Get more comfortable assessing patients for this common disorder, determining whether treatment is appropriate and initiating levothyroxine therapy. Endocrinologist Chienying Liu, MD, illuminates such issues as when to treat subclinical hypothyroidism, where to set TSH targets and how to establish hormone replacement regimens that meet individual needs.
So the topic today is hypothyroidism and I want to just share with you the prescription here. Leaving the rocks and prescription this with data dating back, you know a couple of years ago and you can see the number of prescriptions over time and you can look at the ear here. Okay, It's ranked as number three, Top three prescription in 2000 and 22 in 24,016, sorry, 2000 and 12 and 2016. Number one prescription in comparison. You can see other commonly prescribed medications like Singapore ill, atorvastatin, Metformin. They're not as commonly prescribed as liberal fire accent. So you can see it's very commonly prescribed and and I'm hoping that I can help uh that so you feel comfortable prescribing these medications and managing patients with hypothyroidism. Um all right. So um let's start out with the first case and please, you know, definitely do the chat and I can stop or you know, somebody needs to just monitor the chat a little bit. So start out with this 69 year old healthy active man with abnormal thyroid function tasks. Um And I saw him um in 2000 and 17 back then we had a little bit better capacity. Um and so he's past medical history is significant for BPH and some anxiety, mild hypertension guard and he said to me, he, you know have this type a personality uh family history, a sister in her sixties sixties also being monitored for slightly elevated TSH. Um And he only was taking America's soul uh and on exam review of system. Um it's sort of a non specific right nails a little bit brittle, a bit colder. Last feeling a little bit colder, but then it was the year that was really cold. Um And booker should perhaps slightly higher constipation all his life. And baseline anxiety, undergoing therapy at that time. And I'm exam, blood pressure's a little high. But then he said my blood pressure always was good at home. So maybe a little white coat hypertension, lean healthy. One of the healthier persons I've ever seen in my practice theory exam. Okay, the glen was not enlarged but slightly firm, no palpable nodules. So let me show you the TF TSH TSH mildly elevated 7.3. You can see the normal range here. Free T. Four. Very normal and free T. Three was also very so I think everybody would recognize this is a case of subclinical hypothyroidism. Um So the question from him uh is should I be treated, you know you have this patient sitting in front in front of you in your practice. Uh And and they ask you um should I be treated? One thing one pearl that I want to show you is if TSH is abnormal, please repeat it. And the data came from more than 10 years ago. Um And and so this was published in 2000 and seven from archives of Internal medicine, they have close to half million patients between 2000 and two and 2005, 2006. So they took, you know the T. F. T. S. And and follow these patients. And so this graph shows the second TSH results. So when you have a TSH Uh that was in the normal range in the beginning, 98% will stay normal. Makes sense. Right? When you have a. T. I said that is pretty elevated. Greater than 10 on the first test, 28 actually had normal test. Okay, so it's very important to repeat that. But when you have TSH just between you know, slightly elevated to the more significant elevation of 10, 62% more patients had normal TSH on repeat. So it's very important is you know, you will see some of our feedback to you is um is to repeat T. F. T. S. You know, especially in those patients who are really not very symptomatic. Um And so this is the result I saw him september you know, and then we decided to repeat. Um and this sort of results very similar. Right? Um Now I want to show you then we dug a little bit further and found all the T. F. T. S. Those are the TFT session. He has had, you know, a normal test was 2000 and two and then um and then the TSH was checked in 2010, it was molly elevated, You know close to 10 but then you can see on repeat they're not too bad right there not too bad. Um and and this is just you know, just tells you those mild TFT elevation can stay stable for years and you know looking at listening to his symptoms, I didn't think he was that symptomatic and I hope that you agree with me. Um But you know there's obviously different threshold in terms of treatment, right? Um And you know with this test some people may want to do a tpu antibodies that help them strategize strategize you know uh treatment options or treatment. Um uh In terms of management and some people may want to order lipid profiles right? Um uh If the person has significant hyper lipid e mia you could potentially consider treating uh the level to the normal range and I'm gonna show you a little bit on the lipid data. Uh There's just a lot of mixed results. Alright so I want to briefly review subclinical hypothyroidism