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- [00:01]
A
This is endocrine feedback loop. I am your host Chase Hendrickson and welcome you to this Journal Club Podcast series brought to you by the Enderkin Society. Thanks for joining us as we explore an important article recently published in one of the Society's clinical journals. Welcome again to the Endocrine Feedback Loop podcast for our 70th episode today we review a paper that tries to improve our understanding of remission in Graves disease. Long term thionamide treatment has long been the preferred approach internationally in graves disease and only more recently here in the US So the more we know about dosing and how that might encourage or predict remission, the better. This report is an observational study, as is often the case for papers we look at, so we will discuss how these authors approach this question and give you our thoughts along the way. I host the Endocrine Feedback Loop and work at the Vanderbilt University Medical center as a general endocrinologist and medical director. As this month's regular contributor, Andy Crawford joins the podcast yet again. He works at the Dartmouth Hitchcock Medical center where he is the director of their Fellowship program. He teaches extensively at Dartmouth with scholarly interests that focus on enhancing quality improvement training for fellows. His clinical interests center on thyroid disease and he serves as the lead endocrinologist for the Thyroid Tumor Board at Dartmouth. As this month's guest expert, we welcome Giuseppe Barbacino from the Massachusetts General Hospital and Harvard Medical School. There he focuses his work on thyroid disorders as a member of their thyroid unit. You all as our listeners, will be familiar with him from his research papers and talks on thyroid disease. So as usual, the perfect pair of endocrinologists joins me today to discuss this thyroid article. As is also always the case, everything we say will be our opinions only and not those of our respective institutions or the Endocrine Society Society. This month we discuss Impact of Minimal Dose Strategy before Antithyroid Drug Discontinuation on Relapse Risk in Graves Disease, which the Journal of Clinical Endocrinology and metabolism published in February 2026. Kitaro Miramura served as the first author for this paper and was joined by colleagues at the center for Excellence in Thyroid Care at the Kuma Hospital in Kobe, Japan. I will now turn the discussion over to Andy. He will highlight some of the key points that these authors make in their introduction, as well as asking Giuseppe to provide additional background on these issues.
- [02:36]
B
Andy thank you, Dr. Henricksen. So, as mentioned, antithyroid drugs have overwhelmingly become the first line agents used to treat graves disease. For example, 90% of respondents in a recent international survey stated that they use them as first line for treatment of Graves disease. And there's a growing evidence base demonstrating the long term safety of taking these medications. Dr. Barbacino, could you give us a brief overview in the historical shift towards thionamides becoming the preferred first line treatment for long term treatment in Graves disease?
- [03:11]
C
Well, it's interesting because as it was mentioned before, the United States has a history very different from the rest of the world in which methimazole and carbimazole and PTU were first line for a long time that arise on the fact that really radioactive iodine treatment was developed in the United States. And also it was much more accessible to clinicians in the United States than say in Europe where I practiced for a while. But only some centers were allowed to provide radioactive iodine. When I first came to the United States, private practices were able to treat patients with radioactive iodine for Graves disease very easily. And so there is that difference in style. And to be honest, radioactive iodine was very appealing. It's like telling a person, you know, you have hypertension, you can take hydrochlorotiazide for the rest of your life, or like that, we can fix it with a simple treatment and you'll never have high blood pressure again. So there is that definitive treatment appeal that certainly was meaningful for many clinicians. Then a couple of things I think happened. First of all, it became clear that radioactive iodine increases the risk of the dreaded complication of Graves disease, which is thyroid eye disease. When you go over the consent form and you tell a patient, you may solve the problem that we can also solve with methimazole, but with radioactive iodine, you may also develop this swelling in your eyes. It starts to become very concerning to people. And then obviously there is much more consciousness about the effects of radiation. And then ultimately there is this underlying concern with hypothyroidism being the cause of many, many defects in quality of life that makes people much less likely to desire definitive treatment leading to hypothyroidism. So I think all these factors have really conjured to the change of preference right now in the United States, where antithyroid drugs are really become first line.
