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EFL075 - Methimazole Titration and Initial Disease Severity in Graves' Disease
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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 Endocrine Society. Thanks for joining us as we explore an important article recently published in one of the Society's clinical journals. Welcome back to the Endocrine Feedback Loop podcast for our 75th episode today we return to the JCNM to review an investigation of Graves Disease that looks at the association between initial disease severity, methimazole adjustments, and time to a euthyroid status. As endocrinologists, many of us make frequent decisions about thionamide dosing and the timing of lab reassessments. However, we don't have nearly as much data as we would like to inform these decisions, so we thought this study would be a helpful one to review. As is typically the case for us, these authors use an observational design and we will walk through those intrinsic limitations. As always, we will give you our thoughts along the way and end with our assessment of whether our practice should change. I host Hendrick and Feenbach Loop and work at Vanderbilt Health as a General endocrinologist and Medical Director. Joining us this month in her first stint as one of our regular contributors is Jonaya Lim from the University of Oklahoma. Jonaya is a general endocrinologist and serves as the Fellowship Program Director at ou. I look forward to the podcast benefiting from her extensive clinical and educator experience for both this and future episodes. Today's guest expert is Elizabeth Pierce from Boston University, where she is their Fellowship Program Director and focuses her care on thyroid disease. She is well known to you all as our listeners from her talks and publications in thyroidology, with topics ranging from iodine intake to thyroid dysfunction and pregnancy to environmental disruptors. So the perfect pair of endocrinologists have joined me today to discuss this paper. As usual, everything we discuss will be our opinions only, and not those of our respective institutions or of the Endocrine Society. For this episode of the podcast, we look at initial disease Severity and Methimazal Titration for Graves Disease A Retrospective Longitudinal Cohort Study, which is a forthcoming article in the Journal of Clinical Endocrinology and Metabolism. Erin Hayden Smith served as the first author for this paper, which comes to us from Indiana University. I will now hand things off to Jhenea. She will walk us through some of the main points that the authors make in their introduction and we'll get Elizabeth to give us some additional background information along the way.
- [02:32]
B
Jananna thank you Chase for the introduction and giving us a good Start. Very good to meet you, Elizabeth, and thank you so much for joining us today for this program. So now let's start dissecting this article. So as we know Graves disease is the most common cause of thyrotoxicosis. Medical therapy using antithyroid drug are the preferred initial treatment in the usa. It is typical that clinicians use presenting clinical symptoms paired with biochemical findings using free T4 and total T3 levels to assess initial disease severity and to guide initial antithyroid drug dosing. I'm interested, Elizabeth, in knowing your thoughts on how initial disease severity is best determined.
- [03:18]
C
So I think this is not entirely cookbook or algorithmic. This requires a lot of clinical judgment. The American Thyroid association thyrotoxicosis guidelines currently suggest sort of basing severity on the free T4 level initially, but also on a number of other clinical factors. So that would include the presence of extra thyroidal manifestations like thyroid eye disease. It's a measure of severity, but maybe also an index of how urgent it is to control the hyperthyroidism, the degree of T3 elevation and often correlated the severity of symptoms that a patient's experiencing. The trab titer can be helpful in this. The size of the goiter, which probably reflects the amount of stored hormone in the gland. The presence of comorbidities, which doesn't necessarily reflect the severity of the Graves, but again maybe reflects the urgency of control. And then finally maybe smoking status, which we know worsens severity of Graves eye disease but may actually also worsen severity and prognosis of Graves disease. It's hyperthyroidism.
- [04:18]
B
Thank you. Those are very, very good learning points both to us clinicians as well as training our fellows. So moving on, we know that methimazole, the more commonly used antithyroid drug starting dose, can range from 10 milligrams to 40 milligrams per day. The generally observed follow up approach is antithyroid drug titration to the lowest dose that maintains euthyroid state and avoid stopping methmazole in the first two years of therapy. Elizabeth, do you have any comments about how antithyroid drug titration kit has changed over time and what is your current practice?
