Hypothyroidism | Physiology, Pathophysiology, Diagnosis, Treatment, Myxedema Coma

[Music] what's up ninja nerds in this video today we're going to be talking about hypothyroidism but before we get started please continue to support us by hitting that like button commenting down the comment section and please subscribe also down in the description box you guys can click on the descriptions to our social media platforms like facebook and instagram also we'll have a link to our patreon on our patreon we have comprehensive notes on this topic as well as hand-drawn diagrams by kristin before and after it's been filmed so go check that out to aid in your learning experience all right engineers let's get into it all right engineer so before we start talking about hypothyroidism itself we have to take a quick little dive into the physiology of the thyroid hormone and the hypothalamic pituitary thyroid axis and that sounds like a lot it's really simple and we're going to do a quick little breeze through it because i want us to focus more on the disease than the physiology so the first thing i need is to take a look at here is the anatomical structure here of our hypothalamus and pituitary so up here is our hypothalamus right it's our master endocrine regulator and what it does is is there's nuclei in here that release a particular type of hormone called thyrotropin releasing hormone also known as trh trh then when released by the hypothalamus moves down via the hypophyseal portal system into the anterior pituitary and the anterior pituitary their cells called thyrotropes that are stimulated by trh and again once these cells in the anterior pituitary are stimulated by trh it triggers them to release another hormone called tsh also known as thyroid stimulating hormone the thyroid stimulating hormone that's made by the anterior pituitary then goes to the thyroid gland itself and if we look at it at the cellular level it actually binds on to receptors on follicular cells but the overall effect the generalized effect is once it stimulates the thyroid gland it tells the thyroid gland to make two particular hormones but the collective combination of them is thyroid hormone and that is t4 and t3 the majority of this combo of thyroid hormone that's made 90 of it is t4 and only the remaining 10 percent of it is t3 that's made by the thyroid gland but the combo is thyroid hormone now let's zoom in on the follicular cell and actually kind of see the mechanism because it's perta to the pathophys so if we take a look zoom in on a follicular cell here and here we have it here we're going to have that thyroid stimulating hormone and what it does is it binds on to a tsh receptor you see that blue little protein there it binds onto a g protein coupled receptor we're not going to go through this path but we in engineers we know it already what would it do it increases cyclic amp increases protein kinase a and protein kinase a phosphorylates transcription factors that stimulate genes and these genes once activated will transcribe and translate particular proteins and you know what that protein is that is made with response to tsh production it is thyroglobulin it's a very important protein that is needed for thyroid hormone synthesis so that's one effect of the tsh it's stimulating thyroglobulin synthesis the second effect is it increases cyclic amp increases protein kinase a and phosphorylates another particular protein which is a very integral enzyme here and this is called we're going to abbreviate thyroid peroxidase tpo very important one here now what does tpo do in order for us to understand its effect we have to talk about one quick thing here you know these follicular cells they really depend upon iodine they need iodine in order to function and so what happens is in our blood we have a nice beautiful concentration of iodide and what happens is we bring the iodide into the follicular cells via what's called sodium iodide symporters and once we bring this iodide here we use this enzyme called tpo it's really interesting all it does is it removes the electrons from iodide and converts it into iodine so that's the first thing the thyroperoxidase does the second thing it does is is the thyroid peroxidase takes iodine and thyroglobulin and stimulates the fusion of these two and by the result of that what do we get we get what's called iodinated thyroglobulin not super complex right here's what's interesting within the structure of iodinated thyroglobulin is t4 and t3 thyroid hormone it's within this structure so what we need to do is we need to cleave the t3 and t4 out of it how do we do that we need proteolytic enzymes where are they in the cell take the iodinated thyroid globulin bring it back into this follicular cell after we bring it back into the follicular cell we utilize proteolytic enzymes that cleave out of the iodinated thyroid globulin and what hormones t3 and t4 that's where we get that t3 and t4 from the thyroid gland now really quickly so you guys understand where is all of this stuff happening i just want to give you a quick little diagram when you look at a thyroid follicle your follicular cells are making this edge like a little kind of circle if you will and here's all the follicular cells so we're just zooming let's say that we're zooming in on just that follicular cell that follicular cell was stimulated by the tsh and it was producing all of that thyroglobulin here in the center so when i'm saying all of this thyroid globulin iodination process where it's occurring it's occurring inside of the central portion of the follicle and then some of that thyroglobulin will get taken back up into the cells and then what will we do with it make t3 and t4 so i just want you guys to understand a little bit about the anatomy of that first okay okay so we've made thyroid hormone now that we've made it how does it exert its metabolic effect i don't want us to go too crazy here but what happens is t4 let's say we take any cell any nucleated cell okay that is capable of performing metabolism okay any kind of metabolic function what it does is it primarily takes up t4 once t4 is inside of our metabolic cells there's an enzyme called d-iodinases which convert t4 into t3 what i need you guys to remember is t3 is the active form of thyroid hormone this is the one that can exert its effect so then what happens is t3 binds onto intracellular receptors activates genes and increases the expression of proteins you know what kind of proteins it makes there's tons of proteins that it makes but one that i really want you to know is these sodium potassium atp aces these are the big ones i really don't want you to forget about and here's why what do these do i'm not really worried about that what i want you guys to know is that every time these pumps are working they use atp and they use a lot of it and if i increase the expression of these sodium potassium atp i use more atp if i use more atp that means i need to generate more atp how do we generate atp in the body we break down food molecules to generate atp what are the processes that thyroid hormone needs to generate to help make atp the big one here is glycogenolysis which is breaking down glycogen into glucose and then sending it through the glycolytic pathway with that being said it also will stimulate glycolysis which is breaking down glucose into pyruvate and acetyl coa and then again making atp and the real big one that you need to know is it also helps to stimulate lipolysis breaking down lipids into fatty acids and glycerol all of these things generate atp but increase your metabolism within all of your cells okay so the next thing is talking about how thyroid hormone affects other target organs other than just nucleated cells the big thing i really want you to remember is the heart and it does a couple things to the heart one of the big things is that it kind of helps to increase beta adrenergic so beta adrenergic receptor sensitivity and all that means is is if i have my sensitivity of those beta adrenergic receptors increased every time epinephrine norepinephrine binds to them their effects are a little bit more amplified and the effects that you primarily see with that is that you see an increase in heart rate a chronotropic action and an increase in contractility and that is a inotropic action there's one more thing though that we really need to mention and that it also thyroid hormone its levels maintains vaso motor tone what does that mean it means it kind of has a nice balance between vasoconstriction and vasodilation so the next thing i want you to remember is that it maintains vaso motor tone very very important one i need you to know here the next thing acts on the bones and it maintains a beautiful balance between osteoclasts so maintains a balance between osteoclasts and osteoblasts that's a big one okay maintains osteoblasts and osteoclasts okay and again osteoblasts deposit bone or deposit calcium into the bone osteoclasts pull calcium from the bone there's another big thing that you need to know and that is that it helps to control the development of our skeletal system and the maturation of our skeletal system so it plays a role within bone development as well as bone maturation okay very important it also helps with our central nervous system right so it helps particularly within the nervous system to do what increase your sympathetic nervous system activity okay within the gi tract it helps to do what helps to increase the gi motility and it helps to increase the gi secretions within the skin it maintains beautiful blood flow through the skin so that's another important one is that it helps to increase