because it's pretty common. Okay? Um And we know about the definition. TSH is above the upper limit of normal with normal T. Four and T. Three. Uh And it is the most common. The most common cause of subclinical hypothyroidism is alternating parad itis, you could potentially get a T. P. O. To come from that. Uh You know clinically it's probably not necessary. The prevalence. Again you can see the high 40 10%. Uh And the prevalence increases with age more common in women in aydin sufficiency. This is not the type of year. I'd insufficiency. Um And the rate of progression to overt hypothyroidism have It? has been studied their different studies on on the radio progression welcomes survey. You know, one of the older studies back in 1995. Um And this is applying to women. I couldn't find any data in men. Okay, so if you have elevated TSH meaning above normal, say five or six, the progression to overt hypothyroidism meaning elevated TSH and low T. Four and T. Three. The progression uh was um 2.6% per year. Uh And if you only have positive TP open normal TSH the progression was 2%. But if you have both of them meaning elevated is in the positive T. P. O. Then progression was 4.3. It's not fast. Right? So so you know, those patients definitely could be monitored. Um Now this is a more recent study for older patients older than 55 year old. TSH higher than 10 was found to be a predictor of progression to overt hypothyroidism. And you know, this is we do use this threshold for treatment. Um So this slide just to show you that not all elevated TSH represents mild thyroid failure. There can be petrified artists not very common at all. Um And obesity can also lead to um mildly elevated TSH in like four or five range recovering from thyroid itis or nonsteroidal illnesses medications, medications like amiodarone lithium and then very, very rare TSH resistance in that situation. TSH will be, you know, normal or mildly elevated and free T four and T three will be elevated. Uh if there's no, you know, uh antibody interference or say biotech, right? Um aging, aging. Um It's important consideration because TSH does train up with agent. Um It's an it's a adaptation to aging. Okay. And at least for those people who actually live to that, you know, old age. And and so we were able to actually get the data, their TSH is actually higher than younger population. Alright, So let's take a look at the TSH range. Um this is from uh data from any hens. Um and the you can see the very nice bell shaped curve, right? So the bars represent different races. And you can see the TSH range, normal range of 0.45 to 4.12 essentially is 2.5 to 97 0.5 percentile of the T. F. Uh of the TSH in this population. The disease free population. Okay. Um And this is uh the TSH distribution by age. Uh This is this curve here is younger patient 20 to 29. As you get into the middle age, it sort of starts shifting towards the right, the higher TSH level and this is the older age they get definitely shifts towards the the right, the higher TSH levels. Right? So, so TSH of seven, maybe normal, completely normal for those older folks. All right. Um you know, some of you may be aware of the studies, but this is uh you know, I mentioned the study to the, you know, the fellows and students and also even my patient. Um and so this is one of the largest study, the largest study, I would say. Um and it's randomized control study. They did it really, really well. Um um and I was I was summarized on on this table here. Uh, the placebo group. Again, this is older population, right, 70. Uh ming age 70 for similar with the treatment group. Um and then the TSH levels were pretty similar and they look at thyroid symptoms and tiredness scores and other parameters. Um and you can see, you know, all of them have elevated TSH at the start as the trial continue. It's interesting that they go down a little bit right, but with treatment it went down significantly to three something range. And they essentially, there's a lot of outcomes here, essentially no difference, no difference in hypothyroidism symptoms score, no difference entire nous score. Um and then they also look at um blood pressure. Um they found no difference at all, unfortunately, um, they did not have enough power for cardiovascular outcomes. Alright, so I will just summarize some of the smaller RCT studies of subclinical hypothyroidism. Um there, you know, the age of the person, the age of participants vary from 30 to 70. The TSH range? Very very from 4.1 to 11. The sample size from 14 220 duration 3 to 12 months. And most studies uh were really negative. They looked at different outcomes, blood pressure cholesterol B. M. I. And wait. Um This is the study that frequently quoted to my patient's quality of life cognition. Um And again, most studies showed no differences at all except for when the TSH level will hire. Um In one study was close to 10 or higher than 10 fatigue approved improved in one study when the TSS was treated all the way down to 0.5, close to like sort of mildly suppress range. And in one study um the improvement was observed in T. P. O. Positive