This hot off the press paper has appeared in Thyroid. I cannot pentrate the paywall but hope to access this soon. Should be an interesting paper.
Evidence Based Use of LT4/LT3 Combinations in Treating Hypothyroidism: A Consensus Document
Dr. jacqueline Jonklaas, Dr. Antonio Carlos Bianco, Dr. Anne Cappola, Dr. Francesco S Celi, Dr. Eric Fliers, Prof. Heike Heuer, Dr. Elizabeth A McAninch, Prof. Lars C. Moeller, Mrs. Birte Nygaard, Dr. Anna M Sawka, Dr. Torquil Watt, and Dr. Colin Dayan
Fourteen clinical trials have not shown a consistent benefit of combination therapy with levothyroxine (LT4) and liothyronine (LT3). Despite the publication of these trials, combination therapy is widely used and patients reporting benefit continue to generate patient and physician interest in this area. Recent scientific developments may provide insight into this inconsistency and guide future studies.
Methods
The ATA, BTA and ETA held a joint conference on November 3rd 2019 (live-streamed between Chicago and London) to review new basic science and clinical evidence regarding combination therapy with presentations and input from twelve content experts. Following the presentations, the material was synthesized and used to develop Summary Statements of the current state of knowledge. After review and revision of the material and Summary Statements, there was agreement that there was equipoise for a new clinical trial of combination therapy. Consensus Statements encapsulating the implications of the material discussed with respect to the design of future clinical trials of LT4/LT3 combination therapy were generated. Authors voted upon the Consensus Statements. Iterative changes were made in several rounds of voting and following comments from ATA/BTA/ETA members.
Results
Of 34 Consensus Statements available for voting 28 received at least 75% agreement, with 13 receiving 100% agreement. Those with 100% agreement included studies being powered to study the effect of deiodinase and thyroid hormone transporter polymorphisms on study outcomes, inclusion of patients dissatisfied with their current therapy and requiring at least 1.2 mcg/kg of levothyroxine daily, use of twice daily liothyronine or preferably a slow-release preparation if available, use of patient-reported outcomes as a primary outcome (measured by a tool with both relevant content validity and responsiveness) and patient preference as a secondary outcome, and utilization of a randomized, placebo-controlled, adequately powered double-blinded parallel design. The remaining statements are presented as potential additional considerations.
Discussion
This manuscript summarizes the areas discussed and presents Consensus Statements to guide development of future clinical trials of LT4/LT3 combination therapy. The results of such redesigned trials are expected to be of benefit to patients and of value to inform future thyroid hormone replacement clinical practice guidelines treatment recommendations.
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This is wonderful news is it not? Wondering how long it will take for the results of the trials conclusions to be published.... If done properly, I already know what the outcome will be!
use of twice daily liothyronine or preferably a slow-release preparation if available
Is that possibly jumping the gun?
There appears to be an assumption slow release preparations will be better. Given that the abstract clearly implies they don't yet know everything that they need to, I suspect this is without evidence, at least, without sufficient evidence to make it a clear preference.
I am quite content and happy to have a once daily dose of T3 when I get up. From then on I have no problems and feel my health is normal. The 'professionals' are unaware that one dose of T3, when settled into the T3 receptor cells then send out 'waves' throughout the day. As per Dr Lowe.
Totally agree! I spoke with a GP last week who tried to tell me that my T3-only dose is wrong because my TSH is suppressed and my FT3 over range, she clearly had no idea that on T3 only lab ranges are not the way to go.When I told her that I needed to have a supraphysiological dose of T3 to "overcome" the hormone resistance etc etc she replied that T3 must be getting into the cells because I have lost weight. No thought as to how it did reach the cells/ tissues with consequent weight loss.
I'm sure she thinks I've lost the plot and I hate being in the position where, to resolve my health issues, I have to disagree with her and go against her advice. She decided to leave me to self medicate with the caveat that I'm putting myself at risk.
She became involved as I explained to jimh below....
It helps no one!
