Research paper about T3/T4combination treatment. What happened there?

[buddy99]

I became aware of this through "Endocrinology Advisor": pubmed.ncbi.nlm.nih.gov/381... The link to the paper was not given. I found it myself.

"Conclusions: Six months of combination therapy with twice-daily LT3 dose adapted according to TSH-level do not significantly change peripheral tissue response or quality of life, despite an increase in the fT3/fT4 ratio." This is from the paper.

"No between-group differences were observed in quality of life at the end of treatment. Only 11% of combination therapy participants preferred the combination therapy, whereas 56% of combination therapy patients and 60% of placebo patients considered the combination therapy to be more complicated than monotherapy.

Study limitations include reduction of clinical activity and subsequent dropouts due to the COVID-19 pandemic.

This study shows that patients treated with customized twice-daily doses of [liothyronine] in combination with [levothyroxine] have a significant reduction of TSH together with an increase of FT3 and FT3/FT4 compared to placebo,” according to the researchers. “However, no significant differences occur between groups in peripheral tissue markers of thyroid function, [quality of life], and BMI.” This is from Endocrinology Advisor.

Where did they get the percentages for dissatisfaction? Am I missing something?

It seems to me that the dose adjustments might have been made based on TSH. Also 6 months seems rather short for this kind of research. There might not have been a full benefit yet especially with doses still being adjusted. Could that account for patients (feeling no benefit) to find combination therapy too complicated? And where does it mention that specific reason in the research paper? Does EA maybe have additional information not mentioned in the paper? Or are they just making it easier for endos to use that as an argument to deny patients the combination treatment? Because endos will not likely seek out the research paper and just happily take EA's word for it.

Correct me if I went astray somewhere. I'm a bit miffed right now (and worried), which may have caused me to overlook something important.

[DippyDame]

Conclusions: Six months of combination therapy with twice-daily LT3 dose adapted according to TSH-level do not significantly change peripheral tissue response or quality of life, despite an increase in the fT3/fT4 ratio

Here we go again! .....rediculous TSH fixation.

Until they have the courage to climb down from their TSH hobby horses, medics will continue to wrongly diagnose and prescribe, while justifying their decisions by claiming the patient(s) did not respond to ( or comply with) the treatment prescribed.

And then, they need to understand T3 and how it works....most of them fall at the first hurdle.

Many of us can attest to this....but our lived experience is ignored or receives a patronising response..

It is a scandal of monumental proportion

The combination of those two factors is leaving patients confused and unwell

There is more than one way of treating with T3 and if there is no peripheral response then they might consider that the dose level they consider to be optimal is just too small!!

Some of us need a supraphysiological dose of T3 to achieve a response....but that idea terrifies them.

They do not understand, and persist in following guidance that is little more than a set of beliefs established over time as fact... when instead they should be looking to verifiable scientific research and facts.

However, no significant differences occur between groups in peripheral tissue markers of thyroid function, [quality of life], and BMI.

Surely it's clear that if the dose is wrong the response will be wrong.

They need to treat the person and their symptoms....not a list of irrelevant ( TSH) numbers

It's almost certain that I would be dead now if, 10+ years ago, I had looked no further than current guidelines. Nobody recognised that my body was shutting down due to lack of T3.

Yet, papers like this will be used to justify the madness that is TSH fixation...

For a start T3 lowers TSH!!

TSH is a pituitary, not a thyroid, hormone.

The TSH test was devised as a diagnostic test for hypothyroidism by way of high levels of thyroid hormones, both FT4and FT3. Nothing more! It does not show the levels of the individual hormones which are crucial to the diagnosis.

I'm afraid this issue makes me see red .....things need to change, but that is another contentious issue.

I don't think you have missed anything but I do think the researchers have missed and misunderstood a lot!!

[buddy99 in reply to DippyDame]

My main concern is that endos will now say to patients (if they even bother to explain anything), that research showed that 89% of patients who tried the combination treatment did not want to stay on it because it brought no benefits only inconveniences. My own doctor said that he does not know how to interpret research (probably meaning that he doesn't bother). He would likely take this article by EA and pass it on to patients no questions asked and feel quite superior about it, because it is "evidence based medicine".