patients. The lipid again um Mixed mixed results. Okay. Most studied the show lower triglyceride level but the p value was not significant. And so Could it be simple size for sure. Right. Because the size here you can see varying from 14, But what what could be the clinical significance if just maybe five or 10 point reduction in the tricolors. Right? So um It's unclear but you certainly can give it a try if they, you know, have significant hyper epidemiology and their TSS is close to 10. You know? Alright. So I just want to briefly take you through the slides on the bp the sort of clinical trials uh you know, how many the duration of the studies and the age of the participants um you know, 35 for the fifties and sixties and their TSH baselines and how low they treated to the target. TSH again that's treated down to 0.5. Um They found no difference in blood pressure. Okay. So don't don't treat subclinical hypothyroidism because of blood pressure. Um and the same with, you know, our New England General Medicine study with 300 people in this study. The treatment effects on quality of life. Um this I briefly mentioned again the age of the study groups uh in the TSS level, this was 12.8. Okay. And they found a difference in terms of thyroid symptoms scores. Okay. But this is unusual because this is higher TSH level than we typically seeing our patients. And for those patients with you know, TSH above 10 most of us will treat right? Um And then the rest really not very um no difference at all except for this tiredness score got Better. The TSS was treated down to 0.5. But then when you look at other parameters and questionnaires, they found no difference at all. Right. Yeah. So let's see. And then this one is the T. P. O. Population. Okay. They um the conclusion was um those patients treated, this is not randomized controlled trials. This is just a prospective study. They feel better. Again, not the best study. Um But regardless the patients feel better. Um. Alright, so cognition. Um The again if you look at cognition, this is the TSH 12. Um And they found memory composite score got a little bit better, but the rest did not show any improvement. So in your older patients uh if they have memory problems and their TSH was you know, mildly elevated, you know, the treatment is probably not going to make a huge difference. Um And this is the M. I. And wait. I. I found this helpful because many of the patients I see thyroid cancer patients a lot and essentially all of them are hypothyroidism. They have thyroidectomy and this is what I I counsel them. Um You know, all the studies um different durations here. Uh And uh you know, of course the numbers are not the largest members. They found no difference. 8 to 4 B. M. I. Change minus 0.3. This is treated very very normal. No difference in being my Again,- one. Uh No really no difference. Right? In fact the B. M. I. Is actually a little higher with this one. Uh This is treated all the way down to 0.5. No different. Right? Um So really no effect on B. M. I. And wait. Um Alright, so um again, in terms of cardiovascular outcomes, this the power uh in different studies just has not been big enough to address the cardiovascular outcomes. Alright, so to summarize I think TSH above 10. Um it is recommended to treat just because they're more likely symptomatic and and they they are more likely to develop over hypothyroidism and also their data to back this subject because there are several large perspective epidemiological studies suggested that um with TSH greater than 10 when they followed longer to originally those patients uh can have increased heart failure, increased cardiovascular events and mortality uh and probably also increased stroke and mortality in younger patients. Um in one study Um what about less than 10? Uh there are a lot of uncertainties and mixed results. Um the most controversial is really 7 to 9.9. Uh there's tons of results. Especially perspective um longitudinal studies found molly elevated TSH from five up to 6.9. Absolutely, absolutely no effect on cardiovascular outcomes. Uh None so ever at all. But the 7 to 9.9 it's a little bit controversial. Uh maybe borderline significance, but not greatly significant. A lot of mixed data. Um uh and uh you know, and then we have also data support no, you know, no adverse outcomes. Um So this is a consideration especially for younger patients. Okay. Alright, so let's see, I'm going to just move on instead of going through this um studies in detail. Um Alright. So I just want to come to the bottom line of recommendations from consensus groups. Right. Um We have american groups, the american Bar Association and ace and the european theater association This is they use greater than or equal to 10. And then in us we use squared and 10. You know, just You know, I just want to mention that slight difference. Um as for the A's if you have greater than 10. Yes for the US definitely. Okay and for Europe, Yes younger patients definitely. They're a little bit more generous with older patients. Uh Yes. If they have clear symptoms and if their cardiovascular events are high, right? Ah