COMBINATION THERAPY IS NOW UNDER REVIEW

[diogenes]

This review indicates how and why combination therapy may be used in treatment. Interesting in itself, but another example of cherry-picking evidence ( we aren't mentioned in spite of starting this concept in 2012. Good cliquish admission where the "nonprofessionals"are best kept well out of the limelight.

MINI REVIEW article

Front. Endocrinol., 16 November 2023

Sec. Thyroid Endocrinology

Volume 14 - 2023 | doi.org/10.3389/fendo.2023....

This article is part of the Research Topic

(Re)defining Hypothyroidism: The Key to Patient-centered Treatment

View all 7 Articles

Designing a combined liothyronine (LT3), L- thyroxine (LT4) trial in symptomatic hypothyroid subjects on LT4 - the importance of patient selection, choice of LT3 and trial design

Lakdasa D. Premawardhana1* Peter Nicholas Taylor1 Onyebuchi E. Okosieme1 Mohamed A. Adlan2 Emmanuel K. Obuobie2 Colin Mark Dayan1

[Charlie-Farley]

Their determination to keep the echo chamber intact continues to diminish the quality of output - cross-fertilization is required! Some effective bumble bees should be admitted to the chamber. Are they fearful of being outshone??

[jimh111]

Will read it later. Prof Premawardhana gave an excellent talk to the Thyroid Trust recently. Hopefully a recording will be available online. Prof Premawardhana is the first doctor I've seen who has pointed out the significance of T3 derived from type-2 deiodinase which takes place close to the cell nucleus.

[Milkyway88 in reply to jimh111]

Looking forward to that, Jim.

[humanbean]

One of the problems I had with NDT is that the fixed ratio of T4 to T3 it contained was wrong for me. I suppose with hindsight I could have taken additional T3 but since I didn't tolerate NDT very well it seemed like a waste of time. I actually found in the early days of taking thyroid hormones that I couldn't tolerate T4, rather than T3.

It took me about seven years before I found I could tolerate T4, and at least now I can alter the T4 and T3 separately, and it is working better for me doing that than the NDT ever did. However I suspect that many medical researchers will design a box for patients, and will force the patients into it, whether they fit or not.

I remember watching a debate on Youtube involving two doctors and one of them (AW) said that patients should take, at most, a dose of T3 which was 1/14th of the dose of T4. This video :

youtube.com/watch?v=y4J3ItM...(Not working as expected?)

I think his logic was based on a paper from the early 90s by a man called Pilo. This paper is discussed here.

thyroidpatients.ca/2020/08/...

[Hennerton]

It is a pity they didn’t ask me. I was a complete mess on levothyroxine only. The problem is that it takes time to find the right combination and everyone is different. Fortunately I was left to do it myself, which was worrying at first and I remember feeling very indignant that I was not being helped more but in the end I found the right combination and have been on it for many years.

[Pastelart]

Hello Diogenes, interesting. How does one apply to take part in this research?

[jimh111]

There are good and bad points, but much more good than is usual.

From Prof Premawardhana's talk at the Thyroid Trust I got the impression that this paper will be followed by a T3 study that will use T3 sulphate (T3S) as they believe it is a good way to deliver steady T3 levels. They will select subjects who they feel will most benefit from this combination therapy - those inheriting the Thr92Ala DIO2 polymorphism from both parents and on a decent dose of levothyroxine. They will use thyroid specific questions to determine outcomes rather than general health ones.

Their unpublished data shows that NDT is not slow release T3 as seen in Figure 2. This is a little surprising which means there must be another reason some people need NDT.

They use the term 'short acting' which is wrong and annoys me. It has a short serum half life which is not the same as short acting. To use the jargon they confuse pharmacokinetics (how the body absorbs and eliminates a drug) with pharmacodynamics (how the drug affects the body). Whilst T3 doesn't stay long in the blood it's effects are not instant, it takes quite some time for T3 to get to receptors which have to be saturated with T3 for several hours for expression. At one time I was taking 105 mcg LT3 in two doses. Whilst I found my cognitive funtion improved about an hour after my dose my heart rate did not fluctuate during the night (I wore a heart rate monitor in bed). My pulse was too high at 80 bpm but there was no variability in my sleeping pulse. Other effects of T3 such as bone loss may take years to show effect. I've seen no evidence that T3, even in quite high doses, has short term effects.

Buried in this paper they mention T4 lowering D2 activity (T4 to T3 conversion that takes place close to the cell nucleur). They've kept it simple but they are basically saying a high T4 lowers D2 activity and this may affect thyroid hormone activity in tissues that rely on D2 for local T3 regulation - independent of serum T3 levels.

The paper points out that hypothyroid patients on levothyroxine monotherapy have increased cardiac and all cause mortality.

On the down side I don't think this will help those who really need T3 to function normally. The impression I get is that they tend to be people who have a normal or mildly raised T3 and low normal fT3, fT4 levels. They also need much higher doses of T3, more than 6 mcg which is what an average thyroid secretes. These patients are excluded from all studies. A scientific approach would be to identify such patients, determine what doses of T3 they need and then seek reasons. The current approach is to only consider primary hypothyroidism and dictate that normal hormone levels will suffice. This clearly isn't the case.

The research they propose should make it easier to get T3, at least for those who fit their requirements and it is useful. I'm in favour of combination therapy being the standard treatment, because it is safer and will save lives. There is also an urgent need to investigate why some patients need higher than normal doses of T3, to find the underlying causes and seek better treatment options.