There is, at last, an acceptance that there should be trials looking specifically at combination T4/T3 therapy in patients who are dissatisfied with T4 alone and investigation of genetic conversion issues.
About time and thanks to pressure from TUK in particular!
Our group has been advocated this, and criticised the trials on combination therapy for many years, meeting with almost total refusal to debate the problem. It at long last seems as if the authoritive leaders have at last begun to realise that the problem exists and is serious. I do hope for proper trials to be devised, but don' t hold my breath.
I am quite hopeful for 2 reasons. First, they accept that the group of people they should be investigating are those who are not happy on T4 alone and not all hypothyroid patients ( the vast majority of patients are fine on T4) and second, they are specifically going to look at genetic issues.
I have hope........🤞🤞🤞
One aspect of possible concern is that the selection is on the basis of current dissatisfaction.
But something that is reported all too frequently is when those who have been fine on T4-only for years change to needing T3. Investigating the cause of this, and accepting that people can change group, are important additional considerations.
I hope conclusions don't imply that everyone is in one or t'other group. An assumption like that could push understanding off-course. Again.
(Yes - of course - if no-one gets T3, everyone is in the same hand-cart. Wider availability and acceptance of T3 should eventually help everyone.)
I agree..... I am not sure that people should be classified as one group or the other at all. There are so many factors which affect a person’s effective thyroid status and these vary at different times. In particular, the ability of the thyroid gland itself to produce thyroid hormones, the function of the rest of the HPA axis, other concurrent illnesses/ infections, other hormonal states, genetic conditions, stress, hormone insensitivity, weight etc etc. Unless each individual is assessed properly and thoroughly I am not sure how they can be “grouped” together. I would love to see the demise of the generic guidelines that treat everyone the same and doctors with the interest and time to investigate each person as an individual.
This is just a general rant, triggered by the fact that new trials might get done, and my faith in doctors is nil.
My fear would be that the researchers will think that, in patients who are being given T3, that T4 treatment needs to be reduced in quantity by X mcg and they only need it replaced with T3 at the rate of X/20 mcg or X/14 mcg or some other absurd ratio. Doctors seem to take it for granted that hypothyroid patients only need tiny, tiny doses of T3. For example, they take away 50mcg - or more - of Levo from the patient and replace it with 5mcg of T3 a day in some cases, setting them up to fail.
The fact that hypothyroid people (who may be left untreated and gaslighted for many years or even decades) often have very damaged guts by the time they get treated and thus can't absorb food, nutrients and medications very well never seems to be something that gets considered.
I'm also dubious that every healthy person produces the same amount of T4 and T3 always in the same ratio, although the Pilo paper from the early 90s has been used (by others) to suggest this, and that hypothyroid people must be prescribed and end up with the same amounts and ratios as healthy people. It really amazes me that a single paper on a particular subject can be produced and it can be used for decades to destroy the lives of millions.
thyroidpatients.ca/2019/05/...
Other dubious things about thyroid treatment that could be used to scupper any research...
Many doctors don't seem to grasp that T3 is needed by every cell in the body. As a result the number of distinct symptoms that patients can get is absolutely huge but doctors refuse to acknowledge them. Just because low T3 affected my feet (just one of my own many symptoms) doesn't mean that it will affect every hypothyroid patient's feet. Some of us get terrible skin problems, women get gynaecological problems, both sexes get low libido, reduced fertility, lack of motivation, depression, many of us get muscle problems, heart problems, lung problems, damaged kidneys, poorly functioning liver.
But doctors often just reduce the whole condition to "fatigue", while others have been known to deny that fatigue is even a symptom of hypothyroidism. So when a patient describes their many symptoms they are assumed to be a hypochondriac (because doctors appear to think that a single disease can only have, at most, about three symptoms - any more is considered to be a sign of hypochondria.) They may even get their dose lowered or removed and replaced with anti-depressants, and get labels attached to their medical records suggesting they are mentally ill, attention-seeking hypochondriacs.
Doctors also don't take into account that healthy people produce T4 and T3 as and when necessary. Healthy people don't get 75mcg of T4 and 5mcg of T3 at 7am every day. And yet our TSH is almost always compared to that of healthy people whose bodies are receiving thyroid hormones in an entirely different way to people who are hypothyroid and treated. Despite this, we are expected to have a TSH which is usually higher than that of healthy people. And I sincerely doubt that many doctors have a clue what the TSH of healthy people actually is. If they ever even think about it (which must be rare) they probably assume it is middle of the reference range - and it isn't, it is substantially lower.
