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Mathematical paper showing that TSH-controlled T4-T3 conversion inside the thyroid is responsible for circadian rhythm of FT3 lagging TSH

Front. Endocrinol., 21 March 2018 | doi.org/10.3389/fendo.2018....

Mathematical Modeling of the Pituitary–Thyroid Feedback Loop: Role of a TSH-T3-Shunt and Sensitivity Analysis

Julian Berberich, Johannes W. Dietrich, Rudolf Hoermann and Matthias A. Müller

This is a highly and I mean highly complicated theoretical paper from my colleagues + some systems analyst experts from Mercedes Benz in Stuttgart. However what it shows in summary is that the known circadian rhythm for FT3 that lags behind the same rhythm for TSH can only be explained by a TSH-controlling conversion of T4 into T3 INSIDE THE WORKING THYROID. This means that in health the thyroid doesn't just supply T4 for the body to make T3 but also controls the overall T3 production by finetuning the system overall against unwanted surges. It is also important in several other relationships between TSH, and thyroid hormone supply. I did indicate its presence in short form earlier but it is now available in complete form.

Therefore this demonstrates what an important function is lost when the thyroid dies and how oral therapy cannot make up for it.

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Thanks diogenes this is going to make my brain explode.... Again.... Isn't it 🤯 'sigh' Wish brain fog would bog of long enough for me to learn, read and understand... Cos when I was me before this stupid illness I would have understood it all with ease😉🤣

Hehehe

Seriously though thank you

Linda xx

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Fantastic, thank you for your explanation.

I’ll digest the whole of that when I have a good amount of time and quiet!

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Wow. Just wow. Thank you for the interpretation.

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Think I'll take this to my Endo on 6 April and get him to explain it to me. Maybe he will learn something.

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Soundes like that could be a hilarious conversation :p

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Expect he will just fudge it as usual.

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That's what I was thinking. Unless he's one of the rare very good ones, I should think he won't understand a word of it :p

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It would be good for him to see the level of knowledge out there that he does not possess.

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Diogenes

Your amazing eye opening articles are beyond as always . THANK YOU SO MUCH for always bringing GREAT articles to the forefront . I wondered for one who has had TT how the T3 T4 and TSH works for us when supplementing ?

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The upshot is: there is no way to EXACTLY copy how the intact healthy system worked by any kind of oral therapy (T4, T4/T3 combo or T3 alone). It might have been true if the only T4-T3 conversion was by the body, but this isn't the case, so by definition, remedial treatment is a compromise and can never restore the situation exactly back to what you were when healthy with an intact gland.

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Diogenes

THANK YOU SO MUCH for taking the time out to explain it to me . In life nothing is perfect as we all have learned . By my or anyone else with TT or any thyroid deficiencies by dosing with T3 /NDT /T4 will mimic to some degree what our once healthy thyroids did . I assume that adding T3 is very important component if TSH can not convert T4 to T3 .

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All these new finding about the extra complexity of what the thyroid does are bad news for those of us without thyroids :(

Although good to have the knowledge out there, so maybe one day we will get improved treatment. I found a blog once fantasising we might have thyroid transplants in the future, and maybe that's going to become a fantasy for all of us :)

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SilverAvocado

Thank you for your kind reply . I pondered over this for a long time myself if having thyroid transplant would be a great answer for us with no thyroid /minimal thyroid functions . My reasoning for not wanting is that most people today have thyroid issues either knowingly or not knowing . So what am I trading off for ? Only to have a repeat of problems or worse ? I opted for my thyroids from a bottle . I can deal with it better assuming that we can have T3/NDT to our T4 mix .

What we ought to push for is that Dr's learn how to dose thyroid patients with T3/NDT. It should be a natural practice . We should NOT have to fight for our T3 /NDT to feel optimal .

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Good point that many thyroids are not so good :(

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SilverAvocado

I think that some people can somehow get away with having thyroid problems in their life time and not even know it .

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Yes, I think you're right. Or people suffer for year and never realise they're sick.

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....or suffer for years knowing they are sick but get no diagnosis from supposed professionals who ought know better but prefer to insinuate it is all in your head rather than actually apply themselves to getting to the bottom of it.

