Yet another definitive paper on relation between FT4 and TSH

[diogenes]

This paper brings together my collaborator Prof Hoermann and a similar group in Australia who have been studying the phenomena in parallel with us. It shows that TSH and FT4 are linked, but there is no correct way of measuring sensitivity of TSH. In this it brings our two groups together (not without argument I may say, because some ideas on both sides had to be jettisoned, owing to the findings). Nevertheless it authoritatively describes the relationships and implications for treatment. This clearly shows that though TSH and FT4 have linkage,its implications cannot be extended to TSH sensitivity. Downloadable.

Physiological linkage of thyroid and pituitary sensitivities        

 September 2022 Endocrine       

 DOI: 10.1007/s12020-022-03184-8                           

 Stephen Paul Fitzgerald, Nigel G. Bean, Henrik Falhammar and Rudolf Hoermann 

 Objectives. The sensitivities of the pituitary to thyroxine feedback, and the thyroid to thyrotropin stimulation determine the free thyroxine /thyrotropin feedback loop and can be described mathematically by two curves. It is not well understood how the two curves combine in a healthy population with normal thyroid function to express the individual balance points that are observed. This study was directed at this issue testing the possibilities of random combination and directed linkage between the two curves.

Methods. We reverse-engineered two sets of population data, on the assumption of independent combinations of thyroid and pituitary sensitivities, to obtain estimates of the curve describing thyroid sensitivity. Sensitivity studies were performed.

Results. No analysis resulted in a physiologically feasible estimate of the curve describing thyroid sensitivity. There was evidence of linkage of the two curves in terms of their combination throughout the normal range. Thyroid response curves reflecting a low free thyroxine response to thyrotropin tended to be combined in individuals with thyrotropin curves reflecting a high thyrotropin response to free thyroxine, and vice versa.

Conclusions. Thyroid and pituitary sensitivities are linked, being combined in individuals in a non-random directed pattern. Direct mutual interaction may contribute to this linkage. This linkage precludes the derivation of the curves describing these sensitivities from population data of the free thyroxine and thyrotropin relationship and complicates their derivation by physiological experimentation. This linkage and probable interaction may also bestow evolutionary advantage by minimising inter-individual variation in free thyroxine levels and by augmenting homeostasis. 

[ Link to a preprint which is currently accessible: assets.researchsquare.com/f... ]

[Hoxo]

In very simplistic terms does this paper then discredit the sole use of TSH testing for diagnosis or replacement therapy monitoring?

[diogenes Remembering in reply to Hoxo]

Yes, because sensitivities to a given TSH differ among individuals. Thus a given TSH result can have many meanings in a population and certainly can't be used in the "normal range" basis on a "in" or "out" based-decision.

[Hoxo in reply to diogenes]

thank you!

[LindaC in reply to Hoxo]

Yes, I used to say to them, "These ludicrous population ranges [however reached] do not, likely cannot apply to me. Many have been hoodwinked for decades.

[DippyDame]

Excellent diogenes

Thank you!

Yet again, the medical profession need to read closely, learn and act.

We live in hope!

[Musicmonkey]

Thank you diogenes Much appreciated.

[N3ess]

I just had a glance on this paper but there is one point i like to mention. It seems to me that it is a great step to scientific progress. Because there are two groups of scientists with different approaches publishing a kind of consensus paper. Both of them have to critically review their privious results. And this is science how it should work apart from ‚who publishes most‘ issues.

My English is not good and I can‘t express more thoughts on this paper in brief.

[helbell]

Over and over we see people suffering with 'in range" tsh but their general practice refuses to test live thyroid hormone levels. Even some of our beloved private testing services simply refer to tsh as the most important marker. The tsh test might have super sensitive accuracy to tsh, and an invaluable pointer, but so many of us fall outside of that net. I had to practically diagnose myself and never had any kind of acknowledgement of my tsh/thyroid hormone ratio not fitting the box. And the resources wasted investigating separate symptoms when all they had to do was check the free ts. Thank you so much for the work you continue you do, and share.