New Programme to assess T4/T3 combination therapy

[diogenes]

In Frontiers in Thyroid Endocrinology a research project is to be started - US based of course - on assessment of T4/T3 combination therapy. Below is a summary of the aims of the project. Looks like progress is being made:

Combination Therapy for Hypothyroidism

Context/background

The issue of whether or not to consider combination therapy for hypothyroidism remains controversial. Although clinical trials of combination therapy have not shown a benefit of combination therapy over levothyroxine monotherapy, patients still express considerable interest in combination therapy. Moreover, some studies show a discrepancy between serum TSH and other biomarkers of thyroid status, and animal studies show that combination therapy normalizes a number of tissue parameters reflecting euthyroidism better than levothyroxine does.

Goal

The goal of this Research Topic is to review and consolidate current understanding of how to provide physiologic therapy for hypothyroidism that restores euthyroidism in all tissues of the body and ensures patient satisfaction with therapy. The action of T3 in various tissues and the role of deiodinases in maintaining “tissue euthyroidism” and normalizing cellular T3 levels will be discussed.

There will be a focus on the potential role of combination therapy for treating hypothyroidism and design of studies to determine whether there are specific sub-populations who will benefit from combination therapy. This compilation of articles will delineate the current state of this field, provide a stimulus for fresh consideration of the area, and define future directions for research to advance the field.

Scope

Original research articles, reviews, meta-analyses, and opinion pieces will be considered as suitable material, and consideration of both animal and human data is encouraged. Specific areas of interest include, but are not limited to the following:

1. What are the best methods for measuring T3?

2. What parameters best define euthyroidism?

3. What effect does T3 have on specific tissues such as the brain, heart, and liver?

4. What role do deiodinases play in maintaining normal T3 levels in various tissues?

5. What role do polymorphisms in deiodinases and thyroid hormone transporters play in determining the ability of levothyroxine therapy to restore normal physiology?

6. What factors determine patient satisfaction with therapy for hypothyroidism, and how do these factors interact?

7. How is patient satisfaction and quality of life best measured during therapy for hypothyroidism?

8. What constitutes an ideal combination therapy trial?

9. What are the benefits and risks of combination therapy?

10. How can physicians balance patient preferences and ensure good patient outcomes?

11. What is the role of sustained release liothyronine preparations, and what progress has been made in development of such products?

Keywords: Hypothyroidism, Levothyroxine, Combination Therapy, Liothyronine, Satisfaction

[SlowDragon Administrator]

Is there a link......perhaps they would like to hear from patients on T3/T4 therapy, especially if we have had any DNA test as well

[RedApple Administrator in reply to SlowDragon]

Try this frontiersin.org/research-to...

[Hennerton]

I note there is no mention of thyroidectomy patients having extra issues. For instance, loss of calcitonin, T1 and T2. Why does a healthy thyroid make these if they are not necessary for good health? Can anyone answer this?

[diogenes Remembering in reply to Hennerton]

As regards T1 and T2, the former is a breakdown product of T4-T3-T2-T1 in the body and has no known hormonal property, and T2 is primarily made from T3 in the body not from thyroid, and controls mitochondrial action. The project is concentrating on T4/T3 use as this is the main contentious problem at the moment.

[Hennerton in reply to diogenes]

Thank you for the reply but I am not entirely convinced that we do know everything possible about thyroid matters. Time will tell but I feel sure I shall not be around by then. What is your view on calcitonin? Necessary or not?

[diogenes Remembering in reply to Hennerton]

It is, but for this particular programme is a distraction.

[Hennerton in reply to diogenes]

Oh! Then do we TT patients need it and if so, how can we get hold of some? . (TT 2006 for Graves, after no steady success with Carbimazole)

[diogenes Remembering in reply to Hennerton]

Yes calcitonin does play a role in controlling calcium uptake but it seems to be a minor one. I really cannot say that it is essential and that there are not other mechanisms in the body that do the same thing.

[Hennerton in reply to diogenes]

Thank you. One less thing to worry about...

[TSH110 in reply to diogenes]

Why on earth would the thyroid gland make it not just in us but in pigs and I assume sheep, cattle, rats etc if it did not have an important role...as yet to be elucidated? Doesn’t sound like it has been extensively researched.

I do get the general point that T4/T3 therapy is the big issue of course.

[humanbean]

Although clinical trials of combination therapy have not shown a benefit of combination therapy over levothyroxine monotherapy,

This makes me angry. The clinical trial reports I've read have shown such disastrous methodology that they would be impossible to interpret honestly and give a meaningful result.

[diogenes Remembering in reply to humanbean]

This is true, and I think the authors are talking historically, regardless of the quality of the evidence. I think we may well plan to enter the fray because manuscripts etc are invited to be considered as part of the project.

[humanbean in reply to diogenes]

I do hope you get involved. It would be good news for all of us!