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Yes, that's true. At the moment the thing I seem to notice everywhere is people who are sick, but downplay it so much and see it as almost a personal moral failing. Then they don't even think they're entitled to help or to get better :(

Not sure if it comes of doctors telling them over and over its all in their head (or that they are drug addicts for wanting 25 mcg more of Levo), or that society stigmatises and misunderstands illness so much. All part of the same package I suppose :(

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I'm happy to be without my malfunctioning thyroid!

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I'd expect if a person has antibodies then a "replaced" thyroid gland would just be attacked and possibly more so than our original one?

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Thank you for your summary of the gist of the paper. As people throughout the forum have been talking about the difficulty of this paper, I don't think I'll attempt it.

I'm grateful for any comments people make after reading it, though!

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Good to have your summary of the paper diogenes. I shall have a read of the paper to see if I can understand some of it before I show my Endo.

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Not so sure about current practice but I am aware that in the past part removal of thyroid was common does this still happen? Most people here seem to have had the the whole lot removed.

A psychatrist Ionce knew, desperate to treat a overactive patient with clear hyperthyroidism that the endos were refusing to treat on basis on blood results admitted her to hospital and gave her huge doses of lithuim foracouple of weeks and discharged her on a very high dose.He was really pleased with the result and told us all she was much better a couple ofmonths later. He was a lovely man.It would have partly destroyed thyroid

I dont suppose there are many options other than complete removal if thyroid cancer is found.

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With incomplete thyroid removal this internal conversion system will step up to compensate. I think that so long as a significant remnant is left working, this system will do its best to maintain things.

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Yes that is what I was thinking. I dont understand much of the studie but I can appreicaite the gravistas of it. I think one of the problems with all the endo burying thier heads and not reading the important reasurch is that they have to continue in theie jobs and work according to GOV guidelines. I would have to resign if I read this and then was expected to recommend the removal of a thyroid gland. Far tooo much micro management by the state leaving all the patients anddoctors powerless to change thier practice. They dontwant to know as can do next to nothing about it.

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A Finnish friend who has had TT here, says they always leave some of it in Finland.

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Summaries of Japanese guidelines have been posted on the forum in the past, and they prioritise preserving the thyroid, too. Think the UK is just behind the times :(

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It has always struck me that the thyroid has two attributes that seem to be unnecessary - if the old simplistic model of thyroid function were true.

First, a huge blood supply. OK, so perhaps it needs the blood flow to be able to grab any iodine available, but it still seems disproportionately well supplied.

Second, a very large connection to the nervous system. Again, seemingly disproportionate to known functional needs.

A gentle read of the paper (don't think I am capable of much more than that!) suggests to me that a relatively high volume blood flow is necessary for it to work as described.

Is there an explanation for the nerve connections?

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The best and simplest answer is that the activity of the thyroid in all its aspects proves a key controlling function. There are no doubt far more subtle messages flowing back and forth. But the key aim is to get a model that however crudely, mirrors reality. The details could be worked out to refine the model more, but the basic answer is clear for all to see. We will never get to the end of understanding and should acknowledge that.

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Thanks for flagging this up and giving us a summary of what it appears to be saying. Seems to me that it all comes down to what doctors used to do way back before the "gold standard TSH assay" came along - in other words, treat the patient using trial and error until a dosage level is reached that makes the patient feel well again (as practised by the late Dr S).

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Diogenes, thank you for your kind and clear explanation. So it indicates very clearly that without a thyroid gland life can be very tough... as many of us know of course. If only endos and GPs understood this!

In my case I had a partial thyroidectomy in April1980. I had 4 huge nodules... so the surgeon decided to remove most of my gland but left a tiny piece. However post-op they found out I had papillary adenocarcinoma.... no MRI in those days... hence why they left a small part of the gland, not suspecting there was the possibility of cancer. I was put on Levothyroxine... and was told that the levo would eventually "shrink" the small piece of thyroid that had not been removed and that there would not be a risk of cancer spreading.