But the way we are dosed is likely to reduce TSH compared to healthy people and this isn't understood - it usually just leads to the patient having their dose reduced.
Interpretation of thyroid function tests is mostly reduced to being an economic problem rather than a health problem, so we are unlikely (in my life time) to ever be treated well.
I think that until doctors actually understand what hypothyroidism is from the point of view of the patient, what the symptoms are, how varied the symptoms can be, what the long term effects of non-treatment, under-treatment, and low Free T3 is, and how they can't expect us to have TFT results like those of healthy people then many, many patients will be left to suffer, even if, eventually, some of us get 5mcg of T3 a day added to a reduced dose of Levo.
This made me sad. I am so sorry you have had a bad time with doctors. There are good ones out there and I hope you find one!
In my case the two overriding effects of starting T3 which are objective and cannot be due to anything else are a dramatic and visible improvement in my nails and an equally dramatic improvement in my lipids after only 6 weeks. There are many many factors which matter other than thyroid function tests and there are doctors who understand this. Good luck, I am glad you have managed to improve things for yourself.
Thanks for sharing your ‘rant’. You write with superb clarity. I agree with your conclusions. I decided many years ago that I would learn all I could, find a sensible endo and pay privately for the medication I require. This blog has been a marvelous help and people like you are a real ‘shot in the arm’ for us all. Keep ranting!!
Well said. I would also be interested to know more about the long term impacts of low in range ft 3. I will dig out your “rant” before my next endo appointment as it sounds hard to argue with!
A link you might like :
Title - Low-T3 Syndrome
A Strong Prognostic Predictor of Death in Patients With Heart Disease
Link : ahajournals.org/doi/10.1161...
And a recent thread :
healthunlocked.com/thyroidu...
As diogenes says in that thread, sometimes low T3 is protective, but not always. The paper he refers to is here :
frontiersin.org/articles/10...
I don't know if you know or not but diogenes is Dr John Midgley, one of the authors of that paper.
Thank you for this. I shall have to start a little folder of resources!
I was aware that Diogenes was a scientist and researcher, but no more, so that’s definitely helpful. I think I need to put them in the folder or link to the journal articles until I have my basic understanding of hypo/hashis at an better level. I’m moving through whatever reasonable sounding patient-centred thyroid books I can find for under £5 on kindle at the moment and finding them helpful on getting some of those building blocks in order.
"My fear would be that the researchers will think that, in patients who are being given T3, that T4 treatment needs to be reduced in quantity by X mcg and they only need it replaced with T3 at the rate of X/20 mcg or X/14 mcg or some other absurd ratio. Doctors seem to take it for granted that hypothyroid patients only need tiny, tiny doses of T3. For example, they take away 50mcg - or more - of Levo from the patient and replace it with 5mcg of T3 a day in some cases, setting them up to fail."
to be fair the consensus document does address this and acknowledges more needs to be done to elucidate these relationships, perhaps we shouldn't tar the whole profession with the brush of the many many ignorant GPs who try to manage their patients on thyroid replacement as though they (the GPs) are autocratic dictators on a war footing..... while acknowledging that there are potentially quite significant individual differences in thyroid replacement needs we should also remember that if you look at big cohort trial data the most common values are well, very common, so its reasonable to suggest that most people will only need to replace with c.100 mcg T4 and 6-7 mcg T3 and to base research around replacement ratios in that orbit. Patients who don't then do well on this approach should be given much more time and effort to figure out what else may be going on and how to titrate the doses they uniquely require.
consensus document
Please link us to this document, or give us the title.
we shouldn't tar the whole profession with the brush of the many many ignorant GPs who try to manage their patients on thyroid replacement as though they (the GPs) are autocratic dictators on a war footing.....
My own experience of thyroid treatment, and the many appalling stories that I read on this forum, suggests to me that there are very, very few doctors who have a clue on the subject of the thyroid. For example, I was told my thyroid was "borderline underactive" in the early 1990s. It was 23 years before I got my first prescription for Levo, and even that was slammed down on the table in front of me with the doctor scowling ferociously at me. I have a pituitary problem that means my TSH doesn't rise as it should in response to low thyroid hormones. I have seen people with Free T4 and Free T3 similar to mine when untreated and they have a TSH as high as 20 to 30. Mine has never reached 6.