blood flow to the skin if you increase blood flow to the skin remember skin is actually your epidermis but it's also your hair your hair is actually skin cells your nails are skin cells so it's important for the growth of hair skin and nails good blood flow lots of oxygen lots of nutrients to those tissues so increased blood flow is important for growth of what structures hair skin nails it's also important because not just a lot of blood flow but also there's thyroid hormone regulates the activity of your sebaceous glands and your sweat glands so it also helps to increase sebum and sweat production so that's also important beautiful the next thing is your reproductive system it's important not just for helping to develop the reproductive system but also maintenance of the reproductive system so it helps in the role of development of repro but also just your general function from day to day another thing as we'll talk about is it also can control a particular type of hormone called sex horm or protein called sex hormone binding globulin it regulates the levels of this which is important for which carrying particular types of steroid hormones like estrogen and progesterone and there's one other thing trh which we'll talk about a little bit it's related to thyroid hormone also can affect and we'll talk about this very heavily lh and fsh that's very important okay which control estrogen and project testosterone progesterone production so remember development and function of repro sex hormone binding globulin control and that trh which is related to thyroid hormone also can affect lsh and fsh all right beautiful the next thing is your fibroblasts it controls your fibroblasts and how it does this is your fibroblasts make a particular molecule called glycosaminoglycans and what thyroid hormone does is it controls the production of glycosaminoglycans and the degradation of glycosaminoglycans okay so it helps to maintain the glycosaminoglycan production and degradation very important the next thing and the last type of physiological activity is within our muscle cells it plays a role within the development it plays a role within the regeneration of our skeletal muscle cells it also plays a role in muscle contraction and the way it does this is very interesting it controls muscle contraction by regulating the activity of those calcium atp aces that are present on the sarcoplasmic reticulum if we control those that controls the amount of calcium that's in the muscle that regulates our muscle contraction okay so again development regeneration and muscle contraction via the calcium atpases that covers our physiology all right so the first one that i want to talk about is primary hypothyroidism within primary hypothyroidism there's a bunch of different causes let's say that we take these three causes affecting this thyroid gland first though usually one of the most common issues is that there's antibodies that are acting against particular proteins within the thyroid gland and we'll talk about those or that there's a virus that's actually injuring or damaging the thyroid gland or particular drugs that are injuring or damaging the thyroid gland these are very important let's first talk about those diseases that are related to antibodies the first one that i really need you guys to remember is called hashimoto's hashimoto's thyroiditis now hashimoto's first thing i need you to remember is that it is more common in females second thing i need you to remember is that it's an autoimmune disease what does this mean autoimmune diseases are a combination they're multifactorial but usually it's some type of genetic susceptibility genes that are involved in an environmental trigger and that environmental could trigger could be a drug it could be a pathogen it could be a pollutant it could be many different things but when we're exposed to it our immune system will phagocytose or take in that environmental trigger or agent when it does it expresses a piece of it on its mhc2 complex right we know that kind of stuff and whenever you express a particular thing let's say here i have a macrophage i express a particular type of environmental trigger or a particular antigen if you will on my mhc2 complex what type of cells come and react with that your t cells and when your t cells react with this the normal kind of response is you're going to produce cytokines it'll produce cytokines that'll kind of adv you know alert the immune system let them know hey there's some type of a trigger or pathogen or something here that's we don't like and what that'll do is that'll tell these pathogens will tell particular b cells called plasma cells to produce antibodies and these antibodies are supposed to be driven against the environmental pathogen but guess what for some odd reason that environmental pathogen or trigger whatever it is it looks very very similar to the proteins that are found inside of the thyroid gland and because of that not only do those antibodies go and attack the environmental trigger they also attack the thyroid tissue inadvertently and lead to destruction that is also kind of known as molecular mimicry so that's why i wanted to take a quick second to explain that little process here and that means that there's some type of genetic susceptibility genes that are in causing some type of problem here with the mhc2 complex where this response is even more exaggerated and what happens is with these mhc2 complexes there's genes that regulate them and they're called hla dr 3 hla dr5 these are the two primary ones that if there's these genes having mutations this type of effect can be exaggerated and cause this autoimmune disease that we see okay so that's the big thing i want you to remember now what are the names of these antibodies these antibodies are exerted against the thyroid peroxidase and the thyroglobulin so they're called anti-tpo antibodies or anti-thyroglobulin antibodies okay the next one similar to hashimoto's is called postpartum thyroiditis so postpartum thyroiditis now postpartum thyroiditis again you're obviously going to see this in females but the big thing here is that usually it's within one year of birth so some female within a one year after giving birth is experiencing this type of issue now what happens is usually in pregnancy your immune system kind of just the activity of it decreases a little bit after birth the immune system kind of revs back up a little bit and when it revs back up a little bit sometimes it may inadvertently lead to antibodies that are going to be produced that destroy some of the thyroid tissue similar to the way hashimoto's is but here's the big thing i really want you guys to remember with hashimoto's this is chronic so these antibodies will continue to keep damaging this thyroid tissue with postpartum this is more of an acute issue and so it will lead to hypothyroidism but usually there's resolution in time so after some time these individuals postpartum thyroiditis they'll have hypothyroidism but usually after that kind of that immune system settles down a little bit they'll resolve and go back into a eu thyroid or normal thyroid state okay but again what is the pathology behind this it's antibody mediated and it's the same thing tpo antibodies and thyroglobulin antibodies okay the next cause is usually some type of viral infection and that is whenever there's a viral infection that's causing the thyroid to not produce enough thyroid hormone because it's being inflamed or damaged this is called sub acute granulomatous thyroiditis one heck of a name right guys so subacute granulomatous thyroiditis also referred to as a decoyvin's thyroiditis is usually due to a viral infection so i want you to remember that it's a viral infection now here's what i want you to remember whenever you have viral infections sometimes this can maybe produce a little bit of an increase in the white blood cell count but one of the big things that i want you to remember is that usually this produces pain and tenderness of that thyroid gland but what happens is whenever there's a lot of inflammation sometimes it can trigger your liver to make particular proteins that can whenever you do this particular lab test it can be increased you know what that is whenever there's viral infections or inflammation that inflammation may lead to an increase in a erythrocyte sedimentation rate so an increased esr i want you guys to remember that because that's going to come to diagnostic play later the next one here related to this inflammation here is also going to be drug induced now drug induced the big things that i need you to remember there's a couple drugs three primary ones the first one that is really important is amiodarone this is an antiarrhythmic the next one is lithium which is used to treat bipolar disorder and the next one is iodine 131 you know what we give iodine 131 for radioiodine ablation in patients who have high per thyroidism they're producing too much we give that and it basically inhibits thyroid gland of thyroid hormone production by destroying the thyroid tissue but it can destroy it so much that now you develop hypothyroidism now we've talked about all of these causes hashimoto's postpartum subacute granulomas and drug-induced we say that it's damaging the thyroid gland now remember if you guys remember from the hyperthyroidism video that whenever you damage the thyroid gland what spills out of them a little bit thyroid hormone and thyroglobulin remember we talked about that where this can spill out what kind of things it can spill out let's say that we represent the blue here as thyroglobulin and we represent the red here as thyroid hormone