what's up Ninja nerds in this video today we're going to be talking about hyperthyroidism this is part of our clinical medicine section if you guys are liking these videos you're really enjoying them and learning a lot from them please hit the like button comment down in the comment section and subscribe also for you guys' benefit I highly suggest this go down the description box below there's a link to our website on our website we have super high yield notes illustrations and thousands of quiz questions that you guys can test your knowledge on also we're developing exam prep courses for those of you out there so keep your eyes pilled open for those all right let's talk about hyper thyroidism so what is it it's when the thyroid is too day high you got to stop being thyroid you know what I'm saying so what is the concept the pathophysiology the causes Etc behind this well it comes into two categories primary or secondary primary means it's a thyroid problem secondary means is the hypothalamus or pituitary problem we'll focus on the primary causes of hyperthyroidism first when we talk about primary hyperthyroidism the problem is the actual thyroid gland itself now what happens here is this puppy is just pumping out tons of T3 and T4 now when we actually zoom in on these follicular cells and take a look at them and understand a little bit more of the mechanism of how they're actually pumping out that T3 and T4 really helps us one of them is that these thyroid follicles which are the structural and functional unit of the thyroid gland are hyperfunctioning maybe there's two reasons behind it one is they could have hyperactive TSH receptors or they could have their TSH receptors being stimulated by something and we'll talk about what that something is but usually the primary process here is there stimulation of the TSH receptors these tell the folicular cells hey make thyroglobulin which is that black Cid in the middle then combine that with iodine and make thyroid hormone and then release that thyroid hormone into the bloodstream and that's what's happening but it's happening at a hyperactive rate so we're pumping out very large levels of thyroid hormone into the bloodstream now that's one mechanism and so we'll see that this is wherever the thyroid gland is hyperfunctioning let's write that down so this one is that you have a high functioning thyroid gland so hyper function of the thyroid the other one is super interesting the other one that actually can occur here is where the thyroid follicles are busted open now inside the center that black component there the colloid that contains two things one is you have thyroglobulin but if you combine it with iodine break it down into certain pieces you'll make thyroid hormon so there is a combination of both of those that are stored in the center of these these follicles if you bust open the follicles this thyroglobulin and thyroid hormone will be released into the bloodstream so now from here I can release two components here I can release we'll write down both of these thyroglobulin which I'm going to repres as TG and I can actually put in here T3 and T4 so now I can have increased levels of both of these just like in this one up here what am I having high levels of T3 and T4 I'm going to have high levels of all of these puppies here okay this is the concept that I want you guys to understand here is that whenever I destroy the follicles I'll release thyroglobulin and T3 and T4 when I actually hyperfunction these thyroid glands I'll make tons of T3 and T4 that'll get put into the bloodstream either way both of these lead to hyperthyroidism but one of them leads to lots of thyroglobulin being released into the bloodstream this is whenever there is follicle or thyroid destruction so if I destroy the thyroid follicles I will release out the thyroid hormone that'll lead to hyper thyroidism either way the concept is the thyroid is pumping out high levels of thyroid hormone why is that a problem well we'll talk about the metabolic and cardiovascular all the multi-stem involvements next but before we do that I need you guys to understand that T3 and T4 have a very profound effect on hypothalamus and the anti pituitary usually when it's in high levels your hypothalamus says oh dang man too high I got to shut that down and what it'll do is is it'll release less TR all right so to release less TR that will tell the anterior pituitary to make less TSH so as a result here less TR tells the anterior pituitary to make less TSH so we're going to have reduce levels of these in primary hyperthyroidism so that's what I really want you guys to remember here is that in primary hyperthyroidism what do we have we have two components here one is that you're going to have a low TSH and you're going to have a high T3 and T4 and that is super super critical to remember here especially for the Diagnostics of primary hyperthyroidism there's one more cause so either busting open the thyroid follicles or we're telling them to make more thyroid hormone the last one is when patients take thyroid hormone but maybe they're taking higher than normal levels or they're taking it and they don't even have hypothyroidism so often times this is exogenous thyroid hormone we sometimes refer to this or most times refer to this as what's called Leo thyroxine this would be an iatrogenic example of hyperthyroidism in other words the actual person is being prescribed a medication by a a provider of some sort and they're taking that medication and it's exogenously bumping up their thyroid hormone levels without having anything to do with destroying the follicles or anything to do with Hyper actioning hyperactive function of the thyroid gland so this is an example of an iatrogenic cause all right with that being said we've covered the pathophysiology of primary hyperthyroidism let's now get into a little bit more detail on how this hyperfunctioning occurs and this follicle destruction because it's going to be really important with the differential and Diagnostics first thing hyperfunctioning thyroid we said something is going on with the TSH receptors they're either being stimulated or they're hyperactive for some reason why would they be engraves disease which is one of the most common causes of primary hyperthyroidism I really want you guys to remember that this is by far going to be the most common cause of primary hyperthyroidism what happens is your body produces these Auto antibodies right now normally antibodies are produced against pathogens but if you produce it against your own tissues is an example of a autoimmune disease these antibodies are referred to as TSH receptor antibodies now what these things do is is they go and they attack almost every thyroid follicle cell so this is diffuse destruction or diffuse hyperactivity of the thyroid gland now these antibodies why are we producing them what's the trigger usually there's some type of mutation that causes a increased production of these antibodies what is it usually it's a mutation and the two mutations that I want you guys to remember is it's usually an HLA dr3 or an HLA B8 mut mutation when these mutations are present it leads to a hyperactivity of our immune system cells which type of immune system cells you ask the plasma cells or mhc2 complexes from the antigen presenting cells either way these things are hyperactive they respond hyperactively when they respond hyperactively they produce antibodies undesirably against our own tissue cells and so this is an example of an autoimmune disease so these mutations are present it causes