And then for uh TSH level less than 10. Um you want to consider for us, you want to consider, you know, symptoms TPS status, you know, cardiovascular heart failure status and risk factors that we talked about. Um And then for europe, for younger patients, yeah, consider trial. And for other patients you could definitely observe and monitor. So that's you know, summarize this table essentially summarizes the consensus guidelines from different professional groups. All right. So um what about the target of TSH when you treat? Um There are two different opinions here. Um in the U. S. 80 american thyroid association 46 is a reasonable target for people older than 70 to 80. As you saw that, you know, TSH trends up with aging, right? Especially those healthy patients will live to be that age. Um And european society. They say anything normal is fine. 1.5 I you know, um I think either way is fine. You do want to be able to cautious when you you want to make sure you know, your tears. It doesn't get too well. Okay. Alright. So in summary, half of this clinical case of subclinical hypothyroidism when you have abnormal T. F. T. S. You know, you want to repeat it. Um And uh you know, the considerations for artifacts. Uh You could consider checking the T. P. O. To help you strategize management of this patient uh and you want to look at the symptoms um and look at their cardiovascular risk factors and look at their age. Okay. Um So it's very important um The younger the patient is more likely you want to treat. Um This slide just reminds me that all this out. The guidelines do not recommend women desired pregnancy. So it's um I won't go into detail. This is a completely separate topic, but this is just remind you um It's very different um population here. All right, So um I see a lot of T. P. O. And T. T. And T. Party being done. Um And I I I think um it's reasonable. Um But um I don't always measure uh in my patients because I'm going to monitor those TFT uh that that TSS that's going to be mildly elevated. Um T. P. O. We know T. P. O. Um is a part of the factor that is involved in sort of in in terms of risk for progression. But I'm going to monitor them anyway. Right? Um So I don't always check them but it's it's fine. I mean people like to do that but I just want to make sure that um that you also understand that T. P. O. Is a market for autoimmune disease not just fashion models. Um And you really cannot distinguish grave disease from other type of autoimmune disease such as hashimoto's. Um It can be present in 74% of rape disease patients. Um In this study I found 99% passion motives will have positive teepee. Oh I must say um in my practice um I don't always the T. P. O. May not always be positive especially um when I have ultrasound readily available or thorough exam. You know when the exam is abnormal. Um So so this may be I think this is a little bit higher than what I see in my practice. Um And I will get you your question. Um uh And then we have enhanced study right? Look at how common it is. Um And so that's why I you know when T. P. O. Is positive people get so nervous. Do I have autoimmune thyroid disease? Do have Hashimoto's but just look at that this is a disease free population 11% 1 in 10. Um And then you know I got my antibody you know um And then for the for the total population it's even more um society more common. Um and in that in the hole in the enhanced data over hypothyroidism is only 0.6% for subclinical. And the reason I want to use that subclinical as an example is just because it's so common. 4.3% of. Um And then we see this a lot. I mean you know um T. P. O. Positive but completely normal TNT again T. P. O. Doesn't mean the person has hashimoto's is a mark of autoimmune autoimmune disease. Okay. Um so then um this is really the practical point of view as going to initiate legal action right? We talked about the political hypothyroidism right? So I'm not going to repeat that. Um And then primary hypothyroidism Obviously when you have L. V. T. Is such a lovely T. Four And they're about 0.4% of the total population. And secondary hypothyroidism. Um It's not common. We see that in our clinic because you know we're the referral center and we see pituitary disorders. We see um you know big Petri tremors. Um And uh when you measure T. F. T. S. The TSH will be um variable but inappropriate for a very low T. Form. It could be one you 0.5. Um I don't know why it's secrets if it is you know it probably still have some secretion but it's definitely inappropriate. Okay um Usually seeing patients with hypothalamic pituitary disease um And frequently has other associated formal deficiencies by pituitary deficiencies. Um And this is um we like to see them now. They're definitely potential um sort of laboratory interferences for example uh for certain essays, biotech can affect the TSH so it's very important um that you tell your patients not knowing what kind of labs they go to. I usually tell my patients um if they're going to do blood tests they should hold off on biotin for at least 35 days. Um UCSF. Um I know my you know my laboratory assays what