This downloadable paper in Frontiers in Thyroid Endocrinology is worth reading:
Front. Endocrinol., 22 October 2019 | doi.org/10.3389/fendo.2019....
Combination Thyroid Hormone Replacement; Knowns and Unknowns
Peter N. Taylor*, Vinay Eligar, Ilaria Muller, Anna Scholz, Colin Dayan and Onyebuchi Okosieme
They still can't get hold of the basic reason why T4 only therapy doesn't always work though, and rather flap about looking for explanations based on their own faulty understanding.
It is a pity that they still seem surprised that T4 monotherapy doesn't always work!
I thought a lot of the paper was pretty good but the penny hasn't fully dropped for them yet. Thanks for pointing this one out.
I think it will take more than a penny to make them drop their 'guidelines' unfortunately.
Can you imagine that in 2019 we are still having to debate if T3/NDT should be added to T4 . It's very concerning and very frustrating .
“There Is Limited Data About the Safety Profile of Long-Term LT3 Therapy” - They headline - really? I thought NDT was successfully treating hypothyroidism since1898....or was it 1889 until the current day. I don’t need any of these stupid meta studies and double blind trials (conducted by the blind it would seem) to prove combination therapy is superior to T4 monotherapy, I am living proof it is! It solves another “problem” they mention too: the T3 is slow release in the NDT I take.
Why do they also think what nature ensures hormonally in people with healthy thyroids should somehow be irrelevant to us unfortunates who have hypothyroidism. They seem to me just plain stupid.
Thanks for posting
A frustrating and very disappointing read! A dirth of naval gazing and an opportunity missed. They appear to have missed exploring evidence already in circulation. I was hoping for more than 'ifs' or 'maybes' - though I welcome DI02 polymorphism recognition in their conclusion. Overall it's first entry stuff.
My mistake.
Spell check.
Delete: A dirth.
Insert: An excess
Conclusion: Not looking hopeful for UK contribution to BTA, ETA, ATA joint November 2019 symposium
You may not realise that you can edit any posts or responses you have made here.
HealthUnlocked have produced some help for how to do this. You can find this here:
support.healthunlocked.com/...
When you edit the original post in a thread, you will also have the option to add (or remove) a single image. (To replace an image, remove the existing image, then add the new one.) This is the same process as writing a new post:
support.healthunlocked.com/...
I am pointing this out purely to ensure that you know your options. 
(If you make extensive changes, it is sometimes helpful to add a comment so that people can see that you have made changes.)
I wonder if anyone from TUK will be going to the symposium. I was surprised at the very few responses to my posting when I mentioned it the other day. It does seem that finally questions are being asked more generally (hence the symposium) and it could be that there may have been a delay between the team submitting the article and it getting published. Colin Dayan is contributing at the symposium so it would be interesting to hear his views compared to those expressed in the article.
For clarity, the gene that affects T4 to T3 conversion is called DIO2 - that is, three letters and a number. Not D102 - a letter and three numbers. Not DI02 - two letters and two numbers.
The name comes from the enzyme that this gene affects which is a deiodinase. It removes an iodine atom from a thyroid hormone molecule - it deiodinates it.
On this forum we probably understand, but if you wish to look it up anywhere, it might help to get it right. If you are discussing with a doctor, and get it wrong, you are providing an excuse for them to dismiss what you say.
(More strictly, two single-nucleotide polymorphisms (SNPs) on the DIO2 gene, rs225014 and rs225015.)
academic.oup.com/jcem/artic...
The Wiki article provides a basic introduction as to what a single-nucleotide polymorphism (SNP) is and why it can be important:
en.wikipedia.org/wiki/Singl...
Thanks Helvella, test results confirm I have inherited DIO2 SNP rs225014 through one parent, ability to convert T4 to T3 may be affecting my health. I do not have the rarer CC genotype, though. I am adapting to living with Hashimotos. It was kind of you to respond.
