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, levothyroxine prescription. This was data, uh, 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 year here, OK? It's ranked as number 3, top three prescription in 2022 and 2020 2016, 2012 and 2016. Number one prescription in comparison you can see other commonly prescribed medications lisinopril, atorvastatin, metformin. They are not as commonly prescribed as levothyroxine. So you can see, uh, it's very commonly prescribed and, and I, I, I'm hoping that I can help, uh, that so you feel comfortable prescribing, uh, this medications and managing, uh, patients with hypothyroidism. Um, all right, so, um, let's start out with the first case and, uh, please, uh, you know, definitely, uh, 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, uh, 69 year old healthy active man, uh, with abnormal thyroid function test, um, and I saw him, um, in 2017. Back then we had a little bit better capacity, um, and So he's, uh, past medical history is significant for BPH and some anxiety, mild hypertension, GERD, and he said to me, he, you know, had this type A personality, uh, family history, a sister in her 60s also being monitored for slightly elevated TSH, um, and he only was taking omeprazole, uh, and on exam, on review of system. Um, it's sort of non-specific, right? Nails a little bit brittle, a bit colder, last, a feeling a little bit colder, but then it was the ear that was really cold, um, and blood pressure perhaps slightly higher, constipation all his life, and baseline anxiety, uh, undergoing therapy at that time. And on exam blood pressure a little bit 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 healthiest persons I ever seen, uh, in my practice thyroid exam. OK, the gland was not enlarged but slightly firm, no palpable nodules. So let me show you the TFT, TSH mildly elevated 7.3. You can see the normal range here, free T4 very normal and free T3, uh, was also very normal. So I think everybody will 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, 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 2007, uh, from Archives of Internal Medicine. They have Close to half a million patients between 2002 and 2005, uh, 2006, so they took, you know, the TFTs and, and followed these patients. And so this graph shows the second TSH result. 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 TSH that is pretty elevated, greater than 10% on the first test, 20%. 8 actually had normal tests. OK, so it's very important to repeat that. But when you have TSH just between, you know, no, uh, slightly elevated to the more significant elevation of 10, 62% more patients have normal TSH on repeat. So it's very important is, you know, you will see, uh, some of our feedback to you is, um, uh, is to repeat TFTs, you know, especially if, uh, in those patients who are really not very symptomatic. Um, and so this is the result I saw him in September, you know, and then, uh, we decided to repeat, um, and these are the results very similar, right? Um, now I, I wanna show you, then we dug a little bit further and found all the TFTs. Those are the TFTs that, uh, he has had, you know, um, a normal test was 2002, and then, um, and then the TSH was checked in 2010. It was mildly elevated, well, you know, close to 10, but then you can see on repeat they're not too bad, right? They're 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 are obviously different threshold in terms of treatment, right, um, and you know with this test some people may want to do a TPO antibodies that help them strate uh strategize, you know, uh, treatment options or. um, uh, in terms of management and some people may want to order lipid profiles, right, um, uh, if, if the person has significant hyperlipidemia, 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. Right, so I want to briefly, uh, review subclinical hypothyroidism because, um, it's pretty common, OK, um, and we know about the definition TSH is above the upper limit of normal with normal T4 and T3, uh, and it is the most common, the most common cause of, uh, subclinical hypothyroidism is autoimmune thyroiditis. Uh, you could potentially get a TPO to come from that, that, uh, You know, clinically it's probably not necessary. Uh, the prevalence again you can see it's pretty high, 4 to 10%, uh, and, uh, the prevalence increases with age, uh, more common in women in iodine sufficiency. This is not a type of here, iodine sufficiency, um, and, uh, the rate of progression to over hypothyroidism have, has been studied. There are different studies on, on the rate of progression. We can survey, you know, one of the older studies, uh, back in 1995, um. Uh, and this is applying to women. I couldn't find any data in men. OK. So if you have elevated TSH, meaning above normal, say 5 or 6, the progression to overt hypothyroidism, meaning elevated TSH and low T4 and T3, uh, the progression, uh, was, um, 2.6% per year. Uh, and if you only have positive TPO but normal TSH, the progression was 2%. But if you have both of them, meaning elevated TS and a positive TPO, then progression was 4.3. It's not fast, right? So, so, uh, you know, those patients definitely could be monitored. Uh, now this is a more recent study for older patients older than 55 year old. Uh, TSH higher than 10, uh, was found to be a predictor of progression to overt hypothyroidism, and