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- [00:00]
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. Hello and welcome back to the Endocrine Feedback Loop podcast. For our 57th episode today we review a study in the JCEM that gives us insight into how we should wean patients off long term glucocorticoid use and how successful that typically is. We as endocrinologists are often called on to assist in getting patients off exogenous glucocorticoids, though with limited data to guide our recommendations, so we thought that this report was well worth reviewing for the insight it potentially gives us. The authors used an observational study design so we will try to carefully fully consider the limitations intrinsic to such approaches and how they affect the author's conclusions. As a brief reminder, I host this podcast and work at the Vanderbilt University Medical center in Nashville, Tennessee as a general Endocrinologist and Medical Director. Back with us as our regular contributor is the podcast resident Adrenal expert Celia Kura. She comes to us from Columbia University in New York City where she co directs their Adrenal center, serves as their Clinical Chief of Endocrinology and advises as an Associate Dean in their medical school. With us today for the first time is our guest expert is Felix Beuschlein from the University Clinic Zurich in Switzerland. While he too directs their Endocrinology clinic, he is likely most well known to you all as our listeners for his translational research in adrenal pathophysiology and numerous publications and talks coming from that. Importantly for our purposes today, he participated in the writing of the 2024 Endocrine Society Guidelines on Glucocorticoid Induced Adrenal insufficiency. So as you can tell, the perfect pair of adrenal experts joins 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 Endocrine Feedback Loop, we look at a retrospective study on weaning glucocorticoids and recovery of the Hypothalamic Pituitary Adrenal Axis, which was published in November 2024 in the journal of Clinical Endocrinology and Metabolism. Mohammed Fahad Arshad served as the first author for this paper which to us from the University of Sheffield in the uk. I will now turn the Discussion over to Celila. She will walk us through the points that the authors make in their introduction and get Felix's insight on several key concepts along the way. Salila Great.
- [02:39]
B
Thank you Chase, and it's nice to be here with you both today. So, just to discuss the introduction a little bit more detail, about 1 to 3% of the general population is taking systemic glucocorticoids for the treatment of inflammatory conditions and malignancies. Exogenous glucocorticoids can suppress the hypothalamic pituitary adrenal axis, causing tertiary adrenal insufficiency. A previous meta analysis has estimated that up to 50% of patients on oral steroids are at risk of adrenal suppression. The hypothalamic pituitary adrenal axis suppression may occur when glucocorticoids are administered at doses of greater than 5 milligrams per day of prednisolone or equivalent glucocorticoid doses for four weeks or longer. We have experts on the panel here. We just wanted to step back and ask Felix about whether he uses these cutoffs to identify those at risk for developing suppression of the HPA axis.
- [03:29]
C
Yeah, thanks. First of all, great to be here and discuss this matter. So my short answer is yes. Obviously there can always be exceptions of this rule due to comorbidities or comedication. The guideline that you mentioned also appreciates interpersonal differences and suggests rather ranges than fixed numbers such as 4 to 6 millipram prednisolone equivalent and 3 to 4 weeks of duration of pharmacological sterotherapy. But after all, those numbers are completely fine and within the range.
- [04:01]
B
Great, thank you. Tertiary adrenal insufficiency can occur with glucocorticoid administration via any route of administration and the risk rises with increasing cumulative doses and longer duration of treatment. Super physiologic doses of glucorticoids can cause a wide range of adverse effects. For this reason, anti inflammatory doses of glucocorticoids are tapered down as soon as possible after disease control is achieved. Once the glucocorticoid dose is weaned down to a physiologic replacement dose, it's helpful to excess for HPA axis suppression, although this can be done clinically often a more formal biochemical assessment is undertaken by measuring a morning serum cortisol before glucocorticoid administration. If the result indicates possible adrenal suppression, this is then followed by a 250 microgram ACTH stimulation test, the short synactin test. So again Felix, for your expert opinion, is this how you approach assessing whether patients have tertiary adrenal insufficiency?
