We've just been informed that, after some delay, our latest paper in European Journal of Clinical Investigation has been accepted and will appear soon. It's got some pretty formidable maths in it, for which I am not responsible. In short, we examine the importance of the thyroid's ability to directly make T3 and describe what would happen if this didn't exist or wasn't important (this is the present assumption by the medical establishment). What we find is that this ability of the thyroid becomes more and more important as the gland disintegrates, and that only accepting the existence of this ability can explain the small change in FT3 as hypothyroidism progresses. Indeed in the latter stages of thyroid atrophy, the T3 made by the remnant contributes more to the total serum FT3 than does the body's deiodinase enzymes. It is the exstence of this glandular ability against all the odds, which distinguishes reality from what the establishment believes. When they have to accept this fact, as eventually they must, the whole false house of cards collapses (diagnosis, treatment etc). We have another paper in the stocks, where we compare true hyperthyroidism with the ALLEGED circumstance of thyrotoxicosis factiitia ( posh for in simple terms too much T4, as witnessed by TSH suppressed), but not always (taking into account that this and higher FT4 are not good diagnostics in this situation, but FT3 is). It's important to contrast true hyperthyroidism with an overactive gland and thyroidless patients on T4.
New Paper accepted: We've just been informed that... - Thyroid UK
New Paper accepted
This is indeed good news! We are all so very grateful to you all for your hard work. Thank you so much.
Good news well done
Congratulations to you and members of your group deserve a 'Medal' for doing this important research to enable - hopefully - changes in the stupid rules we have at present.
Why are Endocrinologists or the BTA/members so fixed in their attitudes. ~Why do they publish misinformation in order to do so.
Dr L stated that in the USA doctors were paid to prescribe levo only instead of the NDT patients used to get.
I also undersand that many people do recover on levo but I'm not one of them and many others (as we know) are in the same boat.
I did a graph re my hia few years after being on levo due to high pulse (usually early a.m.) and palpitations when on T4, T4/T3 which resolved on T3 alone.
So pleased for you.
Brilliant!!! Thank you!
Lovely early Christmas present for you all, well done and thank you for all your hard work, it is so appreciated.
Many thanks to you and your team! Wonderful news. How long will it take before they have the humility and decency to accept they have been wrong all along and must change their attitude and increase their knowledge?
Please let us know when the paper is out and I will post the link and any introduction you have to it immediately in several places.
Thank you!
Will do! I reckon sometime in January.
Thank you!
The editor of the journal we are publishing in is Dr John P A Ioannidis, who is a scourge of bad science, especially questioning the validity and importance of randomised clinical trials and meta-analyses - of which he says that no more than about 4% come to the correct conclusion or are worth any conclusion at all. Yet it is these very studies that the establishment depends on for their decision making (see NICE guidelines recently). For example, none of the T4/T3 combination trials have any validity whatsoever.
Loved his quote - that most research is about the prevailing bias ... 🤔
This sounds fascinating - thank you!
Great stuff - one day they will have to buckle under the weight of evidence, which they continue to stare hard in the back of the neck. Thanking you and your colleagues. 
Congratulations! And thank you!
This is much needed good news! Thank you and congratulations 🙂
Thank you Diogenes and your coworkers for creating the ‘bow wave’ of Thyroid realism, of which this paper will no doubt be a big part of. How long can organisations like NICE/RCGP continue to try and tell us bare faced thyroid/levothyroxine li.:. Err.. misinformation, because that, in reality, is what it is.
Sounds really good. I'm hoping it's relevant to people who've had partial thyroidectomy too. We always seem to fall between camps. Always been told as still got some thyroid, don't need T3 and no need to check FT3.
It is more likely that with some thyroid left, patients can tolerate T4 better. But unless you know exactly how much thyroid is working, a firm judgment of what to do will rely on a FT3 test - ie are you compensating well or not? That will determine how much T4 is needed to boost T3 production. But remember that when you add T4, you rather balance things out by giving the body deiodinases more T4 to produce T3, whilst lowering TSH and diminishing the thyroid's ability to make T3 direct. It's a tricky balancing act.