you know this is we do use this, uh, threshold for treatment. Um, so, This slide just to show you that not all elevated TSH represents uh mild thyroid failure. There can be petrified antibodies, not very common at all, um, and obesity can also lead to, um, mildly elevated TSH in like 4 or 5 range, recovering from thyroiditis or non-thyroidal illnesses, uh, medications or medications like amiodarone, lithium, and then very, very rare TSH resistance in that situation. TSH will be, you know, normal or mildly elevated. FT1T3 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 TSA does train up with aging um it's an it is an adaptation to aging, OK, and at least for those people who actually live to that, you know, old age and, and so we were able to actually uh 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 enhance, um, and the, you can see the very nice, uh, bell-shaped curve, right? So the bars represent different races and you can see that TSH range, normal range is 0.45 to 4.12 essentially is 2.5 to 97.5 percentile of the TF uh uh. Of the TSH in this population, the disease-re population, OK, um, and this is the, uh, the TSH distribution by age. You, 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 def definitely shift towards the um The right, the higher TSH levels, right? So, so TSH of 7 may be normal, completely normal for those um older uh folks. All right, um, you, you, some of you may be aware of the studies, but this is, uh, uh, you know, I mentioned the study to the, you know, the fellows, the students, and also even my patients. Um, and so this is one of the largest study, 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 summarize on, on this table here, uh, the placebo group. Again, this is older population, right? 70, uh, Uh, mean age 74, similar with the treatment group, um, and then the TSH levels were pretty similar and they look at, uh, 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 it did go down a little bit, right, uh, but with Treatment, it went down significantly um to 3 something range and they essentially there's a lot of outcomes here um essentially no difference, no difference in hypothyroid symptom score, no uh difference in tiredness score um and this 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, I will just, uh, summarize some of the smaller, uh, RCT studies, uh, of subclinical hypothyroidism, um, there, you know, the age, the The age of participants vary from 30 to 70. The TSH range varies, vary from 4.1 to 11. The sample size from 14 to 120 and duration 3 to 12 months. And most studies, uh, were really negative. They looked at different outcomes, blood pressure, cholesterol, BMI, and weight. Um, this is the study that frequently quoted to my patients, quality of life, cognition, um, and again, most studies show no differences at all, uh. Except for when uh the TSH level was higher, um, in one study it was close to 10 or higher than 10, fatigue approved uh improved in one study when the TSH was treated all the way down to 0.5, close to like sort of, um, mildly suppressed range, and in one study, um, the improvement was observed in TPO positive patients. The lipid again, um, mixed, mixed results. OK. Most studies that show lower triglyceride level. Uh, but the P value was not significant. And so could it be sample size for sure, right, um, because the, the size here you can see varying from 14 to 120, but what, what could be the clinical significance if just maybe 5 or 10 points of, of reduction in the triglycerides. So, um, it's unclear, uh, but you certainly can give it a try if they're, you know, have significant, uh, hyperlipidemia and their TSH is close to 10, you know. All right, so I just want to briefly take you through the slides, uh, on the BP, those are the clinical trials, uh, you know, how many the duration of the studies and the age of the participants, um, you know, 34, uh, 50s and 60s and their TSH at baselines and how low they treated to the target, uh, TSH again that's treated down to 0.5. Um, they found no difference in blood pressure. OK, so don't, don't treat subclinic hypothyroidism because of blood pressure. Um, and the same with, you know, our New England General Medicine study with 300 people in the study. The treatment effects on quality of life, um, this I briefly mentioned again the age of the study groups, uh, and. The TSH level this was 12.8, OK, and they found, uh, a difference in terms of thyroid symptom scores. OK, uh, but this is unusual because this is higher TSH level than we typically see in our patients and, uh, 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 but TSH was treated down to 0.5. But then when look at other parameters and uh questionnaires they found no difference at all, right. Um, Yeah, so let's see, and then this one is the TPO population. OK. They, um, the conclusion was, um, those patients treated, this is not randomized control trial. This is just a prospective study. They feel better again, not the best study, um, um, but regardless, they, the patients feel better, um. Right, 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, 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. Uh, and this is BMI and weight. I, I found this helpful because many of, of patients I see thyroid cancer patients a lot and essentially all of them are hypothyroid. They have thyroidectomy, and this is what I, I counsel them, um, you know, all the studies, um, different, um, durations here, uh, and, uh, you know, of course the numbers are not large. members, they found no difference. 