- [05:15]
B
So for all of us that treat patients with Graves disease using thionamide medications, one of the main goals is achieving long term remission and getting patients off of the medications. But of course, relapse is a common issue. A recent study demonstrated, for example, that between 30 and 40% of patients relapse after discontinuing thionamides. So both patients and clinicians want to follow a strategy that's most likely to allow them to be free from thyroid medications over time. Dr. Barbacino, could you discuss what the known risk factors are for relapse and how you currently approach stopping thionamide treatment, including how you use thyroid antibody titers to guide you?
- [05:56]
C
Well, I think a lot of the risk factors that we know of are sort of mirrors of a more active autoimmune process that is the root cause of Graves disease. For example, people who present with larger thyroid, people who present with thyroid eye disease, people who present with more serious hyperthyroidism, they are more likely to be unable to discontinue the methimazole. Obviously, the most proximal factor that we can evaluate is the level of the TSH receptor antibodies. Unlike many other autoimmune diseases, there is one determinant of the manifestations of Graves disease, hyperthyroid, and that's the TSH receptor antibodies. So people with persistently high levels of TSH receptor antibodies are clearly unlikely to experience a remission once they stop the methimazole. And it's important to distinguish the two types of remission. One is endocrinological remission, meaning being able to correct hyperthyroidism with anti thyroid drugs. And the other one is the immunological remission, meaning the ability to maintain euthyroidism without medication because the immune system has lost the ability to stimulate the TSH receptor.
- [07:11]
B
So there's a growing evidence base that prolonged administration of methimazole prior to discontinuation is associated with higher rates of durable long term remission, which is a major goal of patients undergoing antithyroid drug therapy. But little data exists currently to guide clinicians as to the optimal strategies to maintain low dose methimazole, which would allow them to balance maintaining euthyroidism while also maximizing the likelihood of long term remission of Graves disease. It is not clear then how important the final dose of methimazole is prior to tapering in terms of the overall importance of the treatment duration itself. So I'm going to turn over to Dr. Hendrickson to discuss the methods for this paper.
- [07:53]
A
Andy, thank you. So we're going to, first of all, think about the study design that the authors use here. And the authors employ a retrospective cohort study design. We've looked at plenty of these. But as a reminder, first of all, how cohort studies work. These are observational studies. And the key is you have a population of subjects of patients. And you have to divide them into multiple groups. And its simplest, it's two groups where you have a group that's exposed and a group that's unexposed. And then what makes it a cohort study is that you follow those individuals over time, waiting for the outcome or outcomes of interest to develop. Then you can further subdivide that into, well, is it a prospective or a retrospective study? In a prospective study. So that's not what this is. But just as a reminder, in a prospective study, you're following these groups in real time. When you start your study, none of the outcomes have happened yet. You're following along with the patients, waiting for the outcomes to develop. In retrospective studies, you start your study after everything is over, so everything has already occurred. But because of the data that you have, you have the ability to reconstruct that time sequence. Even though everything is historical, you still are able to demonstrate that what you are looking at as your exposure predated what you are labeling as your outcomes. So that's what a retrospective cohort study is. So that's what indeed this study is. It's a retrospective cohort study at a single institution in Japan. And these investigators used their electronic health record to identify newly diagnosed Graves disease. The dates they looked at, they included them from August of 2008 through July 2024. And they mentioned that they chose that beginning date because that was the time period after which they had transitioned to their current method for measuring thyrotropin receptor antibodies, or trab. And then the way that they actually identified the cases for this study was by ICD, 10 codes. And we'll come back to that in a second. They further refined this population is they wanted to find individuals who had been on a stable dose of methimazole. So the way that they define that was based on prescription. So you needed to have at least two prescriptions that use the same dose of methimazole. The idea being they wanted you to have been on this same dose for over three months. And the highest that that dose could be was 2.5 milligrams a day. Though, as you'll see here shortly, there were lots of options for lower doses than that, a few exclusions. If this was post pregnancy, you were excluded from this investigation. If there was evidence that you had had definitive therapy, we talked about that earlier, with radioactive iodine, they also included post thyroidectomy in this group, or you were also excluded if you had not had follow up for