I’ve got that one too and I am sure it is relevant. No amount of T4 monotherapy made me feel vaguely human but NDT fixed it very rapidly. I have close family who love Levothyroxine feel marvellous on it. I was gutted to feel like garbage after 9 months (supposedly optimised) then 2 years of pure hell, when their health was restored almost immediately. I wish I knew if this gene was ok in them or not. My money is on the former.
Thanks for replying TSH110, I feel certain it's relevant, too. Both my parents developed autoimmune conditions, father was in his forties when Rheumatoid arthritis diagnosed. My mother diagnosed with acute myeloid leukaemia when she was 46 and later crohns disease before she died, aged 55. RA occurs within other family members on my father's side - as do growing numbers of cousins reporting hypothyroidism and Hashimotos diagnosis. Unfortunately, this family evidence has been largely ignored by my consultant. Like you, Levothyroxine is not making me well, no matter how much I increase dosage to, for over two years. I remain symptomatic with Serum TSH 0.04 - 1.5 . Medichecks test results have consistently highlighted I may have conversion issues. Forum members were completely justified in warning me not to reduce my Levothyroxine dosage on instructions of consultant. They were so right! After navigating a crisis of symptoms in the summer, I caved in and have been steadily increasing my Levothyroxine every six weeks. Last week, feeling worse than ever, I eventually spoke to a specialist endocrine nurse at the centre I attend. She listened with empathy as I yelped through my symptoms and after relaying my volley of test requests to the consultant, she emailed confirmation I needed FT4, FT3, TSH, B12, Vitamin D, Folate and Ferritin testing on Monday. The nurse did not hesitate in confirming my consistent Thyroglobulin antibodies definitely diagnosed Hashimotos - to date the consultant has refused to act on this evidence. At long last I was pushing at an open door - the consultant had previously refused testing anything other than TSH against a regime of reducing replacement Thyroid medicine in order to achieve an above- range TSH result in line with original diagnosis. At GP surgery on Monday, Hashimotos again confirmed by head of practice and full thyroid and vitamin tests were taken first thing, followed by ANA test for Lupus in the afternoon. T3 and Lupus results due in 2-4 weeks. The specialist endo nurse emailed the others results to me first thing on Tuesday. Consultant away for half term, but nurse updating her. Sleeping better now that evidence has been taken seriously, but being realistic, it is feasible that goalposts could change again. At least Diabetes, Addisons and Coeliac are already ruled out.
Wishing you all the best. I really hope you receive the care you deserve ... it was good hearing from you.
Yes it is hypothyroidism and non Hodgkin’s lymphoma that plague us from the female line there is a more removed branch that all have glaucoma and have all gone blind with it too but we seem to have escaped that horror story. I think the HLA 8 gene is involved if I have got that right. All ignored by the medical profession as I degenerated into overt hypothyroidism and was told it was just the menopause 🙄. I eventually gave up on the NHS bought some NDT and have never looked back. What I find most amazing is how easy it is to get the right dose - no blood test no TSH...you just feel right when you are on the right dose the way is to titrate slowly in small increments. The palaver they make over getting the correct dosage is, quite frankly, ridiculous. We don’t really need doctors to sort out our condition, unless there are complications. Strikes me most of the complications are doctor induced anyway!
My Mum and Hubby's Mum died of NHL. Looking back we think they were both Hashi's/Hypo but undiagnosed. Read a paper once linking NHL and and
Hashi's . We both have Hashi's ...
Sorry to hear that Marz. I often wonder how many never get diagnosed and die of Hashis, I bet there are cases labelled as heart attack or whatever who’s death is really down to hypothyroidism. I wonder if hypothyroidism is ever given as the cause of death. Hope you and your husband are doing ok.
Looking more closely at this paper, it's quite clear that the authors have not the faintest clue about the direct thyroidal contribution of T3 and its critical importance (even though it is apparently a "minor" product) to the fine control of T3 production in the body. They simply cannot grasp the implications of this for therapy when the thyroid is lost. There seems to be a considerable dearth of IQ displayed here. Truly the knowledge of these people about the details of thyroid physiology now known is pitifully inadequate.