a hyperactivity our immune system produces antibodies against our own tissues now when you zoom in you take these antibodies and you zoom in on the follicular level so I do this now I look at one follicle even though it's attacking almost all follicles of the thyroid gland all right that's really important I'm just zooming in on one this is so cool because what happens is that these antibodies click with the TSH receptors so now what I do is I take this TSH receptor that normally is only supposed to be stimulated by TSH this thing acts just like TSH these antibodies it'll hyperactively stimulate these TSH receptors what will they start doing synthesizing tons and tons of thyroglobulin iodinating the thyroglobulin and then releasing into the bloodstream tons of T3 and T4 as a result so you see see how this hyperfunctioning is occurring it's occurring via antibodies these antibodies you have to remember them they're really important for your tests it's the TSH receptor antibodies they're produced in response to autoimmune types of activity due to mutations in these genes now Graves disease we'll talk about this a little bit later within the common classic findings of hyperthyroidism often times these th receptor antibodies have other receptors on fiber blast and on adapost tissue and they increase the production of fibrous tissue or glycosaminoglycan like proteins and adapost tissue and this leads to this weird type of presentation we'll talk about later often times their eyes protrude Eng Graves we call that opthalmopathy which is usually the presentation we refer to as exop thalos they protruding eyeballs and their lower extremities have really nasty like aitous appearance like an orange pill which we call pretibial mix edema this is common and only Graves disease we'll talk about that later though all right Graves most common we're going to come back to this in a little bit let's talk about toxic adenoma toxic adenoma is when you have literally one chunk of follicle tissue it's not like a cancerous mass it's a benign tissue so it's like a benign Mass if you will a benign Mass that's really important usually thyroid cancer is not um secretory in other words it doesn't really make thyroid hormone or TSH uh thyroid hormone in general so this is a benign Mass we refer to as an adenoma this little guy here this chunk of follicular tissue if we were to actually zoom in on it and look at it what happens here is you have these TSH receptors these TSH receptors are becoming autoactivated they're super sensitive and so there is a increased TSH receptor sensitivity and because of that is TS TSH is present it will cause these puppies to become crazy activated when they become crazy activated it will then trigger thyroglobulin production thyroglobulin when combined with iodine will make thyroid hormone and pump out tons and tons of T3 and T4 as a result so this is really important is that these TSH receptors are just Super Hyper sensitive and it's usually the TSH receptors on follicular cells in that chunk of tissue there that mass of tissue and it's usually only one focal Mass all right now toxic multinodular goer is multiple Bine masses so now imagine here I have multiple benign masses all of these little chunks of tissue if you were to zoom in on all of them have the same concept increased TSH receptor sensitivity so if TSH binds boom I pump out tons of thyroid hormone sometimes they can even autoactivate those TSH receptors so either way they're pumping out T3 and T4 due to hypers sensitivity or autoactivation of the TSH receptor how would I be able to differentiate between this and this we'll talk about it later when we get into the testing but another thing is that this causes chunks of tissue so I may be able to to have a mass on my physical exam this one I may be able to find a mass on physical exam and so I think that's something that's also really important to remember that you won't really see in Graves disease because there's no chunks of tissue there so that may be helpful now it is kind of difficult sometimes to find these nodules or these masses but think about it if it comes up in your clinical vignette all right Graves toxic adenoma toxic multi goers chunks of tissue that are hyperactive or an entire thyroid follicle cells being stimulated by antibodies there is this interesting concept it's called jod based out phenomenon this is really interesting so imagine I have a patient here and this patient has a toxic multi goer or they have a toxic adenoma or they have Graves one of them right or all of them I mean it would be kind of weird but if they have one of those and then what I do is I give them a heavy dose of iodine heavy heavy dose of iodine these tissues in toxic anoma toxic multinodular andoer engraves all of these tissues are hyperfunctioning in other words they love to make thyroglobulin if you give them enough iodine they'll combine the iodine with the thyroglobulin and they will start pumping out tons and tons of thyroid hormone so this is often times really really important to remember because this thyroid tissue will consume that iodine use it and pump out massive levels of T3 and T4 so the reason why I'm mentioning this is that there is other causes you may have a patient who has a toxic adenoma a goer that's multinodular or Graves and you give them a radio contrast load of iodine like like a CT scans so if you get like a contrasted CT scan a contrasted CT study or or you know another drug that contains large levels of uh iodine amiodarone amiodarone what these will do is they'll give tons of iodine get consumed by these tissues and make T3 and T4 that's really important it's opposite of the disease the concept called wolf chof effect the wolf chof effect is you give them a ton of iodine that iodine in high amounts will suppress the TPO enzyme and they won't make thyroid hormone but if they have tissues that can use the iodine they'll make tons of thyroid hormone this is oftentimes a trigger for what we call thyroid storm which we'll talk about later all right cool so we got a good concept of this one let's now move into these the big thing I want you to remember here with thyroid destruction is often times this is what we refer to as a transient thyroid toxicosis this is really really important I actually really need you guys to memorize this and remember this this is a transient thyrotoxicosis whereas in a hyperfunctioning thyroid this is usually permanent so in other words they have permanently elevated levels of thyroid hormone this one it's transient let's talk about these now you may look at this and be like wait a second if I watched hypothyroidism video I remember that these cause hypothyroidism exactly they eventually can lead to a thyroid state but the initial injury of the follicle cells causes a transient hypo hyperthyroidism let's explain it all right so how does hashimotos lead to this transient thyroid toxicosis well one is it causes these antibodies to be produced so you have what's called anti- TPO and anti- thyroglobulin antibodies these guys remember from the thyroid elri hypothyroidism there's H drr3 H dr4 mutations hyperactivity of the immune system producing antibodies these go and attack the thyroid follicle tissues where those enzymes are if I zoom in on it what happens is these antibodies lead to an immune reaction that immune reaction leads to destruction of the follicle cells they bust open that colloid containing thyroglobulin and thyroid hormone gets released into the bloodstream so now watch this I release thyroglobulin and I release thyroid