at least six months after that, methimazole was discontinued. They're worried that was highly likely that you'd been lost to follow up, and they didn't want those folks included in this investigation. So with these inclusion here, one comment that I'll mention is that there's always a concern about an imprecision when you use ICD10 codes to make a diagnosis and include people in an investigation here. I'll note though, that the authors do a nice job. They look and they try to investigate to say, well, we made some assumptions here, so can we actually validate this? Or they looked at a smaller subset of their patients to see how accurate this was overall and actually it suggested that it was a fairly accurate way of identifying their patients. But one other question that I had, Giuseppe, is about the antibodies. We've talked about this already, but there are of course a couple of different ways that antibodies can be measured. So we've talked about the T rabs here, but there's also the tsi. So can you give us some insight into Is there an important distinction between that? Does this introduce any limitations into this study or not particularly well, Those two
- [11:36]
C
antibodies are different in the way they're measured with different assays. The TRAB is typically a competitive assay. When you can measure the displacement ability of the antibodies of the TSH from the TSH receptor and the tsi, it's a real biological assay that looks at the ability of those antibody to stimulate the TSH receptor. So the TSI is in reality a subgroup of the trap, because you can have TRAP that are not stimulating the TSH receptor factor blocking. However, in the setting of the patient with hyperthyroid TSH receptor antibodies, no matter how measured, they're almost always diagnostic of Graves disease hyperthyroidism as the cause of the hyperthyroidism, and therefore they are almost equivalent with the difference that may be with subclinical hyperthyroidism. Lower degrees of hyperthyroidism may be a little less sensitive biochemically than the T rap, but other than that I would not have any great concerns about the ability of either one of these assays to correctly diagnose a patient who's hyperthyroid with Graves disease.
- [12:46]
A
This is the population overall as far as the exposure goes, the authors used four different categories of exposure and that was based on the dose of methimazole. So the first group is if you had been maintained on a methimazole dose of less than 1.25mg a day prior to discontinuation of methimazole. The next group were those who had been on exactly 1.25 milligrams a day. The third group was those who had been between 1.25 and 2.5 milligrams a day. And then the final group was those who had been on exactly 2.5 milligrams a day. And again, the inclusion criteria require that 2.5 be the highest dose that you were on. So then nobody was on higher doses than that. For this investigation, as far as the outcomes go, they looked at one primarily, and that was simply the relapse of Graves disease. The way that they determined that was whether you had had your methimazole resumed within a year of having it discontinued. As far as potential confounders, I'm not going to list them all here. Andy's going to talk more about them. So we'll defer most of the discussion around that to the results when we actually go through those. But I do want to mention one here that I think is important. And as I was looking at this study, I think is the biggest limitation of this study, or at least how it's interpreted, is that one thing that that's not captured, and in part because there probably isn't a very good way of capturing it, is trying to understand why a clinician used a different dose. Particularly if you want to say, well, maybe the default was 2.5mg a day, why did some of these patients end up on lower doses? What was in the clinician's mind that caused a lower dose to be prescribed? And one of the reasons, as I was thinking through this, as to where this might come about in clinical practice is, well, if you have somebody who's on 2.5 milligrams a day and you're monitoring TFTs, and those TFTs are suggesting that that dose is more than somebody needs, perhaps because they've developed actual hypothyroidism on that, that would be a reason to then reduce a dose for somebody because that would be evidence that they are going into remission whenever that happens. That term that's used to describe that when this phenomenon occurs in a research study is confounding by indication. Because here, when you've labeled something as a cause and effect in this study, to say, well, maybe the dose is the cause and then the relapse risk is the effect or the outcome, well, it's possible that you could actually see what the outcome was going to be, and then that changed your prescribing behavior, and it flips that cause and effect relationship around a bit. We don't know for sure that that's what happened, but. But it is a question in my mind is could that have been what occurred here and that potentially explains the relationship that we see. We're going to come back to that. The authors have some other good thoughts about what could be explaining this relationship. So we're going to discuss this more in the discussion section itself. But before we move on from confounders, I wanted to give Andy and Giuseppe a chance to mention any other ones that they might have been curious about other than what the authors mention and analyze.
