um toxic multinodular going to their post partum. So um you have a hyperthyroid state in high pregnancy because there's an increased metabolic demand and this can continue after pregnancy causing hyperthyroid picture. What is the John based our reaction? Does anybody know what that is? Someone who is eileen deficient is given iodine? Okay. And then what happens once they're given the iodine? Why doesn't it just make them you thyroid? Why do they suddenly become hyper thyroid? So, it's probably a bit of a tricky question the way I've answered it. So, somebody, yeah, exactly. So, they're chronically iron deficient and their bodies metabolic rate and systems have become used to dealing with that very low, um, thyroxine kind of level. And if you give someone a surge release of iodine because they're, um, systems have become so sensitized, they, they will suddenly go into a hyperthyroid statement because you've given them loads of iodine, they're not used to having this much thyroxine going around and their body is very sensitive to it because they're used to dealing with small numbers. And that's why they get a hypothyroid picture. The opposite of that being a wolf take off effect. What is a wolf chai cough effect? And why is it important as well? Is this something you get after radioiodine therapy for? Exactly. Yeah. So that's why this effect is why radioactive iodine is very useful for treating hyperthyroidism. So it's where you overload somebody on iodine and essentially the colloid and the follicular cells are not able to cope and catch up and they begin to burn out and die. And therefore, that destroys some hyperactive parts of the thyroid gland. And that's why the things like your multi nodular goiters, the radioactive iodine caused inducing this wolf Sykov effect where it ends up actually breaking down and destroying those hot functional areas of thyroid gland become very useful in treatment. Okay. But somebody normal where you indeed give too much iodine and break down the thyroid gland. You can induce the hypothyroidism, which is why it's on that side there. And you can see some other causes of hypothyroidism. Uh, the two I just wanted to touch on is the 1st and 3rd bullet points there. So, the third bullet point very high yield. What is hashimoto's thyroiditis, autoimmune thyroid itis? Yeah. So, what is the particular mechanism there? You touched on it being an autoimmune mechanism? But what exactly is the autoimmune reaction? TPO good. So it's antibodies to that thyroid peroxides um for enzyme and it breaks that enzyme down. So in the colloid, the oxidation I A donation of the thyroglobulin molecules is not able to form. So, no, we're not able to get coupling and secretion of effective thyroxine hormone. Good. So that causes hypothyroidism and then at the top there, what is? So I've kind of given you a bit of a hint there. So, cretinism is the form of congenital, hypothyroidism. Um a lot. And the primary example of that, I guess would be thyroid a genesis uh where the thyroid's Anderson form properly. Just aside from that for bonus points. Does anybody know embryologically where the thyroid gland forms from laryngeal pouch? So, yeah. So it's pharyngeal. Yeah. So it's part of the pharyngeal pouch and arches. I'll give you a clue specifically when you get a thyroglossal cyst, you stick your tongue out and the gland moves down. So it's the Foramen cecum, which also forms part of the post area, part of the tongue. And basically the Foramen cecum forms the base of the tongue. And also the thyroid gland and the thyroid gland descends in a tracked down the neck and into um where, where it sits at the base of the neck just above the superior mediastinum. And that is why that, when that uh looked uh patent and remains, that's why we get a thyroglossal cyst and it protrudes when you stick your tongue out. Okay. So somebody who has cretinism where um they've got a congenital thyroid, a genesis or dis genesis. What kind of features would a young child have? Do you think learning difficulty is good? So it's a very like hypothyroid picture. They'll have difficulty in cognitive processing, learning difficulties. There's a one year, they're quite a dramatic. So they have puffy faces, pot bellies, big tongues, big protruding tongues. Lymnaea, stunted growth. Good. Yeah, these are all features of cretinous and good. So how do you investigate somebody with hyper or hyperthyroidism E C G is important an examination. So I always based when around I'm in an off ski, for example, always bass the investigations into bedside bloods and imaging. So the bedside, you do an examination, you look for the features. We mentioned the ocular defects, the arrhythmias, uh things like that. Blood's full blood count, electrolytes, thyroid function tests. What two antibodies would be important we've touched on them for the auto immune disorders, E TSH and anti TPO good blood glucose and lipid profile in somebody who has hypothyroidism. What will the lipid profile look like? I of LDL? Perfect. Good. So it's a hypercholesterolemia picture. Good year as opposed to things like nephrotic syndrome where we see more of a hypertriglyceridemia picture and then any neck lump, if someone's got a goiter that you found on examination will require a neck ultrasound, we've mentioned are isotopes scans that you've had uh that we've discussed and CT and MRI CT is particularly useful. If someone's got a very large goiter that's got retrosternal extension, we can use a CT to plan operatively for that good. So this is, this is the bread and butter. This is in the exam. Very common kind of question. They'll present you with a thyroid hormonal essay and they will ask you to um interpret it. So this again, endocrine, very straightforward. All you have to think about is that negative feedback system. And if you think about the negative feedback system, you will understand how to interpret these hormonal states. So for example, if we take hyperthyroidism, say we've got a primary hyperthyroid problem. So um we'll see an increase in T four and T three because we've got an increase in the amount of the gland is producing and that will cause a negative feedback. So we won't see as much trh being secreted and we won't see as much TSH being secreted if we've got a secondary problem, that's a problem with the pituitary. So we'll see an increase in TSH being produced and then that will cause an increased in T four and T three secreted from thyroid gland. All right. So, take your time to study this table. Um And this is the kind of thing that will come up in the exam. Okay. We can touch very briefly on subclinical hypo and hyper thyroidism. This is where the bullet subclinical. So subclinical means that the blood test show a picture of hypothyroidism. So we've got low T four and T three or hyperthyroidism, high T four and T three. But the clinical picture is not suggestive of a hypo or hyper thyroidism. And the question is whether do we treat them or not? And for example, focusing, focusing on the hypothyroidism, it's to do with the age and it's to do with how high, what the level of the TSH is. So, if somebody's TSH, which normally sits in a range of 4 to 10 is significantly high, a level of 25 they're quite young, we would be thinking about treating them despite the fact that clinically they are not hypothyroid, if somebody is TSH is actually in a reasonable range and they've got