This preprint discusses the reasons why in T3 (combo or plain) therapy the T3 inhibits the hypothalamus from making TRH, the hormone to stimulate in turn the pituitary to make TSH. I don't fully agree with the maths but think that it is good enough to show the phenomenon. The author is a control engineer interested in modelling thyoid action.
File available
Hypothalamic pituitary thyroid responses during liothyronine mono therapy Author
January 2022
DOI: 10.13140/RG.2.2.26213.52960
Project: hypothalamus pituitary thyroid system applications
Simon L. Goede
Written by
diogenes
Remembering
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Background The thyroid gland produces thyroid hormones indispensible for metabolic activation, growth and development and is part of the hypothalamus-pituitary-thyroid (HPT) system present in numerous vertebrates. The secreted thyroid hormones thyroxine (T4) (average half life of 7 days) together with a smaller amount triiodothyronine (T3) (average half life 21 h) are governed in healthy individuals by means of thyroid stimulating hormone (TSH) which is inhibited via negative feedback control in the HPT. This inhibitory mechanism is normally active in healthy persons as well as in individuals without an operational thyroid gland and is controlled by conversion (deiodination) of T4 to the active T3. Individuals without an operational thyroid gland, with the condition of hypothyroidism, are normally treated with synthetic T4, given as levothyroxine or L-T4, which is commonly accepted as the standard thyroid hormone replacement therapy. About 20% of the individuals treated with synthetic thyroxine (L-T4) report remaining hypothyroidism related complaints after their physician has proclaimed these persons to have reached a euthyroid or TSH normalized state. Sometimes physicians are inclined to use a combination treatment of mainly L-T4 together with some liothyronine (L-T3) with the intention to improve the patient's condition because it is expected that this group would benefit from such an approach.
Objective: In this treatise the effects of L-T3 mono therapy on 18 test subjects will be investigated over a period of 6 weeks where the value of FT3, FT4 and TSH were the main variables of interest. Methods: The first three weeks on a dose of 15 µg L-T3 daily for all participants the last three weeks in three groups one with 9 participants on 30 µg, 8 participants on 45 µg and one participant on 60µg.
Results: 1. The level of FT4 decayed according the specific individual half life value where after a certain period per individual a FT4 plateau, as a result of the remaining thyroid activity could be established. 2. It could be observed that the FT4 set point value decayed as a result of inhibited TRH concentrations to the pituitary. 3. The individual FT3 pharmacodynamic profile revealed large differences.
Conclusion: The use of L-T3 as mono therapy has the drawback that the peripheral deiodinase processes are disturbed by the unwanted intrusion of T3 concentrations. The deiodinase control process of the entire body is unnecessary and unwanted overruled by the daily dose of T3. The use of T3 without the main buffer of T4 as a control mechanism is lost and the hypothalamus will respond with a reduction of TRH to the pituitary resulting in an unnaturally reduced FT4 set point value. This state of the HPT indicates then a critical situation. Therefore, L-T3 as a combination with L-T4 cannot have beneficial effects because in a healthy individual the secreted T3 represents only 20% of the total FT3 concentration where the rest of the FT3 pool is converted from the available FT4. Then the secretion of T3 under healthy conditions has the main function of relative fast down regulation of the FT3 concentration in cases of a temporary too high production of the thyroid.
This is a preprint before publication formally, so the DOI may not work at the moment for anyone keying it in before it has been reviewed and passed. It has some interesting indications so I've posted the abstract - the whole paper would fill TUK for weeks. I can access it because it is sent to me by Researchgate.
This part I don't agree with as he ignores our work and only proceeds by the old algorithms
Therefore, L-T3 as a combination with L-T4 cannot have beneficial effects because in a healthy individual the secreted T3 represents only 20% of the total FT3 concentration where the rest of the FT3 pool is converted from the available FT4.
In another “nut”shell, they reach this largely “ignorant”conclusion based on a trial of 18 patients over 6 weeks without reference to your previous work and old algorithms.
Therefore, L-T3 as a combination with L-T4 cannot have beneficial effects because in a healthy individual the secreted T3 represents only 20% of the total FT3 concentration where the rest of the FT3 pool is converted from the available FT4.