- [04:57]
C
Yeah, well during the discussion with the guideline panel and various rounds of feedback with many stakeholders, we realized that there is actually quite a variation in clinical practice dependent on clinical speciality and availability of laboratory resources. I think the majority of cases tapering is done solely on clinical crowns and in a smaller proportion guided by hormonal evaluation. The guideline backs this up actually and appreciates both as equal possibilities in case of hormonal evaluation. The recommendation is due to a baseline morning cortisol measurement, but of course when patients are referred to me as there's already a higher pretest probability of an HVA axis problem and I think the same setting is described in a manuscript within a specialized adrenal clinic and therefore the approach in this scenario is understandable and now of course gives a nice opportunity for a data source.
- [05:53]
B
Thank you. Tertiary AI is usually reversible with time and individuals are maintained on the lowest physiologic doses and tested at frequent intervals. The international consensus, as we were just discussing, suggests converting prednisolone to hydrocortisone to facilitate weaning. Part of the reasoning behind this recommendation is that prednisolone has a higher glucocoid receptor occupancy and a longer plasma half life than hydrocortisone. So 120 to 360 minutes versus 90 minutes. The biological half life of hydrocortisone is 8 to 12 hours and prednisolone's is 18 to 36 hours, which leads to hydrocortisone usually being prescribed either twice or thrice daily with the highest dose in the morning and prednisolone being prescribed once daily. The supposition is that hydrocortisone regimen is less likely to cause continuous suppression and therefore offers more physiologic weenie potentially encouraging reactivation of the HPA axis more quickly than prednisolone. Some consider prednisolone to be a better glucocorticoid for replacement in general, believing that the multi dose hydrocortisone regimens result in peaks that may perseverate adrenal axis suppression. However, during the weaning process there's no evidence to support either strategy. The primary aim of this study was to examine HPA axis recovery in patients who remained on long term prednisolone throughout the weaning process. The secondary aim was to assess the recovery rates in retrospectively dose matched patients with confirmed tertiary adrenal insufficiency, either on prednisolone or converted to hydroportisone from prednisolone.
- [07:26]
A
We're going to move into the methodology now that we have a better understanding of the background of what the authors are hoping to do here from their introduction and a little bit of the data that's out there currently, or at least enough to know that there's not much out there to guide what we do. We'll think about the study design here in general before we dive into the particulars of this investigation and the authors describe their work as a retrospective cohort study and as a reminder of what that is. First of all, cohort studies are studies that begin by splitting subjects into at least two groups and sometimes multiple. And the splitting into groups is based on a different exposure. And we'll see here, but the exposure that's going to be used is are different types of glucocorticoid replacement. And what you then have to do is you follow those individuals over time. So a time component is key to a cohort study and you are looking for outcomes and it can be one or multiple, but you're trying to see if there's a difference between one group versus another as far as the development of an outcome of interest. What makes this a retrospective study is when you begin the investigation. I think it's helpful to contrast it to a prospective cohort study because those make a bit more sense. Prospective cohort studies are begun before any of the outcomes are developed. That begins when you split people into groups based on their exposure and you then follow them over time in real time, waiting for the development of an outcome. Retrospective studies instead are done after everything is over. So you're usually going back and pulling data out of a database or reviewing charts from a clinic, as is the case here. Important thing is, is you have to be able to reconstruct that time sequence. You have to be able to show that the exposure of interest occurred before the outcome of interest. And as long as you can do that, you can then still do a cohort study before we get into this investigation, I'll point out. So Solis has already given us an overview of what the aims are. I would say this description of the retrospective cohort study really only applies to the secondary aim. I think the primary aim, the design that's used there, would be better described as a case series. I think it's still valuable information. But really, isn't this more Robust study design of the retrospect cohort city. But I do think the secondary aim