hormone so T3 T4 and thyroid globulin all get released so it's a transient hyperthyroidism or transient thyroid toxicosis if there's destruction of this tissue eventually after all of it's released you'll have this hyperthyroid State then what happens is the follicles that are destroyed stop being able to produce thyroid hormone then you start going into a hypothyroid state so in this one what happens is they eventually go into what's called a hypothyroid State and that's what we were referring to in the hypothyroid lecture now in Hashimoto this inflammation is chronic so this is the one where they have chronic hypothyroidism these follicles continue to get destroyed continue to be destroyed and eventually they lose tons of follicular function that it leads to Chronic hypothyroidism in comparison to these two watch this you make anti-tpo antibodies but why do you guys remember the reason that we make them is pregnancy this probably hormone related less than one year of postpartum they produce these antibodies they attack the thyroid tissue if you zoom in on it what we see you'll get attacking here you'll bust these puppies open you release T3 T4 and you'll also release thyroglobulin so these levels will be elevated but here's where it's kind of interesting you'll destroy the tissue cause a transient thyroid toxicosis eventually the thyroid cells will become destroyed and because of that you'll go into a hypothyroid state but in this disease it's usually self-limited meaning it's not going to be chronic they'll actually recover and eventually they go into a u thyroid state so this is what I refer to as the triphasic response that you see in postpartum and dequin thyroiditis so that leads to this next component what's the trigger here it's pretty obvious it's an infection but it's usually a viral upper respiratory tract infection that leads to direct cytotoxic damage of the thyroid follicles if I zoom in you'll see here virus destroys these follicle cells they pump out T3 T4 and thyroglobulin this is becoming like a pretty repetitive right but at least from here you guys won't forget it so you'll have a transient thyrotoxicosis the follicles will be destroyed the lose their ability to make thyroid hormone for a certain amount of time so they'll go into a hypothyroid state but again this is self-limiting the virus will clear you'll then allow for recovery and you'll go into a u thyroid State this is also helpful so if a patient has a period of very trans self-limiting thyrotoxicosis or hypo hyperthyroidism that then resolves over time it's likely postpartum or de querin how do I really tell the difference this one usually the history is the key this one we've talked about before it causes direct injury so often times this causes a very painful thyroid and what else do we say it often leads to this massively elevated arthrite sedimentation rate so often times history will delineate these Hashimoto usually these patients will go into a chronic hypothyroid State all right so we talked about all of the concepts behind a patient developing hyperthyroidism but I really have to have you guys remember this is permanent hypothyroidism this is only a small amount of time some will become chronic hypothyroid some will have a transient hypothyroid and then recovery let's move on to the next concept here the next concept is what if the patient doesn't have primary hyperthyroidism what if it's secondary that means that there's something wrong with the pituitary probably and that's usually the issue usually what happens is the pituitary is pumping out extremely high levels of TSH just pumping it right and when it's pumping these TSH level this TSH out it goes to your thyroid gland to multiple thyroid follicles and then does what directly stimulates the TSH receptors when you stimulate these TSH receptors it'll trigger the production of thyroglobulin combine it with iodine and then release thyroid hormone into the bloodstream so then you're going to get tons of T3 and T4 in the bloodstream that's very interesting because in primary the TSH was low T3 T4 was high in secondary ah this is how I can differentiate them and secondary the problem is I have high TSH and high three High T3 and T4 so both of them are high just like in secondary hypothyroidism it was a low TSH low T3 T4 so you have to be able to remember this to help you to delineate this when it comes to the diagnostic testing question arises though what's causing this pituitary to release tons of TSH well there's one one primary cause it's usually a tumor a smaller tumor what we call a micro adenoma you're like wait a second this sounds really familiar didn't Zach say in the hypothyroidism lecture that pituitary macroadenomas can cause hypothyroidism pituitary microadenomas can cause hyperthyroidism if you remember pituitary macroadenomas compress the pituitary stock leading to less signaling of the TR pituitary micro adomas don't compress the pituitary stock they're they're tiny but what happens is that they gain secretory function and so they gain the capacity to produce large levels of TSH so that is usually the primary cause is you have a tiny little tumor that's pumping out TSH but here is what I want you to remember you can have Mass Effect it is uncommon though the Mass Effect is going to be much much much more common in the macro adenoma because it's a big tumor it's compressing on the optic Asma and it's leading to the bitemporal hopia and the headaches what gives away a pituitary microadenoma is that it not only produces large levels of TSH it also produces other hormones such as high levels of prolactin it also leads to high levels of act it also Lev leads to high levels of growth hormone and so because of these these patients will also develop secondary disorders that affect other organs so H prolactin does what well it really is becomes more prominent in males or females by affecting the breast tissue so what can it do it can cause gynecomastia in males so we call this gyo mastia in the male population but it can cause GAC lacto Ria in the female population it also Alters your estrogen and progesterone level so it can lead to menstral irregularities infertility and reduce libido this also causes your what Your Zona GLA ficula to pump out tons of cortisol and so usually these patients will have massively high levels of cortisol and this produces a disease called Cushings is disease Cushing's disease so that's another common feature here is that this High cortisol level will produce a Cushing like effect but it's called Cushings Disease and then lastly you'll have high levels of growth hormone which will affect multiple tissues I'm just using the bone here it can affect your muscles it can affect your actual liver but what it can do is it can lead to what's what's that disease called when you start growing at an older age we refer to it as acromegaly and so often times these patients will present with macro megal so they'll have like a prominent forehead nose jaw they may have also kind of like sweating they may have these doughy hands and carpal tunnel syndrome obstructive sleep apnea all kinds of presentations we'll talk about that more in the pituitary disorders so this would be a really big giveaway here is if I see other endocrine organs being affected that would make me think about a microadenoma I do want you to remember though there is less likelihood less chance of Mass Effect in other words there is less effect of that compression so remember I use this example here we have the two eyeballs here and then we have the example where we