8 to 4, uh, BMI changed minus 0.3. This is treated very, very normal. No difference in BMI. Again, 5.821. Uh, no, really no difference, right? In fact, the BMI is actually a little higher for this one. this is treated all the way down to 0.5. No difference, right? Um, so really no effect on BMI and weight, um. All right. So, um, again, in terms of cardiovascular outcomes, this, the power, uh, in different studies just has not been, um, big enough to address the cardiovascular outcomes. Right, so to summarize, I think TSH above 10, um, it is recommended to treat, uh, just because they're more likely symptomatic and, and they, uh, uh, they're more likely to, uh, develop overt hypothyroidism and also their data to back this up because there are several large perspective epidemiological. Cohort studies suggested that um with TSH greater than 10 when they followed longitudinally 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, uh, 9.9. Uh, there's tons of results, especially perspective, um, longitudinal studies found mildly elevated TSH from, uh, 5 up to 6.9. Absolutely, absolutely no effect on cardiovascular outcomes, uh, none soever at all, uh, the, the 7 to 9.9 it's a little bit controversial, uh, maybe borderline significance but not greatly significant. Uh, 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, uh, especially for younger patients, OK. Right, so let's see, I'm gonna just move on, uh, instead of going through this, um, studies in detail. Um, all right, so I just want to come to you the bottom line of recommendations from consensus groups, right? Um, we have, uh, American groups, the American Thyroid Association and ACE, and, uh, European Thyroid Association. This is they use greater than or equal to 10, and then in US we use greater than 10, you know, just. You know, I just want to mention that slight difference, um, it's for the Ace, if you have greater than 10, yes, for the US, definitely, OK, and for Europe, um, yes, younger patients definitely, uh, they're a little bit more, uh, generous with older patients. Uh, yes, if they have clear symptoms and if their cardiovascular events are high, right. Uh, and then for, uh, TSH level less than 10, um, you want to consider for US, you want to consider, you know, symptoms, TPO status, you know, cardiovascular and heart failure status and risk factors, uh, that we talk about, um, and then for Europe, um, for younger patients, yeah, consider a trial and for older patients you could, uh, definitely observe and monitor. So that's, you know, uh, summarize this table essentially summarizes the consensus guidelines from different, um, professional groups. All right, so, um, What about the target of, of, uh, TSH when you treat, um, there are two different opinions here um in the US uh AT American Fire Association, uh 4 to 6 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 who live to be that age, um, and European society, they say anything normal is fine, uh, 1.5. I, I, you know, um. I think either way is fine. Uh, you do want to be a little bit cautious when you, you wanna make sure you, you know, your TSA doesn't get too low, OK. Alright, so in summary, half of this subclinical, uh, case of subclinical hypothyroidism, uh, when you have abnormal TFTs, you know, you want to repeat it, um, and, uh, you know, the considerations for artifacts, uh, you could consider checking the TPO. Help you strategize management of this patient, uh, and you wanna look at the symptoms, um, and look at their cardiovascular, uh, risk factors and look at their age, OK, um, so it's very important, um, the younger the patient, the more likely you want to treat. Um, this slide just reminds me that all this out the guidelines do not recommend, uh, women to start pregnancy, so it's, um, I won't go into detail. This is a completely separate topic, but this is just, uh, remind you, um, it's very different, um, population here. All right, so, um, I see a lot of TPO and TT antibody being done, um, and I, I, I, I think, um, it's reasonable, um, but, um, I don't always measure, uh, in my patients because I'm gonna monitor those, uh, TFT, uh, that, that TSA that's going to be mildly elevated, um, TP. We know TPO um is a part of the factor that is involved in sort of uh 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, uh, but I, I just want to make sure that um that you also understand that TPO is a marker for autoimmune disease, not just Hashimoto's, um. And you really cannot distinguish grave disease from uh other types of autoimmune disease such as Hashimoto's. Um, uh, it can be present in 74% of grave disease patients. Um, in this study, I found 99% of Hashimoto's, uh, will have positive TPO. I must say, um, in my practice, um, I don't always, the TPO may not always be positive. Especially, um, when I have ultrasound readily available or thyroid exam, you know, when the exam is abnormal, um, so, so this may, I, I think this is a little bit higher than what I see in my practice, um, and I will get to 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 TPO is positive, people get so nervous. Do I have autoimmune thyroid disease? Do I have Hashimoto's? But just look at that. This is a disease-free population, 