The "wrong T4/T3 ratios in NDT: do they matter?

Over a whisky (or two) I've been thinking about the scientific base for arguing that NDT has the "wrong" T4/T3 ratio compared with the natural ratio in healthy humans, and therefore is putting people at risk by giving too much T3 relative to T4 in treatment. I think now this argument doesn't hold water for this reason. So long as the amount of T3 taken in is that giving a normal FT3, then it does not matter how much or how little the accompanying T4 is held in reserve (so long as there is some reasonable amount available as a conversion backup and it doesn't get significantly depleted over the day). By this I mean that, if a patient is relatively deficient in T4-T3 conversion, and has little or no remaining active thyroid gland, then the normal T4/T3 ratio for healthy people won't be appropriate. This will be even more the case if our indication recently of a significantly greater direct T3 contribution of the thyroid gland holds up. The missing thyroid T3 has to be replaced by taking it directly if the gland's contribution is no longer there and the tissues can't make enough to replace it. In fact, one of our number plans to re-examine this question of T3 production by either gland or by tissue conversion using a more controlled study than has been done hitherto. If it turns out that the direct thyroid contribution of T3 is as high as 35-40% rather than the 20% now believed to be the case, then the arguments against NDT's wrong ratios collapse.

T3-only medication is one I still have problems with. But they would be assuaged if there was available a "slow release" T3 tablet, so that one didn't get the "waves" of temporary overtreatment immediately after taking the hormone. Perhaps in the future such tablets will come into being.

29 Replies

  • Diogenes,

    I have noticed that the T4/T3 ratios in NDT don't seem to suit everyone and some supplement additional T4 while others require additional T3. Interesting that a higher proportion of T3 may be created in the thyroid gland than previously thought.

    Timed release T3 capsules are available in the USA but don't seem to be widely available or used. It may be a cost issue or because the caps are gelatin it's been suggested that the T3 may bind to it and reduce absorption.

  • Clutter, Dr. Holtorf uses timed release a lot. Initially he found a problem with the binder not unbinding but I don't know what he switched to that solved that problem. Dr. Blanchard used timed release T3 and then switched to timed released NDT using the conventional chemical which I can't remember right at this moment. It is very hard to tell how much this is used in the US, definitely a minority though. The other aspect is that I think this is usually done through a compounding pharmacy. Someone did file a patent years ago for a time release and there was a study (trial) I believe recently with time release but I haven't heard about the outcome. PR

  • PR4NOW, I think compounded is more commonin the USA but I'm sure I read of a member who had T/R brand imported from the USA to UK. Can't remember the name of the manufacturer.

  • My thoughts on NDT were merely asking the question: "Is the T3/T4 ratio a potential danger to patients taking it?" My contention still remains that it is not so long as FT3 is not outside its reference range (and highish up in that range), People who are very poor converters of T4 to T3 may need more T3 to supplement the NDT doses, whilst very good converters many need more T4 and less NDT (or even no NDT at all). I agree that according to the individual's conversion efficiencies presented, some juggling has to be done to get the ratios right.

  • Diogenes, I'm having to juggle my T4+T3 combi (under supervision) as I've overshot the FT3 range. Obviously over medicated on T3 but I wonder whether conversion improves once there are adequate levels of FT3 in the body?

  • I would guess not. Once "set points" get set up by genetic disposition or by physiological stress they tend to stay. Eg people who have been critically ill with nonthyroidal diseases and survive often do not get back their original thyroid behaviour, because the stress of the illness has changed their set points for good - ie the rest of their lives.

  • Thank you, Diogenes.

  • Diogenes, it would be great if science could actually achieve an understanding of why NDT seems to work so well for so many. I'm all for a better understanding of the greater thyroid system. I no longer believe that Synthroid works for the majority. I also believe that a great many patients end up being under dosed and suffering needless complications because of that fact. Like Clutter I have also seen patients who use NDT add a little extra T4 or T3. At this point we don't have a simple way to determine what ratio the patient needs other than by trial and error and observation. I doubt very much there will ever be a successful 'one size fits all' approach. T3 is still a mystery. There is always a persistent minority of patients that don't regain their health until they get on T3. From what I have read science has very little understanding of this situation. I look forward to what you and your colleagues discover. PR

  • Diogenes, another possible aspect. You said in one of our recent conversations, ""and secondly that TSH influences not only the thyroid output of T4/3 but also controls the T4-T3 conversion in the tissues other than thyroid in a "feed forward" mode." If this is true and you start supplementation wouldn't this then suppress TSH and effect the extra thyroidal conversion? PR

  • It certainly could do - suppressing TSH may well interfere with T4-T3 conversion in the tissues even if you have no working thyroid left- all of this shows what a complex interlocking and interdependent system the body is, and how naive interference (eg T4 only) can have unlooked for effects.