so it can spill some thyroid globulin out into the blood because of the follicular destruction and spill some of the thyroid hormone out because of the follicular destruction what's the problem with that if you spill some of the thyroid hormone out of these follicular cells what could that do it could produce a transient or temporary hyperthyroidism but after time as you continue to destroy or inflame or agitate or damage these thyroid follicles they're not going to be able to produce enough thyroid hormone and so because of that eventually their production of t3 and t4 will plummet and drop okay so that's important to remember the most common one though that you will see this with is hashimoto's thyroiditis the next one is a very interesting disease usually this is related to other autoimmune diseases and these are antibodies but it's a little bit different from the hashimoto's and postpartum type of thing and so what happens is there's other autoimmune diseases that are related to this and they're producing a particular type of antibody called igg for antibodies and what happens is these igg-4 antibodies are activating particular types of fibroblasts within the around the thyroid gland as it does that as you activate some of these fibroblasts what does that do it starts causing fibrosis of the thyroid gland as you start causing fibrosis of the thyroid gland and replacing the normal thyroid tissue with fibrous tissue can fibrous tissue release thyroid hormone no so in some cases about one-third of patients who develop severe inflammation and fibrosis due to these igg-4 antibodies and one third of patients they may develop enough fibrosis that they develop hypothyroidism okay very important here what is this disease that is related to this igg for production this disease is referred to as reedl's thyroiditis what is it called it's called reedles thyroiditis now renal thyroiditis is again it's related it's kind of an autoimmune related disease and it's related to some type of elevation and these igg4 antibodies what are other types of autoimmune diseases that you commonly see renal styroditis associated with the big thing i want you to remember is that you can also see this in what's called uh retroperitoneal fibrosis non-infectious aortitis non-infectious heretitis and the big one is auto immune pancreatitis that is very important that you guys remember these okay so again usually in all of these related autoimmune diseases they also have elevated igg4 that is producing some type of fibrosis and inflammation of these surrounding structures again big thing i need you guys to know is that in these patients if there is enough fibrosis enough infiltration due to the fibroblast activation it can lead to hypothyroidism okay that covers renal thyroiditis the next one here is usually very interesting okay it's dependent upon iodine and this may sound odd but you can develop hypothyroidism because of very little iodine and you can develop this because of too much iodine let's explain why if someone is iodine deficient so let's say that they have low iodine or of the opposite pole here you have high iodine let's make sense of how these could potentially lead to what if you have this issue the whole idea behind this is that this may lead to a decrease in t3 and t4 thyroid hormone right how it's really simple what did we need iodine for when we talked about the synthesis of it we talked about it for a reason right what do we need iodine for we needed to add the iodine onto thyroglobulin so if i have decreased iodine i don't make enough iodinated thyroid globulin and so because of that if you have decreased iodinated thyroglobulin can you make functional thyroid hormone remember thyroid hormone in order for it to be functional it needs iodine on it if you don't have that you can't make it that's pretty straightforward right this is the most common cause most common cause worldwide for hypothyroidism hashimoto's is the most common within iodine sufficient areas and iodine deficient hypothyroidism is the most common cause worldwide okay where areas that they're iodine deficient foods are not fortified with it the opposite one though whenever there's high iodide i know you're probably like whoa what the heck how does this do it there's a particular mechanism called the wolf chai cough effect and all this says is that if you give too much iodine to somebody really high amounts of iodine what it'll do is the high amounts of iodine will inhibit t3 and t4 synthesis how if you have too much iodine what it'll do is it'll inhibit a particular enzyme called thyroid peroxidase they'll say hey there's too much thyroid hormone that's being produced there's too much that you guys are making here we need to slow this down i'm going to inhibit you thyroid peroxidase from continuing to do that process there oh proteolytic enzymes you guys are cleaving too much iodinated thyroid globulin making too much thyroid hormone i'm going to inhibit you so it'll also inhibit the proteolysis and the overall effect of inhibiting the thyroid peroxidase inhibiting the proteolysis due to too much iodine via negative feedback leads to decreased thyroid hormone synthesis so that gives us the primary reasons that someone would develop hypothyroidism due to a thyroid issue itself now let's talk about central hypothyroidism causes so let's take in a scenario here let's say that it's a hypothalamus issue you guys got to remember what does the hypothalamus make what is that hormone it is trh trh then does what it tells the antipituitary to make tsh and tsh does what it tells the thyroid gland to make thyroid hormone okay so as a result here it's going to tell the thyroid gland hey make thyroid hormone let's say that there's an issue where there's something wrong with the hypothalamus or there's something wrong with the pituitary let's take the first scenario something's wrong with the hypothalamus if the hypothalamus is not working what's going to happen to the trh production it's going to drop what happens to the tsh production that's going to drop what happens to the thyroid hormone production that's going to drop that's hypothyroidism another scenario what if there's something wrong with the hypoth i mean the pituitary antipituitary it's not making a lot of tsh then what's going to happen to the thyroid hormone that's going to drop now here's the interesting effect here usually let's say that we took the scenario and avoided this issue here we don't even know that this is going on if someone has hypothyroidism what is the normal negative feedback type of effect i know you guys know this the normal feedback mechanism is that whenever there's low thyroid hormone that's going to come over here and stimulate the hypothalamus and stimulate the anterior pituitary to make more trh and more tsh but if there's something wrong with the hypothalamus or something wrong with the pituitary is it going to be able to make trh no so it won't respond and trh will continue to be low or if there's something wrong with the anti-pituitaries they're going to respond and make tsh no so even though there's hypothyroidism it's still going to be low that's very important diagnostically now the next question that you should have is what in the heck can cause the hypothalamus to have a problem or the pituitary to have a problem it's actually relatively easy if you think about it what if somebody experienced some type of traumatic brain injury if they had a traumatic brain injury and that damaged the underlying brain tissue particularly the hypothalamus or what if they have some type of tumor on near the hypothalamus that tumor is compressing on these nuclei and affecting their ability to make trh that could be another reason but the overall effect here regardless of what the cause is is that they have some decrease in trh production if you take the other scenario where you take into consideration the anterior pituitary what's going on on with the anti-pituitary that it's not making tsh a big one here is that it could also be related to some type of trauma maybe an underlying traumatic brain injury but you know what another one is it could be a tumor but the big one that i really need you to remember is an underlying infarction there's a particular name that can happen in post whenever someone gives birth and they bleed a lot and they lose too much blood they don't get enough blood going to the pituitary gland and the actual pituitary gland can infarct and affect its ability to not just to make tsh but a bunch of other hormones that it makes what is that condition called very important you guys remember it it's called shihan syndrome and shihan syndrome is associated with postpartum hemorrhage not getting enough blood flow to the pituitary infarcting and then what's the result of that decreased tsh resulting in decreased t3 and t4 boom baby we good all right so congenital hypothyroidism so this issue here i want you guys to remember that there's a problem with the development the maturation of the thyroid gland or that there's one more issue and that there's not enough iodine same thing in adults so what will be the issues here the first one that i want you guys to remember here is that there could be antibody mediated destruction and here's the big thing this antibody mediated destruction of the baby thyroid gland is due to the maternal antibody mediated destruction very very important there the reason why has not been completely figured out but again what happens is these antibodies injure and destroy the baby's developing thyroid gland if the baby's thyroid gland can't develop is it going to be able to make thyroid hormone