- [15:49]
B
I guess I'll mention a big one for me that was not investigated in this paper was the presence of Hashimoto's thyroiditis, specifically in terms of measuring thyroid peroxidase autoantibodies and establishing whether patients were positive, having those antibody titers elevated or having normal titers. The reason that I'd be interested in seeing that data would be that there's evidence clearly that patients that have elevated TPO antibodies have an increased likelihood of going into remission and a decreased risk of relapse over time if they've been successfully tapered off of methimazole.
- [16:24]
C
Well, as you mentioned, Chase, my concern is exactly the same as yours. What led people who take smaller doses of methymazole to that point. And I can imagine in my mind that progressive tapering to a lowest maintenance dose you can get like we do ordinarily. And some people made it into the small dose and other did it. And those people may be different from one another and that may have had an impact on the result. I will mention, however, that the study design also includes this propensity score matching, which is the next best thing you can have close to randomization. But it's only as good as you mentioned as what variables you used in the matching process. And unfortunately the variables are limited. Andy mentioned TP antibodies as a potential, but there are others that may have played a role. So obviously there is always a little bit of sort of concern about the accuracy of these studies, but you know, can't get any better than that with retrospective studies.
- [17:25]
A
A few other words on the statistics. So the main method that the authors use is a multivariable regression analysis. All those confounders that I alluded to but didn't list those got plugged into this model and we're going to hear about those results shortly. But Giuseppe has also mentioned it. And something I really liked what the authors did is they did a sensitivity analysis and the idea of a sensitivity analysis in general is that you acknowledge that we had to make several decisions along the way about how we're going to design this study. And we want to understand, well, how important was that decision. If we made a decision to analyze something this way or to define something this way, what if we had chosen a different way, would we have gotten a totally different answer? So in a sensitivity analysis, you try to answer that, you say, well, let's go back and say, let's imagine we had made a different decision there. Would it have changed things? So they specifically do a sensitivity analysis with their methodology around the statistics. And so they use multiple other analyses. We heard about one already that propensity score matching, but they did several others. And so I really like that because they want to say we have multiple different ways that this data could be analyzed. Do we get different answers based on the method or is the method doesn't matter and we get the same answer either way? We'll hear a little bit about that. But I think that's definitely a strength of this study that the authors decided to do that. Andy, I'm going to now turn things back over to you so that you can walk us through those results.
- [18:46]
B
Thank you. So the authors screened over 5,000 patients and 4,352 patients were eligible and included in these analyses. So first in Table 1, the authors show us how the groups are organized, which sets things up moving forward into the different analyses that they perform. So again, just a reminder that they looked at four different dosing groups of methimazole. Less than 1.25 milligrams daily, exactly 1.25 milligrams daily, greater than 1.25 up to less than 2.5 milligrams daily and exactly 2.5 milligrams daily. The trend in this raw data was that there was a lower one year relapse rate in patients under 1.25 milligrams per day. And the risk increased with doses up to 2.5 milligrams per day. The authors note that trab titers were below the detection limit more frequently in the lower dose groups. But the other variables were similar between the dosing groups. The authors demonstrate in Supplementary Tables 1 and 2 that covariate balance was achieved in their propensity matched cohorts. So now let's discuss their propensity matching and how they set up the multivariate regression analysis. So in Table 2, the multivariate regression analysis looked at the association between the pre discontinuation methimazole dose and the one year risk of relapse of Graves disease. So they started off with a crude model where they used the 2.5 milligram per day dosing as a reference and compared it to the other dosing groups. And then they used an adjusted model which accounted for age, gender, thyroid volume, smoking status, duration of methimazole treatment, duration of maintenance dose, trab titer at discontinuation being the final one. And what the authors noted was that the P value was less than 0.05 for both the crude and adjusted models for the comparisons of less than 1.25mg per day and exactly 1.25mg per day dosing compared to the 2.5mg per day dosing. Dr. Hendrickson, could you comment on the benefit of seeing both accrued and adjusted results together?