  • Diogenes, there is another aspect which is not discussed in conventional science called 'secondary suppression'. Hopefully I can express this correctly. It goes something like this, as you start supplementation the body reacts and cuts back production, as you increase supplementation the body cuts back even more. In order to get the necessary amount in the system you end up overriding the bodies control system.

    Dr. Derry talked about that the doctors of the day ( 40s-60s? ) usually did not see a physiological change in the patient until about 3 grains using the best tools of the day including the BMR and close observation. This wasn't 100%, nothing ever is, but it is fairly common in patients using NDT to suppress their TSH before we feel 'normal'. Dr. Christianson said in his presentation that he sees a fair amount of patients that he believes are overmedicated.

    I agree that the goal is to always use the least amount of hormone possible to achieve results and I also agree that there may be tradeoffs as we have discussed before.

    One of the things I now wonder about when you suppress TSH is what affect does that have on TRH. We tend to think of TRH as only the messenger between the hypothalamus and the pituitary but after reading some of Dr. Pierpaoli's work I wonder if it actually does a lot more than that.

    It is always tricky trying to figure out what gets a person their life back without causing further damage. Once you have spent some time in 'Zombieland, the land of the living dead', you don't ever want to go back there again because it is anything but actually 'living'. Part of the problem is that science really has a very limited understanding of the greater thyroid system and all the ways it can malfunction. PR

  • I think TRH is quite specific in its action on the pituitary production of TSH, but of course there are other release hormones like LH-RH and FSH-RH that also have their specific effects. I think that if you suppress TSH, the various feedback loops suppress TRH as well. TRH is affected by FT3/4 levels. Regarding optimum treatment, I think it should be renamed "adequate" treatment - the optimum is rarely achieved, but "good enough" is often what has to be accepted. My aim is to get a protocol (individually devised) that restores a patient's input and use of T4/T3 to as close a resemblance to their original normal nondiseased state as possible or, if that has irrevocably changed, to an acceptable state. For that we need a) to know exactly what is going on between the thyroid and the tissues and how they interact, b) therefore understand what various treatments do and what their strengths and weaknesses are and c) have reliable consistent tests to use. a) and b) we're trying to fathom out, c) is still an ongoing scandal.

  • Diogenes, I'm quite in favor of your goal, that would work well for the vast majority of people and be a tremendous improvement over the current standard. Just keep in mind there will always be outliers and for us a test will not tell an accurate or complete story, at least not yet. As you once said when you were talking about trying to refine your reference ranges, 'you would think there are aliens among us'. PR

  • Not sure what your on about here, but i wonder if all of this is more or less piontless,since ive had no tablets for 3 and half months and im ok tierd but thats normal ive allways needed extra sleep, 15 years ago i had radio active131 and had 150mg a day no change ever since,untill may this year,im now not taking them in protest of scoring no pionts in the dwp disabled work test ,while having aurthitus from yes age7,twisted hands (main right only half opens,joints are all 2x bigger),from havin a genectic disorder that my ligarments were all 25% shorter, and hospital shoes 14 years,and told in 1992 no more sicknotes ever,since my doctors are unsympathetic my plan when i fail my 2nd and last try to stay on the sick,to hang myself outside my doctors for them to find in the morning,,np when you really do belief in life after death and you really are suffering,,people in the uk have no idea whats happening to thousands who were on the sick ness benifits,and dont realise how unfare the tests are,why is it i had no more sick notes ever in 1992 after seeing dhsss real docters one time only,,now its a test on paper and "no pionts" 2 main sections on hands and mine score nothing haha wait till the media gets hold of that with my twisted shows how wrong the test is,anyway ill leave you all be,,thyriods lol thats nothing stu

  • I can't help feeling that this is a red Herring, and just a good excuse for not prescribing it with no scientific proof. OK, I'm not as well up on these things as you, but I can use my common sense. If NDT was bad because the T4/T3 ratio was wrong, then so would T4 only treatment be. T4 only is totally un-natural. But nobody in the medical profession seems to think about that. Because that's what they want to prescribe. They don't want to prescribe NDT because the drug companies have told them not to.