no so i know it seems super obvious and it's because it is is that if there is this continuous damage and not proper growth of the thyroid gland it'll lead to hypothyroidism the next thing is what if we don't even form the thyroid gland what would that be called so what if i don't develop the thyroid gland not developing the thyroid gland is called agenesis so thyroid agenesis that could be one reason the other reason is the thyroid gland forms but it doesn't form completely and it forms abnormally if that happens what is that called that is referred to as thyroid hormone disgenesis so it could either be not forming the thyroid gland meaning that you don't produce any thyroid hormone or abnormally forming the thyroid gland and producing very little thyroid hormone so in this situation you may produce no t3 and t4 and in this scenario you may produce very little t3 and t4 so again this is a developmental issue that's becoming a problem here so it could be maternal antibody mediated not forming it abnormally forming it what's the last one here the last one here is that there's something intrinsically wrong with the follicular cell proteins and enzymes you know there's that beautiful little enzyme that's present in the follicular cells called thyroid peroxidase what happens do you think if i decrease the expression of this enzyme or i don't express it at all am i going to be able to make thyroid hormone no because what a tpo do it help to oxidize the iodide into iodine and add iodine onto thyroid globulin making iodinated thyroid globulin if i don't have this enzyme what's going to happen to my thyroid hormone production it's going to significantly drop where i'm not going to be able to make t3 and t4 there's a particular name for this it's called dis hormonal genetic goiter let me explain why there's a goiter now tpo what does it do it we already know it i it undergoes oxidation of iodine and adds iodine onto thyroglobulin if you don't add iodine onto thyroglobulin can you make thyroid hormone no that means can you release any of that thyroglobulin out of that follicle that we showed over there no so that thyroglobulin continues to build up in those follicles more and more and more and more and more because it's not getting released out into the blood as thyroid hormone and that makes a big old sucker in the neck called a greater and that's referred to as disc hormonal genetic goiter due to a defect within the tpo enzyme the last cause of congenital hypothyroidism is usually due to iodine deficiency and it's the same thing that we talked about before if you don't have enough iodine you can't make what functional thyroid hormone could they develop a goiter absolutely anybody with iodine deficiency that's not releasing thyroid hormone and accumulating thyroglobulin can develop a goiter so again this will lead to decrease t3 and decrease t4 now we're going to talk about the clinical features next for all hypothyroidism but congenital hypothyroidism is very interesting because there's a high-yield mnemonic that i want you guys to remember for someone who has congenital hypothyroidism they can have all these symptoms as we're going to talk about but they also have these additional features that you guys need to remember what are they you can remember the clinical features of someone with congenital hypothyroidism whether it be due to any of these causes one of the big ones is actually iodine deficiency but it can be remembered by the seven ps the first one is they have a pot belly so they got a big old belly they're pale they have a puffy face they have a protuberant tongue they have a pro a a protruding umbilicus they have poor brain development and last but not least they have prolonged neonatal jaundice so these are the big things that i need you guys to remember and take away if someone has congenital hypothyroidism these are the common clinical features that you will see associated with these based upon this 7p mnemonic all right now that we've drilled in the pathophys and the causes let's really start talking about the clinical features related to the pathophysiology all right engineers so now start talking about the clinical features associated with the pathophys this is where you guys really need to remember all that fizz that we talked about it's coming back there was a reason why i went over it right now for my own good it's to help you guys to really understand the clinical features so the first thing that you need to know with someone who has hypothyroidism a common manifestation can be a goiter and again we already talked about this the whole concept behind someone developing a goiter is because they're not releasing the thyroid hormone from the thyroid follicles and that may be because of an iodine deficient situation that may be because of uh they're actually continuously destroying the thyroid gland and as that thyroid gland is being destroyed it's continuing to hypertrophy whatever it may be they can develop goiters so there's many different reasons for goiters one of the common reasons is that if they're iodine deficient they're not releasing functional thyroid hormone in other words that thyroglobulin that you were producing and putting into that central portion it's not being iodinated and you're not pulling it into the cells to release that hormone it's just accumulating accumulating and accumulating okay that's one thing the next thing is do you guys remember every nucleated cell that was capable of performing metabolism we're just going to do what decrease the activity of it we're going to decrease the activity of everything that we talked about over with physiology so if i decrease the metabolic activity of my cells right particularly remember what we said if i had decreased the metabolic activity i'm going to decrease glycolysis i'm going to decrease lipolysis and i'm going to decrease glycogenolysis that means that there's going to be less metabolism less atp that's being produced if that happens that means my metabolism is really shutting down it's really decreasing if i have a decreased metabolic activity am i going to break down lipids and glycogen and stuff as well no so because of that what happens you gain weight so one of the effects of this is weight gain the next thing that i need you guys to remember is that whenever you guys perform cellular respiration you break down glycogen you break down glucose you break down lipids every metabolic activity that goes through aerobic cellular respiration you generate co2 you generate water and you generate atp but there's one more byproduct that you generate heat that's a natural byproduct of cellular metabolism if you're having decreased metabolism are you going to generate as much body heat no so because of that there's going to be decreased heat production and this decreased heat will lead to a low body temp sometimes referred to as cold intolerant so they can experience weight gain they can experience a decrease in body temp another thing is if you're having a decreased metabolism of these substances what happens is it also changes your appetite and so because of that in situations of hypothyroidism where they have this weight gain they have a decreased appetite okay and that could also be because of the gut brain signaling mechanisms i don't want to get too deep into it but again big thing weight gain because of decreased metabolism and decreased body temperature because of decreased heat from cellular respiration boom the next effect is on the heart remember we said it increases the beta adrenergic uh receptor sensitivity well if there's decreased thyroid hormone we decrease the beta 1 adrenergic receptor sensitivity remember what we said that would do well and before it said if we had it it would increase heart rate a little bit and increase contractility a little bit well if we have less of that sensitivity what is it going to do it's going to lower the heart rate so it can maybe lead to a little bit of bradycardia and it's going to mildly decrease the contractility not as significant as the heart rate so there'll be a significant drop in heart rate a small drop in contractility one more thing remember we said that thyroid hormone regulates the vasomotor tone on our blood vessels in other words constriction dilation whenever you have little thyroid hormone guess what it tips the balance towards vasoconstriction so if i increase the vasoconstriction and this may seem odd i know but this is what the mechanisms have shown us that's going to lead to squeezing and clamping down on the blood vessel what does that do that decreases diameter it increases resistance and does what increases blood pressure you're like whoa zach i thought you said in hyperthyroidism it also increases blood pressure it does remember our video on the pathophysiology of hypertension we said hypo and hyperthyroidism both can be causes for secondary hypertension even though it is weird yes it is possible so they can experience bradycardia as well as hypertension okay the next thing here remember i told you that thyroid hormone is important for osteoclast and osteoblastic activity that is very important and maintaining the balance between it but you know what else i told you it's important for bone growth and maturation if you don't have enough thyroid hormone it's very problematic whenever you're developing and maturing bones very important and so decreased thyroid hormone leads to decreased bone growth and bone maturation and you know why that's a problem whenever your skeletal system is developing it's not going to have all the things that needs to continue to grow so what will happen they'll develop a short