is. Okay, so now back to this investigation. We'll start with the study population. And this population was made up of all adult patients who were diagnosed with tertiary adrenal insufficiency at a dedicated endocrine steroid clinic. And the the dates of this, they ranged from September of 2015 through April of 2022. And this was at the Sheffield Teaching Hospital in the UK I think it's helpful here to point out that the fact that this is a dedicated steroid clinic, fel referenced it already, is that this does likely introduce a referral bias. Many of you all as our listeners will likely recognize that that hospital and, and many of the authors here and know that it's a well known place. And, and that's not just an interesting tidbit. It has practical implications in that potentially that these folks are higher risk individuals or at least a different group of individuals than say, might be generalizable. So it's at least possible that this isn't just a run of the mill everybody who has been on steroids and might have adrenal insufficiency. It's possible that more likely to be complicated cases or other challenges or something that would make this group not as well, representative of the general population as we might like. So nothing wrong here, no problem with this. Just something we always have to recognize as a possibility when we have these investigations that come out of these dedicated clinics. Okay, so back to this investigation. This is the process that the investigators use to identify these patients. So they started first of all by looking at everybody who had undergone one of these ACTH stimulation tests. They then went back and they got rid of all of the individuals who had this stimulation test for any other reason besides suspected tertiary adrenal insufficiency from oral and or inhaled glucocorticoids. They then removed anybody who was on an oral glucocorticoid besides prednisolone. We're going to come back to that in a second. And I think something that's important to note, the authors point out that they excluded individuals who had protein losing disorders or who had recently worked in night shifts, as they said that the diagnosis of adrenal insufficiency wouldn't have been based on the results of that simulation test. And then so that's why they did not include them. Okay, so Felix, back to you here. I've got a couple of questions for you. We'll start with the first thing and Actually, something I think that you helpfully pointed out as we were all analyzing this article, is you had some thoughts about that, that it might be interesting if the authors maybe hadn't excluded all of those individuals who they took out who weren't on prednisolone at baseline. Would you elaborate on that just a little bit and kind of what your thinking was around on what other possible approaches could have been utilized here?
- [12:05]
C
Yeah, you know, one of the possibilities, of course, by excluding patients and you know, I understand the design and the purpose of this is to improve comparability of the remaining cohort. Of course you want to make them as comparable as possible. However, for example, excluding the patients who had been under hydrocortisone from the start for whatever reason, I mean, there had been decision of the treating physician, I assume, as that also is somewhat of a missed opportunity because that group would have potentially served as another control group and it would have been quite informative to know how their HVX BIS recovery actually evolved. So that would have been another endpoint which is unfortunately not really covered in the article.
- [12:51]
A
And second question for you, I was just hoping you could clarify. So we've got prednisolone here, though I think a lot of us, certainly Salila and myself in the United States are probably far more familiar with prednisone. And so just curious if you could comment on. Can we just think of those things as equivalent? Are there differences we need to have in mind? Why does that vary around the world depending upon where you are? So any insight that you can give us on that would be helpful. Felix.
- [13:15]
C
Yeah, maybe I just again refer to the guideline where we use prednisolone and prednisolone interchangeably. Really. I mean, there are some minor differences in kinetics and some differences in patients with liver disease and hyperalbuminuria, hypo mania. But I would not make it more complicated than that. From the work with the guidelines, I learned that availability of preparations worldwide is quite different and particular for the availability of low dosage tablets. So in Europe we have 1mg prednisolone tablets, but this is not the case in other parts of the world. And that can pose some practical challenges in the lower dose of the tapering, you know, where breaking down 5 milligrams once and twice and three times and really makes a challenge. So I think this is rather a very practical difference that, you know, halts us in the, in our clinical practice.