    As I understand it, most of our T3 comes form conversion, anyway. So what does it matter how much is in the NDT. If we have problems converting, then that's another matter, and T3 can be added to the NDT. But there are an awful lot of people that find NDT excellent just the way it is! And that's what counts.

    Myself, I did very badly on NDT. I cannot tolerate T4 in any form. I am on T3 only and feeling much better for it. I also find that the ranges have nothing to do with me! I need a high dose of T3 and I need my FT3 over the top of the range. But I in no way feel hyper - quite the contrary! Also, I take it all in one go at night. It doesn't stop me sleeping, and I don't feel dips throughout the day. These are the things that suit me best. However, I would never say that everyone should do it this way. We are all different and there is never going to be a one-siz-fits-all solution - which is a pretty stupid idea to start with, if you think about it!

    So, that's my opinion. It may be totally unscientific, but it comes from experience.

    Hugs, Grey

  • No, I think you misunderstand in a way. The evidence slowly coming together is showing that there is not one way of proceeding when thyroid deficiency strikes. The real question is: how many people don't respond to standard treatment and what to do about it. NDT has been castigated as an illcontrolled, wrongly constituted alternative to T4 only therapy. Thyroid UK and its contributors have educated me on this. I've discovered by delving into what is actually the case today that the pharmacological control is better than I feared, and believe now that the product itself is not harmful with the right precautions taken re within range FT3. I'm not going to diagnose for you or anyone else: I have no right to do so. BUT if you say that you need your FT3 consistently over the top of the range then warning signals come up. It's the long term effects of this that I worry about for you. Maybe your system will adapt to it, maybe the consequences in later life will be troublesome to say the least. We simply do not know what the adaptation of the human body is capable of. Studies in this area would take decades to discover. All I can say is that when my wife in about 1970 was diagnosed with rampant Hashimoto's the professor overseeing her said " you'll be OK until 65, then difficulties will begin". Well, with care about dosing etc those didn't come in till 75 years. And re AF here they come. But any abnormal longterm imbalance of thyroid hormone uptake will ultimately take its toll; this is unavoidable. So be careful of your high FT3; it may come to haunt you later.

  • Darling, I'm a couple of months short of 70! Live now (if you can call it a life), pay later, has always been my motto! If there is a later. And at this age, who knows!

    How do you know it will take its toll? (And what toll are you talking about?) How many people actually get to find out! We're all kept on such rediculously low doses if the doctors have their way (but then, they know nothing about thyroid). You need the dose you need. And if mine is high, then so be it. Besides, low T3 gives you heart problems too.

    The ranges are rubbish and shouldn't be used. It's how you feel that counts. There was a time when they didn't have ranges and people got to feel better - Watch Weetman's famous lecture in the US (can't rmember who to), although he lies about it.

    The body is amazing for adaptation. It adapts to all sorts of things that you think it couldn't. If it can adapt to T4 only - which it does in some people - then it can adapt to a slight difference in the T3 content of NDT. If this were a problem, how come so many people do so well on it?

    I don't think I misunderstood. On the contrary. I've always known that there is more than one way to treat a thyroid hormone deficiency. It's not news. And I'm certainly not asking you to diagnose for me. I'm not even asking your advice! You were asking what other people thought, so I told you!

    Lots of people need their T3 over-range, they just aren't allowed to have it that way. Of course my system will adapt to it - it adapted to 55+ years of being hypo! And I repeat, the ranges are a red Herring. I think you're making a bit of a fuss about nothing.

    I understand that very few people know anything about this - especially doctors - but I understand that the patient knows his own body but is never listened too. And I understand that they want to keep us sick and undertreated, and taking lots of extremely danerous drugs - far more dangerous than a bit of T3 - to treat the symptoms. Big Pharma rules! Yay!

    So, if you still think I don't understand, please explain it to me in words of one syllable so that my poor little layman's brain can understand. Thank you.