I cannot see how secondary or tertiary hypothyroidism can even be diagnosed by doctors based on "TSH-only" practices in the UK, so I feel entirely justified in tarring the entire profession with the same brush.
Doctors appear to think that because the numbers of people with thyroid disease is increasing then it means they are dealing with a larger number of hypochondriacs than they've ever dealt with before.
But think about the diet of people today compared to 100 years ago. People eat a lot of processed crap containing chemicals that the human body had never been exposed to until the 20th century.
I read several years ago that humans are exposed to over 70,000 more chemicals in plastics, medicines, food, in furniture and clothing, in technology and farming, and in fuels than they did in the 1950s. Yet doctors think they know that all these are people whose bodies are constantly under attack by modern life are hypochondriacs.
And women suffer from all this medical mismanagement and disbelief far more than men do. They get less pain-relief than men. They are more likely to get sedatives than treated with proper painkillers. Women have more complicated reproductive organs than men and they go wrong in numerous ways that can't affect men. And yet male doctors can get these articles published in a major newspaper.
theguardian.com/commentisfr...
theguardian.com/society/202...
Doctors expect to be lauded by all and sundry, and for their treatment of, say accident victims, I would agree. But for chronic disease, which is far more common than acute illness, injury and disease, all I see is a group of people who think it is perfectly fine to let lots of people suffer for decades when they could be helped. And when those patients start to complain... The attitude is that, well they're all mad aren't they - because so many of them are women.
pub in THYROID
Volume 31, Number 2, 2021
a Mary Ann Liebert, Inc.
a American Thyroid Association
a European Thyroid Association (Published by S. Karger AG, Basel) DOI: 10.1089/thy.2020.0720
Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism:
A Consensus Document
Jacqueline Jonklaas,1 Antonio C. Bianco,2 Anne R. Cappola,3 Francesco S. Celi,4 Eric Fliers,5 Heike Heuer,6 Elizabeth A. McAninch,7 Lars C. Moeller,6 Birte Nygaard,8 Anna M. Sawka,9 Torquil Watt,10 and Colin M. Dayan11
I agree up to a point that it may be unfair to tar all with the same brush.
However in the six decades of being treated for hypothyroidism I have seen significant changes in attitudes to treatment and how pat are treated.
All my experiences are of declining quality of treatment and care.
I think the worst has to be “ I took an oath to do you no harm. Therefor I cannot refer you to an endocrinologist”. Really? That’s worse than the previous excuse that only a Hashimotos patient could be referred. Thyroid destroyed by radiation in the 1950s was much too simple cause of hypothyroidism!
I have spent many months getting the latest GP on board following the retirement of a lovely lady. It’s hard work, all done by telephone so far. A face to face on Friday for a particular blood draw she needs to do in person. Can’t wait to hear the details of that one. The letter asking me to make the appointment sent out in January was very vague. Do they actually do that as a module at med school?
My last excellent GP was in the 1980s.
I will be thrilled if we see trials which lead to a more open minded approach to patients awaiting some significant improvement in daily life as a result of treatment suited to each individual.
it will happen, the old dinosaurs will not prevail for ever over good science, patients could usefully be more scientific and objective too, if they can (not that we always can) and those of us with the stomach for it should complain via PALS and to the ombudsman about negligent healthcare and disability discrimination that riddles these crap doctors attitudes and decisions every time they get in the way. The consensus paper acknowledges the tide is turning, explicitly in parts, not just reading it between the lines eg. referring to how common it is becoming for endocrinologists to be challenged by patients not doing well on levothyroxine alone and that there are no good clinical studies to expedite consistent decision making (in other words the endocrinologists know they are on thin ice). Push the dinosaur element out on the ice let it crack under them.
I posted healthunlocked.com/thyroidu... on the original document recently. One concern I have is the comment from Jacqueline Jonklaas "There is also a caution to not use nonphysiological doses (high doses), to monitor for side effects, and to discontinue treatment if the patient does not experience benefits,". This is going away from basic science. We must first identify the hormone levels people have when hypothyroid and the levels / doses that are required to make them clinically euthyroid. By assuming patients do not sometimes require nonphysiolocal doses we are putting the cart before the horse, demanding that the endocrinologists' theory must override experimental results. This is not how science works.