low T four and T three with the continue monitoring that. Okay, I'm very quickly on the management as well of hypo and hyper thyroidism. So for hyperthyroidism, particularly um in thyrotoxic Crites storm crisis, which I'm sure you guys are aware of and we have some questions on so we can discuss as well. We very much need to symptom control. For example, if somebody goes into a f from uh from a a thyroid storm or somebody is going into a sinus tachycardia, if somebody is profusely sweating, we need to stop that potentiating of the catacholamines. And we do that freebie to blockade thioamide. Things like your carbimazole on your proposed a year or so, they inhibit the thyroid peroxide, these enzyme and that reduces the production of our T four. We've touched on radio iding and also reception of the thyroid gland for hyperthyroidism and hypothyroidism. Simple. You just give hormonal replacement, okay. And we've kind of touched on the subclinical hypothyroidism and the sick. You thyroid already. Okay. Any questions on hypo and hyper thyroidism before we quickly talk about thyroid tumors to finish off the thyroid gland section? No. Okay. So, very quick um discussion around thyroid tumor's maybe one or two questions will come up in your finals. Um Relatively common, particularly amongst middle aged females. I have a Caucasian ethnicity. Most common being the papillary histological diagnosis popular very popular. His theological features we see as some moma bodies which are showing here, get these calcifications, um orphan, any nuclei, orphan Annie because they're empty nuclei. They don't, they have a reduced amount of our mitochondrial are endoplasm reticulum size. They're kind of lonely and sad. So they're orphans, lympho lymphatic invasion. It tends to be common microscopically as opposed to the follicular type where we see vascular invasion. And these papillary tumors tend to be non encapsulated. Okay. These have the best prognosis due to a range of things, they tend to be able to be detected quite early. They tend to be in younger age groups as a variety of reasons why they, they have the best prognosis. Then we have follicular which is encapsulated vascular invasion on a microscope, as I mentioned. And these have quite a good prognosis as well. Both of these are monitored with thorough globulin once they are respected or um and received radioiodine and this has done annually. Medullary is part of the multiple endocrine neoplasia, two A and two Beasts Syndromes, which I'm sure you're aware of. Um these originated in the C cells that produce the calcitonin C cell, parafollicular cells, same thing and calcitonin therefore, is used to monitor uh these after resection is done. We also have lymphoma which is a, an an increase in patient's who have, who have hashimoto's thyroiditis. Um It is a diffuse large b cell lymphoma and it is monitored using C D 20 which is a surface cell marker of our non hodgkin lymphomas, which hopefully you can remember from your hematology lectures. And we also have anaplastic, which are very poorly differentiated, common in elderly patient's, which have a very poor prognosis. These tend to present quite rapid growth, again, extend the basement membrane and the capsule very quickly. And these often tend to be non operable by the time of presentation because of their rapid growth. Okay. So very quickly, we've just got a couple of questions on thyroid before we wrap up on thyroid and move on to the next um section. So just reading this question, does anyone have an answer? Duque vision's perfect. Good. So key features there, you've got a hyperthyroidism picture. Quite acute. Recent Kreisel symptoms suggest a viral infection as a trigger. Um Something I didn't mention is that because it's inflammation, it tends to be pay tenderness around the neck. Uh and she's also had a technetium scan which does not suggest good uptake suggesting that the thyroid gland has been broken down, which is why we see a subacute thyroiditis picture here. Good question too. Perfect. Calcitonin and the last thyroid question. So a bit cheeky cause we haven't properly talked on this. If somebody, if you're not able to know the answer, does somebody at least know what they think the likely diagnosis is here. Thyrotoxic crisis. Good. And we have triggers for thyrotoxic crisis. Like we have triggers for the crisis version of hypothyroidism, which is a mix edematous coma and triggers include things like infection I T U stays similar to the subacute thyroiditis surgery, which is probably the case here. Um And in the thyrotoxic storm picture we see people in fast af hypertensive, confused sweaty to keep apneic. The fact that she's got these pretibial mix, it matters, changes, suggesting maybe hasn't underlying undiagnosed graves' disease. But it's unclear unless we do testing for antibodies of the TSH receptor. And the reverse of this would be the myxomatous coma where we would see people being drowsy, sleepy, hypertensive, low GSG CS concerns about managing their airways, very cold. Um And yeah, that would be a mix edematous clona picture which is the um emergency of hypothyroidism. Does anybody know the management of thyrotoxic crisis? E good. So beta blocker to control the symptoms, get them out of fast. Af we need to die. Um I'd which um is important to break down, stop the production of our thyroxine hormone, try and reduce the amount that's in the bloodstream. And then we need to steroid as well which inhibits the peripheral conversion of the T four into T three. I remember, remember the D I nine today's enzymes I talked about in the peripheral uh system so that inhibits those enzymes and prevents peripheral conversion and reduces uh inhibits the weakens the Axion of our T four um hormone good. So the answer there is the bottom one, fine, so quick breather and then we'll move on to the second part of section one, which is pituitary gland, anatomy and physiology. So our pituitary gland is this tiny thing here sitting on the store coming down from the hypothalamus, hypothalamus actually extends into the uh into the post as an extension in as the posterior pituitary. And then we have the anterior pituitary sitting wrapping around that, which is what we're going to mainly talk about here and the hormones secreted from there. Um The pituitary gland has its own blood supply. It's got a portal system like the liver. So it recycles its own blood. And that's important for when it receives the signals from the hypothalamus to regulate the production and secretion of the pituitary hormones. Okay. And it sits in the cellar tutor sica wrapped around the diaphragm. Sell a which is a folding of the jura matter. Okay. These are the hormones secreted by the anterior uh pituitary. So it has these trophic cells here and these are split into acidophil, a Sidot um bill troughs which are the cortical atrocious and the lactose troughs and then a Brazil a fill troughs which are the thyrotropin uh gonna atrocious and some autotrophs. And this is to do with acidic staining. Okay. Our lactose chose the Creek PRL thorough secretes. TSH, pretty self explanatory that you can see from uh that die from. Okay. And again, we've got um the hypothalamus regulating these, these hormones above just to note somatotrope. So we've got growth hormone, releasing hormone stimulating growth hormone secretion. And then we've got growth hormone inhibiting hormone or some