Study contrasting the different relationship of TSH, FT4 and FT3 in subclinical/overt hyperthyoidism and overdosed patients on therapy

[diogenes]

Our new paper is freely available for downloading in the Journal of Clinical and Translative Endocrinology. It is a study parallel to our others looking at underdosing but this time looking at overdosing and its consequences.

In this have looked at the other end of the thyroid system, namely true hyperthyroidism (subclinical or overt) versus overtreatment on thyroid horomne therapy. It is crucially important to realise that whereas a suppressed TSH may indicate hyperthyroidism, this is not necessarily true for patients on T4. This is a key argument against the current discredited belief that suppressed TSH on therapy is. like hyperthyroidism, always dangerous. What has happened is that doctors have assumed wrongly that the two situations give the same diagnosic result from TSH, FT4, FT3 relationships. You can see the different relationships in the figures.

Heterogenous Biochemical Expression of Hormone Activity in Subclinical/

Overt Hyperthyroidism and Exogenous Thyrotoxicosis

Rudolf Hoermann, John E.M. Midgley, Rolf Larisch, Johannes W. Dietrich

PII: S2214-6237(19)30152-8

DOI: doi.org/10.1016/j.jcte.2020...

Reference: JCTE 100219

[london81]

brilliant thank you

[Musicmonkey]

Very helpful, thank you diogenes

[Gcart]

I am so thick can you condense it, briefly please , for me and maybe others ?

🤞

[diogenes Remembering in reply to Gcart]

Taking it step by step. First the overlap of FT4 and FT3 results between euthyroid and hypothyroid people is much greater than between euthyroid and hyperthyroid people (forgetting subclinical hyperthyroidism, which is not a real disease but a mixture).

Second there is a certain individual relation between TSH, FT4 and FT3 in healthy people.

In hypothyroidism whether untreated or undertreated by T4, the healthy relationship between TSH and the FT4/3 is lost. What we've shown is that this still applies on overdosing - ie the whole thyroid response spectrum is distorted. This means that TSH measurement and diagnosis by it is suspect wherever the patient lies on the treatment spectrum.

[Hidden in reply to diogenes]

"the overlap of FT4 and FT3 results between euthyroid and hypothyroid people is much greater than between euthyroid and hyperthyroid people"

Is that one reason hypothyroidism treatment is so difficult to adjust? Or is it the same with hyperthyroidism as well?

At the moment I don't know if I'm overmedicated (on thyroxine only, so far) or if I need slightly above the T3 reference range to feel really well, or what.

[diogenes Remembering in reply to Hidden]

Hyperthyrodism has a much clearer and cleaner boundary and there is not much ambiguity when diagnosing. Hypothyroidism however is a different problem. The body is trying to keep up as much FT3 as it can whilst the thyroid is dying. Our last paper but one showed that in the late stages of gland loss, the remnant tries to compensate for the lack of T4 to be converted to T3 by the body cells by making as much T3 as it can. This is why the overlaps in FT4 and FT3 are so large The thyroid remnant becomes a T3-producing gland essentially in the last stages and when the gland is gone a new siituation arises and the only source of T4 is by mouth. Now the TSH,FT4,FT3 balance typical health is lost. In hyperthyroidism, the switch from euthyroid to hyperthyroid is straightforward - the thyroid is now overproducing T4 and the T3 produced by it in the body also rises. Its thus not a matter of thyroid loss but of thyroid overactivity.

[Hidden in reply to diogenes]

Thank you. That is a great help

[Gcart in reply to diogenes]

Thank you for that Diogenes

It’s clearer now

[Hidden]

‘This is a key argument against the current discredited belief that suppressed TSH on therapy is. like hyperthyroidism, always dangerous.’

Is it completely without risk?

[diogenes Remembering in reply to Hidden]

No it has a risk especially for those patients who still have working thyroid left. But less so for those who have none. Medical art (conversing with and examining the patient) should be paramount, and the numbersbrought into the argument afterwards.

[Hidden in reply to diogenes]

So, for risks such as atrial fibrillation and osteoporosis is there any kind of estimate of risk that could be applied to the situation.. is low, medium or high if figures not possible?

[diogenes Remembering in reply to Hidden]

This is a thorny problem because the trials looking at these problems come to different answers. The truth is that the trials are fatally flawed and cannot safely give a correct answer. However there's one paper which says that suppressed TSH on therapy gives an increased likelihood of OP fractures of 1 extra break per 1000 patient years. Considering OP will arise much more frequently from other reasons, it doesn't seem much to worry about It's also shown that for AF the increased risk is small and hardly correlates with TSH at all. The essential point is that someone with suppressed TSH and high FT3 (forget FT4 it is no use in therapy diagnosis except to follow compliance by the patient in taking the tablets regularly) should lower their dose. But people with no thyroid whose dose suppresses TSH but doesn't raise FT3 outside its range are not overtreated.

[Hidden in reply to diogenes]

"suppressed TSH on therapy gives an increased likelihood of OP fractures of 1 extra break per 1000 patient years."

WOW! What a huge risk!!!

[Hidden]

Maybe it's when TSH stops responding to changes in thyroid hormone levels. I remember someone on here saying that their TSH seemed stuck on 0.01 and didn't change at all.

But long before that, most of us probably get an erratic TSH response that isn't directly related to thyroid levels, or is out of proportion to them.

[diogenes Remembering]

No direct one - only by looking at FT4/3 in response to a given TSH.

[Hidden]

The subjects in this trial had toxic adenoma, untreated graves and thyroid cancer on treatment.... so no hypothyroid subjects?

[Hidden in reply to Hidden]

there's another study that deals with that

[Hidden in reply to Hidden]

Ah ok! Clearly no relevance for treated hypothyroid people with thyroids then!!! I didn’t initially pick that up in the way it was presented!

[Hidden in reply to Hidden]

I tried to copy the link to the most recent one for you, but got another paper instead (also about hypothyroidism). Here is, but if you do a search for the latest one on the site...

Hoermann et al Eur J Clin Invest 2020 Triiodothyronine secretion in early thyroid failure- The adapt(3.pdf)

[Hidden]

Has the relationship between T4, T4 and TSH been looked at in people taking T4 for autoimmune hypothyroidism ( who have a thyroid) in comparison to people with endogenous subclinical hyperthyroidism?

Finally read my way through this all!!!

[vocalEK]

Thank you. I hope my GP will stop worrying and learn to love the bomb. Oops. Sorry, that was (close to) the tag line for the movie "Dr. Strangelove". But very close to the situation for effective treatment with thyroid hormones.

Actually, I have been gently nudging her along, all the while she has been expressing strong concern over my TSH of 0.07 (0.30 - 4.20 uIU/mL). Up from 0.108 a year ago. She has been lowering my Thyroxine dose which began (very) slowly raising the TSH. Still not in range. She wants to refer me to an endocrinologist. I just sent her the abstract and a link to your article. Fingers crossed.