Living in south Wales, I am really disappointed because of reading somewhere that Dr Taylor was pretty good.
Thanks for that diogenes - have you thought about writing to them with your observations 😊
Shouting at the deaf is futile. So is shining a light in the eyes of the blind!
Had some hopes that Prof Dayan could make a difference.
😟 If we feel better and the blood tests show increased levels ( in range of course) reflecting same excluding the TSH, what can’t they grasp ?
"Management should be straightforward but appears not to be the case."
Now there is an understatement if ever I saw one!
I'm just speechless really, considering all the time and all the money wasted in coming to a conclusion that is simply not worth the paper it's written on.
It is so disappointing and I'm just thinking what is the point of all this ?
There is the kudos and the professional, medical networking :
In spite of the reality being, to keep a percentage of patients, mostly women, ill.
I just read the beginning preamble. Basically it says "Here is a list of things we don't know. We don't know why we don't know, we just don't"
They fail to understand also why their poor hypo patients 'don't know, why they don't know how to help their patients recover. What is the purpose of their 'profession? It might be too big a word to put on a forum.
Sorry, can't resist - got to be of a certain age... I was only a child 
"My name is Harry Worth: I don't know why but there it is".
I remember Harry Worth!
Ha ha xox
Didn’t he stand by a shop window and use it like a mirror to make bonkers moves? He had a little porkpie hat and everyone adored him
Read nearly half of it but don't have the energy for any more. I get the impression that whenever they say something correct, they add so many cautions, ifs, buts and backtracking that the truth disappears in the waffle. It's almost like the story of the donkey starving between two bales of hay!
Yes, in science you aren't supposed to say that anything is "Proven", only "Verified", but do they have to be so excessively cautious?
Maybe they afraid of falling foul of the powers that be if they make too strong a case for combination therapy?
It strikes me that the powers-that- be wield considerable clout and woe betide anyone who mentionsT4/ T3 combination....far less T3 only!
We are indebted to all of the researchers who keep seeking to enable other doctors/endocrinologists to 'see the light' so that we patients are treated as individuals and not as collectives as we all have so many different symptoms and some thyroid hormone replacements don't suit everyone. Mine is levo which made me far worse than before diagnosis and TSH of 100 and I was in and out of the cardiac dept like a yo-yo. Thankfully before the withdrawal of NDT and T3.
A huge thank you to diogenes and colleagues for your ongoing help and support.
And a huge nod to: Dr John Lowe, Dr Mark Starr, Dr Gordon Skinner [whose qualifications I always print to emphasise whichever *&^%* I'm writing to who has criticized him], Dr Barry D Peatfield and that staunch advocate, [several are ] now deceased, Sheila Turner.
What is the faulty understanding? Sorry I am a novice here!
Amongst other things I imagine it's reliance on TSH and overlooking the importance of FT3.
Ok thanks 😁
You may find this useful
bmcendocrdisord.biomedcentr...
Co-authored by "diogenes" aka Dr Midgely a researcher and one of TUK's advisors
Brill thanks! Actually I had read this already as it was in the references for the above paper (reference 7). I thought both seemed to be saying a lot of the same things!!! Both saying urgent research is needed anyway....
The difference between us and them is that they haven't got much idea as to how to do a meaningful trial at the moment, whereas we know exactly how to design one but unfortunately aren't in the position to actually do it. All we can do is lay down the criteria and hope they are bright enough to grasp them.
Is there any possibility of direct contact between you (and your colleagues) and the Cardiff people?
At my most optimistic I imagine them coming up to see you and spending a couple of days immersed in discussion and learning.