  • If you've got this far without problems, then you must be T3 and thus T4-resistant - that is your body is a poor responder to T3 (and especially T4). They are known, but you are rare - enjoy the uniqueness.

    But don't extrapolate to everyone else. Its the mass I'm interesting in. Getting everyone into a sensible diagnostic protocol given the variation in human response would cost the earth. Someone must always fall out of the basket unless the enormous cost is met.

  • Diogenes, what is T4 resistance, is it the inability to convert to T3? If you have T3 resistance do you automatically have T4 resistance? I thought it was possible to be T3 resistant without having T4 resistance. T3 resistance being a problem at the receptor site. PR

  • It's often the inability of the receptors (genetically defined) in cells to adequately bind T4/3 and thus you get poor cell uptake and resulting poor conversion. Thus supernormal levels of T4/3 are needed to force things through adequately. This is perhaps what is happening in this post.

  • Diogenes, we had an OB/GYN on a few days ago. He said he has a background in science and research. He said "TSH is more sensitive when TSH is high (thus the >10 use), but in the range 1-2 it is not." I asked him to expand on this but haven't heard back, I may have scared him off, didn't mean to. Is there a variance in sensitivity, and therefore accuracy, over the reference range in the TSH test or only at the extremes past the top and bottom of the reference range? I'd never heard of this before. PR

  • Sensitivity is not the issue. Accuracy of diagnosis is. The former relates to determining the degree of any functional/dysfunctional situation, the latter to whether you've got the disease or not. What I think is being confused therefore is diagnosis of the position and extent of a disease state rather than its existence per se. Top limit of 3-4 is still right for diagnosis using TSH.

  • Extrapolate to everyone else??? Would you care to enlarge on that statement? As far as I remember of what I've written, I've been saying that everyone is different. How is that extrapolating my 'uniqueness' to everyone else?

    I've also been saying that everyone should be allowed to take the dose that they need. I'm sorry if that's revolutionary talk, but it makes sense to me.

    And being 'unique' is not all it's cracked up to be, I can assure you. I don't see much to enjoy.

  • Grey if you don't mind my asking how much T3 do you take? PR

  • Sorry, PR4NOW, I feel like talking about it Under the circumastances. I don't like to flash my 'uniqueness' around. Someone might get jealous.

  • Diogenes, I wish there was some way to collect information about and study some of us that don't fit the normal picture. I bet we could come up with a fair number of us here on TUK HU. I'm afraid by the time science realizes the importance of taking a look at us, it will be too late for many of us to contribute. Your point is quite valid, we need a better understanding of what the body does with the various doses, both short and long term. Along with that we need a better understanding of why people react so differently. However, I have no doubt there will always be outliers and thus there will be subjects available to study when science gets around to it. PR

  • Wouldn't it be better if we just excepted that everyone is different and stopped trying to stuff them in the same mould? In the short term at any rate, until we know more. Because they definately are all different, you can see that on here.

  • Grey, everyone is different, Diogenes is well aware of that and has pushed for an individualized approach (personalized medicine) with more intelligent testing for many years. All the hard work he has put in with his collaborators has been working towards that end. Unfortunately he is correct, those of us who are outliers will almost always have a more difficult time and it will not get easier until science has a better understanding of how our bodies operate or more recognition that we exist. Doctors need a general framework to work within, an understanding of how the system works. Just saying everyone is different is not quite as helpful as you might think because it leaves doctors without a frame of reference to work from. This is not meant to excuse the inferior standard we are subjected to now, that must be replaced by more intelligent guidelines, which is what Diogenes has been working for. PR

  • The idea of thyroid hormone replacement, basically, it to increase the dose until the patient feels better - i.e. dose by symptoms. This is not being done. That's all I've been saying.

    But even if there are more intelligent guidelines - which we all hope for - doctors have to realise that not everybody is going to fit in them. Doctors have to be able - and be allowed to - think outside the box. Making comments such as 'well, I've never known anybody who didn't get better on levo' and 'well, your TSH is in range so you must be feeling better' isn't helping anyone.

    And now I've completely lost the thread of this thread, so I will bow out, wishing I had never bowed in! I'll just say that if people ask the question 'what do others think' they should be prepared for 'others' to tell them what they think!

    Hugs, Grey

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