Thanks for that explanation. It might explain why I feel unwell when TSH is suppressed or even on the low side. It was impossible to get a balance when levothyroxine bioequivalence was uncertain due to the quality issues and NHS insisting they were all the same. It's been better since 2015 but I wish the doctors understood how thyroid hormone works and how even small imbalances impact us. And that we need FT3 testing instead of a blanket ban on the tests when TSH is anywhere in range.
I wonder if its better to suppress TSH with the addition of T3 in the case of thyroid cancer to avoid feeling ill from lack of T3?
Again it's a balance. In the past, suppressing TSH in thyroid cancer patients gave a higher incidence of overtreatment. Lowering that to detectable TSH gave a higher incidence of under treatment. We're back to treating the patient as an individual not a statistic.
‘Indeed in the latter stages of thyroid atrophy, the T3 made by the remnant contributes more to the total serum FT3 than does the body's deiodinase enzymes.’
Sorry for being thick, but are you saying people in the later stages of thyroid atrophy need T3 treatment?
Do the deiodinase enzymes repond to changes in serum T3 and alter their activity to maintain intercellular T3 levels?
What is the conclusion and how would this impact clinical care or are more studies needed to guide this?
No I do not say that. At the later stages of thyroid atrophy there is a progressive lack of T4 supplied for the body's deiodinases to adequately convert to T3. However, the remaining tissue in the thyroid nearly makes up for this by a high-TSH-stimulated change from predominately making T4, when the gland was whole, to predominately making T3. This nearly but not quite makes up for the loss of body conversion ability. When the gland finally dies entirely, this source of T3 dries up, and could only be supplied as either T4, or combination therapy or T3 only, as the case may be.
Ok thanks for clarifying. I wasn’t sure about the establishment statement, but it’s more about blood testing in diagnosis is it? So can replacement treatment perhaps be delayed in thyroid disease (ie autoimmune type)? What sort of serum T3 level would prompt treatment... below or low in range? Would you favour this as a guide over TSH level then? Does the TSH rise before the T3 drops?
A lot of questions. First, the onset of autoimmune disease can be very protracted even over years. One of my collaborators has been following a patient with AIT over 10 years and notes the slow worsening, which needs monitoring but at the moment is still unfelt by the patient. TSH rise is the best detector of the onset of hypothyroidism, the argument being at what level to initiate T4 therapy. TSH does rise before FT3 changes, because of the balance phenomenon I've described. At this stage T3 measurement would not help. The important situation where FT3 comes into its own and TSH's value falls is in therapy (T4, combination of T3 only). This again I've spelled out the reason in the other remarks.
Ok thanks... sorry to bombard you! I was just wondering if you were saying this research has the potential to alter current treatment of hypothyroidism and how! I wasn’t sure about that.
I do say that, but the emphasis is on the change in the approach to hormone dosing, once the disease has begun. The initial diagnosis should be TSH-based, but with the proviso that treatment should be started at TSH a lot lower than the 10 units recommended. After then, dosing with T4 or/and T3 sho ld be done pragmatically, used mostly from a) patient presentation and b) FT3 levels.
Regarding dosing and FT3 levels... If on leveothyroxine only, when is best to check levels.. presume it may be different to when on liothyronine (though also wondered about whether peak or trough blood testing is better in that case?)
FT4 levels don't change much when on T4 only, but best to have a few hours between dosing and testing. T3 is a different matter - it spikes after dosing and testing should be about 6 hr after dosing to let the spike die down.
Ah so a little earlier than the 8-12 hours frequently recommended on this forum? Or is that after taking T3 rather than Levothyroxine only?
I'm merely thinking of convenience regarding time of testing after taking T3. If you take T3 in the morning say 9 am then 6 hours will get you to a testing doctor at about 3pm. If it was 8 hours, then the surgery will likely be closed. On the other hand if you take T3 last thing at night, say 10-11pm then the gap between dosing and convenient testing would have to be 8 hr plus. I leave it to those who need T3 to make their own regime.