stature so someone can develop a short stature as a result of this boom okay what about the effect on the nervous system now we said that normally thyroid hormone increases sympathetic nervous system activity well we have less so that's going to decrease sympathetic nervous system activity so now what would that lead to that can lead to depression you know because you're having a little bit more parasympathetic drive in this situation when you have less sympathetic drive it can lead to fatigue and it may even lead to a very ambiguous term referred to as lethargy but another one is that thyroid hormone is also important for your memory circuits the pay circuit that we talked about neuro and so because of that less thyroid hormone can have less activity within your your memory circuits and so that may lead to some memory loss or deficits or mental dulling if you will okay the next thing is if you have less thyroid hormone it affects your reflex pathways and what happens is very something very interesting where when there's less thyroid hormone you can test a deep tendon reflex and that decrease what happens is with decreased thyroid hormone their deep tendon reflex will occur but it'll occur much more delayed than usual so they can have what's called delayed deep tendon reflexes there's a particular name for this it's called waltman sign okay all right that covers that the next one here is the gi tract remember we said it normally increases gi motility and increases gi secretions but we have hypothyroidism so it's going to decrease gm motility decrease gic creations if i don't move things through the gi tract as much it's going to absorb more water absorb more of the electrolytes and become more hard and stiff what is that going to do it's going to form a big old poop ball and that's going to cause constipation and no nobody wants no constipation because guess what whenever you try to poop that sucker out you're gonna end up with hemorrhoids okay so constipation could also be another issue that can be seen with this all right let's come back up here and keep working our way down the next issue that you can start to see is that remember we said that this helps the muscles it plays a role within muscle contraction and it plays a role within muscle growth and regeneration what if i don't have enough thyroid hormone is it going to grow as well is it going to be able to regenerate whenever it's been stimulated or injured no and because of that due to decreased muscle growth and regeneration this can lead to what type of effect here it can lead to myopathy where there's damage to the muscle tissue whenever there's damage to the muscle tissue particularly damage itself it can spill out a lot of a particular enzyme called creatinine kinase so whenever there's significant amounts of myopathy or damage to the muscle tissue due to not being able to grow it or not being able to regenerate it when it's injured it spills a lot of these ck out the next thing is with progressive myopathy and injury to the muscles and not being able to regenerate and grow what happens to them they become weak and so they develop weakness and you know where this weakness is most commonly seen within the proximal muscle groups shoulder hip areas okay the last thing i need you guys to remember is that it also is going to decrease muscle contraction again can playing a role with that weakness not just because of the myopathy but also decreased muscle contractions how it decreases the expression of what remember it maintains the activity of calcium atp aces if we have less of that do we have as many calcium atps activity no so there's decreased calcium atpase activity think about that as less calcium within the cell when you need it if there's less calcium in the muscle cell you'll be able to contract the muscle cell as well no at least to decrease muscle contractions playing a role within proximal muscle weakness but boom we good baby all right let's move on to the skin the skin what do we do normally it increases blood flow to the hair the skin the nails and helps to play a role within sebum and sweat gland production if you have decreased blood flow because you have hypothyroidism what happens with that well now with decreased blood flow you're not providing as much oxygen and nutrients to the hair the skin the nails there'll be hair loss and you know there's a particular area where they lose hair which is kind of a a buzz term kind of thing where they lose it on the outer third of the eyebrows it's called queens and signs so remember that sometimes that may pop up on your exams as a queen's and sign is hair loss on the outer third portion of the eyebrows the other thing is that you're not providing enough blood flow to the to the nails and so the nails can become kind of brittle and thin right the other thing is that the skin is not getting enough blood flow so the skin is not getting enough blood flow so it's gonna appear more dry as well so they're gonna feel more pale actually because you're not getting a lot of blood flow and a little bit dry because you're not having as much secretions right so that goes back to this next thing so we have the hair skin nail effect but remember we have to think about it plays a role within sebum and sweat gland production if there's decreased sebum production what does that lead to so decreased sebum production is going to lead to a lot of dry skin and if you're going to have decreased sweating because you're not having as much activity of those eccrine sweat glands as well beautiful now let's move on to the liver the liver remember what did a thyroid hormone do it it maintained the uh receptors what type of receptors on the liver it maintained the activity of the ldl receptors that are expressed on your liver to pull ldl from the blood if you have low thyroid hormone what's gonna happen to the ldl receptors you guys already know right you're gonna drop the ldl receptors so now these receptors are gone if you have ldl floating here through the blood and also another one is you pull triglycerides into there's other things for triglycerides as well but if you're trying to have ldl primarily ldl get pulled out of the blood and into the liver you need ldl receptors if you have less of these ldl receptors are you going to pull as much ldl into the blood into the liver no so the ldl and triglycerides will build up and you can develop hypercholesterolemia and hypertriglyceridemia okay so that could be problematic all right so the next thing is we talked about the liver the next thing is reproductive system this one's very interesting if you guys remember from the hypothyroidism we talked about sex hormone binding globulins here hypothyroidism can affect those sex hormone-binding globulins like hyperthyroidism but not as significant as whenever someone's hyperthyroid the reproductive effect actually comes from something very interesting known as hyperprolactinemia okay so i want you to remember reproductive effects from hypothyroidism is due to hyperprolactinemia reproductive effects from hyperthyroidism is due to the increased sex hormone binding globulins so with hypothyroidism how does this work well here's what i want you to remember in hypothyroidism someone is their thyroid gland it's like say primary issue they are making less thyroid hormone the natural effect that we talked about before is that this will go back to the hypothalamus the hypothalamus will respond to this low thyroid hormone and make a hormone called what thyrotropin releasing hormone it'll make more of it that thyrotropin-releasing hormone when you increase the production of it it stimulates two cells in the anterior pituitary one of them is it releases an increase in tsh because you need more tsh to try to drive this thyroid hormone level up that's one effect all right so not only is there an increase in this tsh but there's also an increase in prolactin whenever there's these higher than usual levels of that trh so remember that elevated levels of tsh as well as elevated levels of prolactin what's the problem with that whenever you have high levels of prolactin that loves to inhibit fsh and lh production when you inhibit fsh in lh production you inhibit the production of testosterone and you inhibit the production of estrogen that's very important why because in males what happens if you have very low testosterone we're gonna put test there what would happen remember we need it for sperm production if you don't have enough testosterone that leads to a decreased sperm production what happens to the sex drive because it plays a role in sex drive there's a decreased sex drive also known as a decrease in libido what else it's also important for masculinization of the male so because of that decreased testosterone leads to decreased masculinization particularly within the breast tissue and they develop little you know little moves called gynecomastia now these are the primary effects right so you can see a decreased burn production you can see decreased sex drive you can see gynecomastia if you want to remember one more it also plays a role within the activity of the so it can lead to erectile dysfunction as well the next thing is what can this do within the females so remember there's decreased estrogen production if there's decreased estrogen we need this in order for ovulation to occur so if there's not enough there's decreased ovulation what happens if there's decreased ovulation infertility because if you don't pop a little oocyte out there to be fertilized by the sperm then you can't actually develop a a potential pregnancy so they can lead to infertility it also is important for