Thyroid UK
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New paper on guidance for combination T4/T3 treatment

Here's a new paper discussing guidance for combination treatment

Management of hypothyroidism with combination thyroxine (T4) and triiodothyronine (T3) hormone replacement in clinical practice: a review of suggested guidance

December 2018 Thyroid Research 11(1):1

DOI10.1186/s13044-018-0045-x

Colin Dayan Vijay Panicker

I hope the date is wrong otherwise we'll have to wait a year. These are UK authors.

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Is it possible to give a link?

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I typed in google; Thyroid Research. Then got a page. Clicked on Home Page and article comes up to open.

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Thank you Susie!

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You're welcome :)

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Thanks, great paper.

What to think about the conclusion that it’s not recommended to take natural thyroid as animals have a 4:1 ratio of T4:T3 and humans have a range from 13:1 to 20:1

Am I correct in understanding their advice is, take synthetics to get human sized ratio’s and to avoid immune system complications due to the extra bits in natural thyroid apart from the hormones. Yet, as they say in the Paper, people were taking their chances with it before modern medicine and experimenting.

I’ve just ordered bovine metavive as WP thyroid is apparently not currently available. It’s pure thyroid, so it will have 4:1 T4:T3 ratio. So should I take a synthetic T4 alongside it? Anyone’s guess.

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Shouldn't really matter. If T4 isn't active and T3 is, then getting the FT3 right is the chief aim. However to mimic the healthy situation a bit of T4 added to NDT should do the trick.

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😀 thanks Diogenes.

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This puts my mind at rest

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Melodie,

Metavive don't say how much active T4 and T3 is in each tablet so don't assume it is the same as prescription NDT which has 4:1 T4:T3 ratio or that each batch will be consistent.

As we don't know how much active T4 and T3 is in it we can't advise how much you should take or whether you need to take T4 with it. You will have to do it by trial and error.

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Thank you Clutter. I’m amazed at the help here after struggling on my for so many years. I’ll get off this thread now so the discussion about the Paper can resume 😊

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The discussion about T4:T3 ratio seems to be a bit of a bear-pit.

There is one ratio for the Thyroid gland output.

From what I have read, a healthy Thyroid gland's daily output is very approximately 96mcg T4 and 9mcg T3.

The 9mcg T3 apparently represents approximately 20% of the T3 in circulation (again, assuming that everything is working normally).

But, before we get too engrossed in the debate over the correct ratio (presumably as measured in FT4 and FT3 blood results), it should be remembered that it is the absorption/uptake of T3 at a tissue level that drives our symptoms.

Once we consider the absorption/uptake of T3, then other things come into play that may interfere with this process.

In my case, it took me years of experimenting with my T4 and T3 doses to find my 'sweet-spot', which would have been virtually impossible if I had been solely reliant on TSH, FT4 and FT3 results. (FT3 is the one that I keep an eye on.)

My doses are 50mcg T4 and 25mcg T3. Illogical if only looking at the numbers, but it works for me.

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Thank you SS, I'm not very good at jumping through hoops at present.

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It looks like they were both at Bristol and Panicker was the thyroid expert. He’s just moved back to Australia!

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I thought Dayan was at Cardiff - maybe both !

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Yep - just checked 😊 I remember reading his name before somewhere .... must have been here !

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I don't see this research as helpful, but perhaps I read it too quickly. It seems to say that any benefit of combination therapy is questionable.

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Musicmonkey

We’re the canaries in the coal mine. Don’t have any other choice if std prescription isn’t the total solution for us. Some of us (me) don’t even get as far as being given the std T4 only medication.

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I don't think it's very helpful either, having written an accidentally huge summary below.

But I do think the whole paper gives a sense of very patchy existing research, and highlights some of the important things we need to find out.

I think the authors are very slightly more on our side than the body of research is. Rather depressing :(

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I just found it interesting that they've obviously seen our papers and at least partially understand what we wrote, but carefuly omit any reference to any of the papers. Bit of green-eye I think. Typical of medicine. They want to be seen as leaders not as trailers.

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diogenes,

One of the first things I did was to check all the references...

Your absence was duly noted. :-)

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Interesting paper. A lot of it repeats the standard medical view, including a few notable examples where they specifically state that there is no evidence for them! But there are definitely a few gems in here, particularly for those trying to get a T3 prescription.

It repeats many many times that there is no evidence T4/T3 treatment is superior to T4 monotherapy, but that there may be a subset of patients who require T4/T3. They are quite generous with this, as they don't present any actual evidence for this sub group, they just strongly suggest that they probably exist.

The best news of all for those trying to get T3 prescribed is that they give guidelines for who should be trialed on T3, and most of the suggestions are quite generous. They say the person needs to be demonstrated to have a thyroid condition, to have tried Levo with a proper dose adjustment (altho doesn't specify exactly what the right dose would be), and still has symptoms. Unfortunately there are a lot of hints that such a candidate might be depressed, so it isn't as useful for use with doctors who are pushing antidepressants.

Overall the paper is fine with what we would call a very high TSH, and suggests that the median TSH at diagnosis of around 6 or 8 are low! But in the case of Levo dosing for hard cases, it does allow that people might feel better with the TSH in the lower part of the range.

Almost everything about how to dose T3 would be disagreed with by the forum I think. Especially that blood tests should be taken while freeT3 is peaking shortly after taking a tablet, and unfortunately it gives no guidance that a relatively high freeT3 should therefore be accepted.