assets we use. We actually our labs actually do not our assets actually are not affected by biotech so you know we can trust our essays but again for your practice, you know depending on where they go, you have to know your essays. Um And so if you have low TSH, one consideration is it could be biotin. Okay. But but again um it would be nice to repeat it because they could be also in transition recovering from right. They get um you know they will get better depending on clinical presentation. Um So it's it's good to repeat um Alright so let's see. Okay so leave all these rocks and I think you guys should be well versed on this. If not feel free to stop me and I can go over in more details. We definitely have generics, right? Just leave both our oxen and then you have all different brand names of the century live axle unit three. I love a thyroid comparison. Um and the to be mind that the active ingredient is the same, the same amino acid structure your receptors in the thyroid hormone receptor sees the same thing. Um even though it's synthetic. Um I don't know why some of our patients are so um wanting the quote unquote natural hormones. So so the difference is obviously it's you know, most of these are in pills, right? So you have fillers just like Tylenol have fillers. Um you know, I be prevented fillers, You know they have fillers in there. Harrison is the most pure really doesn't have much filler. Um uh so uh you probably know that they're color coded. Uh they're different. Uh dozing red doses here from 25 50 strange dose and rice 75 88 then 112 and all this, they have 300 Pills as Well. Tara's, it has a small doses 13 Okay. Um allergies very rare. Just think of it. It's the same amino acid structure as our salary claims, you know, as a native hormone made by our thyroid gland. Um but if this allergy usually rash and itching is because of the die, Okay, they're different because they are color coded, right? And very rarely fillers of some patients I know are super super sensitive. They cannot eat corn, they cannot have anything. And so you could consider terraces. Okay. Um a trick is 15 micrograms is white pill dependent. It doesn't matter which kind of brains or manufacturers has no dye and so you know, the person uh is found to be allergic to certain die, you could switch to 50 and they would tell you, you know, I have patients who was on 25 3 tablets. Um You know, no problems at all. We thought we simplify to 75 and she's developed So then we know that she was alerted to you know, the guy associated with 75 um and so we switched her back to 25 hours a day. Um Again, Tarzan very inner inactive ingredients. Um So if there's any allergies issues then you can give Tarzan. Alright, so those are the ingredients inactive ingredients. I you know, some of the physicians um I found this very helpful um and this can be available to you if you wanted, but it definitely is available on the PDR. Um so you can see some of them. Um Some patients have lactose intolerance, I don't know why they put a lactose in there, but sensory has lactose. Um and um and then you have, you know, you know, so we also have lactose. Um The boxes actually doesn't, so some of the components you can look up um let's see um I think this is democratic. Sorry about that. Okay, so the natural ingredients in desiccated preparations armor. Okay, so those are, you get very similar just like you know the synthetic right? You can see very similar failures here. Um speed. Alright so this is uh this slide shows you the ingredients in T. Three active ingredients in T. Three side amount. Uh And then um the generic form of serum LDL Saarinen. Mhm And then there's different manufacturers here. Um Alright so little forks in um we talked about half life is um seven days. So it's it's it's really the best form of treatment because it's long half life. You don't have to take it multiple times. Um The absorption takes place in the small intestine 45%. And um then the rest you can see that here. So if people have um you know sort of bypass surgery or having um got issues, you want to consider male absorption for sure. And those patients will frequently require a larger dose um And gastric um asset is actually very important for absorption. So it's best taken fasting. You we have patients who TF TF very widely and you talk to them, they just they take it anytime and and so it's important to interrupt them to take it correctly. Um And uh I think yeah so this is if you work in the hospital you want to convert the oral to ivy it's about 70-80%. Um Alright so the absorption uh food and I you know this is the first thing that I always want to make sure when people have questions about why are my T. F. T. S. You know varying from 2 to 4 to one. You know this is something that you want to discuss with your patients. Are they doing it correctly? The best absorption is really 60 minutes before breakfast. Um And then um and then you can take it at bedtime. You want to do it really at least three or four hours um after last meal. And then and then the third best absorption 30 minutes before breakfast and then horses