11%, 1 in 10, um, and then, you know, if I got my antibody, you know, um, and then for the, for the total population, it, it's even more, um, slightly more common. Um, and in that, in the whole 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 total population. Um, And then we see this a lot. I mean, you know, um, TPO positive, but completely normal TFTs. Again, TPO doesn't mean the person, uh, has Hashimoto. is, is, is a marker of auto autoimmune disease, OK, um, so then, um, this is really the practical point of view as when to initiate levothyroxine, right? We talked about subclinical hypothyroidism, right? So I'm not going to repeat that, um, and then primary hypothyroidism, obviously when you have elevated TSH and low free T4. And they're about 0.4% of the total population and secondary hyperthyroidism, um, is 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 pituitary tumors, um, and, uh, when you measure, uh, TFTs, uh, the TSH will be, um, variable but inappropriate for a very low T4. It could be 1, it could be 0.5. Um, don't know why it secretes if it is, you know, it probably still has some secretion, but it's definitely inappropriate, OK, um, usually seeing, uh, patients with hypothalamic pituitary disease, um, and frequently has other associated hormone deficiencies by pituitary deficiencies, um, and this is, um, we like to see them now. They're definitely, um, potential, um. Sort of laboratory interferences, uh, for example, uh, uh, certain assays 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, uh, biotin for at least 3 to 5 days, um, at UCSF, um. I know my, you know, my laboratory assays, what assays we use, we actually, our labs actually do not, our assays actually are not, um, affected by bioton. So you know we can trust our assays. But again, for your practice, you know, depending on where they go, you have to know your assays, um, and so if you have low TSH, one consideration is it could be bioin effect, OK. But, uh, but again, um, it would be nice to repeat it because they could be also in transition recovering from euthyri sick, right? They get, um, um, you know, they will get better depending on clinical, uh, presentation, um, so it's, it's, it's good to repeat, um. All right, so let's see. OK, so levothyroxine, I think you guys, uh, should be well versed on this. If not, if, uh, feel free to stop me and I can go over in more details. Uh, we definitely have generics, right? Just levothyroxine, and then you have all different, uh, brand names the Synthroid, Levoxyl, Unothroid, uh, levothroid. Tyrosin, um, and keep in mind that the active ingredient is the same, the same amino acid structure your receptors, uh, the thyroid hormone receptor sees the same thing, uh, even though it's synthetic, um, I, I don't know why some of our patients are so, um, wanting. The quote unquote natural hormones, uh, uh, so, so the difference is obviously it's, you know, most of these are in pills, right? So you have fillers just like Tylenol has fillers, um, you know, uh, ibuprofen have fillers, you know, they have fillers in there. Tyrosine is the most pure, um, really doesn't have much filler, um. Uh, so, uh, you probably know that they're color coded, uh, they're different, uh, dosing, uh, doses here from, uh, 25, 50 strange dosing, right? 75, 88 and then 112 and all this, they have 300, um. Uh, pills as well. Tyrosine has a small dose of 13, OK, um, allergy is very rare. Just think of it. It's the same amino acid structure as our thyroid gland, you know, as a native hormone of, made by our thyroid gland. Um, but if this allergy, usually rash and itching is because of the dye, OK? They're just because they're color coded, right, uh, and very rarely fillers of some patients I know are super, super sensitive. They cannot. cannot eat corn. They cannot have anything. And, and so you could consider tyrosine, OK, um, a trick is 50 mcg is white pill depending. It doesn't matter which kind of brands or manufacturers, uh, has no dye. And so if the person, uh, is found to be allergic to certain dye, 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 simplified to 75, and she's developed itching. Uh, so then we know that she was allergic to, you know, uh, the dye with associated with 75, um, and so we switched her back to 25 3 tablets a day. Um, again, tyrosin very inert inactive ingredients, um, so if there's any allergies, uh, issues, then we can give tyrosin. Right, so those are the ingredient in active ingredients I, you know, some of the um Physicians, um, I found this very helpful, um, and this can be available to you if you want it, but it definitely is, um, available on the, uh, PDR, um, so you can see some of them, um, some patients have lactose intolerance. Um, I don't know why they put a lactose in there, um, but Synthroid has lactose, um, and, um, and then you have, you know, unohoro also have lactose, um, uh, the laxo actually doesn't, so some of the components you can, um, look up. Um, let's see, um, I think this is duplicate. Sorry about that. OK, so the active ingredients in desiccated preparations armor, OK, so those are again very similar, just like, you know, the, the synthetic, right? You can see very similar, uh, failures here. Um, See. All right, so this is, uh, this, uh, slide shows you the ingredients in T3 active ingredients in T3 cytomel, OK. Uh, and then, um, the generic, uh, form