I’m hoping that the full version of the paper if it proceeds further will be honest about the limitations of the study and it’s conclusions, which will be seized on by the LT-3 antagonists and the old algorithmics!
It is not the results that I disagree with but the conclusions that are based on the limitations in healthy patients. Most patients eventually treated with LT-3, and we all know the arduous journey most of them will have had to endure just to get to an LT-3 trial, are not “healthy” for a complex range of reasons, despite the standard LT-4 treatments or blood tests that might suggest a biochemical thyroid balance!
Shlomo Melmed wrote about this in his book The Pituitary (first published in 1995). T3 is a much more potent suppressor of TSH than T4. He didn't go into any maths but this was a very clear observation he had made through the use of T3 way back then.
Simon L. Goede's conclusion that T3 monotherapy or combination therapy has serious drawbacks is largely irrelevant to those people who cannot get well without either T4/T3 or true T3 monotherapy for those who need to be fully sufficient on T3. In the latter case, any perturbations of deiodinases are irrelevant if the individual has enough T3 to be completely healthy.
I wonder why so many endocrinologists just can't see that sometimes the best thing for the patient is simply to be completely well and be able to live a happy and functional life. The goal ought not to be the normalisation of TSH, FT4, FT3 according to lab ranges that work for healthy people whose systems behave as they ought to.
It would be interesting to find out from a large population of endocrinologists what their main goal is when dealing with patients. It seems obvious to me that it ought to be: to ensure that the patients feel completely well again and can live healthy, happy and productive lives. However, I suspect many of them simply think that they have been successful if: the thyroid hormones have been corrected to fit within the lab ranges.
Thanks once more for updating us on what is being published, Diogenes.
Paul your comment " the best thing for the patient is simply to be completely well..." absolutely hits the nail on the head. Most practitioners treating us thyroidies simply want us to be in range and absolutely not to have a suppressed TSH. I responded to someone in an earlier post that my TSH was suppressed long before T3 was added to T4 and I felt awful. Now on combo therapy I feel so much better. I told my GP I was not interested in bone density and heart health, I wanted a life. It just might be a bit shorter but at least I will have lived and not just "existed"
There is plenty of research that shows that a suppressed TSH is not a risk for heart issues or bone loss as long as the patient does not have any clinical signs or symptoms of being hyperthyroid and as long as FT3 is not over the top of the reference range. I would also add that in some cases, being over on FT3 is also not an issue - this often happens if someone is on a lot of T3 with T4 or on T3 monotherapy.
So, I doubt you have any risk of a shorter life. Quite the opposite is likely. If you feel well on your T4/T3 combo then you are probably at a lower risk of cardiovascular issues and bone loss as hypothyroidism is linked to both of these health issues.
Well done to you Crimple for managing to get your GP to do the right thing!
Thank you Paul. Yes getting the GP to do the right thing!! there's a challenge. I just feel I got my life back after about 20 years of being TATT and brain fog. I am sure my earlier GP notes are littered with TATT and hypochondria as opposed to hypothyroidism LOL. We have to keep hoping that eventually the message will get through re TSH being the most important thing NOT.
Hi Paul, do you know which papers cover this? I am trying to put a case together to keep t3 combo at the end of my trial. I don’t think they will like my suppressed TSH (0.03), even though ft4 and ft3 (which they are not interested in) were still only mid range and i don’t have any hyper symptoms. Thanks
I don't reply to individual patients on Thyroid UK's Health Unlocked open page Jasp6. Many of my posts in the past have been removed when I do this.
I would post back directly to Diogenes on his original comment for this.
However, I mention research papers in the research section of my blog which I am not going to provide a link to because that too will get removed.
It is definitely a well-known fact that T3 tends to suppress TSH more than T4. But more than this, some people just have pituitary glands that don't make a lot of TSH.
I often get very surprised that endos and doctors always think that the pituitary gland has to be perfect. Why should this gland always work perfectly when every other bit of our body can fail with one condition or another? It makes no sense that they always trust TSH.
Love ❤️ it! I would rather have a full life and die early than a mere existence and go on in misery for longer. How dare they decide the latter on our behalf!
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