matter statin which decreases growth hormone secretion from our somatotroph. Okay. And the G N R H here, the amplitude and frequency of the pulsatile way form release of GNRH. If you remember that secreted in a pulsatile mechanism depends on whether FSH or LH is secreted from the gonadotroph stow. Essentially, we have two types of pituitary mass that can be in there. We can have a macro adenoma which is usually non functional and is defined as the adenoma being greater than 10 millimeters in its largest diameter. These are usually non functional, but they can also be associated with prolactinoma as as well. We have microadenoma which tend to be more functional by functional, I mean hormones creating and these are less than 10 millimeters in diameter. And on the side there, you can see the symptoms of what a macro adenoma, nonfunctional uh adenoma would look like. So it would, you'd have a headache. Um you would have by visual changes. So if you remember the anatomy, we've got the optic chiasm sitting around the pituitary gland and uh passing and crossing over up the optic chiasm is the nasal fibers that are projecting from the retina and the nasal fibers look at the temporal lateral aspects of our visual field. So if the pituitary gland enlarges, it compresses those nasal fibers crossing over at the optic chiasm and that caused the defect in our temporal visual field. There's two things that can cause a bitemporal hemianopia. In this region. We have the pituitary gland being enlarged and just above that um a defect in Wrath keys pouch, which is where the pituitary gland forms causing a cry craniopharyngioma, which is a type of tumor seen which grows from the Wrath keys pouch. As the pituitary gland is inferior to this. We have an in for we have the inferior portion of the nasal fields affected by the pituitary gland enlarging and that causes a superior quadrantanopia if you remember the retinas reversed. And then likewise, if we've got a craniopharyngioma compressing those um superior nasal nasal tracks, we get an inferior quadrantanopia with our craniopharyngioma. Ok. Difficult to think about. Just imagine the optic tract in the optic pathway and whereabouts the fibers that are getting compressed, whereabouts they're projecting on the retina. So the main two things I want to focus on here is first acromegaly gigantism and then also prolactinoma as well. Okay. So what hormone is getting secreted in acromegaly and gigantism growth or no good. So, it's a matter trophy in related acromegaly is the clinical picture post puberty. Once the growth plates have closed, gigantism is the clinical picture before puberty when the growth plates have not closed and therefore you become extremely tall. So the growth hormone, what does it do? Well, does what it says on the tin really? It causes us to grow. It causes our soft tissues to mature and enlarge. It causes hyper hyper trophy of our glandular tissue. It also causes um glucose release as well. And um protein synthesis. And uh it also causes modeling as well of the heart and other organs as well. And that will result in some of the pick feet clinical features that you can see right here on the side of acromegaly. So we see gradual soft tissue enlargement noted mainly in the peripheries. You see organomegaly, we see diabetes due to increased glucose being produced. Uh and we see car things like carpal tunnel because of nerve compression and also um hearing changes as well because of the soft tissue around the ear canal being changed. And then also symptoms of heart failure, not only from hypertension due to vascular remodeling, but also the fact that we get um concentric uh sorry eccentric hypertrophy of our heart as well. Um growth hormone effects are mediated by um I G F one. And therefore, this is the first line um uh thing that is used to uh suggest a clinical picture of acromegaly. So if this is an increased, we would then move on to a uh an oral glucose tolerance test. A measurement of G H to confirm a diagnosis of acromegaly and operative planning and location of the tumor is um MRI pituitary is sensitive for that. In terms of management, we've got surgical resection some after statin analogs. Those if you remember that's an inhibitor of the somatotroph. So you're going to get reduction in your growth hormone secretion. Others said hypertension, heart failure of features of acromegaly New York. So we need to modify a cardiovascular risk factors and then the bottom there, we also need to do annually. Colonoscopy surveillance. Does anybody know why that's important? Increased risk of colon colorectal cancer? Good. So like it does with all parts of the tissue, it also in stimulates the endothelium and lining of our good. So we get increased formation of colonic polyps. And also if these um grow out uncontrollably, that can increase our risk of colorectal cancer moving on to prolactinoma. So what does prolactin do? Does anybody know what prolactin does milk secretion good? So it stimulates milk synthesis in the glandular tissue and then it's the oxy toes in that stimulates the smooth muscle cells to actually eject and secrete the milk. But yeah. So it's important in milk and synthesis. And that's why clinical features. When we've got too much of see galactorrhea, we see gynecomastia because of that increasing growth of our milk producing glandular tissue, prolactinoma prolactin also inhibits our gonadotroph in releasing hormone. So that's why we see a reduction in L S LH FSH and these limp to symptoms of ill ago, amenorrhea, loss of libido and impotence. We see extremely high levels of prolactin in the serum, greater than 6000. And in terms of management of prolactinoma, um a lot of studies have been done and actually dopamine agonist. So, dopamine inhibits the release of prolactin. Dopamine actually seems to be just as effective if not more effective than surgery um for the management of prolactinoma because they have a high recurrence rate because these tend to be quite large tumor's. So dopamine medical therapy is actually the first line. So things, things like bromocriptine and the carb medellin tend to be our first line management of prolactinomas. And if this fails, then we try to move on to surgical resection. Okay. So less high yield is our hypopituitarism. So, um things like a pituitary adenoma that is compressing. The other cells are a craniopharyngioma. These compressed the other cells in the pituitary causing reduction in their action and secretion of hormones can cause hypo pituitary is um if you've got an infection, we've got an infiltration from our infiltrative diseases. Um Iatrogenic causes such as surgery, trauma and radiation. She hands, which is an infarct following a postpartum hemorrhage. We get reduction in our blood supply to the pituitary gland in April plexi, which is a vascular anomaly of the pituitary gland. When we get a bleed inside the pituitary gland causing it to become um the functioned and and tertiary. So, Kallmann syndrome is a disorder of optic migration of our in your optic bulb. And uh that is important because those uh neurons secrete the kiss pepped in which is important in stimulating our hypothalamus to release uh particularly gonna uh G H R H and uh GNRH gonadotropin releasing hormone and growth hormone releasing hormone. So, in Kallmann syndrome, we send to see a reduction in the pituitary gland being able to produce, uh FSH and