Targeting the right population for T3 + T4 combined therapy: where are we now and where to next?

[helvella]

Can't help thinking this paper is somewhat naïve. Yes, each patient needs the best therapy they can get - which will at least sometimes imply some T3. But to get there by genetic investigations - no chance.

DNA/genome investigations can be of use. But that would completely ignore epigenetics.

Further, one set of thyroid-related genes in one person could operate differently to how they operate in another person. The differences could be non-thyroid related genetic composition or separate issues.

Scrabbling around for an example, let us suppose haemochromatosis is present in one person but not the other. This could result in one having very high ferritin and suffering iron overload; the other being iron deficient. Yet it frequently appears that low ferritin/iron deficiency impacts on thyroid hormone treatment and our ability to utilise thyroid hormones. And the person without haemochromatosis would also be impacted by their diet and any supplementation.

So a non-thyroid genetic variant impacting thyroid yet quite possibly ignored.

I always end up in the same place. The only answer is to try it and see. For some, the tiniest amount of T3 might be transformative. For others, T3-only might be required.

• Viewpoint

• Published: 22 June 2020

Targeting the right population for T3 + T4 combined therapy: where are we now and where to next?

• Tommaso Porcelli &

• Domenico Salvatore

Endocrine (2020)

Abstract

The universal applicability of levothyroxine (LT4) monotherapy for the treatment of hypothyroidism has been questioned in recent years. Indeed, it is now clear that about 10–15% of LT4-treated hypothyroid patients are dissatisfied with their treatment. It is plausible that this subset of hypothyroid patients may need T3 + T4 combined therapy to restore peripheral euthyroidism. To address this issue, many clinical trials have investigated the effect of T3 + T4 combinations versus standard LT4-based therapy. However, to date, results have been inconclusive, mainly due to the lack of markers that identify candidates for combination therapy. A breakthrough in this field came with the recent finding that several single-nucleotide polymorphisms in the deiodinase genes are associated with the persistence of hypothyroid symptoms in biochemically euthyroid LT4-treated patients, and are thus markers of candidates for combination therapy. In addition, whole-genome association studies are expanding our knowledge of other genes of the thyroid hormone (TH) pathway that affect serum TH levels. To target the right population for the T3 + T4 combined therapy, the next step is to translate these new findings into prospective trials. Hopefully, this will pave the way to personalized therapy for each hypothyroid patient.

link.springer.com/article/1...

[jimh111]

Studies so far have been incredibly hopeless (possibly deliberate to get the result they want). Not read the article, not free and not really bothered! This is a tiny step forward in that they suggest using genes to target patients who may respond to a trial. But the research so far shows these polymorphisms have small effects, they don't explain the severe symptoms many patients have and the high doses of T3 they need (bringing fT3 above average levels).

The correct study would be one that selected symptomatic patients and gave them increasing doses of L-T3 until they showed signs of thyrotoxicity or became healthy.

[tattybogle in reply to jimh111]

Jimh, you are as cynical as me. That was my first thought too; NICE have been forced to include a recommendation for further research in the thyroid guidelines, so presumably some researchers will be looking t provide them with exactly what they want.

Anybody that really wanted to prove a case for combination therapy in dissatisfied Levo only patient's just has to find some and give them some T3 or NDT and see if they feel better.

It's hardly rocket science....

Even the term dissatisfied annoys me, yet another subtle suggestion of a 'head 'problem.

I would prefer 'with remaining hypothyroid symptoms'

I wonder if any researchers will consider doing anything as radical as actually measuring FT3 ?

Maybe they should have a read of Tania Smith's latest piece on deiodinases and epigenitics vs genetics. She has some advice for researchers too.

academic.oup.com/jcem/artic...

[jimh111 in reply to tattybogle]

They are driving the research according to the theory that only primary hypothyroidism exists and the only therapy is to normalise TFTs. This is bad science. Science must be driven by the experimental data, the patients' signs and symptoms versus response to therapy. All the combination studies are a waste of time, founded on a false hypothesis.

[diogenes Remembering]

Relevant paper in full with Louise Roberts.

[helvella Administrator in reply to diogenes]

Thank you.