It has been (in their view) fine to keep us all on nonphysiological doses of T3 for decades! Zero is, pretty much by definition, nonphysiological! And that is what by far the majority of us receive.
Worse, they have no idea whether our bodies, as individuals, can compensate for that zero dose because T3 is so rarely measured.
Very true!
It seems to my simplistic mind that people who can’t utilise T4 for whatever reason need a higher plasma concentration of T3 than someone who can. If the serum T3 level is “normal” they are missing the amount of T3 that would have been available from conversion from T4.
In the absence of a test for tissue T3, surely the only rational way to titrate the dose is to look at thyroid function in the body. Objectively in pulse, BP, cholesterol, weight, nail and hair quality, basal temperature, tendon reflexes etc and subjectively in how the patient feels.
I just do not see how TSH or serum T3 in the “normal range” are sensitive enough.
Agree with you although basal temperature is not much use but deep tendon reflexes are incredibly specific for hypothyroidism and can be measured precisely with the correct equipment. Of course they never do a study of tendon reflexes v. T3 doses for fear of the result.
I’m sure many patients don’t do well on levothyroxine monotherapy because they have inadequate conversion due to subnormal TSH, both in quantity and quality. As you alluded to, just restoring normal blood T3 levels will be insufficient because this T3 usually comes from deep within the cells from type-deiodinase.
I agree with you about deep tendon reflexes being a test that could be used more often.. i don't think i would ever have been diagnosed without an NHS Gp who was curious enough to test my ankles. I never 'looked' like a case of hypothyroidism, hadn't put noticable weight on and my TSH was not much over range 6.8, and TT4 was about 30%. But bless him , even though he had to repeat it about 4 times because he didn't seem very confident about what he was seeing with the naked eye... he was convinced enough to order a TPOab and it was 2499 and rising.
I didn't know there was 'equipment' for measuring it precisely.... but my guy did OK with a little hammer and his eyes..... i wondered what the hell he was up to at the time , but with hindsight ,seeing how infrequently the test is used, and how hard it is for some to get diagnosed, my opinion of him as a Doctor has gone up a lot.
Measuring the reflex time accurately involves high speed cameras so is for research only, although there probably is an 'App' for your mobile somewhere nowadays.
This paper might be of interest - not there yet, I fear. But very promising.
Implementation of a smartphone as a wireless gyroscope application for the quantification of reflex response
R. LeMoyne and T. Mastroianni, "Implementation of a smartphone as a wireless gyroscope application for the quantification of reflex response," 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Chicago, IL, USA, 2014, pp. 3654-3657, doi: 10.1109/EMBC.2014.6944415.
ieeexplore.ieee.org/documen...
However, that paper was 2014 and I would have hoped for more progress since then.
I have been hoping metabolomics might help!
Published: 06 October 2020
Analysis of metabolomics profile in hypothyroid patients before and after thyroid hormone replacement
• C. Piras, • M. Pibiri, • V. P. Leoni, • A. Balsamo, • L. Tronci, • N. Arisci, • S. Mariotti & • L. Atzori
Purpose
The serum metabolic changes occurring during the transition from hypothyroidism to euthyroidism are not known. This study aimed to determine the metabolomic profile in hypothyroid patients before (HypoT0) and after (HypoT1) euthyroidism achieved through levothyroxine (L-T4) treatment.
Methods
Eighteen patients with overt primary hypothyroidism were recruited for the study. All patients were treated with L-T4 to achieve euthyroidism. Thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and metabolomics profiles were measured before and after 3 months of treatment. The euthyroid control group consisted of 28 healthy volunteers. Metabolomics analysis was performed using Nuclear Magnetic Resonance (NMR) spectroscopy.
Results
1H NMR-based metabolomics profiling of patients with newly diagnosed hypothyroidism (HypoT0) showed significantly higher levels of citrate, creatinine, glycerol, myo-inositol and serine, and lower levels of proline and taurine compared to controls. Interestingly, some metabolic changes were persistent three months after pharmacological treatments, despite normal serum TSH and thyroid hormone concentrations (HypoT1). When an Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) model was built to evaluate possible differences in the metabolic profile between HypoT0 and HypoT1, the data obtained were not significantly different.
