What does our unconverted T4 from our thyroid and /or, our unconverted T4 from our NDT medication actually do in our bodies?

[Gillybean1]

If a large % of our T4 gets converted to T3, what happens to the remaining T4 and what action does it have on our body before it get expelled please?

Im curious to know why some of us need some T4 (despite the DIO2 fault) and what its action is and to which organs in particular it assists.

Any advise greatly appreciated, forgive me if this sounds scrambled, im barely with it at all today....yes still searching to get well.... kind regards, and every best wish, G

[jimh111]

Only a tiny bit of T4 gets converted to T3. If you look at the total T4 and total T3 reference intervals you can see the relative proportions in the blood. Going from memory we have about 60x as much T4 as T3.

A much higher fraction of T3 is unbound than T4 which is why the difference between fT4 and fT3 levels is not so great.

T4 is able to bind to receptors on the cell membrane but I don't think anyone knows much about it.

So, some T4 is converted to T3 or rT3 but most of it is broken down into other substances and eliminated.

[helvella Administrator in reply to jimh111]

I have a feeling your figures are very different to mine!

Normally, about one-third of T4 is converted to T3 and about one-third to rT3. The remainder of T4 is metabolized by different pathways, in particular glucuronidation and sulfation.

Metabolism of Thyroid Hormone

Robin P Peeters, M.D. Ph.D. and Theo J Visser, Ph.D.

Last Update: January 1, 2017.

ncbi.nlm.nih.gov/books/NBK2...

The faster processing of T3 would result in a lower serum level.

And a significant portion of T4 does so much get broken down but added to - sulfated or glucoronidated, then excreted. Though there is also the possibility of recirculation via these substances and the gut.

[Gillybean1 in reply to helvella]

Many thanks helvella, kind regards G

[jimh111 in reply to helvella]

Yes, after I posted I remembered the half life of T3 is one day v. seven days for T4. Thus, T3 would disappear 7x as quickly and rT3 even more quickly. I should have written 'only a fraction gets converted to T3'.

The one third to T3 would presumably apply to each T4 molecule created which is a little different to the T4 (total) we measure in the blood.

[helvella Administrator in reply to jimh111]

I just grabbed the examples from Wiki's thyroid function tests and whizzed up a crude spreadsheet.

With molarity, the numbers are proportional to the numbers of molecules. But if you use masses, you have to allow that T3 is a bit lighter than T4.

All ratios are expressed as is number:1.

T4 and T3 ratios

[jimh111 in reply to helvella]

I think your TT4:TT3 has got the decimal point I the wrong place? nmol / pmol mix up?

Anyway I would go with one third or a little less being converted to T3. The important point being that T4 goes multiple ways, not just to T3.

T4 also seems to have some actions other than acting on thyroid hormone receptors either directly (less than 1%) or indirectly by being converted to T3. I don’t think these other actions are crucial as I and others have been on high dose T3 therapy with little or no T4 in our blood and not noticed anything unusual.

[helvella Administrator in reply to jimh111]

Quite right - now corrected.

[Gillybean1 in reply to jimh111]

Thank you jimh111, Kind regards G

[SlowDragon Administrator]

DIO2 gene doesn’t mean we can’t convert Ft4 into Ft3

It means, if you test positive for Dio2 gene variation that you need access to some Ft3 regularly.....especially in brain

Adding T3 alongside levothyroxine helps maintain constant levels of Ft3

[Gillybean1 in reply to SlowDragon]

Ok many thanks SlowDragon, kind regards G