I would like to try, but there are two basic problems. One is that I'm not a medic, and therefore do not think like a medic. If anyone in the medical profession outside my direct colleagues felt it useful to contact me they would have done so years ago. I would have welcomed that. I did once put feelers out, with no response let alone the courtesy of direct refusal. But my second point is that it is now clear to me that there is a huge intellectual gulf between practicing medics in thyroidology and scientists who examine the physiological details to find out how things work and what to do. This has been brought home to me in that those medics who wish to clarify matters within their own understanding are now hoping to solve things by simply tacking on genetic variation onto the false T4-is-all paradigm with a view to rescuing it. This is another futile exercise in that genetic difference has a role to play, but far more complicatedly than they realise, with many variants large and small in many facets of the physiology. I would have thought that the Cardiff group would at least be aware of the new understanding of what the healthy thyroid does and how it reacts to stress and what the implications are for diagnosis and treatment. But they simply cannot logically move their thinking from the 35-40 year old mantra they have repeated as a immovable given. It is really clear from their paper and those of others. Until they take the giant leap of scrapping the whole of the last 35 years thinking and restart from scratch matters cannot properly move on. And that is so big a step to ask, with so many reputations , both now and earlier, seriously questioned that I'm not surprised we're subject to attempted marginalisation (eg Bianco's group and the US in general) and dismissal.
What is the new understanding of what the healthy thyroid does?
It is that the thyroid is not just a T4 factory as is currently assumed by the profession. The healthy thyroid produces BOTH T4 and T3, and the T3 made has a critical control over the conversion of T4 to T3 by the rest of the body. When you lose the thyroid this T3 source and control is lost. You have to make up for this by taking more T4 than otherwise you would had to. Some people cannot do this and cannot convert T4 to enough T3 however much T4 they take. It's these people who have to take T3 direct as well as T4.
I don’t know how that can be... my grandmothers nursing physiology book stated the thyroid produces T3 and T4.... in the 50s or 60s!! That’s surely not new knowledge??
Mollyjp, you're quite correct in asserting that the fact the healthy thyroid produces both T3 and T4 is not new knowledge. But the bit that medics (world wide) simply refuse to acknowledge is that:
"the T3 made has a critical control over the conversion of T4 to T3 by the rest of the body. When you lose the thyroid this T3 source and control is lost."
and that some people:
"cannot convert T4 to enough T3 however much T4 they take. It's these people who have to take T3 direct as well as T4."
Ah ok, thanks 😊
It was known, but the importance of direct T3 production has been ignored. Only a minority of the T3 comes from the thyroid (about 25%), so it was believed to be unimportant. But its influence is vastly greater than its small amount would suggest. Present-day assessment of therapy ignores this contribution entirely. That is why it's believed by the profession that T4 only therapy should satisfy everyone.
Ok that makes sense. Do you think everyone with hypothyroidism should take both hormones?
I think that is the obvious conclusion to be drawn especially as those on T4 appear to have abnormal levels and balance of thyroid hormones in their blood compared to people without thyroid problems. How can it possibly be optimum for health given how important these hormones are to all aspects of one’s well being? There was a time when everyone did get combination therapy when NDT was the only treatment for hypothyroidism and appears to have successfully treated it for very much longer than T4 monotherapy. I think Broda Barnes (?) did some very interesting research on longevity and causes of death of those taking NDT and it appeared to be pretty beneficial. All this is totally ignored or deconcocted to one sentence saying it is not recommended by the all knowing all seeing god like agglomerations of all powerful endocrinologists who have decided they will ram T4 monotherapy down our throats even it makes us ill or kills us and label us as mentally deranged and not worth listening to because their TSH numbers are sacred. All based on a pack of lies, a lack of acumen and/or complete ignorance.
Not that I am claiming to speak for diogenes who may beg to differ. I must admit that apart from me the rest of my hypothyroid family are big fans of Levothyroxine. They had cancer of the thyroid too so got /get TSH suppressive doses of it. Perhaps it is fine for many. Freedom of choice of therapies would decide that one of course.
Ok, where could I find this Broda Barnes research? Thanks! 🙂
A short bibliography of Broda Otto Barnes
Many of these published articles and books are not available. Secondhand book companies might be able to supply some of the books.