- [20:49]
A
Yeah. So this is another thing I really liked when Andy and I were working through this. It was something that I noticed and I love it when authors do this and they don't always do it, but the authors here did. And that's including both those crude and adjusted. Ultimately the adjusted, you feel a lot more confident that that's actually what it that you're interested in, what you're looking at. But for an example, just to give you a few of the specifics, so the relative risk with that multivariable regression, looking at that group that was on less than 1.25 and comparing it to the 2.5, so that relative risk was just under 0.2, then that was the crude. And when they adjusted it, it was almost exactly the same. And that really increases your confidence that whatever the authors are finding here, they're onto something that not just being driven by confounders, whenever you make these adjustments, there's always going to be residual confounding. And if you make an adjustment and it shifts your crude number quite a bit to when you get to the adjusted number, then you get really worried that, well, what if the residual confounding that I know is there, what if that accounts for whatever is left of that difference? So you get really confident whenever you have a crude number that suggests a fairly strong association, including statistical significance, and then it doesn't shift very much once you've adjusted. And that's exactly what we see here. So I think it's both great that the authors included it and it's also very supportive of their findings that there was not much of a shift whenever they did adjustment, despite the Fact that they adjusted for quite a few things in their model.
- [22:18]
B
So moving into Tables 3 and 4, this did a different type of regression analysis called a Poisson regression analysis, again looking at the association between pre discontinuation methimazole dose and the one year relapse risk. And the author stated that they used this model because the relapse risk was relatively low compared to published literature. It was only 13% at one year. And the Poisson analysis is good when events of interest are infrequent. What the authors demonstrated was that the observation that they had in Table 2 for both accrued and adjusted models held up doing this Poisson regression analysis, validating what they had seen earlier. Furthermore, they mentioned that the E value was relatively large, implying that it was very unlikely that there was a presence of an influential unidentified confounder. Finally, In Supplemental Tables 5 and 6, the authors mentioned that the relative risk and confidence interval in the sensitivity analysis was consistent with the findings in the main and propensity score matched analysis. And this was the analysis looking at patients with at least one year of follow up after methimazole discontinuation and also the analysis excluding patients who received levothyroxine at the time of methimazole discontinuation. And now I'll turn it back over to Dr. Henricksen for the discussion points.
- [23:38]
A
Andy, thanks again. So the authors summarized their work by stating that lower pre discontinuation doses of methimazole were associated with a reduced risk for relapse in patients with Graves disease. The authors comment that previous studies have focused on the duration of maintenance therapy. As far as they're aware, this is the first study to focus on the dose of the maintenance therapy. The authors then go on to propose a potential mechanism for why a lower maintenance dose could lead to a higher remission rate. And really they focus on an idea, one that I had not encountered before, that maybe this somehow stabilizes the immune system. And in a second I'm going to ask Giuseppe to give us his thoughts on that. I'm approaching this from somebody who is not an expert in thyroid disease, but looking at this, it sure seems more likely that an alternative explanation would be what is driving this? Again, part of it is this confounding by indications that there is something about these patients that's indicating that they are going into a remission which is then changing the behavior of the prescriber and then also a survivor bias. We have not talked about this. The authors mention this later on in their discussion, but it would be an idea that if, say you had lowered somebody's methimazole dose and then potentially their number started going up, they became thyroid toxic again. Well, you would then naturally bump that dose back up. And so then the explanation for that would be, well, people who are on lower doses who are able to stay on that, they survive, so to speak. And so that could be another way that would bias these results. There's a few other ways that that bias could come into effect here. That's just one way of thinking about it. In my mind, though, I think that's a fairly compelling alternative explanation, that it's predicting who's going to have a sustained remission, but not necessarily driving or causing that remission. But Giuseppe, give us your thoughts. You are an expert in thyroid disease. So when you think about these different explanations for what could be going on here, what strikes you as perhaps the more likely explanation?