obviously with breakfast. Okay. Uh And then it is being demonstrated that the most consistent TSH levels are achieved as a fasting state. And the coffee there's something about coffee. So I always counsel them. Don't drink your coffee, just have water. Okay? Um And because you know there's something about coffee that they can sequester T. Four in the small intestine the fiber very important soy products as well. Um So those sort of things that you wanna tell your patients to stay away from level three Roxanne. Uh The coffee an hour will be fine. The fiber and soy products probably a couple of hours I would say four hours. Um And this is I want to show you this is the sensory insert um that you know those um Uh supplements uh really should be administered um four hours after the orthodoxy same thing here. Um And then you can see many of your patients probably take supplements and they have iron deficiency and so that those you know calcium again. Multivitamin that has calcium, iron I would tell them you know take it at dinner time really. Make sure the PP. I. Is frequently people frequently take T. P. I usually have them take it. I have to leave a fire oxen because it's you know H two blocker and acid blocker. Right? So you wanna give them thyroid fasting and then they can take their P. B. I. 30 minutes or six minutes later. Um See anything else? I'll pause here a little bit just for you to look through this. Um Right um So if you have patients who says I am following your guidelines I'm following the rules I'm taking it away it's supposed to be and they are not missing the dose. Oh by the way if they do miss a dose because half life is so long I tell them take to the next day because half life is so long, they're gonna feel fine by not taking it for a couple of days, right? Uh So that if they go to Tahoe for a trip and they forget their liberal parents they're going to be fine right? Because half life is seven days. And so I tell them when they come back they can take those three missed doses um by taking essentially extra half of the next several days to make up the missed three doses. Okay so that's one trick that we can tell my patients now. So if they follow the rules and TSH is not coming down. Right so you want to consider malabsorption or any diseases that can affect absorption diseases affect gastric acid production, H pylori or autoimmune traffic gastritis. So those are the antibodies that you want to check. Okay patients with hashimoto's that they can have other automatic diseases. Right? So um those are considerations and what do you do if you do find them? Um you sort of you just keep on going on the dose. Um You don't have any options other than you know um going on dose and then obviously replace acid I think those are the patients um that you have to refer to a gastroenterologist if it is really severe. Um and then diseases affecting the small intestine because we both thought it can be absorbed in the small intestine. Right Celia disease. Okay consider doing checking facility app um and the and then also the G. I. Surgery, The bypass surgery. Okay. Um although the data are mixed uh lactose intolerance surprisingly can also affect absorption as well. And then um intestinal uh to your um intestinal infection here that can also affect the absorption. Um Let's see um and then you guys know about this replacement. Um the formula right? Full replacement if the person is um completely hypo thyroid um for example the person has thyroidectomy you put them on leave Orthodox and 1.6. My principles. No question at all. And if their TSH say for example is 30 and they're free T four is like six, like not measurable um Normal being 82 12 9 essay. So you know, pretty profound hypothyroidism. Then you use this For older patients because they don't have a bigger muscle mass. Um you probably want to use, you probably wanted to start out with 1.2, you know, just be cautious. Um and for people for patients who supported hypothyroidism um you don't want to give them a photo, you want to start slow depending on their um B. M. I. If they're like really really tiny like um you know 40 kicks um you know um older The woman then you probably want to start very very slow, right? Even 2.5 depending on their levels as well. In terms of treatment goal, this is the 88 guidelines. Um 46 um in Europe, you know, once you fight is okay because half life is seven days, so you wanna check a tear and stage about 46 weeks not infrequent ology 6-8 weeks because sometimes it does take a little longer for them to um stabilized. Um And uh yeah so I I think you probably know this stuff already right? Um in terms of TSS goal for younger patients, I think they can handle the lower TSH, so I will have no reservation to give them um a little bit more to keep that t is actually a little bit lower. Um as long as that she said, she's not surprised. Um So what do you do if people do not feel well? We see that a lot right. In my practice I see that a lot because I have very cancer patients they all have to reject. Uh They do need to I do keep them mildly suppressed so they're already mildly suppressed. Um