LH. And the symptoms will come from a reduction in all of these hormones which you've kind of talked about already. It's important to note in hyperpituitarism where we've got something like a kind of a space occupying lesion causing the hyperpituitarism. We see a particular cereal loss of our hormones and the body does it quite clear cleverly and that it loses first the hormones that at least relevant. So growth growth hormone tends to be the first one that goes next to, that tends to be the sex hormones. So the FSH and LH tend to decrease after that. Then we get a C T H, then TSH, and then finally, the prolactin and the reason why the prolactin is actually the last one is because trh and stimulates the production of prolactin. So when we get a reduction in TSH, which is one of the final hormones which used, we get a negative feedback and lots of trh being secreted, which continues to stimulate our prolactin secretion. And that's why prolactin actually counterintuitively because you think it's not that important, actually tends to be the last hormone that uh ends up going in terms of investigation. So this kind of is is a summary of how to manage and investigate and manage all of the pituitary hormones. So we can screen for our cortisol, our thyroid function tests our steroids. We do a combined from pituitary function test, which we'll talk about mainly on the next slide and we can do some imaging and then management again, is mainly replacing the hormones. The only thing to note with that is the hormone you need to replace first is hydrocortisone. Because if you start replacing things like thyroxine first, this can precipitate a thyroid toxic crisis because you're not able to manage um the metabolic function rates and things without the steroids just very quickly. The um combined pituitary function test. This is wearing administered GNRH trh and insulin to the patient and watch the response of our hormones. If you administer G N R H in a pulsatile uh physiological fashion, which two hormones there would you expect to increase LH and FSH good trh point. Self explanatory would be TSH and insulin. Which hormones would you expect to increase if insulin is given G H N Courtis? All good. So they try to increase combat the reduction in serum blood glucose, which is produced by insulin. So that's the end of pituitary. So we've got a few more questions and then we can take a 10 minute break and answer any questions. In the meantime, before we move on to the second section, which is a bit shorter than this one. So anybody got the answer to this question be good. So, nonfunctioning macroadenoma, um some people might get a bit confused with the prolactin being elevated there. Remember I said that in non, from in macro adenoma as um sometimes the cat, these can be prolactinomas themselves. But the other reason why we tend to see a slight increase in our collecting level is because that tumor compresses that stock pituitary stalk where some dopamine neurons allying and that prevents dopamine inhibiting the release of prolactin. So that's why we end up seeing a slight rays and prolactin there. Remember that prolactinoma slide, it needs to be levels of 6000 and above. Most people have 8 to 10,000 as the value of prolactin when they have a prolactinoma. So it's not quite high enough for a diagnosis of prolactinoma. Plus, she doesn't have really any symptoms of prolactinoma, which is why nonfunctioning macroadenoma is the diagnosis here. And then the final question before the break. Um Anyone got the answer to this one. Be good. Yeah. So identified, it's a bitemporal hemianopia. And I remember the pituitary gland lies in line with our inferior uh nasal fiber. So therefore, split the retina around. We see a superior quadrantanopia by temporarily. Okay, good. Anybody got any questions about thyroid gland, opportunity gland? No. Okay. So we'll just take a quick five minute um break just to stretch your legs and things stand up, get some water. So you're able to concentrate and then we'll move on to the second section which will mainly focus on the adrenal stuff. Bit of diabetes and then a very quick slide on for three years. Okay. Okay guys, let's go back to it. Hopefully you can see my slides again. Just send a message in the try if you can't see them and you can hear me as well. Okay. There is these may quickly back onto the slide about hyper pituitary in testing. Was there a particular person was a particular question you wanted to ask about that slide or was it just to drop stuff down? But I think they, they get the slides at the end of the thing. So what was the pouch above the optic chiasm called Wrath keys pouch is where um is part of where the pituitary gland forms the anterior pituitary and a tumor that can develop from Wrath keys pouch is the craniopharyngioma. Does that make sense? Yeah. Alden, great. Okay. So let's move on to adrenal anatomy. Adrenals sit on top of our kidneys. They're, they've got three arteries and one vein supplying them. Uh They sit cushioned nicely in the perinephric. That capsule very protected, very handy glands. They've got um an adrenal cortex and the adrenal medulla. The adrenal cortex is what produces our steroids on the adrenal medulla is what is part of the sympathetic nervous system. So they actually have to embry logical different origins. The adrenal cortex originates from the metanephric ducks along with the kidneys and migrates upwards from the pelvis and the cloak her to the abdomen and the adrenal medulla um actually descends from the note of cord and the spinal system um along with the para para ganglionic cells uh and forms the adrenal gland uh like the sympathetic train into the adrenal glands. And this is important when we think about things like pheochromocytoma. That's why the embryology is important there. Okay. So what are the three layers of the adrenal cortex? And what do each of them secrete glomerulosa all dust their own good sorrows. Remember the order as G F R like kidneys. So glomerulosa being the most outer particular to being the middle one and reticularis being the most inner layer of the cortex. So G F R S, how I remember it glomerulosa secretes. Our mineralocorticoid is mainly being aldosterone. I'm sure you know what aldosterone does. It's part of the wrath system important for maintaining salt water and BP levels. We've got the Fasciculus Arctic which mainly secretes our cortical steroids. So the main one, they're being cortisol and then we've got our reticularis, which is what secretes the sex steroids. So things like R D H E A and then we've got the medulla here which I mentioned before which the creases are catacholamines very quick. I'm not going to jump on this too much because again, and I think you might have another lecture on it. But this pathway extremely important. There will be a question about it in the exam. It's one of those things you just have to learn the night before and try and remember. Okay. The main important in dimes to remember is 21 hydroxylase. 