This recent paper in Jan of this year is a panel of "distinguished" scientists who have issued a consensus statement regarding use of and designing better future clinical trials to prove the efficacy of combined treatment. Behind a paywall:
Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document
January 2021
European Thyroid Journal 10(1):10-38
DOI: 10.1159/000512970
Jacqueline Jonklaas, Antonio C. Bianco, Anne R. Cappola, Colin M. Dayan et al
Written by
diogenes
Remembering
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Perhaps, for endocrinologists rather than GPs, patients could show the summary and source of the article on appointment, to demonstrate that it's not the bearer of the paper (the patient) who is doubting current testing/diagnostic strategy, it's the head gurus in many countries themselves who are jumping onto a bandwagon (can you hear the creaking as they jostle for collective displays of at-long-last demonstrated wisdom/forget the past). No longer can endos hide behind their particular point of view. The patient has a statement they can no longer dismiss. For GPs the summary might do.
It doesn't surprise me in the least that the consensus will only go slowly and dip slow hesitant toes in the water. The whole paradigm between TSH and the other hormones needs shaking up root and branch, but you are never going to get "mea culpa" from the influencers here. There is no way they will finally change until they have conducted (we hope well) new studies on T3/T4 combination to convince themselves. Notice that THEY have to do it from their own work. No-one outside this cabal will be acknowledged, only the ideas stolen and re-presented as if they themselves had thought of it. They begin to question the diagnostic role of TSH, but can't yet bring themselves to act, because when they do, they know the whole edifice will topple. It's clear what "insufficient evidence" means when the authorities trot it out to dismiss an idea. What they really mean is that "sufficient" wil only be admitted when they rediscover it.
Prof Pearce on Twitter yesterday was very pleased with the paper, from the tone. I’m afraid I found it same ole, same ole. In contrast the previous paper I’d read was that from Harada et al. doi.org/10.1007/s12020-019-... which I felt had more to offer, though much shorter in length.
Thank you so much Diogenes for your consistent hard work bringing great studies proving that thyroid patients do so much better with a combo of T3 and T4. Who are Endo/Dr going to believe some papers or patients or both ???
A few comments on the first paragraph of the introduction.
Endocrinologists are frequently asked to consult on adult patients with hypothyroidism taking levothyroxine (LT4) who are dissatisfied with their therapy.
Not as frequently as would be the case if all dissatisfied adult patients were referred and actually got to see endocrinologists.
Once other non-thyroid related causes of these symptoms have been fully excluded, the patient and their physician may wish to explore alternative therapies for optimization of health and well-being.
I have yet to see a patient in whom “other non-thyroid related causes of these symptoms have been fully excluded” – at least by reports here and elsewhere.
Given the time it can take to go through other possibilities, possibly years, during which the patient is continuing to suffer, this is very much not in patients’ interests. After all, we KNOW right at the beginning that the patient has a thyroid issue. So, whilst reasonable to look at other possible causes, why delay looking more deeply into their existing, known treatment – thyroid hormone replacement.
However, the use of combination therapy with both LT4 and liothyronine (LT3) remains highly controversial with conflicting results from published clinical trials, with two studies showing benefit in most measures and two showing benefit in some measures.
The controversy is primarily among endocrinologists. This spills over into controversy between endocrinologists and patients when the patients continue to suffer and are refused even the possibility of trying some form of combination treatment.
Recent scientific studies have provided new mechanistic insight into such issues as the complex relationship between serum and tissue thyroid hormone levels, providing a rationale for re-consideration of the design of future LT4/LT3 combination therapy clinical trials by incorporating features that might increase the likelihood of showing efficacy.
Lack of a mechanistic insight, providing a rationale, should not be taken as evidence that combination treatment does not benefit at least some patients. There are many treatments which lack full understanding. Last I read, there was no biochemical understanding of paracetamol.
Thus, our aim in this consensus document was that consideration of mechanism might provide a path toward better designed trials, also focusing on clinically relevant outcomes, including patient-centered outcomes.
While mechanistic understanding is highly desirable, and could indeed help better design trials, that is no excuse for the poor quality of at least the majority of trials so far. Most particularly, that the trials are criticised elsewhere in this paper for producing inconsistent results.
“Will to live” is getting to be in desperately short supply before I even reach the second paragraph…
You have made some good points helvella . I particularly like this comment one! 👍
However, the use of combination therapy with both LT4 and liothyronine (LT3) remains highly controversial with conflicting results from published clinical trials, with two studies showing benefit in most measures and two showing benefit in some measures.
The controversy is primarily among endocrinologists. This spills over into controversy between endocrinologists and patients when the patients continue to suffer and are refused even the possibility of trying some form of combination treatment.
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T4 & T3 combination therapy... day 9... awesome! 
Combined T4 / T3 therapy Tests