Not her fault.....nobody has taught her the facts or has given her the tools she needs to understand more than the basic principles of thyroid disease.
The education of med students must improve and good research has a huge part to play
What about my GP who told me "your TSH is too low, your FT3 is too high and FT4 too low". Yes doctor I replied that's because I take T3 only, therefore FT4 will be low and FT3 higher. BUT the doctor responded, 'T3 converts to T4' I responded No doctor - it's the other way around..
Thank you - I remain on x4 quarters a day - got up to 75 mcg - but on ludicrious endo advice [who didn't prescribe either that or Armour] UN-diagnosed me, saying to wean down from T3 - got to 37.5 mcg - heart back to jerking me out of sleep as when untreated. Back up to 50 - concerned to up it again... due to heart. Moral of the Story, Stay Away From #'s-based/T4 only Endos. I was only referred due to 'freezing shins', punch-drunk, stumbling, uncoordinated... NOT for a diagnosis made 5+ years earlier.
I suspect TSH110 was implying that desiccated thyroid is thought by some to be intrinsically slow release, or at least somewhat slower release, than standard fast release levothyroxine and liothyronine products.
It has been hypothesised that this relatively slower release might be one of the factors which makes desiccated thyroid preferred by some patients.
The thought is not that Thyroid S has a slow release coating (I think much has been made with very little evidence- some even claim a sugar coating is making it slow release which I consider extremely unlikely).
It is that all desiccated thyroid products contain thyroglobulin and the T4 and T3 are bound to that. Rather than simply floating off in solution like the synthetic products, the link to the thyroglobulin takes longer to break and then release the hormone.
Even just being a few percent slower might be enough to reduce the peak T4 and/or T3 levels in the bloodstream.
i remember you mentioned previously that t3 molecules are too large be absorbed via skin. i’m still wishing that we could find a way to dose t3 that would be slow release and bypass the gut. i wonder if a t3 under-skin implant (similar to a contraceptive implant) could be effective if it were invented.
If you think about sand on the beach. Twice a day the tide comes in and covers it in seawater. Then the tide goes out and the sand dries out - not completely, but ends up damp rather than soaking.
The average wetness is somewhere between 100% wet and 100% dry across the entire tidal zone.
Whereas, if we find a non-tidal area, an inland lake?, with a beach, sand above the waterline never gets wet. And that below the waterline is always 100% soaking. With effectively no tidal zone.
If we need 50% wetness, a tidal area will approximate to that. A non-tidal area will never get near.
ha i’m afraid you’ve lost me a bit helvella. i understand your descriptions of tidal areas but not sure how that relates.
were you meaning that an implant having constant release of T3 hormone would be like being 100% below the waterline, regardless of the tiny amount being constantly released? for sure constant release of hormone wouldn’t match the circadian rhythm of natural T3 release, and not sure there would be any way to adjust that in an implant. or did i miss your point completely? i’m assuming the latter
The evidence in health is that TSH values peak in the night, followed shortly after by FT3. But the FT3 peak is very small (about 10% or less higher than the average during the day). During the day when measurements are taken, there's scarcely any change. With no thyroid, taking T3 things are very different. There 's a peak in FT3 shortly after taking a pill, followed by a steady drop, half being lost in 1 day.
oh interesting. i didn’t realize the overnight peak was only higher by 10% and otherwise levels remained pretty steady, i had thought the differences were greater. though i know trying to mimic how things work in health (assuming we’re referring to a healthy euthyroid population) can sometimes be problematic, it sounds like perhaps a constant release could be beneficial. thanks for clarifying. though still not sure i caught helvella’s point
i guess the problem with implants would be difficulty in adjusting doses. or maybe that could factored in somehow or done by topping off with oral thyroid hormone as needed. maybe would be worth a pharma’s time to at least look into such an option since the technology already exists for contraception...