11 beta hydroxy lays in 17 a hydroxylase. They are the three most commonly ones that become deficient. Um We see this in um congenital adrenal hyperplasia. Ch 21 hydroxylase deficiency is where you don't get the deoxy quarter Cerrone. So these guys present with the hyperaldosteronism picture. So the hypertension hypercholesterolemia, hyponatremia picture. The 11 be to hydroxylase guys. So these guys produce the deoxy corticosteroid, which was able to cross um uh stimulate the aldosterone mineralocorticoid receptor. So these guys actually present with a hyper uh intensive picture hypernatremia and a hypokalemia. And we've got 17 a hydroxylase where we are not getting as much sticks, stories being produced. So we see reduction in arm uh pubic hair and also everything gets shunted down this way. So these guys also present with a similar picture to these guys. Stove top guy famous for having this uh condition. Well, are famous for having one of the conditions on this list. Does anybody know which condition? It is so famous for having Addison's disease, which is an autoimmune condition where we get antibodies attacking the adrenal cortex. Okay. And that results in a reduction in our production of mineralocorticoid and cortisol picture of adrenal insufficiency. So we have causes iatrogenic medical causes autoimmune have touched on TB. So TB is the most common cause of a primary adrenal sufficiency worldwide. Whilst in Europe, the most common primary adrenal insufficiency cause is Addison's the autoimmune. We have Waterhouse Fredrickson syndrome. That's where we have a infection septic septic. See me a picture which causes hemorrhagic uh infarct of the adrenal gland. Does anybody know which organism most commonly causes waterhouse fredericks and syndrome Neisseria? Good. So it's normally in um, meningococcal septicemia. Yeah, is the most common uh causing what helps Fredrickson Syndrome. We also see infarcts and malignancies very rare in the adrenal gland adrenal tumour and they tend to be non functioning when they are present. Um And then we've got um hypes syndromes as well. So, autoimmune poly endocrine um syndromes one and two. So one is where we get an adrenal insufficiency and hypoparathyroidism picture. And then two otherwise known as Schmidt syndrome is where we see adrenal insufficiency with hypothyroidism picture. Okay. And in secondary, if you remember our negative feedbacks hierarchy, that would be an issue with the pituitary gland. So the clinical features are very essentially a reduction in having those steroids. So our mineralocorticoid and our glucocorticoids. So, mineralocorticoid as we get the postural um symptoms, we get reduced uh water and salt re absorption. We get vomiting and salt craving. I don't know if it's just me, but I can't see the slides anymore. Is that an issue for everybody? Same? Um I can see them. I couldn't see them. I could, I could, I couldn't see them for a bit but they're back. So can you see them now? Oh, no, they've gone watch. Uh, yeah, I want fine. Can everyone see the slides now? Yeah. Uh, no, that's great. Ok. So, mineralocorticoid symptoms, reduction from aldosterone. We see postural symptoms. We see vomiting and salt craving reduction from our glucocorticoids. We see weight loss, anorexia, hypoglycemia, fatigue, um, and reduction from our sex steroids. We see decreased arm and pubic hair. Does anybody know why we get skin mucosal pigmentation? Because the pro hormone at some of that, what was that? Sorry? There's um melanin secreted hormone couple with a C T H, the pro hormone good. So they cross um they cross stimulate the same receptor good. So the ACTH acts at the MSH receptor and it causes hyper pigmentation of our skin and mucosal services and we get that in primary. So we wouldn't get that in secondary adrenal insufficiency because we're not getting the ACTH production, but we would get it in our primary adrenal sufficiency. Where from the negative feedback, we have an increase in A C T H being released from the pituitary. In terms of investigation, we need to do nine AM cortisol levels important in the morning because that's when we get our surge of cortisol and cortisol should be the highest we see electrolyte abnormalities that I've mentioned before. We need to check our glue tose. We could do seats imaging to see if there's any tumor or anything in the adrenal gland. And then we can also do the synthetic ACTH test as well. We administer a C T H and we watch the response of the adrenal glands. And if the adrenal glands are able to produce and sufficient courters, all glucocorticoids and mineralocorticoid. And this suggests that there's a secondary problem if they're not able to produce um uh the steroids. And that suggests there could be a primary adrenal gland issue itself and it's not responding to the ACTH management tends to be with our hydrocortisone. So, um which mainly replaces the glucocorticoids, but it does also have mineralocorticoid activity and they're fludrocortisone is a very strong mineralocorticoid, but that has very weak glucocorticoid effects. So, there's less evidence to give fludrocortisone adrenal sufficiency. The main one that we use is hydrocortisone. So that's adrenal insufficiency. Now, let's talk about the other way if we've got hyper Aldara aldosteronism and then later when we've got hypercortisolism or Cushing syndrome. So, hyper all aldosteronism, uh the main primary cause being bilateral idiopathic hyperplasia, adrenal adenoma is that a functional can cause it. And there's also glucocorticoid re mediated aldosteronism as well where actually the ACTH and cross binds with that 11 beta hydrolase enzyme that was on the steroid pathway and that causes excess aldosterone. In that first column, we get excess aldosterone being produced, secondary causes of hyperaldosteronism tend to be related to the ras pathway. So, we've got renal artery stenosis, fibromuscular dysplasia and heart failure as well where we get fluid, overloaded pictures and increased secretion of Renan, the signs, you know how aldosterone works. So, you know what the signs are. We get increased salt and water attention, hypertension, hypernatremia, uh increased secretion of potassium in the kidneys causing hypokalemia. And um through the osmotic effect, we get pa literary in people becoming thirsty with polydipsia as well in terms of investigation. So we look for those electrolyte abnormalities on our bloods. The first line investigation is our aldosterone to Renan ratio because that will tell us if it's an issue with the Renan RAAS system being activated or aldosterone alone is being secreted. So, very useful imaging adrenal vein sampling is important as well. If you've got too much aldosterone secreted, you'll be seeing increased amount of it coming out of the gland and into the vein management is with aldosterone antagonist such as spironolactone or surgical resection if there's a tumor moving on to Cushing Syndrome. Now. So um um Cushing syndrome is from excess secretion of our Glucocorticoids. So we think about what things like cortisol do. They cause hypercalcemia, they cause um increased like policy like a genesis. So fat storage, um they can affect our skin making our skin more brittle, they can cause increased fragility of our blood vessels, causing us to bleed more and get purple striae and bruising. And um they also affect the secretion of our sex steroids. They cause the negative feedback causing an inhibition of our G N R H and our ACTH being secreted. So we get decreased sex steroids and amen amenorrhea from the reduction in the estrogen component. But um especially when we've got things like Cushing's disease and we have increased, it's a secondary cause. We get increase stimulation of the steroid pathway and that will in that will cause shunting of the