- [04:57]
C
So methimazole, the antithyroid drugs were first developed by Astwood and colleagues back in the 1940s. I was certainly not around at that time, so I can't speak from personal experience as to how these were initially used. But certainly historically I think people started everybody on sort of a highest dose of methimazole and then if Patients became hypothyroid on that high dose, they would add in some levothyroxine, the so called block and replace regimen. That has really fallen out of favor. And I think largely because there's been sort of a recognition over time that the toxicities of the antithyroid drug are probably dose related. So it is probably not a good idea to keep everybody on the highest dose of methimazole for the long term. And so I think typically most people will test thyroid function tests and titrate the antithyroid drug down as indicated as hyperthyroidism improves.
- [05:50]
B
Thank you. I think the more recent approach is probably what is being applied in current practice. Current practice relies heavily on clinicians. Judgment as predictors of dose trajectory are lacking. Frequently asked questions include does initial disease severity influence methimazole titration, dose pattern or how much dose are reduced per encounter? How quickly do patients reach euthyroid status? How frequent does hypo or hyperthyroidism occur during titration? We have limited evidence on whether titration should differ based on initial disease severity. It is also unknown whether initial disease severity influences long term maintenance dose after stabilization. The study authors conducted a retrospective review examining real world dosing pattern to identify trends in dosing practices and if there are differences such as age and or sex between groups of patients categorized by initial disease severity. This study attempts to fill an evidence gap rather than resolving contradictory findings. Now I'm going to hand over to Chase to go over the methods of the study.
- [07:05]
A
In this study, the authors describe their work as a retrospective cohort study. And I think that's exactly what it is. That's well described here as a brief reminder of what that is. Cohort studies starts in observational study design and you have to have at least two groups and sometimes you have more than two. And the difference between those groups is an exposure. And that can be a variety of things. We'll look at this. I think in this particular study there's a couple different ways that we could think about what that exposure is or whether it's really a combination of things. But that's what defines your group. You then follow those subjects over time. That's what makes it a cohort study as opposed to a cross sectional study. And what you're looking for is an outcome or outcomes of interest occurring more or less frequently in one of those groups. The retrospective component means that you start your study after all of this data is complete. You're not following these folks in real time. That would be a prospective Cohort study, if that was the case, retrospective studies, you're going back, you have to be able to reconstruct that time sequence. So that's a key thing that you have to do. But if you can do that from charts or databases or whatever your source is, then you can put this together as a cohort study. And that's exactly what these authors do. In this study, they will look specifically at patients with Graves disease, and they all came from a tertiary care center and they were all seen by a single provider. I'll mention here just as a brief comment that we always have to keep in mind when, whenever we have a really focused way that care is delivered, that we're going to look at a lot of different things that the authors report. But when it's a single provider who is providing all of this care, that there can be some unique features that may not be captured very well. And so we may be seeing the influence of a very specific practice pattern that's not well captured by the data. Don't have any particular concerns about this here having occurred, but something we always have to keep in the back of our mind. So again, in this study. So the dates where this data was collected from, it was from back in May of 2018 all the way up through April of 2024 and yielded 152 patients. Initially, the way the authors found these patients were through ICD10 codes. But they then went through all of these individuals and did a manual chart review, first of all to confirm the diagnosis. And that was based on a standard assessment of labs or imaging. And then also they wanted to confirm that these individuals had been treated with only methimazole. That was one of the requirements for inclusion in this study, some of the exclusion criteria. So as you could guess, if you were treated with anything other than methimazole, you were excluded. If you didn't follow the recommended