I don't think i'd fancy T3 implants even if it would work as away to deliver T3 continuously . These contraceptive implants are all very well... until they are put in and taken out by nurses who get it wrong. My daughter's got one left so dangerously close to her Ulnar nerve it's probably going to have to stay there forever. They put another one the other arm before they could take that one out, so now she's got two in.... not ideal. They don't take into account girls doing manual work and getting muscles in their arms... it makes the implants go wandering around, especially if they put them in too deep to start with.
thanks, it is a bit worrying . They couldn't find it first time , so booked her another appointment for removal somewhere else, but put the replacement one in the other arm anyway, cos the first one had reached it's time limit for contraception guarantee, And we just thought , oh, that's a nuisance, but it will get sorted out.But then she came back from the next appointment telling me about feeling them touching the nerve while trying to get it , and they stopped because they weren't comfortable and referred her to somewhere else 50 miles away miles away, even though we've got a big local hospital.
The whole thing including the odd places she was being sent to, seemed so shambolic, that i told her not to let anyone else touch it unless they were a proper skilled surgeon. I was really worried that there were people without the appropriate skills poking around in her arm.
On balance , given that if you damage that nerve it affects your fingers and hand badly, it seemed like less of a risk to leave it where it is. But i'm not happy about that either.
It sounds like it might have been put in the wrong place initially , and then over a few years it seems to have worked it's way deeper , and her muscle has stuck itself to the plastic.
I'm really not impressed, ... and then there was a pandemic and to be honest we forgot about looking into getting anything done.
Now i've remembered , maybe i should suggest she goes to GP and tries to get referred to hospital, cos it wasn't done at the doctors , it was some sort of sexual health clinic.
It doesn't cause any noticeable problems , but i do worry about what effects are of leaving a bit of foreign body in your body, i don't suppose it just stops working when it reaches it's removal date, so no idea how long it continues to give off some progestrogen.
I'm really unsure whether it's something to worry about or not.
Yes - an implant or even a real continual slow release form would be like a just-covered with water situation.
But it was really looking at it from the other direction that seems more significant. Despite the high tide covering it completely twice a day, the sand is effectively damp rather than waterlogged.
But it is just a way of discussing - not to be taken too, too literally!
As diogenes has posted, T3 levels in someone who has no thyroid issues are tightly controlled with just a small variation through the day.
Really, I am simply suggesting that when taking T3, it might be all too possible for some parts to never quite get enough - if a barely adequate slow release mechanism is used.
Most slow release mechanisms are very approximate.
thanks helvella, yes i think i see what you’re saying. and i agree it does seem like slow release under-skin dosing would be very hard to get right, though i can’t say i understand anything at all about the current technology for doing so via implants, besides that it exists. perhaps an improved and more exact mechanism is something biotechnologists can create in the future - something that can more closely mimic the way t3 is released by a healthy thyroid gland. in any case, whether via implant or some other form, i have some hope (perhaps unfounded!) that we can find better or at least additional options for more naturally dosing t3 besides the kinds of (more or less) immediate release oral doses most of us take now.
I always end up hoping that there will be an implant which can squirt tiny amounts of thyroid hormone right into the bloodstream. Under very precise control regarding time and dose.
Probably too much to hope for a device which can actually check thyroid hormone levels continuously - but that would be the obvious end result. Until then, simply a way of programming dosing regimes and monitoring those things we can - heart rate, blood pressure, temperature (?), oxygen saturation, etc. Maybe look at what Apple, Samsung, and various other companies have come up with - even if they have had to buy in the technology.
But it’s effect appears to be intrinsically slow release. At first I had to dose twice a day but not any more. I get no obvious dips in energy throughout the day. It surely can’t all hit me in one sudden blast. I can take other medications which seem to be pretty effective and don’t impair the thyroid hormone therapy either. I do leave a four hour gap after taking the NDT before taking anything else.
Oh no need to apologise - discussion helps provoke interesting explanations such as helvella’s as to why I feel my NTD must be slow release. It has increased my knowledge and one swallow doesn’t make a summer as they say ☺️
I dabbled with T3 but found it difficult to dose and gave up with it. I was adding it to NDT to try and increase the free T3, it seemed a bit harsh compared to NDT. Perhaps it works better with T4 only. No doubt if you get a good dosing regimen it should be fine. I really shows why a choice in combination therapies is so important.
