I am wondering if it is the actual Free t4 that gets converted to reverse t3, or is it T4?
So the two ways you would get high reverse t3 would be if your ft4 gets too high (overmedicated) or if you are unable to convert ft4 to ft3, it will go to reverse t3?
So far as I am aware, the bound T4 is unable to take part in any activity whatsoever. (Total T4 is measure of all the bound and free T4.)
It is a bit like asking about the water in your cold water tank in your loft. It can't do anything up there! It is only when it changes from being "stored" in the tank to flowing in the pipe/coming out of the taps that it can "do" anything.
However, I am far from being an expert, so if anyone has information which suggests otherwise, please post it. 
You might get something more out of the paper below - but it is far from easy reading!
Whether T4 is actually 'free' when deiodinased I don't know but deiodinase acts on the total T4 and rT3 is TOTAL rT3. So when looking. at how much T4 is converted to T3 or rT3 you should be looking at the total figures. EXCEPT bear in mind that rT3 has a shorter half life and so you can't make. use of the numbers. If you think of it four fifths of the total T3 has come from converting T4, so conversion works on the total not the free portion.
Forgot to say that if you look at the fT4 and rT3 numbers you will see that rT3 is much larger, suggesting it must come from total T4.
The sequence of events is as follows.The thyroid makes T4 and T3 bound onto thyroglobulin. Enzymes free the T4 and T3 from this protein and the hormones enter the bloodstream. In blood 99.97% of T4 and 99.7% of T3 on average is bound on to transport proteins which circulate through the system passing the cells. These hormones are loosely bound so that if a cell requires some T4 or T3 the appropriate amount comes off the proteins. It is this fraction (free T4 or free T3) which is subject to further transformation. FT4 converts to FT3 and some reverse T3. The reverse T3 is also weakly bound to the transport proteins, but as the free reverse T3 degrades to T2 and then to T1 then it is stripped off the proteins in harmony with its loss through degradation. Both FT3 and reverse T3 are degraded to T2, but only one form of T2 is active in influencing mitochondrial activity. T4 has a half-life of about 8 days, T3 1 day and rT3 only an hour or so. If rT£ was measured properly, it would be free rT3, but since rT3 is rarely measured anyway there is no pressure to develop a free rT3 test (which would be easy).
Does rT3 compete with, for example, T3 to bind? That is, could rT3 be having an impact by changing the availability of binding sites on the various binding proteins?
It does compete for protein binding, but effectively only with T3. This is because T3 and rT3 bind about 1/10 the strength of T4, and there is much more T4 on the proteins than either of the others. So rT3 can in a way add a further control twist in helping to arrive at a suitable FT3 level by modulating the bound T3-free T3 equilibrium. So a given total T3 in these circumstances gives a slightly higher FT3 than you would expect. I wouldn't expect the effect to be great however, only if rT3 was much higher than T3.
Wow! Thanks for the thorough explanation.
So if one is on T4/t3 combo at a dose equivalent to say 100mcg of t4 and 10mcg t3, would the extra t4 from the Levo dose that isn't being used because you are already taking some replacement t3, end up causing a higher reverse t3?
High reverse t3 on T4 only
Do you only get reverse T3 problems with T4?
High Reverse T3 - what does it mean?
How useful is a reverse T3 test in diagnosing HYPOTHYROIDISM?
What causes hyper symptoms - raised T3 or raised T4?
