Yesterday I gave notice of a new publication that would be of interest to TUK readers insofar as it discusses the interacting roles of TSH, FT4 and FT3 in normal and T4-treated patients. I received the following from my colleague Rudolf Hoermann which I thought summarised the findings very nicely. Hope you also find it informative if you read the paper (deposited with Louise Warvill) as well. It begins:
A lot of people including authors of guidelines think that when they "throw in" a certain amount of replacement L-T4 that the body would take care of this itself via "peripheral autoregulation"
by getting the right amount of T3 out of it. However, this is not the case.
Unlike in the healthy subject where the FT3 concentration is indeed stable over wide variations in endogenous thyroid hormone production, in an athyreotic patient without a thyroid remnant, FT3 is unstable, varying with exogenous T4 supply. T3 adequacy is no longer guaranteed and "autoregulated" as in the heathy situation.
We believe that T3 stability in the healthy individual is controlled by TSH, which interlocks the central and peripheral regulatory pathways.
Yes, we postulate a novel regulatory pathway and role of TSH in T3 conversion, technically a feed-forward motif.
That way, TSH regulates production of T3 from T4 and it does this particularly in the thyroid gland itself.
Conversely, we observed regulatory and capacity deficiencies in athyreotic patients.
Two mistakes in popular thinking.
1) Exogenous T4 supply is the same as endogenous production. It is not.
2) T3 "autoregulation" still works on L-T4 replacement. It apparently doesn’t in the athyreotic patient, owing to impaired intrathyroidal conversion.
3) The thyroid gland is a production organ, but has no role in T3 homeostasis. It surely has.
The thyroid itself is both a T3 contributor and has a T3-balancing role.
That is why the situation changes so dramatically in the absence of a thyroid gland and the athyreotic patient is so vulnerable to T3 fluctuations and sensitive to dose inadequacies.
By the way, people "feel" their T3, not the TSH so to speak. Another piece of the unfolding story, see abstract to be published soon.