of uh cytomelbuyenine, uh, and the diff different manufacturers here. Um, all right, so levothyroxine, um, we talked about the half-life is, um, 7 days, so it's, it's, it's really, uh, the best, uh, form of treatment because it's long half-life, uh, you don't have to take it multiple times. Um, the absorption takes place in the small intestine, 45% upper dugenum, and, um, then the rest you can see that here. So if people have, um, you know, sort of bypass, uh, surgery or having, um, The gut issues you wanna consider, uh, male absorption for sure and those patients will frequently require a larger dose, um, and gastric, um, acid is actually very important for absorption. So it's best taken, uh, fasting. You, we have patients who TFTs very widely and you talk to them, they just, they take it anytime and, and so it's important to instruct them to take it correctly, um, and, uh. I think, yeah, so this is if you work in a hospital, you want to convert the oral to uh IV it's about 70 to 80%. Um All right, so the absorption of food and I, I, you know, this is the first thing that I always wanna make sure when uh people have questions about why are my TFTs, you know, varying from 2 to 4 to 1, you know, this is something that you wanna, um, 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 if you want to do it really at least 3 or 4 hours um after last meal and then, and then the third best absorption 30 minutes before breakfast uh and then worst is obviously with breakfast, OK. Uh, and then it's been demonstrated that the most consistent TSH levels are achieved as fasting state. And the coffee, there's something about coffee, so I always counsel them, don't drink your coffee, just have water, OK, um, and, and because you know there's something about coffee that they can sequester T4 in the small intestine. The fiber, very important, soy products as well, um, so those are the things that you wanna tell your patient to stay away from le. peroxide, uh, the coffee an hour will be fine. The fiber and soy products probably a couple of hours, I would say, uh, 4 hours, um, and this is, I want to show you this is the synthroid insert, um, that you know those, um, uh, supplements, uh, really should be administered, um, 4 hours after levothyroxine. OK, same thing here. Um, and then you can see many of your patients probably take supplements and they have iron deficiency and so 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 PPI is frequently, people frequently take PPI. I usually have them take it after levothyroxine because it's, you know, H2 blocker and acid blocker, right? So you want to give them thyroid fasting and then they can take their PPI, uh, 30 minutes or 60 minutes later. Um, Anything else? Um, I'll, I'll pause here a little bit just for you to look through this. Um. All right. Um, so if you have a patient who says, I am following your guidelines, I'm following the rules, I'm taking it the way 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 two the next day. Um. 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 levothyrox, they're gonna be fine, right? Uh, because half-life is 7 days. And so I tell them when they come back, uh, they can take those 3 missed doses, um. By taking essentially extra half for the next several days to make up the missed 3 doses, OK, so that's, uh, one trick that frequently 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, uh, absorption. Uh, disease affect gastric acid production, H. pylori, or autoimmune, uh, trophic gastritis. So those are the, uh, antibodies that you want to check, OK? Patients with, um, Hashimoto. they can have other autoimmune 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 a dose and then obviously replace acid. I think those are patients, um, that you have to refer to gastroenterologist, uh, if it is really severe, um, and then diseases affecting the small intestine because. Levothyroxine absorbed in the small intestine, right? celiac disease. OK. Consider doing, uh, checking for celiac, um, and the, uh, and then also the GI surgery, the bypass surgery, OK, um, although the data are mixed, uh, lactose intolerance surprisingly can also, uh, affect, uh, absorption as well, and then, um, intestinal, uh, geo, um, intestinal infection here that can also affect the absorption. Um, let's see, um, and then you guys know about this replacement, um, Uh, the formula, right, uh, full replacement if the person is, uh, completely hypothyroid, um, for example, the person has thyroidectomy, you put them on levothyroxine 1.6 mcg per gig, no question at all. And if their TSH, uh, say for example, is 30 and their free T4 is like 6, like non-measurable, um. Uh, normal being, uh, 8 to 12 in that assay, uh, so you know, pretty profound hypothyroidism, then you use this, OK, for older patients, uh, because they don't have as, as a bigger muscle mass, um, you probably wanna use, you probably want to start out with 1.2, you know, just be cautious. Um, and, uh, uh, for people, for patients with subclinical hyperthyroidism, um, you don't want to give them a full dose, you wanna start slow depending on their, um, BMI. If they're like really, really tiny, like, um, you know, 40 kicks, um, you know, um. Older, uh, woman, then you probably want to start very, very slow, right, um, even 12.5, uh, depending on their levels as well. But in terms of treatment goal, this