steroid precursors into the sex steroid pathway causing her suited in. Uh So on the left here, we have some um causes primary being adrenal secrete in tumor's secondary being a pituitary adenoma, otherwise known as Cushing's disease. So, don't confuse the two between Cushing's syndrome and Cushing's disease. The disease refers specifically to the ACTH secrete in tumor of the pituitary gland. And then commonly we get ectopic paraneoplastic syndromes of ACTH secretion. The main one known being squamous cell, uh small cell cancer of the lung investigations. So we start by um diagnosing a rise in steroids by demonstrating that with a plasma cortisol or a urinary cortisol. The next stages, then basically determining whether we have a true Cushing syndrome or a pseudo Falls Cushing syndrome. True pseudo Cushing syndromes can be someone on exogenous steroids already. It can be somebody with an increased alcohol intake or other causes of increased steroids in our bloodstream to detect a true Cushing syndrome, which is shown by demonstrating a negative feedback loop. We do a low dose dexamethasone test and suppression test where we give dexamethasone and try to suppress the negative feedback loop. And if we're able to do that, that suggests that there's, except the, the system is working correctly and there's excess excess excess exogenous steroids in the serum. If we're not able to demonstrate a suppression, then that suggests that there is some added excess amount of steroid being produced. And that would say that we've got a true Cushing syndrome here, a true amount of um steroid being produced. What we can then do is increase the dose of steroid to try and get it to control the negative feedback soup. And that's when we give a high dose dexamethasone suppression test. And in the case where we've got Cushing's disease, we are in fact able to reduce the amount of ACTH secreted when we increase the dexamethasone to the high test because of that negative feedback loop. And that's why if we've got suppression in a high dose dexamethasone test that diagnosis, our Cushing's disease, our ACTH secreted tumour. If the high dose decks method methadone test is not able to suppress our steroid levels, then that suggests that the source of the steroids is coming from outside the control of the negative feedback loop. And this suggests an ectopic cause such as S crh secrete ng tumor or A C T H paranoid neoplastic syndromes that we see in our lung cancers. And we've got the management of um the Cushing Syndrome on the side here, which you can read in your own time quite self explanatory. Now, the last tumor to mention in the adrenal section is the pheochromocytoma. So this is now moving away from the adrenal cortex. And we're now looking at tumors of the adrenal medulla, the sympathetic nervous system. And as I mentioned before, these are formed from the nervous system which is embryologically derived from the also with the skin and the ectoderm. So that's why these tend to be associated with our neurocutaneous syndromes such as neurofibromatosis. They follow the 10% rule where 10% of malignant, 10% are extra adrenal. So mainly paraganglion e Omagh's are in the same kind of category as our pheochromocyto hmas. 10% tend to be bilateral and 10% of patient's will actually present with a normal intensive picture. You can imagine in a fair Chromos item. A we've got excess secretion of our adrenaline and our nor adrenaline's the catacholamines mainly nor adrenaline that is converted uh peripherally into adrenaline. So we see a classic triad of throbbing headache, palpitations and sweating. And this is intermitted in terms of the investigations, uh urinary metanephrines, which is the breakdown of our catacholamines, some secreted in the kidneys is a very useful test. We can see some false positives here. The other causes of a raised catecholamine serum level. And um the main ones to focus on in terms of confirming the fair Chromos I toma and localizing it would be a CT abdomen and uh M I B G scan as well, which again is a radioisotope and looks at the monitoring the breakdown of catecholamine precursors. And we can see that in the adrenal medulla and to manage pheochromocytoma, we do a surgical resection and it's important to give the alpha blockade first before the beta blockade. As you might, if you give the beta blockade first, you will decrease the heart rate and cause a negative chronotropic and iron atropic effect. But we still have the vasoconstriction from the alpha blockade. So therefore, you will cause a hypertensive crisis. And this is just something to read in your own time of distinguishing between con syndrome, which is another name for our aldosterone secreting tumor of the adrenal gland with a fair Chromos it toma because both can present sometimes in similar ways. Just a very briefly touch on multiple endocrine neoplasia. I'm sure you guys were aware of this. So remember it as the three ps and one, the two ps in to a and then the one P in to be so pituitary adenomas parathyroid. Um they can be either hyperplasia or adenoma seen in men. One and our pancreatic tumor is so they're the three ps in men. One and pancreatic tumors will include things like our black gastrinoma as our insulinomas and our VIP Omagh's which tend to be all quite benign tumor's men to a, we've got 22 ps. So we've got the parathyroid and in this case, it is mainly hyperplasia and the pheochromocyto mus. So the fails are part of the men twos. And then, as I mentioned before, in the thyroid section, we also see medullary thyroid carcinoma as well. And then in to be, we've got one P just to fail there. And these tend to provide present with a marfanoid habitats as well. So in the exam, you'll see the marfanoid features of the patient and that's how you'll be able to identify that this patient like there's a men to be syndrome. So will be a marfanoid person with a pheochromocytoma. Okay. So just do it before we do the questions of the adrenal gland. Anybody got any questions for me? No. So does anyone have the answer to? Question six? See good. Um What do you think the diagnosis is good? Other sins? Question seven, be good. And what are you thinking as a diagnosis for this patient? Mhm Cons or hyperaldosteronism? Good hyperaldosteronism and the most common cause of that being bilateral idiopathic hyperplasia of the adrenal cortex. And then the last question here, a good IV hydrocortisone. So this person had add is only in crisis, likely triggered by the surgery. Good. Any questions on that before we move on to the final section? No. Okay. So we'll move on to the final section now which is the pancreas and we're mainly just going to focus on diabetes here. Um So we all know the pancreas, the head of it sits in the jordon in the tail extends to the spleen. It's a retro secondarily retro peritoneal organ. It's got a secretary function, a digestive function and also an endocrine function as well. The endocrine function is part of the islet cells. The alpha cells accreting glucagon which stimulates glucose secretion on the beta cells and uh being the majority in the eyelid population which secrete our insulin which reduce glucose levels in the blood. So, diabetes type one and type two. So type ones tend to be lean and obese. You can see the differences between the two in the, in, in here. I think the main things you can read this mainly in your own time. The main things