ThyroidS I have also tried Acella - not bad was a while ago and naturethroid before they re formulated it and some say ruined it, I found it fine. I think ThyroidS is pretty good but I’m worried about future supply.
Where do you get ThyroidS from? I have seen it on <source removed> in a red and white box. I just wanted to ask because usually People on here source meds from 'other Countries' 🙂 TSH110
I could cry! Usually I’d respect the members of the forum that are maybe more refined than me. However!!
I.Could.Actually.**.Cry when I read such headlines!! Where are these so called ‘great and good’! Why don’t they call me up and ask me how life is on combination therapy! Why don’t they ask my husband, my children, my extended family, my workplace, my college, even my bloody GP who I haven’t seen for 18mths because I no longer have ANYTHING to worry about!
Adding T3 has been a live changer for me. And now these types of publishing are just another stick for my NHS Endo to beat me with so that I have to continue to get my prescription privately filled! Gah! Hell and damn!!
A sense of irony is inexplicable and totally English. We aren't called "perfidious Albion" especially by the French for no reason. This attitude is widely seen in the distrust in our motives in the Brexit negotiations.
Yes- but not useless; merely bigoted. And no appetite for mature reconsideration unless forced. As they have been here to even admit past mistakes and refusal to properly engage with patients.
I hope they can convince the establishment and the decision makers to listen to any effective conclusions.
If the aim of this trial is to accurately detect the exact cause of each patient's ill health and to consequently find the correct T4/T3 dose for each of them then thatwould be a huge achievement! The end of "trial and error"...
However, is it not the case that combination treatment cannot follow a specific dosing protocol because it depends entirely on the individual's requirements and unless those requirements are met then the result is failure? Perhaps this is addressed in "remaining statements".
I hope in time, with feet firmly planted on the ground, with open minds and ears and with opinions - not only their own - ringing in those ears that they make a concerted effort to listen to patients and to talk to them... not at them and/or over them! That would be a start!
From a patient's perspective, the medics have to take the science on board...let's hope we see improved thyroid care as a result of this work.
"The results of such redesigned trials are expected to be of benefit to patients and of value to inform future thyroid hormone replacement clinical practice guidelines treatment recommendations."
I had a conversation with my (fairly new) GP yesterday and she decided what dose of T3 I should be taking without being fully aware of the cause of my problem
That simply does not work...
As you know I self medicate with high dose T3 but she became involved after a review test was sprung on me and she saw my suppressed TSH and well over range FT3.
She thought I was endangering my life!
I declined another test and she asked how I was dosing without tests.
Symptoms and signs....as was the way before tests. Silence.
Frankly it was depressing....and so much more problematic when the patient depends on the medic to be the expert.
I believe she is a good doctor but with limited thyroid experience......not her fault but that of those by whom she was taught. Cue......better research and teaching!
"The scientific way is to find what doses work for various groups of patients and the try to find the cause."
Surely one has to determine the problem/fault before deciding how to treat it.
Sorry for the rant Jim ....just thoroughly p'd off with the way thyroid patients are being treated.
Agree. For many conditions we treat without knowing the underlying mechanism. Ideally we would understand the aetiology in detail but until we do we have to go by ‘symptoms and signs’ (as someone said!).
The principal problem is that doctors think they understand hypothyroidism when they barely scratch the surface. It’s vitally important to know what you don’t know.
Sounds good to me. Surely the more studies on this topic the better even if there may be faults to be found with them. The fact that there's a recognition there that more studies are needed is good because scientists learn from the mistakes of those who have gone before by teasing out flaws from previous research studies. You have to crack a few eggs to make an omelette and in T3s case that's a lot of eggs 😄
They have already had years to crack the eggs, they are struggling to make the omelette! Patients have raised this issue for years and still there is very little discernible improvement in diagnoses and/or treatments.
It's not the volume of studies that count it's the quality!
