Studies comparing Levo mono vs Levo/Lio combo T4/T3 treatment

[FallingInReverse]

  Batty1 shared an article here healthunlocked.com/thyroidu...

That lead me to a rabbit hole on the American Thyroid Association website.

Sharing a summary of what I found to be a very comprehensive presentation of studies grouped by clinical objective, and the structure of the whole article is a review of the data objectively, vs advocating for one outcome or another. All together I found I could evaluate the primary research and draw my own nuanced conclusions.

It’s from 2014 - but I still think it’s worth sharing for the methodical way it breaks down some key aspects of how thyroid issues are broken down today, in my experience.

The paper collected the 24 questions doctors examine when treating hypo patients.

It takes each question, shares the clinical studies related to each, and articulates observations on how strong the research is to support various treatment decisions.

I found the question about whether T4/T3 combo therapy was superior to T4 mono very informative in particular.

Full article - very long - is linked here:

liebertpub.com/doi/full/10....

Search about half way through for question 13c:

13c. In adults requiring thyroid hormone replacement treatment for primary hypothyroidism who feel unwell while taking levothyroxine, is combination treatment including levothyroxine and liothyronine superior to the use of levothyroxine alone?

There are three sections:

1) Recommendation (with a conclusion of insufficient evidence)

2) Mechanistic background

3) Discussion of Clinical Literature (which included Reviewing the results of 13 original RCTs, as well as four systematic reviews or meta-analyses of selected RCTs.

It goes through each aspect of the question, pointing out which studies support or not the use of combo therapy.

The end part of the section says:

Our view is generally in keeping with a recent joint statement from the AACE and the ATA, indicating that “the evidence does not support using L-thyroxine and L-triiodiothyronine combinations to treat hypothyroidism” (3). However, the joint AACE/ATA hypothyroidism treatment guideline acknowledged that there are “still-unresolved issues raised by studies that reported some patients prefer and some patient subgroups may benefit from a combination of L-thyroxine and L-triiodothyronine” (3). In a recent clinical practice guideline, the ETA has also stated that “there is insufficient evidence that LT4 and LT3 combination therapy serves the hypothyroid patient better than T4 monotherapy” and that “LT4 remains the standard treatment for hypothyroidism” (5). However, the ETA has suggested that “LT4 and LT3 combination therapy might be considered as an experimental approach in compliant LT4–treated hypothyroid patients who have persistent complaints despite serum TSH values in the reference range, provided they have previously been given support to deal with the chronic nature of their disease and associated auto-immune diseases have been ruled out.”

It also clarifies:

Published trials of combination therapy have not targeted patients who have relatively low serum T3 values during monotherapy. In addition, the serum T3 values achieved during combination therapy have not been a specific endpoint of these trials. It is possible that future trials that include having both a relatively low serum T3 and a normal serum TSH concentration during monotherapy as entry criteria, in the absence of nonthyroidal illness, might have different outcomes from the trials conducted thus far. Future research addressing this subgroup of patients should be encouraged because this is currently an unproven approach.

One other general takeaway when I read the details for how many studies supported combo as superior or not - there wasn’t a clear consensus. Some supported, some did not. And notably it was also inconclusive whether there were more risks/adverse effects from combo.

I do agree with their conclusion which is / the studies weren’t quite set up to prove superiority, and there just aren’t enough studies that all say the same thing about what is superior. And therefore, they conclude- evidence inconclusive, but worth a try, and hopefully there will be more well designed studies in the future.

[noquitter]

Thank you for sharing this info. I will read it again carefully.

I find it difficult to comment even more generally, as until recently doctors never asked me any questions but felt confident to write me off as 'depressed' without actually being within 25 miles of me (ie phone appointments etc). But I do think that thyroid problems are very individual, nuanced and complex. There really isn't a one size fits all in treatment, and the doctors are also feeling their way and lack knowledge. We must be tuned in to how we feel personally, and go from there, I think.

PS I have finally improved with a combo approach.

[FallingInReverse in reply to noquitter]

I wish I could find a more recently article with newer studies included.

My main takeaway is that they haven’t set up the clinical trials with the right design (patient profile, controls, objectives) to be conclusive about any of it.

I loved the article I linked above because it gives the data/info vs jumping to conclusions.

When you read the study conclusions one by one, you can understand how it is actually true there really isn’t any undeniable “evidence” from the studies that Lio/combo works and is safe … but also there isn’t any evidence it doesn’t work and is dangerous either.

That being said, of course there have to be studies post-2014, and so it goes.

[noquitter in reply to FallingInReverse]

Yes to all you write, with the caveat that 'experts' often lack common sense, and studies - however well intentioned - can be misleading (I'm not saying this one is).Would an improvement in a patient's health with treatment constitute undeniable 'evidence' for example? Using the TSH blood test as the holy grail for diagnosing thyroid disease, adopted in the 1970's I think , was nice and simple (and cheap) for doctors but totally inadequate given the individual nature of the disease.

And yes, the clinical trials are flawed in design. But even if they weren't, it might still be difficult to state that Lio/combo treatment works - or doesn't work - because it depends on the patient, which means it requires more thought, more imagination, more questions, more flexibility of approach. And crucially, more time per patient. Science likes it to be 2+2=4. It isn't always so.

Thanks again for sharing the link.

Kind regards