have the optic Asma that's coming right here there is a smaller tumor so there's less likely to cause compression of this optic Asma so there's less likelihood to develop bites and poal hopia and headaches it is possible but it's less likely I want you to remember that more for the pituitary macro adenoma and hypothyroidism all right my friends we talked about the patho fiz the causes of hyperthyroidism let's start going over what are the main characteristics in classic findings and what's the worst complication we can experience all right my friends let's move on to the next component here which is what are the classic findings of hyperthyroidism and then what's the most scariest complication that can arise in patients with hyper thyroidism that is thyroid storm so the thyroid hormone has multi- system involved so many systems can be affected I'll go over this in a particular categories that I think is helpful but also I'll highlight along the way the most common findings that you'll see in the Ws or the boards so first one is a goer this is really common I'd say it's especially common in patients who have Graves disease but it also can be a common and secondary hyperthyroidism so let's have a concept of why gers form we talked about this in hypothyroidism but in hypothyroidism it would trigger the low T3 T4 would trigger the pituitary to make tons of TSH the TSH would hit the TSH receptors and cause hyperplasia of those cells cause more thyro globulin production and then the thyroid follicular cells will get bigger and you get enlargement of the thyroid it's the same concept you just have to think about there has to be high levels of TSH so one is I have a pituitary microadenoma or tumor that is just pumping out that TSH right so that would be one definite cause here because this TSH will then come here it'll bind onto this TSH receptor cause increased stimulation of this TSH receptor and then as a result it can definitely lead to what enlargement of the actual thyroid gland so represent this kind of like dotted line here as enlargement of the thyroid gland which we're going to refer to as a goiter so that definitely be one cause we can say that one of these causes would most certainly be secondary hyperthyroidism 100% right so you could see this in like a pituitary micro adenoma right the other concept here is that maybe there is not increased TSH this could also be due to uh receptor antibodies that are binding to the TSH receptors and hyperactivating them so another one is this could be due to let's use these here these blue struct here they're binding on to this TSH receptor what are these things here called This is engrav disease this is a TSH receptor antibodies if you have an increased presence of these these will hyperactivate the TSH receptor and they'll cause enlargement because they'll cause that hyperplasia thyroglobulin synthesis and just enlargement of these follicular cells and so this will be representative by enlargement so what could cause this again this would usually be in something like Graves disease so Graves is a very common cause for triggering this process now there is other types of disorders technically toxic multinodular goer the name is within that you may see these present toxic adenomas not so much you can see these in the thyroiditis right but it's usually when they're in the hypothyroid state so we'll make those more applicable and keep them in that particular category of hypothyroidism where that hypothyroidism from the follicular destruction leads to hypothyroidism increased TSH and then goer formation but truly in hyperthyroidism they don't belong because it's very transient and these Graves and secondary hyperthyroidism they will most certainly precipitate thyroid enlargement and goer formation you can also consider the presence of a toxic multinodular goer given the name itself all right so these may also Prof find goers all right the next concept here is that thyroid hormone has a profound metabolic function so what happens is whenever you have exceedingly high levels of T3 and T4 this will act on your me uh your tissue cells almost every single tissue in your entire body what it'll do is it'll hyperactivate these pumps here that are found in almost every cell in your body which are called sodium pottassium atpases so what they're going to do is they're going to help to be able to pump the sodium out of the cell and they're going to help to pump the potassium into the cell and it's usually in a 3:2 ratio but in this concept you're consuming ATP to help to generate this process so what happens is you deplete ATP when you deplete the ATP your body is going to have to generate more ATP so what's the end result here the end result here is that you'll end up with a depletion and ATP because these pumps require ATP when you reduce the ATP your body will have to tap into all the different types of macronutrients fats maybe glycogen maybe proteins and start breaking down those molecules so what it'll do is is it'll cause an increase in your catabolic State when you cause an increase in the catabolic State you will start breaking down tons of nutrients so this will lead to weight loss all right you're going to start experiencing weight loss because of this and whenever you have a massive weight loss in this increased catabolic State sometimes these patients are insanely hungry so that's another thing is that they may also have increased hunger because they're in this excessive catabolic State the other thing is that when you're in a catabolic State you generate heat from metabolism this is a natural concept so whenever you generate tons and tons of heat that heat production is somewhat problematic whenever it's excessive because what this will do is is this will cause your body temperature to start rising and so what this will do is this will produce what we call heat intolerance and so this is where the patients just are literally they feel like they are constantly hot maybe they're a little bit diaphoretic this is super super common and you definitely want to think about these so if I have a patient who has heat intolerance weight loss and a goer I'm certainly thinking about hyperthyroidism the other concept is it has a very profound effect on our neurological system so I really want you to think about hyperthyroidism is it really ramps up the metabolic activity and multiple system activity everything is on hyperdrive so in the same thing in the brain imagine increasing the metabolic activity of multiple neurons so if I have increased levels of T3 T4 it's going to act on all the neurons within my CNS and what it's going to do is it's going to increase the neurons basil metabolic rate and it's going to cause neuron activity to be through the roof right now these neurons are going to be like wam it's going to be firing and hyperdrive and so because of this if your neuron activities on hyperdrive what this can do is this can make the patient a little bit more agitated irritable may be difficult for them to even fall asleep at night sometimes the neuron activity can be so excessive that it may cause a certain focus of the brain to become hyperactive and they can start seizing and so this is something to definitely think about but often times the most common manifestations is usually going to be what we call hyperactive types of behavior so hyperactive Behavior so usually this is what we refer to as agitation U maybe anxiety y insomnia but it also can lead to your deep tendon reflexes being insane you tap that thing right knee is going to be all the way up right