Growth Hormone Deficiency Learning Zone
Transcript: Expert discussion
Professor Mehul Dattani, Dr. Charlotte Höybye, Professor Steven Simoens, Dr. Shankar Kanumakala and Dr. Robert Murray
Interview recorded Jul 2023. All transcripts are created from interview footage and directly reflect the content of the interview at the time. The content is that of the speaker and is not adjusted by Medthority.
We need to move to the next section, which is really questions relating to all aspects of growth hormone deficiency that we've discussed today. And perhaps, maybe I'll start a little of the discussion but all sort of intersect with any particular points or questions that you feel need to be addressed and taken further. So one of the things we haven't discussed, I suppose, is when we monitor patients on growth hormone, growth hormone deficient patients, how are we going to decide on the dose that we use and how do we change the dose? I mean, I personally use a combination of the growth rate and the IGF-1, and I would normally like to try and keep the IGF-1 in the top half of the normal range, and the growth rate obviously as normal as I can get it. Any other sort of takers on that? Any other points from there? Shankar, did you want to say something? In reality, a number of factors need to come into that equation, as you rightly said. And we are here to optimize the growth outcome for the patient. And IGF-1 levels, height increments, or height velocity, and patient adherence all will play a role. Not only it is important in those age increments, but it is also important not to increase the dose when things are moving in the right direction, or when we are seeing the optimum height outcomes. And so I think what is that it is important when the IGF-1 level is at the top end of the range, and you are not hitting the 35 micrograms per kilogram, I do not think in increasing it further to 35 micrograms is the right thing to do. So I would accept when it is at the top end of the range, the dosage might be a tiny bit low, but those patients might be a bit more sensitive to the growth hormone, and they are getting the best outcome out of it.
So I do see, not only optimizing it when necessary, but also not increasing the dose when not necessary is also important. Yeah, no, I think I agree, you know. And you do see some children who are very responsive to low doses maintain good IGF-1s, and maintain a good growth rate. And again, you know, I saw someone in clinic two days ago who was on five mics per kilo per day and doing beautifully, with a high... Septo-optic, abnormal pituitary and the height right up on the 97th centile. So, you know, I think the variability is really amazing and you know, difficult to understand but it is there. So certainly, I would agree with that. And I think Charlotte, one topic we didn't really have time to go into in detail is when you talked about the adverse effects, I mean the impact of the SAGhE study on our thinking and how has that made us really change our approach to the treatment of growth hormone deficiency. Particularly the papers coming from France, I guess. Yes, and think some following papers did not find the same risk but of course, I think most of us have it in mind. But yeah, it has affected us in some way. I think it's made us more aware.
But there's still a lot of unanswered questions. Yeah. And I think and that's what's sort of driven I guess the joint PES, GRS and ESE guidelines suggesting that certainly more monitoring certainly of certain groups of patients and then Kerstin's paper as well which show that actually there are some vulnerable groups of patients in whom you've gotta be extremely careful. Yeah. So I think that certainly brought that to our attention. And can I also just sort of raise Shankar the idea of antibodies with long acting growth hormone and what the current view is on that antibody generation In some of the studies, they have tested for the antibodies and those who where the antibodies have tested, it hasn't come through in everyone. It has come through in some people only, and the presence of antibodies has not, within inverted commas, "affected" the height of outcomes of those patients. And they think that the antibodies are probably not what is that clinically significant, but one also has to be, what is that? Careful in dismissing that thought because they might not be important, or we might not have recognized it importance at this point in time. But is there an importance that time will unravel and that's what the long-term studies are needed very much in this area because some of the side effects may be due to the presence of these antibodies which only time will uncover in the future. Yeah, I think that's right. I mean basically, the incidence of neutralizing antibodies is very, very low from the looks of it. Not completely unknown but low.