is the ATA guidelines, um, 4 to 6, um, in Europe, you know, 1 to 5 is OK, uh, because half-life is 7 days, so you wanna, um, check a TASH about, um. 4 to 6 weeks, not infrequent allergy 6 to 8 weeks because sometimes it does take a little bit longer for them to, um, uh, stabilize, um, and, uh, yeah, so I, I think you probably know this stuff already, right? Um, uh, in terms of TSH goal for younger patients, I, I think they can handle a lower TSH, so I will have no reservation to give them, um, a little bit more to keep that TSH a little bit lower, um. As long as the TSH is not suppressed, uh, 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 thyroid cancer patients, they all have thyroidectomy. Uh, they do need to, uh, I do keep them mildly suppressed, so they are 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 typo here, one consideration is you could give them, uh, more, uh, more levothyroxine to keep 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 placebo, uh because what's the next step is they're going to see a specialist if you don't work with them and then when they get to us uh we're gonna say we don't have data but if you want to try it we could um or they're going to see somebody else where they will start you know armor thyroid or T3, um, that really have no um evidence let's see. Um, again, uh, we, we, we see that, right? I mean this is really a huge drive for specialty consultation, right? Um, unfortunately we don't have good solutions, we don't, um, um, you know, this is what we also, you know, we have to discuss. With patients, are they going to perimenopause? You look at perimenopause. They have hot flashes. They have fatigue. They have arthralgia. They have, uh, anxiety. I mean, all the symptoms are shown non-specific, but all those symptoms can mimic thyroid symptoms, right? Um, and so you wanna, you know, consider those, and sleep apnea is very, very important. Do they, do they, are they tired because they have sleep apnea? Do they wake up tired? And I actually have discovered diagnosed sleep apnea 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 lie down. So consider that, um, and the usual general internal internal medicine workup, OK, um, you know, most of patients taking levothyroxine do have Hashimoto's, um, and so they can have other autoimmune diseases, so you wanna look it up. Um, and work it out, OK, um, and then concurrent adrenal insufficiencies can be really, really, really rare, although we see them just because we're a referral, uh, center. So if you have any, uh, sort of, uh, um, suspicion that this could be adrenal insufficiency, especially if sodium is low, uh, potassium is high, then, you know, you wanna do, uh, formal testing. You can get a cortisol, you can do ACTH stimulation test. Um, and then again there's no data to support that. You could consider dose increase, uh, to lower TSH to the second half of normal. Uh, so in this study, uh, really they found no difference between higher TSH and lower TSH, um, and this was published in. In 2006 and more recent studies, they found no difference uh in terms of mood, quality of life combination in terms of uh three different TSH groups 0.34 to 2.5, 2.5 to 5.6, 5.6 to 12, no difference at all. OK. Um, so when you have a well conducted studies, you, you don't find any differences. Um, all right, so let's talk about T3. I think some of your patients probably, um, are on T3 already or asking for T3. It is the active hormone, uh, and, and only 20% is from the thyroid, 80%, majority of it is really from the, uh, peripheral conversion of T4 to T3, uh, and the ratio of T4 and T3 secreted by thyroid is 13 to 1. If you look at desiccated thyroid extract, it's 41. So as an endocrinologist, I'm treating, I'm replacing, so I wanna do this ratio. So I don't know what I'm doing when I do this 4 to 1 ratio. What am I treating, right? Um, also, if you remember in the older days, um, and even nowadays, uh, some psychiatrists use T3 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 T3 than is necessary than physiology, uh, with, you know, would allow us to say this is the replacement. Uh, in terms of potency, um, just for, uh, information is 1 mcg of T3 about 3 or 4 mcg of T4. Half-life is only one day, so you have to do it, you know, the, the, a lot of us would do twice a day, but even that you can get a really peak and rough, um, and so there have been, um, sort of studies looking into. Um, long acting T3, I don't know where that is, um, yet, but there definitely momentum and study in the background maybe in a few years or, um, you know, it could be, uh, a reality for, uh, long acting T3, 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 T3 which um can potentially cause problems. Um, so, uh, just one slide on T3, uh. And I think some of you want to know about desiccated thyroid extract. Um, they're from, you know, animal, right? Um, and they do, um, they ran out of the stock. Uh, you probably heard that some patients maybe last year or sometime, I cannot remember when they couldn't find, uh, armor thyroid, um. Um, and there are different brand names here. They're all the same, OK. They're all the same, and, um, this is just to give you, um, sort of an idea of the breakdown of T4 and T3 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 T4, here's a conversion table here. Uh, this is actually from USP drug information.