so you're going to have super hyperactive deep tendon reflexes it can also cause a little bit of increased uh trimmer as well so watch out for trimmer activity in this patient population but I think the really big thing is hyperactive Behavior so agitation irritability anxiety as well as increased deep tin and reflex is weight loss heat intolerance goer think about hyperthyroidism all right we come to the next one cardiovascular dysfunction this one's actually super interesting whenever your T3 and T4 levels are super high we remember that this has a very profound effect in the beta 1 receptors so what you guys have to remember is these T3 T4 it basically acts on the beta 1 receptors and affects the sensitivity in other words imagine epinephrine norepinephrine they bind to a beta 1 receptor it exhibits an effect but if I have thyroid hormone and higher levels the sensitivity is insane epinephrine norepinephrine binds onto that thing W there's going to be increased activity of the myocardial cells and so what we see here is that whenever T3 and T4 are present it acts on The myocardium it increases the beta 1 receptor sensitivity so when norepinephrine epinephrine binds to them it increases the depolarization of atrial cells and the AV node and increases the contraction of the ventricular cells and so as a result we get two effects here one is your AV node will fire like a son of a gun So the patient's heart rate will go through the roof and the other thing is that their contractility of the myocardial cells can actually be pretty profound especially if it's really really high and so what we may see is an increase in heart rate and an increase in contractility but often times in these patients with increasing heart rate the most common manifestation is usually they may present in like atrial fibrillation or in an SVT so that's something to definitely think about the other thing is that when your contractility is really high what does that do to your uh your cardiac output do you guys know well it actually increases your cardiac output if you increase your cardiac output what does that do to your systolic blood pressure it increases it and so often times these patients have an increase in their cardiac output and what we know is that cardiac output has a very profound effect on your systolic blood pressure and so these patients have what we refer to as systolic hypertension whereas hypothyroidism causes diastolic hypertension this is really important to be able to remember this the other concept that's actually kind of important here I want to just mention it now because it'll actually come very helpful ful in thyroid storm is that T3 and T4 control the balance of your actual vessel tone so we said normally it keeps a maintenance of vasil dilation vasil constriction but whenever there's too high of this level what it actually can do on the actual vessels is it can trigger them to undergo baso dilation now that may not be a bad thing but in patients who have uh thyroid storm this can be somewhat disastrous because it can really really really drop your systemic vascular resistance and so that's something to think about I'm going to leave this here for now but we will retouch and recap on this when we get into thyroid storm so big things here is do not forget that it causes tacac cardia and increase aoic blood pressure in combination with hyperactive Behavior increased deep tended reflexes heat in tolerance weight loss and goer think hyperthyroidism reproductive dysfunction again we don't really think about this commonly as a very particular manifestation in patients who have hyperthyroidism we think about it in a patient who comes in they're saying hey I'm having difficulty with my menstrual cycles I'm having difficulty getting pregnant I'm having difficulty with my libido and then we work them up looking at their thyroid hormone levels believe it or not hyper and hypothyroidism cause menstrual irregularities reduce libido and even infertility it's just the mechanism is different and hypo it caused hyperprolactinemia and hyper it causes a very interesting process so whenever you have high T3 and T4 levels what it actually does is it causes your liver to produce a hor a protein called thyroxine binding globulins it's a protein and this protein binds onto steroid hormones and thyroid hormone so whenever there's higher levels of thyroid hormone there's increased levels of thyroxine binding GL globulin what this does is is this soaks up estrogen progesterone and testosterone I'm going to represent this as an e a p and a t these all get bound up by the thyroxine binding globulin so you end up with reduced free levels right because they're going to be bound to this protein reduced free levels of e p and t estrogen progesterone testosterone what's the result this can cause the patient to develop reduce libido menstrual regularities and infertility so this can cause a reduction in libido this can cause infertility and it can cause menstrual abnormalities so with that being said what would that look like with menal abnormalities they could have no cycle they could have heavy cycles and they may have difficulty with being able to get pregnant so that's really really important to think about in patients who are having sexual dysfunction the next one is actually kind of important so gastrointestinal dysfunction so whenever you have high levels of T3 and T4 again it increases basil metabolic rate and that can cause an increase in the smooth muscle metabolic activity when smooth muscle is becoming super hyperactive especially of the git this causes the motility to go up so you'll end up with an increase in your git motility if the small bowel is Contracting and Contracting Contracting it's moving the actual feces quickly or the actual intestinal fluid contents through the git quickly not giving an adequate amount of time to absorb some of those substances as a result this can lead to diarrhea so if I have a patient who comes in and they're presenting with diarrhea they're presenting with what else tacac cardia hypertension systolic hypertension they're presenting with features of hyperactive Behavior delay hyperactive deter reflexes they're also presenting with weight loss they're presenting with heat and tolerance and a goer I'm really thinking hyperthyroidism now I told you the most common cause of primary hyperthyroidism is grav disease it's pretty much the most common cause of hyperthyroidism in general and so what helps us to add more utility to suspecting Graves is this next system dysfunction the integumentary system what happens is is in Graves so this is I need you guys to remember this concept this is Graves only all right I'm going to put some exclamation points there so in Graves there is the increased production of TSH receptor antibodies here they are here right we know that these Act on the TSH receptors and lead to hyperthyroidism one thing that you may not know is that these TSH receptors also act on fibroblasts and they also act on atopos tissue so when they act on these fibroblasts and they act on these adapost tissue it leads to some very interesting effects so here when we activate fibro blast we'll increase the production of these things called glycose Amino glycans when we activate adapost tissue will cause an increase in the adipocytes we'll call this the adipocytes it actually causes an increase in adose tissue formation so we're going to get an increase in Gag formation an increase in atopos tissue formation right the combination of these things leads to something very interesting