Thanks Shambles and Rod.
That seems like an incredibly important paper, and a pretty definitive answer to a long standing question as to the role of TSH in determining correct dosage of T3.
If i have it right it seems to point out (based on previous research) that plasma (blood) T3 levels are the critical indicator of proper thyroid replacement, but more to the point it also seems to drive another very large nail into the coffin of the view that TSH is a suitable indicator for use in the management of this.
In that it seems to say that while TRH and TSH are involved in the regulation of blood levels of T4 (i.e. control of the production of the precursor hormone by the thyroid) that they do not regulate the levels of plasma T3. (presumably how much of that T4 is converted to T3 and used)
Plasma T3 levels it seems are regulated by other means. They found that inactivating an enzyme in the pituitary that produced major changes in TRH, TSH and T4 did not affect T3 levels in the plasma.
This is me extrapolating - but if the regulatory systems (for T4 and conversion to T3) are separate then that surely confirms that it's possible to have perfect blood TSH and T4 levels, but to be heavily hypothyroid due to problems in the other system.
This seems to have been my own case for many years, and is likely the case for many of those being told their thyroid is 'normal' based on the stock TSH/T4 blood test. The research used specially bred mice, but the results presumably are applicable.
It seems like your doctor might as well look out the window to check the weathercock on the roof of the house next door and use the result to diagnose whether or not you are hypo as use the T4/TSH blood test to check whether or not your replacement is correct.
Another interesting implication may be that if TSH is useless as an indicator of what's happening then management of dosage by symptoms and/or the testing of blood plasma levels of T3 are the available options to determine correct replacement.
Sounds like it might be wise to be cautious about using blood plasma levels to decide the correct dosage of T3 too. (at least not unless the test circumstances were very closely controlled) I think it was you Rod, but there was a UK paper linked not so long ago here that tracked plasma T3 levels through the day and the night.
It seemed (if i have it right) to conclude that the levels of blood T3 varied quite widely during this period, and that there was a definite 24hr cycle - that they ramped up quite a lot in the evening and at night. (perhaps to assist recovery?)
It seems by this (and by experience) that the timing of the amounts of T3 we take is not the only factor that determines blood levels/the profile of this cycle. (?) The body (?) presumably has other means by which it can store T3 (the bound version?) and then release it in an active form for use when needed throughout this 24hr cycle....