And so this is a situation um that um in your practice you could one consideration is, sorry there's a type of year one considerations you could give them more tea more liberal direction to keep the lower half, but there's really no data to support this, but at least it demonstrates that you're working with them and it could be completely procedural because what's the next step is we're going to see a specialist if you don't work with them and then when they get to us uh we're going to say we don't have data, but if you want to try we could um or they're going to see somebody else where they will start, you know, armor thyroid or T three um that really have no evidence. Let's see. Um Again we we we see that, right. I mean this is really a huge drive for speciality consultation, right? Um Unfortunately we don't have the solutions. We don't um you know, this is what we also, you know, we have to discuss those patients. Are they going to perimenopause you look at perimenopause they have half lashes. They have fatigue. They have astrology to they have anxiety. I mean all the symptoms are shown on specific all the symptoms can mimic various symptoms right? Um And so you want to you know consider those and sleep apnea is very very important. Do they do they are they tired because they still have sleep apnea. Do they wake up tired? And I actually have discovered diagnosis back in um you know like a handful of my patients because I just said I cannot explain your TSH and you know their body happiness is they have you know central obesity and you look down their throat, there's really little space for them to breathe right when they write down. So consider that. Um And the usual general internal internal medicine workout copy um you know most of patients taking leave of their accent do have hashimoto's um And so they can have other alternative diseases. So you want to look it up um and then work it out okay. Um And then concurrent adrenal insufficiency will be really really really rare. Although we see them just because you were a referral center. So if you have any uh sort of um suspicion that this could be a dream sufficiency especially if sodium is low potassium is high. Then you know you want to do a formal testing you can get in cortisol. You can do a C. T. S. Stimulation test. Um And then again there's no data to support that. You could consider those increase um To lower TSH the second half than normal. Um So in this study really they have found no difference between higher TSH and lower TSH. Um And this was published in 2006 And more recent studies they found no difference in terms of mood quality of life companies In terms of three different TSS groups. 0.3422 point 52.5 to 5.65 point 6 to 12. No difference at all. Okay. Um So when you have a well conducted studies you you don't play any differences. Um Alright so let's talk about T. Three. I think some of your patients probably um are on T. Three already or asking for T. Three. It is the active hormone. Uh And and only 20% is from the thyroid, 80%. Majority of it is really from the peripheral conversion of T. 40 T. Three. Uh And the ratio of T. Four and T. Three. Security by thyroid is 13 to 1. If you look at desiccated thyroid extract it's 41. So as the endocrinologist treating I'm replacing so I want to do this ratio so I don't know what I'm doing when I do this for 21 ratio what am I treating? Right. Um Also if you remember in the older days um and even nowadays some psychiatrists you see three to treat depression. Um And so that is always in the back of my mind. What am I treating when I'm giving a lot more T. Three than it's necessary than physiology with you know would allow us to say this is a replacement. Uh In terms of potency just for information is one micrograms of T. Three style three or four micrograms of T. Four half life is only one day. So you have to do it you know that a lot of us will do twice a day but even that you can get a really peak and trump. Um And so they're having um sort of studies looking into um long acting T. Three. I don't know where that is um yet but there's definitely momentum and studying the background maybe in a few years or um you know it could be a reality for um long acting T. Three and we can definitely do that. Um Because you know as long as you you do the replacement strategy rather than this um You know sort of excessive T. three which can potentially cause problems. Um So just one slide on T. Three. Uh And I think some of you want to know about desiccated thyroid extract um there from you know animal right? Um And they do um they ran out of the stock. You probably heard that some patients maybe last year sometime. I cannot remember when they couldn't find a more thyroid. Um um and there are different brand names here. They're all the same. Okay, they're all the same. And um this is just to give you um Sort of an idea of the breakdown of t. here. Um And if you want to convert, um if you actually are able to convince your patients to convert to be converted back to T. four, here's a conversion table here. Uh This is actually from USP drug information, mm hmm.