- [14:07]
A
Move on now to definitions that the authors use, and that's specifically around the definition of tertiary adrenal insufficiency. So the authors point out that they would consider that once the prednisolone dose was 5 milligrams or less, and at that point then they would do an ACTH stimulation test and the cutoff that they used was at the 30 minute mark and that was a cortisol that was less than 430 nanomoles per liter, which would be equivalent to 15.6 micrograms per deciliter. Okay, so Felix, right back to you. So this is maybe a more complicated question, but give us some insight. So first of all, does that cut off make sense? I asked that because there has been a lot of discussion and more data coming out recently that's saying, well, we just used to have these hard and fast cutoffs. Maybe they were different to use the micrograms per deciliter. It could have been 18 or 20. But now more and more data saying maybe that should be a lower cutoff. And well, maybe it depends on the assay that you use. You've got to figure out what your institution does and we keep lowering that. So, so help us understand maybe that broader context. But then also hear a conclusion of do you think that the authors came up with a good cutoff to use or maybe should we have questions about that?
- [15:16]
C
Yeah, well, thanks for opening this kind of worm so widely here. So the definition of a strict cutoff for clinical patches is quite problematic. I mean, this really has been also a very long discussion within the guideline panel. The review of the literature shows that patients following glucocortical therapy. In those patients, there's a quite good correlation between the baseline cortisol levels and those following ACTH stimulation. Whatever cutoff you use, however, the correlation with clinical outcome is much more complicated as signs and symptoms of even a relative adrenal insufficiency are quite variable, often unspecific, and can be further be blurred by flares of the underlying gluocorticoid dependent disease. Cases of really adrenal crisis are fortunately overall quite rare, which makes it from a research perspect, also a difficult endpoint. And I mean, this is kind of the point that you depend on whatever cutoff you're using. And finally, while the recovery of the HV axis is very likely in the setting of glucocorticoid induced adrenal insufficiency, in many cases the underlying disease will require further rounds of glucocorticoid therapy, which further complicates matters. So I'm avoiding your question on this particular cutoff by just stating that this is a difficult topic indeed.
- [16:34]
B
Good.
- [16:35]
A
Okay, so now we'll think more about the study design and so we'll describe what the authors do as far as how they manage these individuals, these patients. They report that patients were evaluated every 6 to 12 months until they had recovery of their HPA axis. And if subsequent ACTH stimulation tests failed, then the subjects were maintained on physiological replacement doses of prednisolone as low as the patients could tolerate. As an interesting point, this will be key for understanding. The second secondary aim is that if on that physiologic replacement dose of prednisolone, the subjects were symptomatic, then they were switched to hydrocortisone. So again, this is getting to those two different groups, the two different exposures, one exposed to prednisolone, the other one now to hydrocortisone. And one thing that I'll point out is that this definitely introduces the possibility of a bias. Now, the, the authors were very good about this. They're very clear that they understand this possibility and that that's a reality of what they're doing here. And we'll talk about in a second about one of the things that they did try to mitigate this. But the point being is that in a randomized clinical trial, the individuals get in different groups because they are randomized to get in that group. That is not what's happening here. So somebody is choosing to put them in a group. And that choosing is very much related to, to symptoms that the patients are having. Felix has mentioned it already, but you always have to wonder is even if you've got your symptoms that you're labeling as ones that could be from adrenal insufficiency, if these individuals are being treated with glucocorticoids to treat some other condition, it's always possible that it's that underlying condition that's contribut. It could also make you wonder other things of, well, might this person have a different degree of adrenal insufficiency? And maybe that's what's contributing here. And so lots of questions I think that that raises. Felix, I was interested as a final question here in this section for you, for your insight into this and additionally just the, the clinical rationale for why you might want to switch somebody from prednisolone to hydrocortisone because of these ongoing symptoms that a patient has.
- [18:34]
C
So first of all, I would agree on the notion of the selection bias, and I think this is an important One, and we might come back to this later on. In general, of course, I understand the approach of changing a regiment if a problem occurs because we do this all the time. This is clinical practice. However, what the guideline would recommend is rather increasing the steroid dose to the lowest possible amount rather than switching it to another preparation. I think this is in variance of what has been here implemented in this study or in this clinical approach.