whenever you have lots of glycosaminoglycans what do they do they're water retainers right so they grab a lot of water and bind them up and when they cause increased water retention it causes this water retention to occur primarily in the tibial region so in the lower extremities and when it does that it causes the skin to become SW swollen and kind of hard like imagine like an orange peel that's what it like feels like in their tibial region and it's non-pitting that means you push on it it will not cause an indentation this is called pre-tibial miedema now some of you are like hold up I swear upon a star that you told me that pre-tibial mix edema is only found in hypothyroidism well definitely is found in hypothyroidism no doubt about it but pre-tibial mix edema can be also found in only and I mean only Graves disease because of this mechanism the other concept that really adds utility here and this is really really important here is that gags lead to water retention adapost tissue especially around the posterior portion of the eyeball so here there's a lot of adapost tissue here right and then imagine on top of that I add some water retention into this area here so now there's going to be some swelling in the tissue behind the eye and there's going to be more atopos tissue behind the eye that means less space for the eyeball to sit into the socket so what does it do it pushes the eyeball forward this precipitates a very interesting presentation which we refer to as exop phalos this is an example of what we refer to as opthalmopathy Graves opthalmopathy this is so high yield and one of the most common characteristics that we will see in Graves disease that really makes you think think about it so if I see opthalmopathy and pretibial mix edema in Con in combination with other features like diarrhea tachicardia systolic hypertension uh weight loss heat intolerance hyperactive Behavior increased dettin reflexes and goiter I'm really banking on this patient having likely hyperthyroidism due to Graves disease if they don't have this but they have those other features it's probably hyperthyroidism but unlikely from graves disease but that's the big concept that I want you to understand so you'll see how it's so many systems that can affect the last thing that I want to do is I want to talk about something that's kind of like the opposite of mixed deacom that we see in hypothyroidism this is the most common complication of hyperthyroidism and that is thyroid storm it can actually be relatively fatal the concept behind this is very straightforward you have a patient who has chronic hyperthyroidism of some sort right so they have chronic chronically elevated levels of T3 and T4 and then what you do is you combine in a massive stressor on their body all right so you add a massive stress onto the body and what that stress does is is it increases your sympathetic nervous system and you know your sympathetic nervous system will kind of like amp up your thyroid hormone activity so that's actually what's really interesting so a combination of increased stress and chronic hyperthyroidism this is a recipe for disaster man because the combination of these two lead to uh an increase in your sympathetic nervous system and an increase and the effectiveness or the levels of your T3 and your T4 this is terrifying so if I have high levels of my T3 and T4 and hyperactive sympathetic nervous system I'm going to see a really scary complications question that arises what is this stress that's increasing the demand of the body well there's variable amounts of stress right one is you could have a really bad infection right often times this is something like sepsis this can really trigger that process surgical procedures so sometimes if patients are just having a recent surgery and they're postoperative and they develop these features that we're going to talk about you really want to think about that as being the stressor on the body another one is going to be usually it's because of I talked about this before remember the jod basedow phenomenon that was whenever we loaded them with contrast which contains iodine so a massive iodine load in What scenario does this have to be in you have to remember this you can can only see this effect in what toxic adenomas toxic multid goers and Graves disease what's the most common cause of hyperthyroidism Graves this can also increase the stress in the body and increase the T3 and T4 levels the last one is it could be due to non-compliance and we'll talk about these meds a little bit later but remember I told you in mixoma is non- compliance with levo thyroxine which is your your actual steroid the thyroid hormone and this one it's the opposite something that's going to block the actual thyroid hormone so it's non-compliance with I'm going to put these as anti-thyroid drugs we will talk about these later these are going to be things like propo uracil and this is going to be things like methol but all of these concept here is that there's an added stress in the body that amplifies your sympathetic nervous system and amplifies your T3 and T4 levels more than normal so it's just like hyperthyroidism on steroids what does this do activates like Goes Ham you start doing what causing hyperactivity of the sodium potassium pumps you cause a massive catabolic reaction that massive catabolic reaction leads to massive heat production and what does that do that heat production causes the patient to be at high risk of something called hyperthermia hyper thermia this is whenever the body temperature is greater than 41.5 degrees C we talking about cooking right that is cooking that's straight cooking so if a patient has hypothermia I'm talking like super high temperature they're diaphoretic they're sweating bullets and they have these things you really want to be thinking about thyroid storm especially if they have a history of hyperthyroidism the next thing is that we know that this hyperthyroidism also affects the central nervous system boom hyperactive uh neurons these hyperactive neurons what do they do so again we have high levels of T3 T4 and we have high levels of sympathetic nervous system activity this is going to cause these neurons to go into hyperdrive but what it's going to do is it's going to cause a patient to become so agitated and Delirious and that is usually the key finding here is that these patients will develop something called agitated delirium but it also can make these neurons so hyperactive that it could trigger a patient to develop a seizure that's relatively rare but I think it's something to consider I would focus more on the presence of agitated delirium though hypothermia agitated delirium are super super important and here's the kicker here's the biggest one when you have high levels of T3 T4 and this hyperactive sympathetic nervous system they have a very profound effect on your cardiovascular system they will pump up your heart rate I'm talking these patients usually become kind of profoundly tacac cardic this is something that I see in the ICU sometimes where a patient has refractory apib or refractory SVT they're crazy tartic and they're not responding to a lot of therapies definitely want to think about that especially if they're hypothermic and altered so they can develop really Mass apib or SVT that is refractory to a lot of your normal therapies the other thing and this is what's crazy and I wanted to come back to this it can do something very interesting remember I told you it contracts the heart like a sun of a gun so you're going to get an increase in your