[DippyDame in reply to buddy99]

Indeed!

I find it hard to believe that your GP cannot get the gist of what a research paper is investigating...in his own subject area.

Perhaps he/they may not bother to read this!! Too busy!!

But, I absolutely agree, it is a concern and totally unforgivable.

We are at the mercy of medical, political and financial clout.....they can close ranks and shut us out.

I'm afraid we have to educate ourselves in matters thyroid - we have all the information in the world at our finger tips - and, in extremis, learn to diagnose and treat ourselves as many of us have been forced to do.

Doctors also have to remember that guidelines are just.....guidelines

NICE says this of guidelines

The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals and practitioners are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or the people using their service. It is not mandatory to apply the recommendations, and the guideline does not override the responsibility to make decisions appropriate to the circumstances of the individual, in consultation with them and their families and carers or guardian. "

[Hashiboy in reply to DippyDame]

And just scanned the paper - the dosing is so arbitrary. If you just gave me 5mcg T3 I’d be flat out on the floor. This paper is TSH focused but still makes it clear that if you need T3 then dose depends on how much thyroid tissue you have left.

pubmed.ncbi.nlm.nih.gov/318...

[Hashiboy in reply to DippyDame]

DippyDame please keeping seeing red, your post is brilliant

[buddy99]

I find it hard to believe that your GP cannot get the gist of what a research paper is investigating...in his own subject area.

I think he did not mean to "disclose" that. He was reaming me out, as a lay person with no medical back ground, about an information leaflet by the Cochrane Institute for lay people and said that not even he, with his medical education, can interpret research, so how would a lay person presume that they could. I assume that in addition to not being able to read research he also has issues with listening skills.

[DippyDame in reply to buddy99]

....and, his patronising , poor comunication skills reveal that he considers non medically trained patients to lack any grey matter that might enable them to get the gist of the paper. Rubbish! He could start at the end and read the conclusions

[BenLabrador]

I think the results are understandable. For a patient who converts T4 to T3 well I can imagine they find no additional benefit in a combination therapy. However for those like me who have the DI02 gene the inability to adequately convert T4 to T3 means I need the combination therapy to have a decent quality of life.

The researchers, through plain or wilful ignorance because of a desire to promote T4 monotherapy, did not include patients who do not adequately convert. They did not look at that factor and did not find the evidence. Simple.

I use the results of the DI02 test as evidence to my GP that I need T3. And my GP daughter is rather sceptical about such papers as in her opinion research can ‘prove anything’’. I think this is such a case, incomplete data in incomplete answers out.

[DippyDame in reply to BenLabrador]

The patients concerned are totally thyroidectomized.

You say...

The researchers, through plain or wilful ignorance because of a desire to promote T4 monotherapy, did not include patients who do not adequately convert.

Have I missed something, where does it refer to the research subject's T4 to T3 conversion status?

They are prescribing T3 which is a good indication of poor conversion

Moreover this research refers to thyoidectomised patients who no longer have a thyroid gland producing thyroid hormones

I think you'll find that it's medics who promote T4 mono not scientific researchers. Medics, it seems, tend to rely on what they believe to be true rather than referring to verifiable research.....eg medics persist in warning of additional risk of atrial fibrillation, cardiovascular disease or fractures when taking long termT3, when robust research proves otherwise

Knowledgeable people in the field will soon pick out errors/ omissions in research papers. In reliable journals these should be identified at Peer Review stage before publication.

"Wilful ignorance" would be unethical!

You will note from the Objective that Changes in other tissue markers and quality of life considering DIO2-rs225014 and MCT10-rs17606253 genetic variants were also assessed.

You refer to having the Dio2 polymorphism. Conversion status depends on whether the Dio2 snp is homozygous or heterozygous...the former has a greater impact on T4 to T3 conversion than the latter but I doubt most GPs understand this.