- [19:05]
A
And finally, we will think more about the outcomes. So Leela told us a little bit about the aims already, but to be a bit more specific, so the primary outcome here is simply looking at the percent of patients who were on prednisolone throughout the study and then recovered normal HPA function. So this primary outcome does not include those individuals switched to hydrocortisone, just kept on prednisolone. The secondary aim though is that comparison of HPA recovery between those maintained on prednisolone and those who were converted to hydrocortisone. As Felix mentioned, this is, it can often be a challenge with these retrospective studies is you're left with the data that you've got and, and prospective ones. You can be a bit more specific about what you want to do. Retrospective. The data is what it is, you've got to figure out what to do with it. So one of the things that the authors did here that I did really like is they said, they, they acknowledged, hey, these groups are likely going to be different and they're going to have confounders for that reason. So we need to try to minimize that as much as possible. So one thing that they did is they dose match. So for everybody who is in the hydrocortisone group, they dose matched them with individuals who were maintained on prednisolone. And they said this is not going to get rid of confounding, but our hope is that this will help minimize that. So I like that the authors did that. Okay, so now with that in mind, all of those methods, I'm going to kick things back over to Salila and she's going to walk us through the results as reported by the authors.
- [20:24]
B
Great, thank you Chase and Felix. So I just wanted to get into a little bit more detail about the discussion. So it started with 837 patients who underwent an ACTH stim test during the study period of six years and eight months after excluding those who underwent a stim test for another indication, a total of 276 patients on Long term glucocorticoids suspected of having tertiary adrenal insufficiency remained, so you had 254 on oral glucocorticoids plus minus the inhaled glucocorticoids and 22 on inhaled glucocorticoids only after excluding the patients on glucocorticoids other than prednisolone plus or minus a steroid inhaler at the start of the study, there were 206 patients who were included in this study. So with regards to the primary outcome which as a reminder was to examine the HPA axis recovery in patients who remained on long term prednisolone, of the 206 patients on prednisolone plus or minus a steroid inhaler at the start of the study, 176 remained on prednisolone throughout the study period while 30 symptomatic patients who all failed their first stim test were converted to hydrocortisone. In total, 112 of the 176 patients on prednisolone passed their first stim test and were successfully weaned off glucocorticoids within the study period. Of the remaining 64 patients, 41 patients underwent a second stim test after which another 18 patients recovered their HPA axis. A further 10 patients underwent subsequent short synactin tests and seven were successfully weaned off glucocorticoids. Only three patients did not recover the HPA axis after three or more stim tests. The remaining 36 patients were awaiting a subsequent stim test, lost a follow up or had died before the subsequent stim test. Thus, the overall HPA axis recovery rate for those patients who are on prednisolone plus or minus the glucocorticoid inhaler at the study start and who remained on prednisolone throughout the study period was 66.5% or 137 of the 206 patients. When excluding patients who were converted to hydrocortisone, there were 77.8% or 137of the 176 patients on prednisolone plus or minus the inhaler who reactivated their HPA axis with regards to the secondary outcome, which as a reminder was to assess the recovery rates in retrospectively dose matched patients with confirmed tertiary adrenaline sufficiency either on prednisolone or converted to hydrocortisone from prednisolone during the study period. There are 161 patients who had failed an ACTH stim test and therefore had confirmed tertiary AI. Of these, there were 71 patients on prednisolone plus or minus glucocorticoid inhaler at the start of the study and underwent subsequent testing with ACTH stim t tests to assess whether conversion to hydrocortisone influenced recovery outcome. 10 patients on prednisolone 4 or 5 milligrams and 13 patients on dose match hydrocortisone 20 milligrams were analyzed, so these are patients that were considered to be on physiologic doses. The recovery rate in the prednisolone group was 70% while those patients converted to hydrocortisone it was 15% with a significant P value of 0.008. Results were similar for reactivation of the HPA axis in all adrenally suppressed patients who underwent subsequent testing. Of the 41 patients in the prednisolone either less than or equal to 5 milligrams a day, 61% recovered adrenal function and 27% of the 30 patients on hydrocortisone less than or equal to 25 milligrams per day recovered and the P value there was 0.004. A comparison of the demographic and clinical factors between the two dose match groups showed that there was no difference in age indication for cucocorticoid treatment, treatment or duration of glucocorticoids between the two groups. There were more females in the hydrocortisone group, albeit the difference fell short of statistical significance. The p value was 0.074. However, there was significantly higher use of opioids in the prednisolone group with a p value of 0.034. The mean baseline cortisol at 0 minutes and the median ACTH at the first stim test was not different between the two groups. The mean number of stim tests per patient was significantly fewer and the follow up duration time in the prednisolone group significantly shorter than in the hydrocortisone group. During the study period there were no hospital admissions due to adrenal crisis in the prednisolone group, while there were two patients in the hydrocortisone group who had at least one hospital admission due to adrenal crisis and there was one patient who had five hospital admissions. There were no inpatient mortality during any of the admissions and the total number of admissions for Any indication was 14 in the prednisolone group and 26 in the hydrocortisone converter group.