Probably the best thing about this paper is that it shows up a lot of inadequacies in the currently existing research, and highlights some of the questions that need to be asked. One I found very interesting they pointed out, is that there's been no study comparing patients with the kind of nice low TSHs this forum recommends, and those who are dosed as patients in the general population so often are, with TSHs all over the place and often over range.

Generally it reports very little is known about how to dose T3, whether to split doses, what ratio of T4 to T3 to dose with, and even how much T3 is equivalent to how much T4. In this paper they assume T3 is 3x as potent, which is quite generous when adding T3 to a previous T4 monotherapy, and I think is the most generous equivalency we ever see, with 4x - 6x being common, and I've even seen 10x quoted. The paper does go on a bit about the overall ratio in a dose, and prefers 14:1 T4 to T3, although does quote animal studies that suggest we might need more T3 to raise levels.

The paper is also useful in that it talks about NDT. I think we're lucky this even gets a mention, and its made clear there is almost no research about it. The tone is overall knowledgeable (relatively), and describes things like the T2 and T3 and other proteins, although mentions these might cause allergic reactions. Also pointing out that there is no research into how human thyroids might produce these, and if they have any use. It also notes that people do self medicate, and that this in itself is a reason for more research. As usual it takes that slightly hurt but confused tone as to why anyone would, when doctor's solutions are so perfect. But it does overall acknowledge that people are dissatisfied, even though their reasons don't show up when symptoms are measured. Usefully it points out there is close to zero research on NDT as a whole.

If someone wants to hand this paper to a doctor there are a lot of dangers to watch out for, for example saying the deiodinase polymorphisms are irrelevant, and getting very excitable about danger to bones and heart from even the tiniest T3 addition - this paper suggests regular ECGs, bone scans, and I think other things I've forgotten. But maybe just the extract about choosing to give a trial. I don't think it contains much that isn't common knowledge on the forums, but does include things the average doctor wouldn't know. It does usefully raise a lot of questions about how incomplete the current research is. With the way this paper is laid out, it's clear almost all T4/T3 research was with fixed doses, and asked very similar research questions. So the body of work ends up not telling us very much about how to use T4/T3 in real life.

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Oops, my notes are almost as long as the paper ;) I hope it's useful to someone :p

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Am wondering if some of the points you have raised about various things being as they were - so to speak - is possibly due to the Researchers having to jump through hoops and modify the paper in order to conform and eventually get published. I remember diogenes telling us about the problems they had with their papers. So perhaps at the end of the day - they have done a good job.

Your notes were great by the way :-) So good :-)

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Thanks :)

I think you're right that they may have had to jump through hoops. The overall tone is the status quo, but there are a lot of critical moments in it.

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.... and you highlighted them all - thank you !

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Very impressed Silver Avocado. Thanks for the analysis

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Thanks for the excellent summary, SilverA. :-)

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Some spurious statements in this paper, 'small subset' referring to those patients who may benefit from some T3. One wonders just how small when there appears to be an epidemic on this forum. Also the suggestion that patients to be selected for T3/T4 combo should be by 'a clinician with adequate knowledge and experience in the area'. Possibly a needle in a haystack scenario if postings here are any thing to go by.

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Here's a an interesting paper too

thyroidresearchjournal.biom...

P7 on page 6 - also by Thyroid research group at Cardiff - including Colin Dayan

Results

In total there were 58 patients (Female to male ratio, 57:1) in the cohort.

The average age was 50.5 years.

Of these patients 58% had been diagnosed with autoimmune hypothyroidism, 14% with subclinical hypothyroidism, 7% Post radioiodine hypothyroidism, 7% with post-thyroidectomy hypothyroidism and 14% of which diagnosis was uncertain.

With those on treatment, thyroid stimulating hormone (TSH) was suppressed in 69%. A total of 44 (75%) of patients were on liothyronine (L-T3) or Natural Desiccated Extract (NDT) and 84% of them benefitted from this treatment.

P5 on the same page is interesting on price increase

Also P3 on Page 5 - about vitamin D and its link to TSH

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diogenes,

Quite what do we make of a paper which cannot even spell desiccated (dessicated in the paper)?

Consistently wrong throughout the paper - except in titles of referenced papers.

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It continues...

Table 2

Available formulations of LT3 and combination LT3/LT4

Name T3 dose T4 dose Available

Cytomel 5, 25, 50mcg US, Canada, Netherlands

Thybon 20, 100mcg UK

Tertroxin 20 mcg Australia, South Africa

Liotyr 5 mcg (soft gel) Italy

Prothyroid 10 mcg 100 mcg Germany

Novothyral 5/15/20 mcg 25/75/100 mcg Several Europe

Thyreotom forte 10/30 mcg 40/120 mcg Czech republic

Thybon is a German product, available in 20, 50 and 100 microgram dosages. So why do they only mention 20 and 100 microgram tablets in the UK?

Liotir (different spelling) is a liquid product not a soft gel. Dosage of 5 micrograms if, obviously, nonsense for a liquid.

These are just the easy pickings of very obvious mistakes. How many more subtle mistakes are there?

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Not very encouraging, is it?

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Desiccate is one of those words that I dither over in regard to spelling.

I have a dictionary add-on that highlights words that I misspell and I can check and correct as necessary.

But, sadly, I've discovered that it accepts both dessicate and desiccate as correct and I can't correct it in the add-on. Waaaaa!

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humanbean,

Maybe think of Sicca Syndrome?

jamanetwork.com/journals/ja...

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Ooh, what a good idea! Thanks. :)

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