My Dio2 snp is homozygous but my thyroid problems extended beyond that....I need a supraphysiological dose of T3 to function but that's another tale.

We may not agree with the conclusion, but might the authors be able to claim that their objective was fulfilled...it may be flawed but it was their objective.

Despite having normal thyroid-stimulating hormone levels, many hypothyroid patients are dissatisfied with the treatment. The primary aim of this study was to evaluate the effect of twice-daily, combination therapy with levothyroxine (LT4) and liothyronine (LT3), at doses adapted according to TSH-level, on peripheral tissues as reflected by sex hormone binding globulin (SHBG) levels in totally thyroidectomized patients. Changes in other tissue markers and quality of life considering DIO2-rs225014 and MCT10-rs17606253 genetic variants were also assessed.

Their objective was not to specifically prove that the subjects needed T3, it was to evaluate a T4/ T3 combination for patients with no thyroid.

But....they did not investigate dosage with reference to FT4 and FT3 but relied on TSH which research proves is an unreliable marker and unlikely to aid the achievement of a therapeutic dose

They don't understand TSH. It is a pituitary, not a thyroid, hormone and is unreliable for diagnosis in the absence of FT4 and FT3..

FT3, the active thyroid hormone, is the most important reading

thyroidpatients.ca/2021/07/...

If " research can prove anything" we might still be living in caves....robust research, on the other hand, aims to prove something worthwhile.

Robust research exists but it isn't always given the attention it deserves

My earlier comments stand.... poor research with poor justification will continue to be used to support the madness that is TSH fixation.

[jgelliss in reply to BenLabrador]

Thank you. I'm in the same camp like you. After my TT being on high doses of T4 made me ill. Once I started T3 with the right nutrients it made a world of a difference. I must have the same gene.

[BenLabrador in reply to jgelliss]

You can test for the mutation in the DI02 gene through Regenerus Labs in Redhill, Surrey.

[DippyDame in reply to BenLabrador]

You can also compare FT4 with FT3.....high FT4 with low FT3 = poor conversion....any clued up endo should recognise this without testing for the Dio2 snp.

Quicker, easier and cheaper!

[Sleepman]

Shame we cannot see full paper.

From abstract, I read into it, that 71 people, who were presumably OK before hand and perhaps not short of T3 ?

They took 5mg of T3(in 2 doses /less patient friendly) and reduced T4 by 15 mg and then saw no change and were still OK. (but 60% found it more complicated than 1 T4 tablet a day --- wow not )

Is this a surprise ? Is it not expected not change if they were not short of T3 in the first place and were OK?

They say the T3/T4 ratio increased compared to control group.

I guess it shows it did not do any harm and they stayed OK as T3 to T4 ratio increased.

Also tissue marker stuff, with higher levels of T3 versus T4 did not have any effect on markers they were looking at.

As you pointed out they changed T3 based on TSH, how many were dose changed ?

Says they looked at Genetic variants but it did not have an effect. How many DiO2s

Would be nice to see the full paper.

[Cornwaller]

"only 11% preferred the combination treatment" not sure why the need for "only". Whether 11% or 60% or 5% preferred it doesn't invalidate the option. Unless of course you only want a result that works for everyone and you wish to impose a single clinical treatment option on the entire population - Soviet style.

The alternative paradigm is that combination therapy is preferred by a proportion of patients and therefore should be available to them as the aim is to increase the quality of life for each individual using the best treatment option for them. Personalised medicine?

[Judithdalston in reply to Cornwaller]

Many of us would agree using T3 is fiddly to titrate and use split thru the day etc, and if T4 conversion is reasonable then concentrate for eg on optimising your minerals/ vitamins first rather than go down T3 route. But perhaps like this research 11% think it well worth all the effort, including the many disagreements with drs.over our diminished TSH! 11% is a lot of a population in other circumstances.

[Cornwaller]

Absolutely.

[serenfach]

"60% of placebo patients considered the combination therapy to be more complicated than monotherapy." Taking two pills is so much more complicated than taking one, poor things...

And I dont see where the placebo patients said they felt worse or better. A shoddy piece of work!