regulating your menstrual cycles maintaining the normalcy of menstrual cycles if there's less of it that can lead to oligomenorrhea and if there is not enough at all and it affects it to the point where you don't have any menstrual cycles this can lead to amenorrhea one more thing whenever there's high prolactin levels not only can it cause exacerbate the gynecomastia within males but it can also do something within females very interesting where it's important for milk production we know that prolactin is important for milk production but sometimes it can lead to inappropriate milk production within females and it can lead to milk actual like being let out from the nipple and that's called galactoria galactoria so remember that issue as well okay i think we really drilled home the reproductive effects let's take it home with the last one which is this fibroblast activity now remember what i told you the thyroid hormone regulates the activity of the fibroblast glycosaminoglycan production and degradation whenever there is low t3 and t4 there's still going to be some gag production but here's the problem so the gags will still be produced but you know what happens the degradation of the gags are that's not going to happen so what happens is this results in decreased degradation so the decreased degradation of gags and that leads to what an increase in the amount of glycosaminoglycans why is that a problem whenever there's a lot of glycosaminoglycans that pulls a lot of water to where the glycosaminoglycans are and so if you pull a lot of water where there's a lot of glycosaminoglycans it can lead to that space being a little bit more edematous where do we see these gags really accumulating particularly within the body the first one is we see these gags accumulating in the dermis within the actual tibial region and it pulls a lot of water into that area leading to a lot of edema where the tibia is and this is called pre-tibial a mixed edema that's the first thing i want you guys to remember so pre-tibial max edema is due to a lot of gags within the dermis because of less degradation of the gags because of hypothyroidism and that causes edema there the next thing is it can also accumulate in the tissue and the dermis around the eyes and as it does that that leads to a lot of water being pulled into those tissues if you pull a lot of water into those tissues what's going to happen it's going to lead to edema and this edema that's occurring around the eye is called periorbital edema all right beautiful so we have pre-tibial mixed edema periorbital edema there's one last one this is actually probably the coolest one the gags can also accumulate near the carpal tunnel and the tissues the connective tissue and muscles around the carpal tunnel if that happens a lot of water gets pulled into the tissue around the carpal tunnel if you pull a lot of water into there what's that going to do it's going to cause edema and that edema around the muscles and fibrous tissue and tendons in that area is going to become a little bit more edematous and put pressure on that little orange nerve that's running through there you know what that is the median nerve and whenever you compress that sucker it's called carpal tunnel syndrome and that could be due due to what an increase in gags because they're not being degraded because of the hypothyroidism so again increasing gags because of decreased degradation leads to pre-tibial maxidemia periorbital edema or carpal tunnel syndrome we hit all of the clinical features let's go into the diagnostics all right beautiful now let's start talking about the diagnosis of hypothyroidism the first thing that we need to talk about is is it primary versus central that's the first question that we need to ask and this should be very easy we've already kind of gone through this a little bit so the first thing is is it primary how do we determine if it's primary or central the first thing that you need to remember is that you have to order what's called thyroid function tests and with the thyroid function test comes two things free t4 is going to be one of the things that you obtain and the second thing is going to be a tsh one other thing that we may add on here for the simplicity of this diagnosis part is a trh we might add that one on okay so let's talk about what would we get what would it look like with these three parameters versus primary and central so if someone had primary so let's say that we have primary hypothyroidism low t3 and low t4 in this situation here in this scenario we know that hypothyroidism all of these primary versus central all of them are going to have low t4 right we know that so in this scenario here this first scenario is we're going to see a low free t4 now if someone has a primary hypothyroidism meaning it's a thyroid issue there's nothing wrong with the pituitary gland what should happen negative feedback mechanism wise low free t4 should tell the anterior pituitary to do what it should tell the anterior pituitary to make tsh and so response to that is it would stimulate the anterior pituitary and the anterior pituitary would increase its production of tsh so if someone had primary hypothyroidism they would have low free t4 and high tsh now let's take for example the central causes the central causes you have to remember there was two types there was hypothalamus that was one of the issues there was a hypothalamus lesion or there was a hypothalamus trauma or something of that nature and then the other one was there a a pituitary issue so there was something wrong with the pituitary how do we know which one it is again same concept here they're both going to have a low free t4 so both of them will have a low free t4 because it's hypothyroidism right generally if someone has a normal hypothalamus or a normal anterior pituitary let's say hypothalamus first what would happen if they have low free t4 the hypothalamus it would tell the hypothalamus hey you need to make trh so that you can tell the anterior pituitary to make more tsh but the hypothalamus is not responding because there's something wrong with it so the trh production is going to decrease it's not going to respond to the low free t4 and as a response to that that's going to lead to decreased tsh and that decreased tsh is going to lead to a continuous low free t4 okay so that's how we would determine hypothalamus low trh low tsh and low free t4 if there's a pituitary problem that means that there's low free t4 again it would tell your hypothalamus and your pituitary but generally you can also tell the pituitary and what happens is if there's low free t4 the pituitary the anterior pituitary should respond and say okay hey you're telling me there's low-free t4 i got you baby i'm going to go ahead and produce your tsh for you but there's a problem with the pituitary if there's a problem with the pituitary it's not going to make the tsh it's going to cause a decreased tsh production a decreased tsh production will continue to lead to low free t4 and again the pituitary will still not respond and the tsh production will continue to drop so if you had to differentiate primary they have high as they have low free t4 high tsh central if it's hypothalamic they both have low free t4 but hypothalamus has low trh low tsh and pituitary would have low free t4 and just low tsh what's another way that we could differentiate if it's hypothalamic or pituitary once we've kind of gotten these lab values back and we find ah there's something wrong with either the hypothalamus or the pituitary get an mri so obtain an mri and mri may be the thing that you need to determine oh i see there's a tumor in the hypothalamus oh there's some hemorrhage near the hypothalamus oh there's some infarction in the pituitary or there's some injuries to the pituitary that may give us and clue us into really what's the problem okay all right now that we've gone through this and we've determined oh all right we've figured out that it's actually central boom we know how to go about that way but now we have primary and there was a ton of different types of primary causes how do i know what the cause of the primary hypothyroidism hypothyroidism is the way that we go about this is a couple different ways let's actually go through a couple of those and write them down the first one is we said hashimoto's what is one way that we can determine hashimoto's thyroiditis well one way is we could say all right more common to females that could help epidemiologically but the next thing we should say is okay we remembered that they have positive tpo and positive antithyroid globulin antibodies so i would have antibodies against tpo antibodies and i would have thyroglobulin antibodies that would be one thing that would come back positive the next thing is remember i told you that whenever there's injury to the thyroid gland what leaks out from the fat between the follicles thyroglobulin so another thing is they could have elevated serum thyroglobulin but there's one more thing if we wanted to take it to the next level and really come up with a definitive diagnosis of hashimoto's the only particular definitive way is to do a biopsy and to actually look at the tissue for the particular types of infiltration so biopsy would be the definitive diagnosis okay all right so that's one way we could go about this another thing is you could do the radioactive iodine uptake there's no need to but it would show low uptake or no uptake okay the next thing that we set is postpartum thyroiditis so if someone has postpartum thyroiditis what's going to be the issue with this one postpartum thyroiditis again we can take into