Some of the articles are available online (where I have found them, I have inserted a link), others there is only a reference to them, others seem to have disappeared almost entirely.
If you find any more working links, please let me know.
Books
• Barnes, Broda Otto (1976). Hypothyroidism: The Unsuspected Illness. HarperCollins. ISBN 069001029X.
• Barnes, Broda Otto (1989). Hope for Hypoglycemia: It's not your mind, it's your liver. Fries Communications. ISBN 0913730262.
• Barnes, Broda Otto; Charlotte W. Barnes (1976). Solved: The Riddle of Heart Attacks. Robinson Press. ISBN 0913730270.
• Barnes, Broda Otto; Charlotte W. Barnes (1972). Heart Attack Rareness in Thyroid-treated Patients. Springfield, Ill.: Thomas. ISBN 0398025193.
Peer-reviewed journal articles
• Thyroid supplements and breast cancer" Barnes BO JAMA 236 Issue: 24 Pages: 2743-2744 : 1976
jamanetwork.com/journals/ja...
• "Thyroid-adrenocortical relationships in the safe treatment of arthritis, allergy, and skin disorders with prednisone." Barnes BO.J. Am. Geriatr. Soc. 1975 Dec;23(12):548-50. PMID: 1206190
• "Hypertension and the thyroid gland." Barnes BO. Clin Exp Pharmacol Physiol. 1975;Suppl 2:167-70. PMID: 1183088
• "The role of natural consequences in the changing death patterns". Barnes BO, Ratzenhofer M, Gisi R. J Am Geriatr Soc. 1974 Apr;22(4):176-9. PMID: 4594123
• onlinelibrary.wiley.com/doi...
• "On the genesis of atherosclerosis." Barnes BO. J Am Geriatr Soc. 1973 Aug;21(8):350-4. PMID: 4720848
• onlinelibrary.wiley.com/doi...
• "One factor in increase of bronchial carcinoma." Barnes BO. JAMA. 1960 Dec 31;174:2229-30. PMID: 13687094
• thelancet.com/journals/lanc... [Paywall]
• "Prophylaxis of ischaemic heart-disease by thyroid therapy." by Barnes BO. Lancet. 1959 Aug 22;2(7095):149-52. PMID: 1379687
• "The early diagnosis and treatment of pertusis." by Barnes BO, Mason P. Ariz Med. 1950 Jan;7(1):34. PMID: 15408931
• The treatment of menstrual disorders in general practice. Barnes BO. Ariz Med. 1949 Jan;6(1):33. PMID: 18106263
europepmc.org/abstract/MED/... [No abstract]
• "On the origin of the substance in urine which produces elongation of the bitterling ovipositor" Kanter AE, Klawans AH, Barnes BO Amer. J. Obstetrics & Gyn. 35 Pages: 984-989 1938
• "Bitterling ovipositor lengthening produced by adrenal extracts." Barnes BO, Kanter AE, Klawans AH. Science. 1936 Oct 2;84(2179):310. PMID: 17837041
• science.sciencemag.org/cont...
• "The relation of the parathyroid hormone to the state of calcium in the blood" McLean FC, Barnes BO, Hastings AB Amer J Physiol Volume: 113 Issue: 1 Pages: 141-149 (1935)
• "The relation of the hypophysis to experimental diabetes" Regan JF, Barnes BO. Science 1933 Feb 24;77(1991):214. PMID: 17814070
• science.sciencemag.org/cont...