treatment course or lab monitoring, then you were excluded for that reason. There were a few other ones, but those are some of the most important ones. Now we're going to think about exposure. And again with cohort studies, that's how you put your subjects into one group versus another is what they have been exposed to. There are a couple of related ones that we want to be thinking about here. The authors assess thyroid function and they categorize it in a couple of different ways. And the first one is thinking about initial disease severity. That's one of the ways that they figured out how to consider, consider an exposure here. And this is based on labs. So specifically they use the free T4 to categorize that. And they use three different categories. You could be mild, where your free T4 was less than 1.6, moderate if you were between 1.6 and 3.0, or severe, which is where you would be greater than 3.0. I'm going to skip ahead because the authors use thyroid levels in a different way later on, and this is more assessing a response to treatment. So this is how they would define a clinical thyroid status, more of an outcome. But I want us to think about these things together. This reassessment, this way of figuring out the clinical thyroid status. They used all three labs. They used TSH, free T4 and total T3. And then based on different cutoffs, they put those into three different categories that are relevant for us here, whether you are at goal, whether you are mildly hyperthyroid, or whether you are severely hyperthyroid. So, Elizabeth, can you walk us through how you would think about this? There are a lot of other things, obviously, that affect disease severity. You know, walked us through some of those already. But as far as trying to simplify it for terms of being able to do a research study, what are your thoughts on this method of categorization and some of the cutoffs that the authors use?
- [11:09]
C
This is challenging to try and reduce sort of complex biological disease to strict categories based on the thyroid function testing. And I think the authors struggled with this a little bit because for many patients, one or two of the thyroid function tests might fall into one of their predefined categories, but the third would discordant. And they note that they wound up when there were these discordances between what the different labs showed, having to just defer to clinical judgment. And I think that might sort of require going back to some of the additional factors that we've discussed already. So I think it was a reasonable attempt to try and put these patients into sort of different buckets for disease severity, but probably a little bit simplistic and just reflecting the challenge. I think that would be hard to come up with the system to do this across the board.
- [12:02]
A
The second thing I want us to think about that a bit fits with exposure is treatment. I think this makes sense to any of us who treat hyperthyroidism as why these two things would go together. But there's a link here is that the dose of methimazole that was used was based on this initial disease severity. So this is another thing that is going to be an exposure for these subjects, for the these patients, and is going to be linked to the initial disease severity. And the way the authors report this with methimazole is they report the dose, the change in dose and then the duration of dose throughout this study. One interesting thing that the authors do is when they report the methimazole dose, they report it as a cumulative dose per week. The outcomes were based on labs. So we talked about those couple of different lab assessment methodologies that they used before. So for the outcome they were using the clinical thyroid status and specifically the outcome of interest was the time to an encounter to reach those different clinical thyroid statuses. A couple comments on the statistics as we wrap up the methodology here. So the authors use a univariate analysis and importantly they recognize that because they are basing their outcomes on encounter based results that they are going to be dependent upon how often these patients came back. So they use what they described as a patient weighted encounter data and that helped to account for patients who had more severe disease because those patients were almost always having more frequent encounters. And this also helped to account for patients who had been followed for longer periods. And so they were going to have more visits where they were well controlled. So they didn't want those factors skew in results. And so they developed this methodology of waiting based on the encounter data to account for that. Okay, there were more statistics. I thought those were the important things that were worth mentioning. So now we're going to go back to Junaia and she's going to walk us through the results that the authors found here.