I must admit I did not really feel this was safe somehow. I have had a difficult journey, and a year later I had the first symptoms of RA and I had a DVT in my left leg. Unfortunately, it took the doctors many years to actually diagnose RA... I was fainting with pain and could hardly walk, still they took ages to give me the diagnosis, and that was while I spent one year on a ward in hospital unable to look after myself or do anything at all, being seriously ill . Looking back, I can see that losing most of my thyroid was the beginning of a series of ill health conditions. Have never been well since then. Getting older is not helping of course...

So my questions are:

A) Is it true that the remnant of thyroid would have shrunk on taking levothyroxine? and

B) Should I have been given T3 or a combination of T4T3 rather than just Levothyroxine? and should I not be "allowed" to have a trial of T3 now considering my medical history?

For the past 3 years my quality of life has drastically decreased. Without any exaggeration it feels like I am dying very slowIy, scary. Am feeling totally exhausted all of the time... absolutely no energy at all. Cannot function at all. It often feels like my legs are going to fold under my body. feeling lightheaded, dizzy and 2 years ago I was fainting while walking or even sitting down on the sofa. Was losing my balance - yet have done taichi for years, (the fainting has stopped since I have had B2 injectiions as well as my balance has been mostly restored). Am feeling cold and my hair had been falling out in clumps and even just falling off while I walk.. can see hair everywhere in the house. My hair is dull, looking very dry, lifeless and my skin is extremely dry (have Sjogren's and uveitis and fibromylgia). Yet my hair was very very thick, glossy, long and strong and feeling soft. I have tinnitus again, it had stopped after I started injecting B12, but have reduced the number of injections and tinnitus has returned.

So clearly there is something wrong and I suspect I am not converting enough T3. Was taking 100 mcg and 75 mcg on alternate days, but have decided to take 100 mcg every day to see if it makes any difference. GP is not helping and I know an NHS endocrinologist will not be more helpful, unless guidelines state that anyone who has had a thyroidectomy because of a form of thyroid cancer should be prescribed T3. In fact G told me over a year ago that she would not prescribe T3 and neither would an endocrioligist.. "because there is no evidence that T3 is safe".. etc.

Sorry about such a long post... but I am desperate to feel better again, to feel alive, at least a little. So thank you if you feel able to answer my question, and for simplifying the explanation of the research.

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Ithink it would be good if you started a new post with all yourcurrent symptoms and some of your blood results. It sounds very much as if your current treatment is inadequate. A lotof people who have hadthier thyroid removed do better on some natural dessicated thyroid which contains most of the hormones the thyroid produces more naturally.I am not sure of some T4 would shrink your remaining little bit of thyroid.

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JGBH, As I was reading down your post I was going to say exactly what Mandyjane said. Make your own post, describe this history, and post any thyroid blood tests, plus vit D, vit B, folate and ferritin.

Then I looked through your past posts and saw you have posted quite a lot. Found your thyroid panel from 6 months ago. Your TSH was a little high, freeT4 top of the range, and freeT3 bottom of the range.

I think it's pretty clear you need T3. But I also think you are a good candidate for buying your own and self medicating. Sounds like you have completely slipped through the cracks in the current system and been let down for decades :( This is a very clear cut case of undermedication, and many of your health problems will have been caused by it :(

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Dear Diogenes,

Is there anything we can do to mitigate the loss of function identified in the article?

How could we respond to the loss of the body (thyroid) making T3?

Is this simply a matter of taking T3 in addition to or instead of T4 replacement medication?

Or are there other treatment programmes out there?

Your comments would be much appreciated and I add my own grateful thanks for your dedicated and expert work.

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For those who can handle T4 only by mouth, an approximation to the normal state can be reached, but adequate FT3 can only be achieved by more T4 than would be the case if the thyroid was working. So you need higher FT4 to get adequate FT3 (never mind TSH). For those who can't handle T4 only, then to get adequate FT3, T3 in combination, or NDT or T3 itself is necessary. But no way will the original state of affairs be achieved.

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Thanks for this information, Diogenes. How I wish I had stuck to my guns back in 1985 and refused to have a partial thyroidectomy. I objected and argued, but the endo won.

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