- [25:38]
C
Well, it's very difficult to wrap your mind about why a lower dose would result in a better efficacy. There is one thing I wanted to note, however, on the results that is also striking is that there is indeed a dose dependent effect which is also linear reverse dependent. That is also what we like to see with positive results. So that I think is part of the interest that this paper raises. I thought a lot about what could be causing this. One thing that comes to mind, and there is an underlying thought that TSH receptor stimulation propagates the immune response by stimulating its own antigen. And this is not well demonstrated, but it's certainly a concept sustainable. And in a way, when you use lower doses of methimazole for maintenance reasons, you also are likely to result in less feedback on TSH secretion and therefore less TSH secretion and less secretion of thyroid antigens that would stimulate the TSH receptor. So that's a potential explanation that I've been thinking about as a potential way to describe these studies. So one way, somehow the methemazole affects the immune response. But you want to achieve that sweet spot that doesn't result in excessive TSH production and therefore excessive production of thyroid antigens. It's kind of a convoluted way to look at it, but that's the only way I came up with.
- [27:13]
B
Thank you.
- [27:14]
A
And we'll now move on to the authors the limitations that they described. We've mentioned a few, but I'll go ahead and list them all here. They first of all say that there's a possibility that they misclassified a relapse. They did note, however, that they wouldn't think it very likely that that would bias the results, meaning that it wouldn't have affected one group more than another. They point out the possibility of residual confounding. We talked about that already, and that's going to be the case in any retrospective observational studies. They point out the survivor bias. We wrestled with that. They do mention that here and say that that could have had an impact on their findings. They mention a referral bias, which that's rightly described here. It's a little bit different from how we typically think about a bias. It's not that it's going to affect one group versus another. It really has to do with the generalizability of these findings, meaning they're a specialized referral center. And so maybe their. Their findings aren't applicable to other places. They also mention that this is a single center in Japan, and so maybe other countries that could be different. So I think they make a bunch of good points about the generalizability of their findings. Other limitations that they include is that it's possible that they included some patients who had had grave disease previously treated at an outside hospital, and so they weren't truly new cases that were showing up at their center. They point out that there's a relatively short availability of those smaller methimazole tablets, the 2.5 milligram tablets that they have access to. We're going to come back to that. And then finally that they have a relatively limited sample size. Then the authors move on to their conclusion and I'll first of all quote them as they summarize their results, where they say, our study suggests that lower minimum maintenance doses of methimazole before discontinuation may be associated with a reduced risk of relapse in patients with Graves disease. They then go on to state what I would describe as an implication where they say physicians should recognize the potential importance of dose reduction in selected patients. I think the authors are appropriately nuanced here, as we should be with any observational studies. But I think they've left us with a lot to think through and wrestle with. Eventually we're going to get to this idea of, well, what do we do with this? We see these folks, we see these patients. Should it change what we do? But before we get to that, I just want us to think about the quality of this report overall. We've made comments along the way, but in a summary or to bring up anything we haven't talked about already. Andy, let's start with you. You spent a long time working through this article what are your thoughts about the quality of this report overall?
- [29:44]
B
I think the quality of this report was very high. The authors do certainly acknowledge the limitations that this is retrospective data, this is observational. But they really did a careful analysis through all these multivariate regression analyses using propensity matching, using a Poissouan regression analysis, acknowledging that the outcome they were looking at, which is relapse risk, was relatively low at one year. So I think for me, I would have really loved, obviously, to have the highest quality data, which would be a prospective randomized trial. But I think the authors did a really nice job with the data that they had at hand.
- [30:20]
A
Giuseppe, any thoughts on the quality of this report overall?