- [14:00]
B
Thank you, Chase. So I will be going over three tables and three figures in this study. So before we do this, just some kind of like summary of the overall results that they have gathered. So again, this is a total of 152 patients. And these patients were followed for a median of 515 days, which is approximately 17 months. The days though range between 282 to 949. The patients had a median of 7 encounters, anywhere from 5 to 11. Median interval visits are 57 days, which is somewhere anywhere between 34 and 96. The initial methemazole dose, 70 milligrams per week, which is 10 milligrams per day on average. But the dosing the is between 50 milligrams per week to 210 milligrams per week. The average dose change is 16% per encounter, indicating dose reduction were common as treatment progressed. Now I'm going to start with table number two in this paper. Table number two is showing association of age on clinical characteristics. The Cohort divided into four age groups of of 18 to 30 for the first group, 31 to 45 years old for the second group, 46 to 64 for the third group and over 65 years old for the fourth group. Their initial laboratory values sh pretty t4 and total t3 were comparable. There were no statistical differences. Patients were noted to have started on similar weekly methimazole dose of 70 milligram per week, but again the dosing is the range is pretty wide, anywhere from 35 milligrams per week to 210 milligrams per week. Patterns of dose adjustments over time, including the magnitude of per encounter, dose reduction and the highest dose required, also did not differ significantly by age. Likewise, visit intervals, numbers of encounters and total duration of follow up were consistent across groups. Clinical status during treatment were similar regardless of age, with each group spending a median of roughly 80% of encounters in a euthyroid state and showing no significant differences in the proportion of hypo or hyperthyroid visits. The summary of Table 2 indicates that age was not associated with significant differences in baseline thyroid function, methymasil dosing pattern, follow up intensity or treatment outcomes in this cohort. Now moving on to Table number three. Table number three is showing association of sex on clinical characteristics. The cohort is female. Predominant with female patients were 119, which is 78.3% of the cohort and male 33 patients 22% of the cohort. Like Table 2, the patients presented with comparable initial TSH free T4 and total T3 values. Both groups also showed similar weekly methimazole doses at 70 milligrams per week. Now the range here is between 55 to 210 milligrams per week. The pattern of dose adjustments over time and the highest dose required did not differ significantly by age, follow up duration. Number of encounters were also similar. Men, however, had slightly longer intervals between visits, though this difference did not translate into differences in biochemical control. So in summary, Table 3 findings indicate sex was not associated with significant differences in initial biochemical findings, methimazole dosing pattern, nor the likelihood of achieving stable control during methimazole therapy. Both groups also showed a median of about 80% of the encounters in EU thyroid state and showed no significant differences in the proportion of the hypo or hyperthyroid visit. Now I'm moving on to table number four. Table number four is where we begin to see variations. Table number four is showing association of initial disease severity on clinical characteristics. In this table the patients were grouped mild, moderate and severe. In the mild there's 59 patients, which is 39% of the cohort. The moderate has 40 patients 26% of the cohort and the severe 53 patients, 35% of the cohort. Here we see an expected statistical differences in the initial lab findings between the three groups. The median for the mild group is a free T4 of 1.0, the median for moderate is 1.9, and for severe it's a free T4 of 4.1. In addition to this, this table also showed statistically significant associations with interval lengths between visits, initial antithyroid drug dose, maximum antithyroid drug dose, percent change in dose with each encounter, and number of encounters per patient with thyroid status at goal. The findings are as follows. Patients with worse initial disease had Shorter Average interval visits 48 days for the severe, 69 days for mild and 57 days for moderate, and also showed a larger dose reduction per visit. The initial dose per week were 35 mg for the mild, 70 mg for the moderate and 210 mg for the severe. Maximum dose per week were 70 mg for mild and moderate and 210 mg for severe. The dose change per encounter was also significant with mild a 12% dose reduction, moderate 16% dose reduction, and versus severe a 22% dose reduction. Methymasil dose after 180 days did not show statistical difference with breakdown as follows 35 milligrams for the mild, 33 milligrams per week for the moderate, and 48 milligrams per week for the severe. Clinical thyroid status showed 95% achieved euthyroid state in the mild group, 80% achieved euthyroid state in the moderate group and 69% achieved euthyroid state in