consideration their history right it's within uh less than one year since birth that could be one particular thing again you can check the tpo antibodies and you can check the thyroglobulin antibodies they'll be positive but what's the big thing i told you that you guys need to remember with this condition usually they may have hypothyroidism but over time they may return to euthyroid states it's acute not chronic in comparison to hashimoto's so it's acute and that means that they may return to you thyroid all right beautiful the next one we said was drug induced this again is another easy thing to figure how you want to know why hey buddy or hey ma'am what uh you taking any medications like amiodarone or lithium or have you had any radioiodine ablation therapies recently oh you have okay well this could be the reason why and so that's something that we'd have to look at is look at their history so do they have a history of you know a use of amiodarone lithium or have they had iodine 131 recently for radio iodine ablation that could be reasons and again these are also injuring the thyroid gland so they may also have an elevated serum thyroglobulin so we'll postpartum thyroiditis but again it's as simple as saying oh you're taking any of these medications oh i see you are okay beautiful the next thing we said is renal thyroiditis renal thyroiditis is actually a little bit more difficult to identify and there's something important that we could actually use as key indicators that it could be renal thyroiditis so one thing that you'd have to do is obviously this would produce a very that from that fibrous tissue that they have it can produce a very hard hard and painless thyroid that's a very important thing i want you guys to remember they're a very hard and painless thyroid but because they develop all this fibrous tissue around them it can compress it can really compress some of the nearby structures and just be a big fibrous tissue mess in that area what are some of the structures that are near the thyroid gland take it take it as simple as possible compress what what if it compresses the esophagus because of that fibrous tissue what can that lead to dysphagia so if they present with maybe a hard nodule with dysphagia or it compresses onto the trachea what can that lead to maybe that leads to dyspnea difficulty breathing maybe it compresses the recurrent laryngeal nerve that may lead to hoarseness so you see how they may have compressive symptoms that are similar to actually like a tumor and so if they have a hard kind of a painless nodule they have these compressive symptoms maybe thinking oh man i think these guys have thyroid cancer and a plastic carcinoma made because that presents similarly the only way that you can really determine that is that you'd actually have to go and you can check their igg4 antibodies not that great of a test they may come back positive but the best way is to go in and take a biopsy and once you biopsy you'll be able to determine is this cancer or is this just a lot of fibrous tissue related to the retail thyroiditis okay all right the next thing that we need to do is we need to test for that we need to think about sub-acute what if they have sub-acute granulomatous thyroiditis so what else could they have sub-acute granulomatous thyroiditis how do i determine this well they may present with a elevated esr remember i told you that that's one of the things that we may see the other one is they may present with flu-like symptoms so they may present with muscle aches joint eggs maybe a low-grade fever what else a painful and tender thyroid upon palpation that's very very important okay so that's one of the ways that we can help to differentiate subacute granulomatous thyroiditis from some of these other ones the next thing that you want to be thinking about is what if this is an iodine issue it's simple check their iodine so is this an iodine deficiency okay is this an iodine deficiency check the serum iodide okay or again take into consideration their area is this an area that particularly iodine deficiency may be more endemic okay that may also be another thing and again remember i told you that sometimes if you have too much iodine it can exert that wolf chakov effect which can also cause a negative feedback inhibiting thyroid hormone synthesis that's very short-lived it doesn't last very long so it's not something that you're going to see with a chronic hypothyroidism so don't worry too much about that diagnosis but again low iodine simple check the iodine okay after we've gone through this this has helped us to rule out particularly any of the primary hypothyroidism one of the big things i really want you guys to talk about because you see it a lot in medicine is that they can have associated conditions which may key you into the hypothyroidism as well i really want to take a quick second to talk about that alright so what are some of these associated conditions i want you guys to be thinking about we kind of talked about a little bit of these later but some of the things that i want you to also be considering to order are things that you may get tested on your boards it may not be just this picture-perfect diagnosis kind of step-by-step process they may give you very little ambiguous symptoms clinical features and then a couple kind of like abnormal labs and i really want you guys to interpret these labs and understand what they're telling you with respect to hypothyroidism so remember one of the things that we said is that whenever you have hypothyroidism and inhibits the ldl receptor uptake okay and so what could that result in high ldls so be on the lookout when someone has high ldls within the blood or high triglycerides in the blood and presenting with the clinical features of hypothyroidism again something to think about not always truly diagnostic but something to think about the next thing is remember we also said that whenever someone has significant hypothyroidism it damages the muscle cells they don't regenerate they cause less muscle contraction and so because of that they may have elevated creatinine kinase levels so that may also be something to think about okay when you're having a person present with these clinical features the next one that i want you guys to remember is that remember it decreases glycolysis glycogenolysis and lipolysis but there's one more pathway that we didn't mention and this is another one it decreases [Music] gluconeogenesis this is a big one and because of that if there's really low thyroid hormone levels this can result in decreased glucose levels within the blood hypoglycemia so if someone also presents with hypoglycemia beyond the alert for that the last thing i want you guys to remember here is that uh whenever there's hypothyroidism right hypothyroidism there's a mechanism that we're look that's being looked into that what happens is this may actually stimulate adh production and adh may increase water reabsorption now if you increase water reabsorption what's the problem with that if it happens a lot it may dilute the sodium that's actually in the blood if you dilute your sodium enough it can cause what's called a hypotonic hyponatremia okay so sometimes you may also see a patient with a hypotonic hyponatremia be on the alert for again someone with hypothyroidism okay so these are some a couple of these associated things that i want you guys to be looking at that can add an aid in the diagnosis of hypothyroidism but again not diagnostic like definitive diagnostics the next thing is congenital hypothyroidism this will finish up for the diagnoses within 24 to 48 hours after a child is born it's actually mandated by law that they test for congenital hypothyroidism and so one of the things that they do is they check tsh so again within 24 to 48 hours post birth by law they have to check a tsh okay now think about this without us even knowing if someone has congenital hypothyroidism we said it was primarily an issue where the thyroid gland wasn't developing it was being destroyed he didn't have enough iodine or the enzymes were all jacked up we're not making thyroid hormone if there's low thyroid hormone but the pituitary is intact what would happen to the tsh it would come back high so if you checked the tsh on a little baby and it came back high that's making you think oh hypothyroidism how do i confirm what do i do order a free t4 and that free t4 would come back what low and that may key you into saying that this patient has hypo congenital hypothyroidism along with the clinical features that we talked about as well with the seven ps okay that keys up our entire diagnosis let's finish up with treatment and then a quick complication all right so the next thing is hypothyroidism how do we treat it it's actually probably the easiest thing possible give them thyroid hormone right so how do we do that there's a particular drug a synthetic thyroid hormone which is called levo thyroxine and this is literally t4 it's literally synthetic t4 so whenever you give someone levothyroxine what happens is that t4 that synthetic thyroid hormone gets taken up into your target cells and then you remember what the mechanism is t4 has to get i uh deionize remove an iodine and convert it into t3 and then t3 binds to an intracellular receptor activates genes and increases the expressions of particular proteins that increase metabolic activity exert all the physiological effects that we saw over there basically trying to reverse the hypothyroidism that is the easiest concept you can also there is another drug and and you basically can give t3 the uh leothyronine but it's not as effective as t4 