to note is diabetes is an autoimmune. Type one is an autoimmune condition where we get description of our beta cells through antibodies being produced. And that means there was little to no insulin being produced. And our interestingly actually a lot of studies now that we have the multi genome sequence and things going on have actually shown that there was more of a genetic type predisposition in type two diabetes and there isn't type one because you don't get the insulin being produced at all. These patient's tend to be a lot more sicker. They can get keto acidosis because they're not producing any insulin at all. So whenever the body feels starved, it will stimulate like pollicis and stimulate keto genesis to try and produce um uh some source of energy for the body. These people tend to therefore produce younger, sorry, present younger and their symptoms tend to be acute onset as opposed to type two diabetes where people are older, often middle aged. And this is more to do with a slight decrease in uh insulin secretion but mainly focusing on insulin resistance at the end organ bodies. Okay. So I'm sure you guys know all of this, the diagnosis of diabetes. When do we call it prediabetes? When do we call it diabetes? Well, the answer is there before HBA one C wasn't used to diagnose. We now do use it to diagnose diabetes if people also are symptomatic at the same time. So if people are symptomatic, I A they've got symptoms of hypoglycemia. Um we only need one positive test in a patient to diagnose diabetes if they're a symptomatic and you happen to find a level like one of these, you need to repeat the test on a separate occasion to get a diagnosis of diabetes. Uh Just before we move on to management, could people shout out some common symptoms that you get of hypoglycemia in diabetes, polyuria. Good. That's true too. The osmotic effect of glucose, excess glucose being filtered in the kidney with polyuria. If you're peeing out lots of fluid, what will happen? Well, he dips. Yeah. Good. So you become more thirsty and drinking more, um more infections, more infections. Good. So lots of glucose in the bud, lots of nice energy source for bacteria to feed on and multiply. So I'd say that definitely polyuria and polydipsia and then I would say fatigue or mainly the common three. And then we've type two, obviously the weight gain and things as well. So in terms of management, so conservative is always important, particularly where you've got a very holistic condition like this, always break your management down into um conservative medical and surgical. It's a great way to talk about it in the Yassky. So we've got lifestyle advice, monitoring, dietary input, essentially monitoring complications of diabetes as well. So our macrovascular and our microvascular complications of diabetes. What are the three macrovascular complications like in in my am I? So cardio um cardiovascular. So cardiac vascular I got two more. You were robust with her uh sorry, like stroke. Yeah, stroke. So cerebrovascular good and then the last you know, renal. So renal would be more of a microvascular. It tends to be the small arteries in the glamorous list that are affected. So the other macro one is peripheral vascular disease, okay. And then the microvascular, as you mentioned, you've got your nephro pathy, you also got new peripheral neuropathy and then retinopathy as well. So there are micro past color complications in terms of medical. So in type one, these guys aren't producing insulin at all. So we need to give them some insulin. This can be done in a basal bolus regime or a biphasic regime. If we've got time, we can talk about that. Otherwise I'd suggest looking that up. But that's very much more of a final year thing when you come to your prescribing and things, knowing a difference between those two. Um, we've type two, we've got our anti diabetic drugs. So we always start them on Metformin and then we can add along the lines depending on what kind of features they've got. So, so finale areas are very useful for our maturity onset diabetes of young people. Um if they've got concurrent heart failure, things like our SGLT two inhibitors are very useful for getting our fluid off. Um But there is a big surge now if uh switch to the G L P one antagonists, because these tend to be the most effective um in actually reducing um sugar levels and excess insulin, uh sorry, helping reduce insulin resistance. Again, if we've got time, we can maybe go through into the mechanism of action of these drugs. But I would definitely recommend this isn't more of a pathology rather than a pharmacology lecture. I definitely make sure that you understand the mechanism mechanism of action of these drugs and then we've got surgery as well. So bariatric surgery as well again, beyond the scope of the talk, this talk, but something that I definitely recommend reading up on and particularly if you're interested in surgery and in type one people because of the complications, I've mentioned. So these people not only obviously have issues with the pancreas, but also they get the microvascular complications of the nephropathy, which someone's mentioned about these patient's can actually get single pancreas, trans kidney transplants, which is a great operation and uh have the look of managing to screw into a couple of them on my last job. So emergency kind of situations where diabetes and actually quite commonly this will be how somebody's diagnosed of diabetes. So they don't come to you and say doc, I've got a high sugar level doc am peeing loads. They will actually present in a DKA diabetic ketoacidosis kick picture if they're a type one diabetic or in a, into a hyper osmolality, hypoglycemic state. If they're um type two diabetic, there is the old term for HHS known as hyperosmolality, non keto acidosis. But we've tended to move away from that now and we use H H S. So D K, I'm sure you guys understand um a lot about it. So again, it's essentially an emergency section of not being able to presentation of not being able to produce enough insulin. So they're not producing anything at all. They've got increased ketogenic sis like pollicis, breakdown of fats. So these guys present extremely anorexic, confused, vomiting, lots dehydrated, um and uh acidotic as well from all the ketones circulating in the blood. And uh that's why they present with this could smell breathing, which is deep inspiration and hyperventilation to combat that metabolic acidosis. If you remember from your renal physiology and we've got triggers, uh for these very similar, all of these under crime crisis, all have very similar triggers in terms of managing again, more of a final year kind of thing. Um, but what you want to do on your investigations is you want to do a blood gas, you want to see how acidotic and how hypoglycemic these people are. You want to be looking for sources? So have they got any infections? Um at the moment, have they, what kind of, what is our electrolytes? What is their lactate? Um And in terms of managing so we don't give people insulin straight away. We want to treat them with fluids first. And the reason for that being is if you take down somebody's glucose level too quickly and you cause them to become hypo osmolality, sorry. Uh hypo osmo a very quickly. It can cause dramatic water shifts and this can affect the brain quite significantly. So when you, if you think about it, in