the severe group. Looking at how initial disease severity affected disease trajectory over time, average thyroid lab values were all trended to normal by 180 days. These are shown in figures that I will be going over next. The first of the three figure is Figure two on the study. Figure two demonstrates that although patients with severe initial disease began with markedly higher free T4 and total T3 levels and require substantially higher methimazole doses, all severity groups show similar biochemical trajectories. FET4 and total T3 fall rapidly and converge into this normal range by approximately 180 days. TSH remains suppressed for a prolonged period regardless of severity. Methimazole dosing curves show that severe cases start at much higher weekly doses and undergo larger early dose reduction, but by six months all groups converge to a similar maintenance dose of roughly 35 milligram per week. This figure also shows that initial disease severity influences early dosing intensity but does not affect speed of biochemical normalization nor long term maintenance dose. It also demonstrated TSH is not a reliable titration marker for the next figure. Figure number three. Figure number three showed methemazole dosing differs significantly by initial disease severity during the first 180 days of treatment. Patients with severe Graves disease require higher doses in the initial 60 day interval and undergo larger dose reduction as their thyroid hormone levels fall. Despite early differences, all severity groups converge to a similar maintenance dose of approximately 35 milligram per week after six months and dose differences are no longer statistically significant beyond day 180. This figure reinforces initial disease severity, drives early titration intensity and follow up frequency, but long term methimazole requirements are essentially uniform. Supporting standardized maintenance approach once biochemical stability is achieved. Hyper and hypothyroid events across initial disease severity can be seen in figure number four. So figure number four has three subfigures. Figure four a, B and C. Figure four a showed time to first hypothyroid event does not differ significantly across groups, but severe patients accumulate more such events over time. The curve highlights initial disease severity predicts treatment lability but not speed, underscoring need for closer early monitoring and more cautious dose adjustments in patients presenting with severe hyperthyroidism. Figure 4b demonstrates that although patients with severe initial Graves disease achieve euthyroid state same rate as with mild or moderate disease, they experience significantly greater biochemical instability throughout treatment. Figure 4C showed a faster time to first hyperthyroid encounter after normalization of thyroid lab values among patients with worse initial disease severity. Overall findings showed severe cases have a higher overall proportion of hypothyroid encounters and a faster recurrence of hyperthyroidism after reaching euthyroid status, reflecting more volatile thyroid hormone dynamics despite appropriate titration. So that was the last figure presented in the study. Now I'm going to hand it over to Chase to take us through the discussion of these findings.
- [24:18]
A
All right, Jonaya walked us through a bunch of data here, so we're going to put it together and we'll use the way the authors do that to describe it and give you our thoughts along the way. I would summarize the author's findings and I'll quote them in part of this here by saying that by utilizing an approach where patients with more severe Graves disease are treated with higher methimazole doses, monitored more frequently and dose reduced more aggressively. Patients with severe thyrotoxicosis reach euthyroid status as quickly as patients with mild or moderate thyrotoxicosis. A couple of key findings that the authors point out. First of all is, as Jonae has pointed out, that that initial disease severity is not associated with a final maintenance dose. And second, that patients with a higher initial disease severity have more labile thyroid control and that is potentially from the higher dose of methimazole or the underlying pathology itself. The authors then go on. I would say that they imply that a higher initial disease severity warrants a higher initial dose of methimazole, and they do cite some references that support that claim that a higher dose is going to lower thyroid levels faster. I'll play devil's advocate here. I clinically do exactly what the authors do here. But just looking at this data in and of itself, you could also make the argument that would say, well, maybe it doesn't matter if it doesn't really matter the severity of your disease or what dose you're on, if you're going to get to the same thyroid levels, maybe this data is just telling us that none of these things really matter. You get there at the same speed. So, Elizabeth, I've just made up an alternative explanation there, but what are your thoughts? Is that worth considering at all or no? We have plenty of data from other studies that clearly back up this idea that higher doses of methimazole get you to a youth outward status quicker.