- [30:23]
C
Yeah, I do agree that for a retrospective study, this is really accurately designed. And sometimes there is a great advantage in working in large institutions that use sort of homogeneous protocols because they allow to collect large populations of patients treated the same way, as opposed to going, as we sometimes have to go, through insurance claims and classifications of diseases that are not really proximal to what really happens. I have a little bit of concerns about the identification of relapse because they only identify those as people who restarted the methemazole as opposed to the demonstration, or someone who is really hyperthyroid. And what is the degree of the relapses? It is possible that people who relapse did not take methemazole and went directly to radioactive iodine. I don't know what the practices are. I know in Japan they don't use a lot of it, but maybe they do still use some. So there are a little bit of fine things that could have been. But overall, for a retrospective study, I do agree it's really high quality and also very well written.
- [31:27]
A
Yeah, I agree on all those fronts, for sure. Okay. Where we always like to end is thinking about should this change our practice. We're practicing endocrinologists and we read these things, study these things, to try to understand how we can provide better care for our patients. So, Andy, we'll start with you. Is this going to change your practice? You see a lot of folks in this situation. How is this going to inform the care that you provide?
- [31:49]
B
Yeah, thank you. I think I have sort of two thoughts overall about that. I think just to circle back to one theme that we've brought up a couple different times is I'm still not sure whether we're seeing a causal relationship, meaning that actually, actually getting patients and maintaining them on a very low dose of methimazole actually does something to promote biologically a higher chance that they'll be relapse free over time, or whether we're just observing sort of a subset of patients that have biologically less active Graves disease around the time of trying to taper them off. So I'm not sure yet. I mean, I would really like to see, as I mentioned, prospective data to really incorporate this into my daily practice. The other thought that I had about it was sort of more practical. It was actually the first thought that I had when I was reading through the methods was just how would I get a person on a 2.5 milligram a day dose? Because we don't have, certainly where I practice in northern New England and to my knowledge, anywhere in the country, easy access to 2.5 milligram tablets, which they did have available in Japan. So patients tell me even splitting in half the 5 milligram tablets is very, very difficult for them. They tell me, you know, Dr. Crawford, I tried to do that, but my tablet just turned to dust. And so when I have to taper somebody below 5 milligrams a day, I have to do things like every other day dosing. So I'm not sure that that's would have the same biologic effect as taking 2.5 milligrams every day would. But I'm hopeful that perhaps this might move, for example, pharmaceutical policy to change so that maybe over time we'll have the availability here of 2.5 milligram tabs.
- [33:23]
A
Giuseppe, will end with you. Thoughts on should this change our practice?
- [33:27]
C
No, I completely agree with Andy. I think it's a little too soon with one single retrospective study to change practice in a way that would require, at least in the United States, creative management system. I hate to give patients alternate day medications because it makes it complicated for them. And so for the time being, I think I will continue what I do. But I do put patients on 2.5 milligrams sometimes asking them to break the pill. And I do recognize that it may be difficult, but from time to time I do that when the TSH is just a little too high, but the TSI are still present, I kind of navigate that a little. But yes, I think 1.25, I don't think we can achieve it practically currently in the United States. And I don't think this evidence is sufficient to make me really want to have that.
- [34:23]
A
And with that, I would like to thank Andy Crawford and Giuseppe Barbacino for joining me for this month's edition of Endocrine Feedback Loop. I learned a great deal and hope that you all did as well. Please join us again next month. And now you're in the loop. This has been Endocrine Feedback Loop. Endocrine Feedback Loop is brought to you by the Endocrine Society with Production Oversight by Brandy Brown. If you want to like and subscribe, you can find us on Apple, Spotify, or wherever you get your podcasts. We'd love to hear your feedback on this episode or the podcast itself. Please email us@podcastrine.org
- [35:01]
B
Endocrine Feedback Loop is a free service of the Endocrine Society. To learn more or to become a member, visit the society's website at www.endocrine.org.