- [25:02]
A
Grief all right, so Leela has given us all of the numbers that the authors present. Now we're going to move into the discussion to see how they wrestle with that and how they try to put that together for us. I will start where the authors do, which is with a summary of their findings and I'll quote them. They say most patients on long term prednisolone have normal HPA axis function when referred for dynamic testing. Couple of other points that they make is that the weaning rate is high and that only 1.7% of patients remained on prednisolone after three or more failed ACTH stimulation test. The authors then go on I think to talk about what's really the interesting point which is this conversion of hydrocortisone and to try to wrestle with that. And they point out that at least in their data the conversion from prednisolone to hydrocortisone did not seem to enhance HPA access recovery. They additionally point out that all hospital admissions for adrenal crisis were in those on hydrocortisone. I'll make an editorial comment here that at least would make me wonder is if yet again maybe these groups weren't exactly the same. There are obviously differences between prednisolone and hydrocortisone certainly in terms of frequency of dosing, but otherwise it wouldn't have a reason to be terribly worried about one group versus the other having more susceptibility to adrenal crisis. So again makes me wonder if there might be a difference in that hydrocortisone group really isn't the same as the prednisolone group. And then a final point on this section here is that the authors point out that the results both of their study and then another one that they c in their paper question the rationale for converting patients to hydrocortisone to attempt to enhance the recovery of the HPA axis. So Felix, particularly interested in your thoughts on this about this claim. How would you put this together? Do you agree with the authors on this? Would you caveat it? Just give us a sense of your view of that?
- [26:51]
C
Yeah, I would caveat a little bit and I might maybe turn it around saying that the study does not indicate that hydrocortisone has a large benefit that would outweigh the potential selection bias that we already covered a little bit. The other state that in the end a prospective randomized and I would really also add blinded study would be required to make this claim and we might actually wait for that for a long time. I think for the time being both theories are possible with no from my perspective really convincing data supporting one or the other. And in that regard, the guideline holds true, which doesn't really make a difference between those. And I think it's also about your personal practice, whether you're rather a hydrocortisone person or a practice alone or pretison person. And if you feel more comfortable with that and treating your patients with that, that should also come into play here.
- [27:44]
B
Good.