- [26:04]
C
Yeah, it is a little surprising that in the study the higher doses did not make a difference. But we do have some trials back from the 1990s, older trials, a couple of them, that suggest that it probably does make a difference, the starting dose in terms of the rapidity of getting to euthyroidism. So in one trial that compared 10 milligrams a day of methimazole compared to 40 milligrams a day of methimazole as a starting dose. The lead author of that study was Ryanwein. It was published in JCNM back in 1993, 85% of patients had normal thyroid function after six weeks on the low dose compared to 92% who got the high dose of 40 mg. So a small difference, but a significant difference. And another randomized trial from about the same time period, this one published in 1996 with first author Paige in Clinical Endocrinology, randomized here, carbimazole to a starting dose of 40 milligrams a day compared to 20 milligrams a day found that clinical responses at 6 and 12 weeks were similar. Drug related hypothyroidism was less likely to occur in the patients who initially received the lower dose, as you might expect, and was I think also seen in this study. But that lower dose was less, less effective at controlling hyperthyroidism in the patients with a more severe hyperthyroidism. So although the study we're talking about today didn't show a difference in time to euthyroidism based on the disease severity or the methimazole dosing, I think we do have older studies that suggest this, this might actually make a difference. And I think also it matters because we have prior large observational data sets that suggest that the longer the cumulative time that somebody spends hyperthyroid, the higher the risk for cardiovasc vascular disease and the higher the risk for mortality.
- [27:52]
A
The authors then go on to say that, well, because of that increased lability in thyroid levels for patients with moderate and severe initial disease severity, that we probably need to have what they've described as an ambitious goal of monthly TFT monitoring. Though I'll note that this is something that would be in line with guideline recommended care. So Elizabeth, thoughts on that as far as a recommendation? Is that something that needs to be pretty consistent for folks who have pretty high thyroid levels and we're using fairly high doses of methimazole? What are your thoughts on that recommendation from the authors?
- [28:27]
C
Yeah, I think that is a reasonable recommendation. And I think for me that's maybe the major take home point of this study is that how much the frequent monitoring does matter. We all have those occasional patients who, you know, miss their follow up visit, miss their labs, come back four months later and the TSH is 80. And we don't like to see this. So the current guidelines do suggest an approach that's really in line with what the authors are suggesting here. Suggest initial assessment of the peripheral thyroid hormones somewhere between two and six weeks after you start the methinsal therapy, kind of depending on severity of the hyperthyroidism. And I will say in my own practice it's more typically six weeks, not usually two. And then you can sort of space out the timing of that testing to, you know, every four to six weeks, then maybe every two to three months. And then if somebody is really stable on kind of low dose maintenance, you know, to every six months, eventually the
- [29:17]
A
authors then wrap up by giving some of their strengths and limitations and we'll walk through those. They do point out that in their study there was variability in the length of time that patients were followed. Though as we talked about in the methodology, they tried to account for that by averaging encounters across each patient. They also mentioned that it's a single center and all the limitations that go along with that. They describe their population as representative of being similar to a Graves population at large. So they didn't think that that would have a major impact. I will reiterate that with single centers and certainly single providers that you can introduce certain practice patterns that that may be different. We may not be capturing all of those things. So I think helpful that the authors point that out as a limitation. Their third limitation that they mention is that it's a relatively small sample size. And then the final one is they point out that there is some missing data or at least data that they would have liked to have have had access to. So some examples that they provided immunosuppressant use, the actual T rab titers, presence of thyroid eye disease. Finally, the authors conclude with a summary and I'll quote them here, where they say this retrospective study provides new insights into how initial severity of Graves disease affects treatment response and dose modification and suggest that long term maintenance dosing is not associated with initial disease severity. And where I would leave this just for somebody to think about is what I might describe as an implication, and we've talked about this already already, but where the authors would suggest that in severe Graves disease that using a higher methimazole dose with more frequent monitoring, stronger dose reductions achieves a euthyroid state just as quickly as in milder Graves disease. Okay, so before we get to our own practice and whether this should change anything that we do, I want us to think about the quality of this report overall. Janaya, you spent a lot of time thinking about this, wrestling with these numbers. What are your, your impressions on the quality of this report?