contractility the other thing it's going to do is it acts on your blood vessels and it causes your blood vessels to become crazy Vaso dilated so then you're going to have a drop in the systemic vascular resistance now if my blood vessels crazy vasod dilate and I drop my systemic vascular resistance what will I do to my afterload I'll drop my afterload if I drop my afterload what will that do to my cardiac output it'll increase my cardiac output what does an increase in contractility do increase my cardiac output the combined effect of this is this will cause a increase in cardiac output I'm going to abbreviate that as Co but here's the weird thing you're probably like oh well they're just pumping tons of blood out of their heart then right they are but it's not enough to meet the metabolic demands of the tissues because this T3 and T4 are just causing your tissues to become super hyperactive that it doesn't matter how much your heart is banging and how much you're actually pushing out into the vessels that cardiac output is not sufficient and so what we refer to this as is I'm going to abbreviate this high output cardiac failure this is a very rare example of where the patient has a massive contractility of the heart their vessels are super dilated but they're not meeting the oxygen demands of the tissues because hyperthyroidism is causing a massive demand and you're not going to be able to meet that demand because the cardiac output won't be active or good enough this is the key things if a patient comes in with tacac cardia hypothermia agitated delirium and then features of heart failure so they're pounding heart their extremities are warm but they have pulmonary edema you definitely want to think about thyroid storm my friends all right that covers hyperthyroidism now what we need to do is go into talking about how do we diagnose it I have a patient come in I suspect they have hyperthyroidism how do I work them up it's all about the tfts baby so get the TSH get the T4 and that'll give you an idea if it's primary or secondary if I get the T4 and it's elevated okay I know it's hyperthyroidism what's the TSH oh that's high that's the pituitary baby all right that's definitely got to be secondary hyperthyroidism so what do I do well you got to remember again in this particular situation this guy's the problem he's pumping out TSH he's telling the thyroid gland to make a lot of T3 and T4 so I got to go and look at this so what would I do well I'm going to get a pituitary MRI and look to see oh they they have a little pituitary micro here that's their Source done the other scenario is if I have a patient who has a high T4 and a low T TSH this is primary because I got to remember in primary problems it's not the pituitary it's the thyroid he is the one that's actually making too much to T3 and T4 that's then going to tell the hypothalamus in the pituitary hey stop pushing out TSH so where do I got to look not here I got to look here so then I got to go through and I think it could be Graves it could be TMG it could be toxic adenoma oh my gosh it could be thyroiditis it could be Leo thyroxine it could be IOD contrast load how do I know which one it is well first thing to do is what's the most common one Graves what's the most common presentation of graves That You Don't See in all the other ones opthalmopathy right and then another thing is they have a really big goer now if I see a goer and on top of that opthalmopathy that really suggest that it's possibly Graves if that is the case you should then consider checking the TSH receptory antibody if that's positive you've diagnosed Graves now let's say that you want to go a little bit further and you want to add to the diagnosis of graves or maybe they did not have a goer opthalmopathy what do you do then I want to find tissues that basically take up iodine excessively and will then use that iodine to make thyroid hormone so what I'm going to do is I'm going to do something called a radioactive iodine uptake scan I'm going to give the patient iodine it's not toxic to them and I'll be able to see do they have areas where they soak up the actual iodine is it in one area like an adenoma is it in a bunch of different areas like a toxic multier is it diffuse like in Graves disease or they not really take it up at all such as in thyroiditis so if I see focal uptake like in this one that's a toxic adenoma if I see diffuse uptake like in this one it's grave disease could also be toxic multiat Ider but again it's going to be more in these DOT type of pattern whereas this entire Gray ish discoloration here the last thing is if I see really no uptake at all that means that it's either thyroiditis or it could be other things like an iodine load um could even be potentially uh maybe even a situation where the patient's taking Leo thyroxine and they're taking too much of a high dose or they're taking it without a doctor's prescription so how do I determine if it's thyroiditis or not well I got to remember when I destroy the thyroid gland what comes leaking out not just thyroid hormone thyroglobulin so what I want to do is I want to check the serum thyroglobulin if it's elevated that tells me one of two things one is it tells me that the thyroid gland was exploding or that the thyroid gland was getting a lot of iodine was using that iodine to make thyroid hormone and some of that can actually be the result so it could be the result of thyroiditis or maybe possibly an iDine load and then you have to take into consideration thyroiditis will present either as dequin or it can present as postpartum thyroiditis and usually the clinical history would give you the idea there all right in this particular scenario if the serum thyroglobulin is low or normal then I know it's not thyroiditis they didn't pop open these cells in that particular scenario it's probably that they've been taking Leo thyroxine and that's the reason why their T4 is high artificially which is dropping down their TSH they're not having TSH orter antibodies they don't have abnormal areas that are producing T T3 and T4 and they're not popping open these thyroid follicles it's just they're taking it in excessive doses or without a doctor's prescription all right a patient has hyperthyroidism they come to you and they say how do you treat me all right first thing you have to treat generally the the problems that are usually arising with these patients so in a patient who comes in with hyperthyroidism they can present really agitated they can have trimmer kind of a presentation but they can also be super tacac cardic and I think one of the biggest things is you have to just kind of shut down the adrenergic Drive in these patients because again hyperthyroidism can augment the activity of the sympathetic nervous system so what if I kind of give a drug that really suppresses or blocks the sympathetic effect that'd be propanal La so propanol La is a really good drug that you should you know Supply to patients or you know prescribe to patients if they present with tardia if they present with trimmers if they present with anxiety irritability agitation this may help to suppress some of that sympathetic effect and tamper that down the other thing that's really important here is you want to suppress thyroid hormone that's also going to be beneficial so in all of these patients you should put them on anti-thyroid medications the different types of medications they can vary and that kind of can have a little bit of a variability and depending upon the patient population one is called PTU which is called propy