"In thyroid disease and therapy, even when TSH is normalized, we can still be genuinely hypothyroid if we do not have enough T3 getting into our thyroid hormone receptors in cells throughout the body.
Most people know there’s two ways we get T3 into our cells’ nuclei:
From circulating Free T3, and
From circulating Free T4 hormone that is converted into T3 at a variable rate.
A good introduction to a complex subject although I haven't read it recently. Beware the description of Bianco's Figure 3 might give the wrong impression that T3 stimulates TSH production in the thyrotrope, it works the other way around. Also, more recent (and very difficult) research posted on this forum by I think Diogenes indicates that cells such as the thyrotrope have a much more complex mechanism than the previously assumed 'negative TRE'. This is way too complex for me to go into and I haven't studied it yet.
I think the cruical point this brings out is the central role of D2, how it regulates intracellular T3 and hence thyroid hormone action. It's generally believed D1 helps regulate circulating T3, rT3 and does not play much of a role in intracellular T3. Also, I don't think there is a direct relationship between intracellular T3 and serum T3, contrary to what is suggested it doesn't seem that all T3 produced in cells finds its way back to the blood. An example is brown fat which drastically increases its D2 activity on exposure to cold but serum T3 rises by just a small amount.
Really informative. Read a few more articles whilst I was there. Thank you for sharing.
I think I have experienced this myself where fT4 goes higher but it does nothing, if not actually reduces my fT3. And my fT3 is not mid range or above but my TSH looks alright.
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