Let's hope that this science is good and that the medics are amenable. It needs both to happen.
Something must change because, if this forum is an example, the ground swell of suffering thyroid patients appears to be growing.
It will be very interesting to read the full paper. When we cut through the jargon it seems they are calling for well conducted studies that include patients dissatisfied with current treatment and as a prime outcome ask the patients how they are doing.
They also plan to include studying polymorphisms of deiodinase and cellular transport - I think they are barking up the wrong tree on this point but the truth lies with the study results and at least someone is willing to try.
This seems like a good step forward, will need to study the full paper to make a judgement. Thanks for bringing it to our attention.
I think it means widely as in a few people across a wide area of medicine . some NHS endo's do prescribe T3 alongside Levo, Other countries too, probably more often then UK. Some patients have T3 added to NHS levo by private prescription . Some Hypothyoidism patients buy it themselves without prescription ,but do tell gp's they are doing so.
nearly all the (flawed) combination therapy trials done so far have concluded that there's no benefit from combo over Levo alone( not that anyone here agrees with that )
So it says what it means ....ie. despite the fact that numerous trials don't show benefit over levo only, lots of Doctors and patients are using it anyway ,and lots of patients are reporting benefit, which is continuing to attract interest from physicians ands patients
No need to apologise , i'd leave your comment up , you won't be the only one reading it that way ... i had to read it several times to try and decide which side of the fence they were sitting on.
There are some negative comments on here so I just want to say that one of the doctors involved in this trial, and I'd guess he instigated it, is very keen on helping those of us who need T3. I can't understand why you are anticipating an undesirable outcome. He and his team have brought me back from falling into a deep black sleep for several hours most days and at times not even being able to feed myself, back to something approaching normality. I had seen a different endo just a few months before who insisted I needed more T4 and no T3, which would have been disastrous. Luckily my GP recognised that. I'm writing that so you can see at least one of the people behind this study is a really good person, highly skilled and he cares about us.
Hi NWA6, My understanding is that this trial is being done because of that background, to question that, because the doctors involved in this new trial don't think that it is right that there is not a benefit to many people. (Lots of negatives in there but if I'd turned it into a simple positive the connection would have been lost). I don't know and of course it's not easy to follow when in order to demonstrate what you want to show, the trial sets out to prove the opposite.
Because that is what the previous trials have shown, (probably because they were done so badly, using the wrong doses, and the wrong people)
I do understand why this stuff get's us so wound up, but i also know that at least one of the names on this paper is highly regarded by people here. So i think we need to see where this goes before getting angry about the wording. It's quite possible that they are not all 'on the same page' with their thinking , but at lest there is some thinking going on. Which is better than none.
I don't think this wording will add anymore negativity to your endo's thinking on the subject, as he will already be referring to these previous flawed studies to back up his current position.
Hopefully a new study which takes more relevant patients and their self reported outcomes into account , even if it's not set up as well as we want it to be, will do good not harm.
and i'm very reassured by the inclusion of one name on this panel. i suspect they would not want to be involved if the intention was to further block combination therapy.
That's really good to hear both that he's involved in the study and that you have regained your health. I think that because we have all been so badly treated we automatically assume that the studies are out to disprove the benefits of T3 treatment. Same goes for the recent questionnaire promoted by Thyroid Trust and mentioned on several recent posts. The way I read that was that they want a radical change in how we are treated. When I completed the questionnaire I felt it was asking about personality traits and mental health etc in order to establish a connection between thyroid problems and depression and anxiety which we all know to be true so if the majority of people who respond to the study do have such problems then it shows the link in that study. Yes sometimes things could be worded more clearly but I think we are all guilty of reading the worst case scenario based on our previous experience. Which I might add is not a Diss of anyone on here, before I get thrown to the dogs by everyone 😂
Thanks for your post, it was very nice to read, and I agree, most of us on here have been treated badly and that does make it very hard to expect something different. Joking here but having posted that based on past experience with the odd person on here I am also expecting to be thrown to the dogs!!!