- [27:44]
A
And in a second, we're going to wrestle a little bit more with how this should impact our practice. But before we do that, I want to touch on the author's limitations so they do a good job. I've mentioned this before, but I'll reiterate it. They've been very upfront about some of the limitations of their study and they list them here. So I'll do the same. They start with that this is a retrospective design. We've talked about that already. But that has limitations. Is your. The data is what the data is and you've got to wrestle with it. You can't really decide what you want to go looking for if it's not there. The next one that they mention is that the adrenal insufficiency rate was based on only those who underwent the ACTH stimulation test, and so it does not include those who were weaned without dynamic testing. Additionally, they point out that they didn't have a good way to assess the cumulative dosing of the glucocorticoid. And then finally, one that we talked about earlier is that the conversion to hydrocortisone was not a random selection. They do point out, and CELA went through these numbers at the very end of the results is is that they didn't see any obvious differences. They looked for different things for a long list with these two different groups to try to say, can we find something that would suggest that, yeah, these groups are pretty different, at least what they looked at. They didn't identify anything. But acknowledging that that reality certainly exists. Finally, the author's conclusions. I got a series of quotes that I will relay to you all. So first of all, the authors state that converting a patient on prednisolone who has symptomatic adrenal suppression to hydrocort does not enhance the adrenal recovery rate. Next, the authors say that prednisolone allows HPA axis recovery in patients being weaned off glucocorticoids. And finally, as Felix has alluded to already, a prospective randomized study to determine the optimal weaning regimen comparing different treatment regimens is needed. Okay, so we're going to wrestle a little bit more with our own practice. We talked about this at the very beginning as this is something we do all the time and we often don't really know exactly how to do this. We just have a pattern that Felix described as we have what we're comfortable with. So we want to wrestle with should this change what we do here. But before we do that, though, I want to just think about the quality of this report overall. So, Leela, let's start with you. You spent a long time wrestling with this article and thinking through the details. What's your impression of just the quality of this report overall?
- [29:54]
B
Yeah, I mean, I think that the authors really identify the limitations that I think make it harder to change practice based on these results. I think the fact that it's a retrospective design makes it difficult to know exactly what to do in your own practice based on these results. And as Felix was saying, I think in the future, if there were a prospective or randomized control trial that would help guide us in whether or not we would change our practice. And you know, to Felix's point, I think that we sort of do fall into two camps, like the I like to wean on prednisone camp versus the I like to wean on hydrofortisone camp. And if anything, like I, since I fall into the weaning on prednisone camp, if anything, it's not inferior to do that based on these results. I probably wouldn't change my practice based on on these results. But it's interesting to think about, but the fact that it was retrospective and there does seem to be some confounding in how the groups were established, I think makes it hard to make any changes based on these data.
- [30:51]
A
Felix, why don't we get your thoughts on the quality of the report overall?
- [30:54]
C
Yeah, not really much to add really onto this. I think it's great to have that study. And I'm actually a fan of making use of data in a meaningful and scientific scrutinizable way. I think that that's great. And we all know the authors, they're doing a great job. But I would also agree it's not the time to really change practice. And I will remain to be a hydrocortisone person rather, because I was raised like that. I would make, maybe this is not completely related to the study, but I would also make the point that from my perspective, sometimes it's important that the patients understand that we are talking about weaning. We are not talking about treating their disease maybe any longer. So we are in a situation where we try to get rid of any kind of steroid and sometimes there the change from their use retinisol that they used for their whatever disease had been treated with. Now we change this into the endocrine field and we use this now to get rid of it altogether. From a psychological point of view. Also, it sometimes helps the patient. Nothing to do with the study, but it's another point that I would like to make here.
- [31:58]
A
One final question for you, Felix. I'm going to circle back to something I think you were alluding to before and this is where the authors landed with that. Well, we need a prospective randomized study you mentioned, ideally a blinded study here, given the reality of a placebo effect. So give us a sense. Is this something that you think think is likely to come or do you think that we would all like that, but we're probably not going to get that. And so we really just need to figure out what we're doing based on these observational studies that we have and then just how we were raised, as you said earlier.
- [32:27]
C
Yeah, so I would love to have that. I mean a head to head comparison hydrocortisone brightness on that could be marvelous. It would really be a prospective randomized and blinded study because, um, you know, if people know they already have the good or the bad stuff, that comes with another problem. I don't think that we're going to get this. However, I'm eager to see the results of the Swiss initiated toast study. You might have heard about that. So that is a study that compares tapering versus stopping. So what you were saying, placebo control. This is a way a placebo controlled randomized blinded study. And if that turns out to be equally possible, so you either taper it down prednisolone or you stop altogether, then the former question about hydrocortisone versus prednisolone might be even less relevant.
- [33:16]
A
And with that I would like to thank Celilakura and Felix Boychline 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 and Andrew Harmon. 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@podcastron.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.