levothyroxine so again this will be your first line treatment what i really wanted to take a quick second to talk about because this is actually more important than just knowing the drug is knowing how is this is this drug even effective you might have am i giving them the right dosage am i giving them too much how do i know think about this let's say that you have a patient here who you give t4 to right and let's take the two scenarios here let's say that you actually have the first one which is you don't give enough of that thyroid hormone if you don't give enough of the thyroid hormone what does that do to the pituitary gland what was the response from that the pituitary gland should respond by doing what increasing the tsh production telling the thyroid gland hey make more thyroid hormone if you can if you're giving too much t4 too much levothyroxine then what would the problem be then this would tell the anterior pituitary hey antipituitary too much of me you got to chill out bro decrease the tsh production so let's say that you give someone levothyroxine but you give them too little they're going to have a high tsh when you monitor to see hey is it this drug if i'm giving him too much is it effective you get the person's lab back after they've been on the level their oxygen for a little bit the tsh comes back high what does that mean i'm not giving them enough increase the dosage so that's very important i want you guys to know that increase the dose of the free t4 or the thyroxine and then recheck if they come back after they've been on the level thyroxine for a little bit and their tsh is low that means that you're giving them too much what do you do drop the dose of the free t4 or in this case the levothyroxine pretty straightforward pretty simple right not too bad the last thing i need you guys to to know because it's very important for real life scenarios because a lot of people could be on other medications that alter the t4 levels as well and so that's very important things that are the most significant here is that let's say that somebody is on an oral contraceptive and that contains a lot of estrogen in it if that's the case what this does is is it actually increases the concentration of what's called thyroxine binding globulins what does that do that binds the t4 in this case it binds more of the levothyroxine so let's say that you give them a dose of levothyroxine but they're on this estrogen pill it's going to increase the amount of tbg which is going to decrease the amount of circulating free t4 that means that even though you're giving them thyroid hormone this estrogen may effectively lower the amount of circulating t4 so what we have to do sometimes in someone who's on estrogen you may have to increase the dose so you may have to increase the dose in these scenarios the last situation is another commonly given drug that's you know used a lot is going to be corticosteroids corticosteroids these ones are very interesting you give these for tons of reasons but one of the things that you need to think about is that it decreases the thyroxine binding globulin and so what that will do is it will actually increase the amount of circulating free t4 or levothyroxine that's being delivered to the tissues if that's the case and i have too much free t4 what would i want to do i'd want to reduce the dose so in these situations i'd want to reduce the dose these are just important little kilo things that you guys should know when you're talking about treating someone and managing someone with hypothyroidism with levothyroxine let's finish up the last conversation here with mixodemocoma all right so myxedemocoma is a very serious complication from hypothyroidism and what i want you guys to take away from this is what are the triggers what are the primary clinical features diagnosis we already talked about it and what's the emergent treatment that you guys should know so what happens is the most common triggers for someone with myxidemacoma is it is the same as actually for the most part the thyrotoxicosis and that is infection so some type of underlying infection maybe it be sepsis or they've had some type of surgery whether that be a thyroidal surgery or non-thyroidal surgery but that's a big trigger as well as some type of trauma and there can be other reasons another common reason could be extreme cold temperatures so extreme cold so here we'll throw that one out there extreme cold temperatures okay you're out there shoveling snow for i don't know too long either way any of these triggers what they do is they increase your sympathetic nervous system drive that's what they want to do but remember what happens when you have low thyroid hormone what does it do to your sympathetic system it decreases the sympathetic system activity so what happens is these things want to increase your sympathetic drive but your thyroid hormone is saying uh-uh i'm going to decrease the sympathetic drive so now what happens the sympathetic drive that you would usually have to deal with these significant stressors is diminished it's gone and because of that the hypothyroid effects are even more pronounced than usual what do i mean i remember the heart this is the big one what did it do what would that that sympathetic effect on the uh the the heart particularly what was it doing it was we were generally increasing beta 1 at genetic receptor sensitivity if i super shut down the sympathetic drive what's going to happen i'm going to shut down my heart rate really really bad right and this is going to lead to severe bradycardia i also can really affect the pumping function of the heart and what happens is this remember we said that there was a mild decrease in contractility due to a decreased beta adrenergic sensitivity if we have really really high low levels of thyroid hormone that contractility drops a lot and that contractility can eventually lead to a decreased cardiac output what happens with the decreased cardiac output decrease blood pressure and so these patients may also go into shock so remember bradycardia shock or hypotension the other thing is it decreases the sympathetic activity within the central nervous system and that's a problematic issue as well because that can lead to altered mental status that can lead to confusion that can lead to significant lethargy and eventually worst case scenario a coma okay the last thing i need you to remember is remember say remember how it really our normal thyroid hormone jacks up our metabolic activity well if we really shut down that sympathetic drive and we really shut down the hypothyroidism issues we really have a really really low thyroid hormone and a really low sympathetic drive that's going to significantly drop the metabolic activity more than usual so the problem where cellular respiration is occurring so little that so little heat is being produced and if so little heat is being produced by our cells what does that lead to with our body temperature that's going to lead to severe hypothermia and that can be super problematic right so what are the cardinal features of scene with this bradycardia hypotension or shock confusion progressing to coma a significant hypothermia and with these underlying triggers okay once you've gone through the same diagnostic steps as you would with someone who has hypothyroidism in general without this complication and you come to the diagnosis you're going to start treating them empirically and you're going to do this with iv substances the first one that you're going to give is you want to give a bunch of t4 so the levothyroxine and you also give another drug called the t3 leothyrone just so that you have an amplified effect of both of them in this severe hypothyroid state the other thing that you're going to want to do is put a lot of fluids in them because they could be hypotensive and their heart rate may be low and we just need to make sure that we maintain a good blood volume in them as well and also fluids are also important when it comes to people with hyponatremia we may want to give a little bit more salt in the fluids again not getting too crazy here though the next thing that we want to give is sometimes severe hypothyroidism like myxodemocoma can mimic someone with a concomitant adrenal insufficiency and sometimes it's really hard to rule that out and so what we do is is we treat them initially the same way as we would treat adrenal insufficiency until we've completely concluded that it's not there so what do we give for adrenaline sufficiency we give iv hydrocortisone hydrocortisone until we rule out adrenal failure and then after we've adrenal fail failure you can decrease the iv hydrocortisone or discontinue it but again most important thing is ivt4t3 fluids iv hydrocortisone until you rule out adrenal crisis or insufficiency that is the treatment of mexidemocoma and that finishes our discussion on hypothyroidism what's up ninja nerds in this video today we talk about hypothyroidism i hope that you guys enjoyed it and i hope it made sense all right ninja nerds thank you and as always until next time [Music] you

Channel: Ninja Nerd

Views: 108,825

Rating: 4.9615765 out of 5

Keywords: Ninja Nerd Lectures, Ninja Nerd, Ninja Nerd Science, education, whiteboard lectures, medicine, science, hypothyroidism, thyroid, myxedema coma, physiology, treatment, pathophysiology, endocrinology, thyroxine, myxedema nursing

Id: 4WigUZMM-yA

Length: 82min 53sec (4973 seconds)

Published: Mon Mar 15 2021

Reddit Comments

[u/kateran723]

Haha not gona lie, this guy single handedly got me into nursing school

[u/FameTrigger]

Sweet, thanks! I'll get a cup of thee and go watch this :)