T3 as an additional therapy for hypothyroidism

[diogenes]

I may have published this here before - if so I apologise. But this is an overview of the use and value of combination therapy and indicates trends in thinking for the future. I thought it important enough to publish and keep it in view, because it gives a clear picture of the problem.

Article

Full-text available

The relevance of T3 in the management of hypothyroidism

February 2022The Lancet Diabetes & Endocrinology 10(5)

DOI: 10.1016/S2213-8587(22)00004-3

Domenico Salvatore, Tommaso Porcelli, Matthew Ettleson, Antonio Bianco

[SarahJane1471]

Is there a link to this please?

[diogenes Remembering in reply to SarahJane1471]

I usually put the doi number into Google to access papers.

[SarahJane1471 in reply to diogenes]

👍

[humanbean in reply to SarahJane1471]

Most links to it aren't full-text, but this one is :

researchgate.net/publicatio...

[SarahJane1471 in reply to humanbean]

👍

[Musicmonkey]

Again the genetic variant is mentioned here, DIO2 to which I am heterozygous for. That is bad enough, goodness knows how those who are homozygous cope!

But when will the medical profession recognise this and include a treatment protocol in the guidance?

My Endo has in my notes that I have this faulty gene. The last few blood tests have shown decreasing levels of FT3. I asked for a small 5mcg increase in liothyronine because some of my (very familiar) hypo symptoms were returning. My TSH is suppressed at 0.01 (as it has been for the last few years).

My Endo has requested a full gamut of hormone tests. If these are negative, he wants my GP to check for sleep apnoea (?) and if negative wants her to refer me to the CFS/ME clinic!

How will this resolve my hypothyroid symptoms?

This is so frustrating and worrying.

[TSH110 in reply to Musicmonkey]

It’s ridiculous

[humanbean]

I am a bit bemused. The authors suggest genetic profiling to decide who might not feel well with levothyroxine and low T3.

Why not just do a TSH/Free T4/Free T3 test and ask the patient how they feel? If genetic profiling is required (and thus is adding to the cost of prescribing T3) before considering a prescription for T3 many patients will simply never get it even when they need it.

Anything which involves additional cost, requires new forms of testing, and additional expertise on behalf of the doctor means the whole idea of prescribing T3 is likely to disappear without trace.

[diogenes Remembering in reply to humanbean]

The fact is that Bianco and coworkers believe that genetic variation in deiodinases fully explains the variety of responses to therapy. They have put their reputations on this approach. They at present do not subscribe to the model we have suggested, that it is the individual responses to the balance between thyroid direct T3 production and deiodinase activity on T4 in the body. This we believe is far more important than genetic differences, as the interplay between various parts of the system for everyone is unique and flexible according to need. It therefore can to a large extent offset genetic differences, which only come into play in patients with the gene for DI02 who have no thyroid.

[humanbean in reply to diogenes]

So Bianco is increasing the risk of patients being ignored for another 30 years? Bah!

[NieuwOndaatje in reply to diogenes]

Reminds me of the UB40 song, “I am the one in ten, even though I don’t exist, a statistical reminder of a world that doesn’t care”. We need to get back to sole patient care, individualised treatment tailored to patients symptoms rather than the statistical norms and aggregated treatments based on averages and norms! We do exist on the margins even if we are on the extremities of the “normal” ranges!

[Musicmonkey]

'It therefore can to a large extent offset genetic differences, which only come into play in patients with the gene for DI02 who have no thyroid.'

I do have a thyroid, but didn't do well on Levothyroxine monotherapy which I took in increasing doses until I was a smidge above the range and if anything, feeling worse!

That was when I began researching my condition myself and discovered that I have DIO2 polymorphism. Combination therapy has made a life-changing difference to me. So not sure where I fit into your paradigm diogenes .... unless you mean that my poor conversion because of the genetic defect has messed up my hpt axis.

[diogenes Remembering in reply to Musicmonkey]

It is unlikely that it messes up thyroid action when healthy, because other balancing steps occur to nullify the different action. But with no thyroid, that T3 supply is lost, and then it is quite on the cards that poor conversion happens because of inferior body deiodinase acivity.

[Mollyfan]

Would it be fair to suggest that people with Hashimotos who end up with effectively no thyroid function and a shrivelled thyroid are in the same boat as people who have had their thyroid removed? Presumably a shrivelled thyroid does not covert T4 to T3 effectively.

[diogenes Remembering in reply to Mollyfan]

The emphasis is on having some working thyroid left versus none at all (rather than the reason for its decline and loss). The thyroid is not just a factory producing the raw material T4 to be converted by the body to the finished product T3. The thyroid itself produces about 20% of the total T3 in the body, direct. This is absolutely of top importance in understanding the situation. As the thyroid declines in say Hashimoto's, T4 production there is steadily diminished, but the thyroid increasingly defends its T3 production, so the T3/T4 ratio from the thyroid goes up. This is essential to fine tune the thyroid hormone action as long as possible. Only when about 90% of the thyroid has gone, does the system collapse completely. This radically alters the suitable T4/3 dose that satisfies the body so that what was taken when some thyroid was left is completely different when one passes through the no-return situation with no thyroid at all.

[Mollyfan in reply to diogenes]

Thank you, that is very helpful and seems to explain why some people fall off a cliff eventually, even having been stable for some time.