terms of your, when you, when you talk about your electrolyte physiology and you're correcting your hypernatremia says, do you remember if you correct that too quickly, you get cerebral edema. It's a very similar picture to these patient's as well. If you cause if you give them into it and call them to become hyperosmolality very quickly, you will called excess fluid shifts and cerebral edema, which can cause significant brain damage. And pediatric population is very prone to this complications. That's why we always make sure that adequately hydrated first before we then go on to make them um hypoglycemic. So we give a liter of fluid over an hour and then we begin our insulin regime at the dose that's listed there. And the other thing important to monitor is our potassium level. If you remember, insulin also increases potassium absorption into the cells. So if you're giving insulin, you can actually cause hypochelemia. So you need to monitor the potassium levels and replace appropriately. HHS is um the emergency picture of our type two diabetics. And again, similar causes. The reason why it used to be called honk is because you tend to not see a key to acidosis in these patient's because remember in the type two diabetics, we still have some basal insulin being produced. So there is still some um kind of glucose being formed and being produced into the cells. So the cells don't feel as starved as they do in DKA. Again, you treat with fluids and only in severe factory faces. Would you feel the need to use your insulin? So just a couple of questions on our diabetes before we uh finish up. Does anybody have um um an answer for question nine, a good IV fluids. So um what kind of diagnosis are you thinking here? DK? Perfect. Um The last question again, probably a bit of a harsh one. Um This is thinking more about pharmacology and things I'm prescribing, which is more of a final year e kind of question but see, so not quite see e good. Yeah. So Dapagliflozin, the SGLT two inhibitors, SITagliptin is a DPP four inhibitor. So that acts by inhibiting the breakdown of our GLP one analog, which kind of helps increase uh breakdown insulin resistance. The reason why the Doppler glitazones are very useful in patients with heart failure is because a patient with heart failure tend to be fluid overloaded. So by inhibiting the reabsorption of glucose um at the proximal convoluted trivial in the Nephron, we p out lots of glucose and therefore that drives an osmotic shift of fluid cause us to p out loads of water as well. Bit like a normal frusemide or bumetanide diuretic. So that's why I also not only treats your diabetes by getting rid of glucose in the body, it also offloads fluid as well and helps treat your heart failure. One drug that I was hoping that nobody said which thankfully they didn't was the pioglitazone because this drug is actually contra indicated in heart failure because it actually increases uh fluid retention. So you definitely do not give pioglitazone to uh somebody I mean, it's not to say that SITagliptin isn't effective. Obviously, there they all are effective apart from pioglitazone in this patient, but it's which one is the most effective and deeply glitazone would be the best answer there because not only does it treat the diabetes would also help with their heart failure as well. So any questions on that before we finish on our final slide? Talking about poor for ears? No. Okay. So not very big topic, porphyria. Um they are essentially disorders of heme synthesis. So, um the heme remember you've got your protoporphyrin ring and then also your iron. Uh they're so this is the formation of the porphyrin ring. Really the only two ones that I want you guys to be aware of that are important and can come up in the exams as the acute intermittent porphyria, it which essentially is an issue with the pathway here. So it's an issue with this enzyme here. You diagnose it by looking at urinary and serum levels of PBG and A L A. I've only seen one case. I mean, I'm not very experienced. So I think to be honest, seeing one case as an F one is uh fair enough to be honest, but acute intermittent porphyria, what you really need to know when you're what you're looking for on the exam is acute abdomen pain with neuro psychiatric psychiatric symptoms should be I I AIP until proven otherwise, I these tests come back negative. So that's the main kind of clinical picture. You see abdominal pain, some gi symptoms, you see confusion, hallucinations disorders, neurological symptoms, such as um sensory loss, weakness, things like that. And that would be your AIP until proven. Otherwise, the P C T is a bit further down. So you see an increase in Europe or foreign again in the urine being produced. And the main thing to note with these guys is that these tend to get um photophobic kind of photo sorry, photosensitive rash is um and blisters on the skin. So if you see somebody with a skin disorder and you're thinking porphyria this in the exam, this one is more likely to be your answer. Okay. So that was the enzyme with that. Sorry. What was the enzyme with the last one that was affected? So it would be your uroporphyrin, a gyn decarboxylase and you get a build up of your uroporphyrin again, which was secreted in the urine. So that would be your what your testing for in the year in and this would be the enzyme that's deficient. Okay. Does that make sense? Yeah, thanks. Good. Okay. So that completes that talk guys. Um I know it's difficult talking nonstop for an hour and 45 minutes and there's quite a lot of content there to cover in a short space of time, which is why I was trying to hopefully make it more of a discussion. So I hope you guys found that useful. Um Pleased to refer to the slides, think about the questions and why they're answered in that kind of way. And obviously there will be some added questions in the mock as Well, on this topic, if you do have any questions, um, you can either ask them now or if you want to email me, I'll drop my email in the chart. Let me just stop. Fairing. Can you can, uh, oh, uh, that's my email in the chat there. If anybody has any questions that they wanted to ask me and it doesn't just have to be about this. It can, uh, about other things as well. You're not quite there yet in terms of applications, but I guess you guys are thinking about them. So if anybody has any um how, how, how life is an F one. Um What you need to know if your finals uh interested in working London, interested in doing an AFP. You guys can ask that as well. Do you ever need to learn the heme synthesis? Catholic? No, I don't think you do. What I think you need to know is the enzyme deficiencies and the precursors that you are testing for, for those two particularly high yield disorders. The AIP and the P C T, which is what I mentioned in the talk because they are the most common poor free is and I think it's important to know that enzyme deficiency under the precursor. So you understand which precursor is being investigated for in which disorder? Any other questions? A few more questions uh link to be back. I really appreciate it. I mean, they're coming on if there's no more questions, guys. I think we'll wrap up there for today and I'll stop the recording now. Thank you very much for coming. Have a good evening of it. Nice. Hopefully we get some feedback forms. All right. Thanks, Jared. I'll speak to later them. Good evening.