Yes I suppose it depends a lot on practicality! So if you are using FT3 to guide dosing does it not really matter when to test it in actual fact? I was just thinking that levels may fluctuate so how do you practically use it? As long as it is in range it is ok? Are your papers looking at things such as outcomes with FT3 based dosing if this is better?
The lifetime of T3 in the body is, that its concentration halves every 24hr.
So in 6 hours, the T3 levels will be 85% about of its starting value and after 8hr about 70-75%. So disregarding the spike you would want FT3 highish in the reference range when measuring. Doctors worry that the spike of T3 after dosing causes temporary overdose. However, they needn't because it takes the body some time to respond and this sluggish response means the T3 effect is evened out over time. We are not able to look at outcomes on T3 because we haven't the number of patients to do so.
Ah ok. How do you know the effect is sluggish? Is there research relating to this?
It's just simple biochemistry. T3 activates the first process in the cell (whatever that may be). Then the increased acton of that stimulates the production of the next process. This takes time to do. There will be a whole lot of effects, each taking its time to respond. Long before this is over, the T3 spike has long gone and the T3 effect damped down..
So is there a biochemical difference between the exogenous ‘subclinical hyperthyroidism scenario and the similar blood result picture whilst on treatment?
Only insofar as subclin hyper is governed by a continuous smooth hormone supply, whereas treatment per se is governed by daily dosing, which does not give a smooth hormone level throughout the day
Let's think of a real situation. Someone's thyroid is dying but not yet in a serious terminal state. So because the dying thyroid is determined to continue making T3 direct at the expense of T4, it is likely the patient will not know this - ie compensation has kept them reasonably well. Only when the thyroid has atrophied so much that it is on the verge of snuffing out will the patient suddenly feel less well. Then of course the patient goes to the doctor with hypo symptoms and gets T4 as a trial dose (hopefully 50 ug) to try to rectify the situation. This may or may not work and the patient may need more T4 or if a poor converter some T3 direct as well. When the thyroid is dying, TSH rises though this too won't be felt until things get drastic, The rise in TSH stimulates the body's enzymes to convert the T4 there more effectively into T3. At the same time that raised TSH also stimulates the thyroid to make more T3 direct (these two effects keep FT3 close to normal as long as it is possible). The conclusion of the paper is that (patient-unique) progress from euthyroid to hypo is a process which is only felt when the system can no longer keep FT3 up to a good level. This is why the onset of frank hypo symptoms is individual for each person as to when the whole thing tips over. For some it may take years after the onset of say Hashimoto's before this tipping point occurs for other with a more virulent attack, a few months. For some others, the process is so insidious that they eventually die of natural causes before the thyroid attack is felt. In the paper we instance a patient who has autoimmune thyroiditis over 10 years of testing, yet is still not symptomatic.
Thank you Diogenes and the rest of the team for providing the evidence for the progression of hypothyroid disease.
Let us all hope that it doesn’t take decades for a change in the current misinformed clinical approach and application that is so detrimental to the quality of life of so many..
Thank you for everything you and your colleagues do!
So following on from Picklet’s question ...are you saying that when the gland dies entirely is when patients will need some T3 ?
No I am not saying that either. Some people can use T4 only to get an adequate FT3, with no thyroid. But they will have to achieve a higher FT4 than when they were well (because to get to their normal FT3 they no longer have the direct help of the thyroid gland, so have to take in more T4 to let the body deiodinases (which now are the only source of T3) produce enough. And this of course increases the hormone load (T4 + T3) so TSH becomes more suppressed. Some people (a minority but a significant one) cannot achieve adequate FT3 no matter how much T4 they are given, so will require combination therapy or even T3 only.
This inability may not show itself until they have no thyroid whatever, as when some is still working, it is partly making up for whatever deficiency the patient may have in conversion. Only when the helping thyroid remnant is entirely gone will inability to convert T4 to T3 really show itself.
Got it! Thank you and thank you for your research. We need lots more. Hashimoto’s is little understood by most clinicians and, as I know only too well from my own experience, even more poorly treated. Do please post a link when the paper is published.
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