- [31:11]
B
I think quality wise, yes, I did agree that it is a small study with missing data that they have acknowledged. And again I think this is also a single center. But in spite of these limitations, I feel like it did give a good snapshot, maybe is a word to describe it of and probably also kind of confirm a little bit it that our clinical practice pattern probably is similar to them, that it does affect initial disease severity, does have an influence in our dosing frequency, initial dosing, the frequency of how we followed up with the patients and, and then eventually basically the dose titration magnitude 2 per encounter. So I Think overall, for me, this study is a pretty reasonable, decent study when it comes to providing a snapshot of what an actual real, you know, real time, real data community practice picture for management of graves disease.
- [32:17]
A
Elizabeth, same question for you thoughts on the quality of this report overall.
- [32:21]
C
So I think it addressed an interesting question and an understudied question, you know, surprisingly understudied question considering how important this comes up in clinical practice. I think think the limitations of the study are sort of well acknowledged by the authors. But the single center, the retrospective nature, the fairly small sample size, all are reasonably significant limitations. And I think because it is an important study question, I would love to see a larger prospective study to see if these results are really replicable across other practice settings and larger populations.
- [32:54]
A
And as always, we will finish with thinking about our clinical practice and whether these results should change what we do, whether it confirms what we do, whether we're going to wait more data comes out. So Jonaea will again start with you. What are your thoughts? The clinical care that you provide, will it be any different based on the results of this paper, I think personally
- [33:12]
B
it may not change because at this point in time there's some similarity with what that single center is experiencing. So I don't think personally at this moment there is a change in clinical practice that I would change at the moment. Second though, I think think maybe because I'm thinking of fellows and education on that line, I think this study also is good way of teaching some fellows to recognize that initial disease severity, especially on the, you know, the mild, moderate, severe cases that we may have to pay more attention to patients presenting with severe cases because of the lability that we are all aware of. So I think from a teaching standpoint, I think this is a good study to be able to point out to the fellows regarding which groups would when they present to our clinic or to the ER or inpatient consultation, which group that we will have to need to have pay more attention to and follow more closely. So that at least is what I would gather after reading this article.
- [34:13]
A
Elizabeth, we will finish up with you. Similar question. What are your thoughts about changing practice but then also just a broader landscape about how does this maybe inform other things. We have similar questions, not just predictors of time to euthyroidism, but also predictors of remission. So related but different questions. So just, just give us a thought about that before we wrap up today.
- [34:33]
C
Yeah, I think I agree with Junia that this is probably not going to change my own practice in the short term, but I think it does reinforce current recommendations about the importance of rapid testing or frequent testing and dose titration in our patients with Graves disease who are treated with methimazole. I think does relate to a similar question, which is predictors, not of sort of time to euthyroidism, but predictors of remission of the Graves disease altogether, which I think for many patients may be kind of a more pressing clinical concern when we're making our initial treatment decisions and having our initial discussion about what modality of therapy we want to use in the first place. And it's interesting that some of the predictors of remission that have been published in other studies, older individuals, for example, are more likely to remit than those under age 40. That was not seen in this study, which I thought was interesting. Other predictors higher thyroid hormone levels at baseline tend to predict somebody who's less likely to go into remission. Higher trab titers, which were not included in the study, but which I think would be really interesting to include in a future similar study, tend to predict less likelihood of long term remission. Smokers less likely to have long term remission, larger goiters, again something that might be important to include in a future study, suggests less likelihood of long term remission. So there's some overlap between what they looked at and what they found in this study and what we know about likelihood of long term remission, but some interesting differences as well that I think are worth exploring down the road.
- [36:07]
A
And with that, I would like to thank Janaya Lim and Elizabeth Pierce for joining me for this month's edition of Endocrine Feedback Loop. I learned a great deal and know 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 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 of the podcast itself. Please email us@podcastrine.org 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.