There have been trials of combination therapy which have not shown benefit (within the terms of those trials).
Which might be thought to undermine any use of combination therapy because of lack of evidence (in their terms).
DESPITE that, there are many patients on combination therapy. Many of whom report that they benefit.
(It is not explained whether these patients on combination therapy are doing so by taking desiccated thyroid, or liothyronine, or some other combination. Nor whether they are doing so with support and prescribing by doctors or on their own.
If doctors are prescribing combination therapy, they are rejecting the reported results of these trials. Or interpreting them differently.)
Thus there is a conflict between the evidence from trials and the actual use and patient reports which has not been explained.
Possibly the simplest and most obvious explanation is that there are real benefits which the trails so far have not demonstrated. In my view, very likely because they have been designed so poorly.
Perhaps the study should focus on T3 first before expending to look at the combo.
Perhaps previous trials failed to show benefits because...oh.....cart before horse again?
Maybe, in the full text they do this, as in clues "deiodinase and thyroid hormone transporter polymorphisms ".
T3 (by any other name) is poorly understood by some medics and therein lies the problem...... alone or in combo. But here we know that!
They need the research, info and tools to understand and use T3 to best advantage. Again, here we know that!
Is this research going to do that. ....positive thinking required!
I'm clearly no expert, but if I could research the possibilities and work out how to improve my failing health ( with the guidance of forum members) then it beggars belief that the medics/experts ( apart from the few we know about) have so far failed to improve the lot of so many thyroid patients. " The truth is out there"
The aims are commendable, "The results of such redesigned trials are expected to be of benefit to patients and of value to inform future thyroid hormone replacement clinical practice guidelines treatment recommendations."
There needs to be a determination to succeed.
Just a thought....said more than enough, probably I need a cup of tea too!
It is widely used but being cut back in the UK, on NHS prescription that is. If we underestimate the extent of patients taking T3 we make it more difficult to get it prescribed.
I saw ThyroidS on <source removed>. Red/white box. Is that the same one you take...Only asking as I read people have to source forms of t3 from Other Countries 🙂 Hidden
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You can pass on this information in a private message but not on the forum.
I just have read of many on here not having seen either a GP/Endo for 'years', just meaning they can't have a prescription', but, mention 'places' they source meds from to feel well without GP's knowledge etc.
I clicked on the link you supplied above '2 years ago'.
I just have read of many on here not having seen a GP nor Endo for 'Years', meaning they cannot have a prescription, but, they mention 'places' they source meds from to feel well without GP'S Knowledge etc.
I have taken on board your message
I appreciate the somewhat old picture from this forum But I haven't seen it before......I only joined the forum this Year
Fully understood! I don't expect everyone to instantly know everything.
At one time there were numerous place to buy Thyroid S (and Thiroyd and TR Man) - when they were available. But currently looks like there is nowhere reliable.
So far, so good on liquid levothyroxine. I have 2 Bottles a Month now as Endo has 'increased dose' to 5mls daily, no doubt next increase will be 7.5mls until TSH, reduces and Ft4 increases...🙂
Is Colin Dayan who is listed not the person who believes that many patients being treated for thyroid problems are actually suffering from ‘somataform disorders’? He and Tony Sweetman. I know I’m cynical but I don’t feel inspired when I see Dr Dayan’s name on the list.
I am sure Professor Dr Colin Dayan does not hold the view that many of us are suffering from somatoform disorders. He argues for us, particularly with regard toT3 and has done so as just one person speaking for all of us hypo people against a whole panel of peers arguing the opposite.
Ah, my fault - I thought he was one of the somataform people. Glad he isn’t and it’s a brave guy these days who will put his neck on the line in favour of T3.
No fault at all Fruitandnutcase, I know where you are coming from. My blooming GP is one of those, just putting TATT in my notes and asking "Well what do you want me to do about it?".
I have to agree with you. Given the remarks he's made in print about thyroid patients and private sector practitioners like Drs Peatfield and Skinner, it doesn't lift my hopes to see Dayan's name on the list.
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