• "The excretion of iodine in experimental hyperthyroidism" Barnes BO Amer J Physiol Volume: 103 Issue: 3 Pages: 699-703 1933
• "The effects of theelin and theelol in latent tetany" Mathieu F, Barnes BO Amer J Physiol Volume: 105 Issue: 1 Pages: 172-176 (1933)
• "Studies on thyroglobulin II. Absorption of thyroglobulin and related substances from the alimentary canal." Barnes BO, Bueno JG Amer J Physiol Volume: 103 Issue: 3 Pages: 570-573 1933
• "Is there a specific diuretic hormone in the anterior pituitary?" Barnes BO, Regan JF, Bueno JG Amer J Physiol 105 Issue: 3 Pages: 559-561 1933
• "Studies on thyroglobulin III. The thyroglobulin content of the thyroid gland." Barnes BO, Jones M Amer J Physiol Volume: 105 Issue: 3 Pages: 556-558 1933
• "Improvement in experimental diabetes following the administration of amniotin." Barnes BO, Regan JF, Nelson WO :JAMA 101: 926-927 1933
• jamanetwork.com/journals/ja...
• "The physiological activity of iodine in thyroglobulin" Barnes BO Amer J Physiol Volume: 101 Issue: 4 Pages: 583-590 1932
• "Variations in blood sugar values of normal and vagotomized dogs following glucose administration" Quigley JP, Hallaran WR, Barnes BO J. Nutrition 5 Issue: 1 Pages: 77-80 1932
• "Studies on thyroglobulin I. The digestibility of thyroglobulin" Barnes BO, Carlson AJ, Riskin AM Amer J Physiol 98 Issue: 1 Pages: 86-92 1931
• " Does insulin antagonize the action of atropine on the cardiac vagus endings?" : Barlow OW, Barnes BO J. Pharmacol. & Exper. Therapeutics 41 Issue: 2 Pages: 209-215 1931
• "Action of insulin on the motility of the gastrointestinal tract VI. Antagonistic action of posterior pituitary lobe preparations" Quigley JP, Barnes BO Amer J Physiol: 95 Issue: 1 Pages: 7-12 1930
Blimey that is a great list! Thanks for posting. I was starting to search for the paper I mentioned and not got as far as a wiki bio en.m.wikipedia.org/wiki/Bro...
Wow! Excellent. Thank you very much 🙏 it’ll take a fair amount of time to look through that!!!!
I think the one I read was about heart disease where he discovered those on NDT so T3 had less heart disease than the general population indicating T3 was protective.
I just re-read what you said, was this mainly for people without thyroids, or do you also mean people with autoimmune hypothyroidism? Can we ‘lose’ our thyroids without having it removed? How would we know? Sorry about all the questions..
People without any thyroid are in the worst state. If you have Hashimoto's with something still working, you are in between health and no thyroid. The thyroid remnant works like crazy to maintain your body's T3 levels, at the expense of making T4, getting more and more frenetic as the gland dies until, at the end, bang, the whole system collapses and any semblance of thyroid control is lost completely. That is the threshold for a complete change of treatment.
Is there any way of knowing for sure if this had happened?
Usually by a mixture of gland scanning and testing for thyroid activity with 125-I or 99m-Tc isotopes in nuclear medicine.. A gland shrunk to a wizened pea definitely won't be working. Glands below a certain limit of size usually are defunct.
Thanks
ncbi.nlm.nih.gov/pmc/articl...
I have been looking back over some of the research I can find online. I just wondered if there had been any progress on the areas mentioned in the conclusion that needed looking into?
Not really. The emphasis has been on biochemical measurements of TSH and (less) FT4 and (v little) FT3 and the mechanical conclusions then drawn as to the patient condition. Presentation by the patient re symptoms has taken a back seat. That has to change, owing to patient individuality.
Thanks. I am finding it hard to sort the good information from the bad information. There seems to be a lot of differing opinions in the world of thyroid medicine and it’s hard to know what’s what. I think the main conclusion I have come to is that it is under-researched!! The last endocrinologist I spoke to said there are definitely people who report benefit from taking T3 and was willing to prescribe, but said it’s more of a trial and error sort of process than a clear science at this stage of what is known. Would you agree?
Yes
As you are new to the Forum I am sure you have clicked onto the username diogenes and found he is involved in Thyroid Research as Dr John Midgley ...
Yes thanks I had grasped that, hence the questions!!! Though I am still a bit bamboozled by what he thinks as opposed to what is written in this paper.