So I think you're right that there may be an option to reconsider it but I think at the moment, it's certainly looking positive from that point of view. Correct. Steven, can I come to you again and say, ask you, do you think that the use of biosimilars, cost apart has other beneficial effects on patient outcomes and treatments? I don't think that a biosimilar by itself has an impact on outcome because it has been demonstrated to be clinically equivalent with the reference biologic, but I do think it can have an impact on the health of a larger group of patients because it expands treatment access, especially in, for example, eastern European countries where there may not be reimbursement for the reference biologic or there may be restrictions applied to reimbursement then thanks to the availability of the biosimilar product and its cheaper price, more patients can be treated and hence, outcomes of that group of patients will improve. And I think we should not forget about that, that in certain groups of countries, biosimilars play a pivotal role in actually providing access to treatment. In western Europe, it's a different story. It's about saving money. Within other countries, we should not forget that issue. Yes, I mean I think that improving access is something we don't think about on a day-to-day basis, but it is extremely important and especially when you look at countries, say like India and at parts of Eastern Europe, that's where I think it will make a difference in allowing more children to be treated, I hope.
Yeah, so that's a really good point there. Any other points that people wanna raise? Otherwise, I'll sort of... Yeah, sorry, Shankar. I want to raise one of the diagnostic dilemmas that we have with using the cutoff level in GHD testing. I mean obviously, growth hormone and GHD test... I mean growth hormone testing is a very complex field. There are multiple layers of difficulties, multiple tests and all those things. One of them is the sex steroid priming. So we use a variable cutoff between 5 and 10 with 7 being accepted as a standard one because it is what is that? Within inverted commas, "not accepted widely." If you use a 7 which is accepted and 10 which is accepted in a different country, now are we treating patients, what is that? effectively all the patients who need access to treatment they're getting or are we treating some patients unnecessarily? Yeah I mean, I think that is a very important point and my personal feeling is the answer to that must be yes, that we are treating some patients unnecessarily. And you know, and why do they reverse then at the end of it? You know, I know the reversal process is very fascinating and you know, it's anything up to 50%, 60% in some studies. And even, I think, Rob, that the Manchester group shown that based off the structural abnormalities of the ectopic posterior pituitary have also reversed their GH secretion. But I think, you know, it does make you think that in some cases, did you get the diagnosis right in the first instance? And then should we then... I mean, we've talked about maybe early puberty retest and maybe that's something that's gonna come into play and we're looking at that as part of the national study at the moment.
But maybe even earlier, you know, maybe after a few years could the child be retested? These are children who've got maybe a normal anterior pituitary MRI or maybe slightly small, structurally normal. And you know, GH peak of say four to five micrograms per liter on initial testing, not completely deficient. So I dunno. I dunno what people's views are on that. I think we need to keep a more open mind that's my personal view. But isn't that the problem with all cutoffs that they will include some without growth hormone deficiency in this case and some will be excluded? I don't know. I think it's a general problem with cutoffs and I would like to add also the problems with the IGF-1 assays and we have also all things that influence on IGF-1 levels that maybe we cannot control for all, you know? Yeah, yeah, and I think we ought to sort of wrap up soon but I'm gonna finish up with one last question and see what people's views are, just very short.
So a child coming with a new diagnosis of growth hormone deficiency, would people offer them long acting growth hormone or not at this stage? I think it probably should be in the mix, shouldn't it? For an option. I mean, it's there available on NICE. I think it needs to be discussed with the caveats over long term safety and that we don't know. But I think it has to be in the discussion because the patients nowadays have probably looked it up already. Some of them are going come in with the NICE printed out, I'm sure. So I think it has to be a discussion of it whether... And often with these things, I think if the clinicians have a negative view on it, then the patients take that as well. So I think it's, yeah, one that needs to be discussed and openly with the caveats. Yeah, I think I agree. Shankar, would you agree with that? Yes, I would also agree and I would probably go half a step ahead of that one. Say if after this open discussion, if there is more than one preparation that is suitable for that patient, then I'll take the NICE guidance and use the lower cost preparation. I think that's a balanced view and I think nobody would disagree with that. Charlotte, did you have any closing comments? Yes, I agree with Rob and Shankar but I think also the patients, they think differently. They think it's smart to have only one injection, but they want it. Yeah, possible. Steven, any final comments? No, I told the thoughts of the other faculty members. Okay, okay, so I'll wrap up now and thank everyone all the faculty members, Rob, Shankar, Steven, and Charlotte for really engaging with the discussions and for their great presentations. And I'd like to thank Medthority for making this work. It's always challenging when you have a lot of international speakers on Zoom, et cetera, so there are pros and cons to it, but you made it work very well, so we are very grateful to you.
This content has been developed independently by Medthority who previously received educational funding from Sandoz in order to help provide its healthcare professional members with access to the highest quality medical and scientific information, education and associated relevant content.
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