Conclusion
These results suggest that metabolic changes in the patients with hypothyroidism may persist after normalization of serum levels of FT3, FT4, and TSH, which currently represent the gold standard in laboratory testing for diagnosis and evaluation of thyroid pathology. So, the metabolomics approach may contribute to integrate classical hormone assays and to determine the euthyroid status achievement with greater efficacy.
Piras, C., Pibiri, M., Leoni, V.P. et al. Analysis of metabolomics profile in hypothyroid patients before and after thyroid hormone replacement. J Endocrinol Invest (2020). doi.org/10.1007/s40618-020-...
link.springer.com/article/1...
that's interesting... i do like thing's you can measure.. never heard the term 'metabolomics'
I agree, it’s wrong not to treat primary hypothyroidism by targeting physiological levels of fT3, fT4 and TSH. Cases that are more complex than simple primary hypothyroidism will probably need non-physiologic doses to get well. We need to dispel the idea that the only causes of hypothyroidism are thyroid failure and rare cases of central hypothyroidism.
actually JJ is representing basic science quite well when you consider that the most common values for healthy thyroid hormone levels are well established, scientifically and she is doing us all a great service by acknowledging that most of the combination therapy trials so far were flawed because of exactly that reason i.e. non physiological doses were preventing the experience and observation of benefits or worse have profound negative consequences (such as iatrogenic hyperthyroid effects) to the extent that the results were at least muddied and inclusive or worse giving the anti-T3 brigade actual trial data that (erroneously) supported their (unproven) T3 world view!
....sadly they only had two hypothyroid patient consulatees to represent stakeholder interest..... given that hypothyroid patients are the primary stakeholder group this representation was woefully inadequate and the consensus document , while the brightest hope for overturning the monotherapy dogma in years, is still overly paternalistic with opinions from academic experts still condescending to those with actual direct experience... not least in accepting that only 2 doses to split t3 and reduce iatrogenic negative effects will be acceptable for future trials given that slow release T3 isn't available. They cite patient difficulties with taking more than two doses of vital medication a day!!!! I take my T3 & T4 split into 4 separate doses and the difference in symptom relief is night and day. Yes its a bit of a pain but not as much of a pain as having thyroid and other related metabolism being kicked around by unphysiological dosing... at least the consensus document acknowledges this is an issue - duh! Anyway, my point is patients could do well to trial multiple split dosing, particularly of T3 but also of T4 since excess T4 will reduce cellular T4 - T3 conversion, then perhaps make it known to clinicians and researchers that it is not beyond the wit of a patient to take 3 or even 4 doses of thyroid hormones if it makes a significant difference to wellbeing and that clinical support to do this, for example in dose titration and pill/capsule compounding can make what seems a pain in the but actually not much different to simply having 3 or 4 healthy balanced meals a day. As it stands the consensus document for future trials is advocating only a 2 dose split while acknowledging this is less than ideal but reflects what parents will tolerate (!) and yet the frequency and amount of T3 doses in all previous trials and studies to establish whether combination therapy is clinically justified were all highly unlikely to be optimal and often inducing adverse effects through cumulative overdose and profoundly destabilising peaks and troughs in every dosing interval; in other words the trials were in effect set up to fail and seldom produced any clear clinical positives (not surprising if T3 doses were excessive, so, this is why the battle to get t3 if you need it has been so heated and drawn out and even acrimonious.... patients need to be pragmatic and flexible and start engaging with the profession more about what we could in fact do to get out health back with their fully collaborative support.
Sorry, what's PN?
To be a clear unhindered trial there needs to be no reference to TSH at all. By continuing to use TSH to determine dosage any trials are doomed to fail. When they see the TSH suppressed during the trials I have read, and the patient has seen no improvement (because the dose is too low) their assumption is that T3 didn’t work. Until a trial ignores TSH and looks at symptom relief in patients, while monitoring all functions of the body especially at cell level, they only add to the ‘T3 doesn’t work’ ethos
Saw new Endocrinologist today - starting trial of Erfa!
Trial of levothyroxine
Trying T4 again trial only🤦♀️