uracil and the other one is called methol the concept behind these is that they're going to help to suppress T3 and T4 formation there is a little bit more extensive effect from one of these but I'll talk about that a little bit later but again I want to suppress the thyroid hormone production so they don't exhibit these complications from a hyperthyroid State often times you start on off in a patient who you give them either PTU or mosol on top of that if they have Tremors if they have anxiety irritability and tardia you give them propanolol usually in these patients which one would you pick between between PTU and methol it really depends so it kind of goes into the place of like okay which one's good for pregnancy and which one's not good for pregnancy mosol may have an effect and can cause teratogenic effects effects especially in the first trimester so mimisol may not be the drug of choice especially if they're pregnant and in their first trimester if that is the case PTU may be the preferred option so start them with propanalol start them on PTU or mosol if they don't respond to that in other words they're not improving with their symptoms of hyperthyroidism then I would move on to the next thing which is I need to ablate and Destroy some of these unfortunate hyperactive or hyperfunctioning thyroid follicles so what I'll do with them I I'll give them something called um iodine 131 it's a radioactive iodine it gets taken up into these thyroid follicle cells and what it does is it literally will destroy the thyroid follicles and stop them from producing large amounts of thyroid hormone however in high enough doses it can potentially put a patient into a hypothyroid state so that's something to consider all right the next thing to remember is if a patient comes in again they're not responding to atds in other words antithyroid drugs they're not improving with propanolol for their sympathetic nervous systems symptoms you tried the radioactive iodine and they're still having hyperthyroid like features then you probably should just go ahead and remove the thyroid gland so this is where do something called a thyroidectomy there's different ways you could potentially if they have like a toxic adenoma or toxic multinodular Gorder you could just do like a lobectomy you could do even more of a lobectomy and extend it over into the other part of the thyroid gland and or you can completely just cut this puppy out and so these are potential options if a patient has failed the response to PT or mosol plus propanolol and they've had maybe a couple treatments of radioactive iodine oblation another reason if their gour is so large that it's actually causing significant problems we go to the next one patient has now thyroid storm they're coming in hypmic they're coming in tartic they're coming in in um high output failure they're also coming in with seizures or um hyperactive and sephy opathy and in these particular scenarios you suspect that they have thyroid storm maybe they have an infection maybe they have some type of recent surgical procedure maybe they forgot to take their medications whatever it may be they're now in a thyroid storm State you got to First treat a couple different things you can treat the hypothermia it's best to maybe just give them some cold Ivy fluids you can potentially consider putting like a what's called a a cooling blanket on them or maybe even doing something like an Arctic Sun uh but generally this is not as needed to be as aggressive because you just got to kind of drop down the thyroid hormone but this can be considered in severe severe States the first thing I want to do is in a patient who has thyroid storm they're going to have tacac cardia they're probably going to be in like a refractory apib they're going to be super tacac cardic prop panol La is usually preferred in that scenario the other thing I do is I need to suppress thyroid hormone immediately and the preferred agent in thyroid storm is PTU it's just been shown to be a little bit more effective and I'll explain why in a second and the other thing that you're going to do is you're going to give them PTU first and then you're going to give them potassium iodide like an hour later now what you'll do is patient comes in they have thyroid storm give them propenol to suppress the tacac cardia and some of the trior trimers then give them PTU as well an hour afterwards the whole reason behind this is that when you give them PTU you're basically going to shut the thyroid gland down and say hey you're not going to be able to make any thyroid hormone then what you're going to do is you're going to give them the Lugal solution which is basically potassium iodide and when you do that it's going to then act via What's called the wolf chai cough effect which is going to suppr press TPO and then basically not allow it for you to convert thyroid globulin into thyroid hormone so it get provides an extra little shutdown of being able to produce thyroid hormone which is very interesting then after you've given them PTU propanolol for the tacac cardia Lugal to shut down the thyroid gland and make no more thyroid hormone the next thing that you can do is you want to then also add another little extra step because yes I want to be able to shut down T3 and T4 formation but you have to remember T4 is going to be 90% of what your thyroid gland produces when it gets to the peripheral tissues in order for it to exert its physiological effect it needs to get converted from T4 to T3 to produce its physiological effect so if I shut down T3 and T4 formation with PTU and Lugal solution and then on top of that I go ahead and I give them another drug like hydrocortisone you know what hydrocortisone does it's going to suppress T4 to T3 conversion another drug that does this just as an add-on is propanol LA and PTU this is why PTU has been shown to be more effective in patients who have thyroid storm methol can't inhibit T4 to T3 conversion so if I give these drugs they're going to suppress T4 to T3 and I'm going to reduce the physiological effect of any of the thyroid hormone that's getting out so you see how this happens again suppress the attach of cardio with propanolol shut down the thyroid gland from making T3 and T4 first PTU methol is not as effective then give them Lugal solution after you give them the PTU because PTU will shut down the thyroid hormone production and then the Lugal solution will then allow for you not to convert any of the thyroid globulin to thyroid hormone any thyroid hormone that's being released out though unfortunately can be suppressed from being converted into the active form by Hydrocortisone and then you also get the added benefit that you've already started these patients on propanalol and PTU that's also going to inhibit that conversion your cutting down multiple Pathways for thyroid hormone and that's the benefit of using this in thyroid storm again important to remember we already kind of talked about this mosol less effective in thyroid storm PTU has more effect in thyroid storm the reason why is this suppresses T3 and T4 formation and it also inhibits T4 to T3 conversion again this one don't give it in pregnancy such as in the first trimester because it's teratogenic this one is safe to give during pregnancy they both can have a little bit of an effect on your lfts and that's important to monitor but we'll talk about that more in Pharmacology all right we talked about hyperthyroidism I know that was a lot I hope it made sense I hope that you guys did enjoy it and as always until next [Music] [Music] time