[TSH110 in reply to humanbean]

What gets me is when the majority or a significant proportion of participants say they feel better on combination therapy yet they still say it has no benefits over T4 monotherapy! This is an absurd conclusion surely the recipients feeling better IS the main benefit. How is making people feel less well on T4 than is possible on T3/T4 therapy beneficial to anyone? Call it science - I call It a complete nonsense dressed up as science.

[humanbean in reply to TSH110]

This is an absurd conclusion surely the recipients feeling better IS the main benefit.

I think that doctors would say publicly that the idea of thyroid treatment is to make people feel better. But in reality they believe their job is to keep the TSH in range, and once they've achieved that their job is done.

[Hidden in reply to TSH110]

Dressed up as money, money, money

[SilverAvocado in reply to TSH110]

It's a constant frustration to me how quality of life and patient satisfaction is measured and discussed in ways that make it sound very distant and ethereal.

[diogenes Remembering]

Perhaps as Rudolf Hoermann has said to me:

"I think they take our papers seriously without admitting it and have realised that the train is about to leave station and are trying to get on"

[mfinn]

What will happen, I wonder, when the guinea pigs are given T3 and their TSH becomes very low? If the researchers play around with the dose until TSH is at an ‘in range’ level there probably won’t be any benefit seen and that will be the final conclusion.

[diogenes Remembering in reply to mfinn]

The TSH in range for healthy people no longer washes for therapy, but subjective response must play the major part rather than mechanistic biochemistry.

[Hennerton in reply to diogenes]

TSH may not wash for therapy in research but try telling that to every GP practice in U.K. and a very blank look will be evident. It is the sum of their thyroid knowledge and as one eminent professor told me "exquisitely accurate".

[helvella Administrator in reply to Hennerton]

Accuracy means absolutely nothing in itself. Sufficient accuracy is, of course, a requirement but beyond that, so what?

The technical accomplishment of the scientists who have developed tests of such astonishing accuracy deserves recognition. But you can be pretty sure that the smug endocrinologist raving about accuracy was not one of those whose brainpower did that development.

That there are still issues like interference from macro-TSH (TSH antibodies) and biotin means that there is still great uncertainty about the result in all too many cases.

If the doctors are going to defer treatment until TSH reaches 10, who cares whether the test can see a difference between 1.000 and 1.001?

We so often see that doses (typically of levothyroxine) are only ever adjusted by 25 micrograms, so what if the TSH is technically accurate to the nearest 0.00001 of a unit per millilitre?

[Hennerton in reply to helvella]

Yes, I hope you realize I was not pointing out the remark about “exquisite accuracy” because I believe it is the way to manage thyroid patients. I was using it tongue in cheek, because this is honestly what 99% of doctors believe to be the case. Sadly I was seeing said eminent professor privately and had to pay handsomely for the privilege of his conviction about TSH blood tests.

[helvella Administrator in reply to Hennerton]

Oh yes - but they go on about it so much!

[diogenes Remembering in reply to helvella]

There are two definitions for a good assay. It must be both precise and accurate. That is, it gives the "right" mathematical answer to a high level of certainty on every occasion. However, neither of these have any relationship to diagnostic accuracy, which is outside the actual test performance and relates to outcome not process..

[SilverAvocado in reply to helvella]

In social research we use the concepts of validity and reliability. Often in conflict with each other.

Reliability is whether the measurement itself is accurate, and you can measure the same thing multiple times and get the same result. TSH is great for that.

Validity is whether the measurement you've got actually means anything useful. Whether you're measuring what you say you're measuring, or it can be translated into something of real world significance. This is the one TSH fails on, if it's used as a measure of how sick a thyroid patient is.

[Hillwoman in reply to SilverAvocado]

I've never seen the TSH argument expressed in quite these terms before, but it could be a very helpful way to put a patient's problem across to the average medic.

[SilverAvocado in reply to Hillwoman]

I don't know how widely these terms are used in medicine and natural sciences. They are a pretty big deal in social sciences.

I did have a search and found out they are mentioned in GCSE science, so you'd hope a doctor would have heard of them!

[Hillwoman in reply to SilverAvocado]

Yes, you would hope so!

[SilverAvocado in reply to mfinn]

They do ask the interesting question, 'What are useful measures of euthyroidism?', which suggests to me that they're aware TSH is no good, and are looking for something better.

Great news for those of us that can have perfect blood tests while still being extremely unwell.

[SilverAvocado]

Ooh, I like that polymorphism in thyroid hormone transporters are being considered. Is this active transport across the cell wall, or are there other kinds of transport, too?

This hardly ever gets mentioned and I suspect is my problem.

[Hillwoman in reply to SilverAvocado]

Transport across the cytoplasm-nuclear membrane? And then there are the mitochondria... Must get back to the books, it's been months.