Since I'm certain that some of this conversation with Tania Smith will be converted to an article eventually in thyroid patients.ca I thought I would relay verbatim her current thoughts after reading it. When the article from her eventually surfaces I am sure it will spout damning flames about what is now assumed for thyroid action and treatment. Readers can find bits that model their own experience. Here goes:
Hi Rudolf and John,
I just sent John a copy of my thoughts on the paper that I already sent to Rudolf.
Today I had time to read further in the "T3 homoeostasis" section and onward, and I thought you might be interested to hear my thoughts as I learned from it.
I notice that in some of the T3 models you refer to specific situations like the absence of a thyroid (System 8), and dosing T3+T4 in the presence of a thyroid (system 11). Very interesting to see how the model shifts.
I see that the Adaptation section goes on to examine peripheral T4-T3 conversion that is adaptable at different rates in different tissues, though dependent on FT4 and altered by nonthyroidal illness. It's refreshing to see someone finally acknowledge that various parts of the HPT axis are independent of TSH control, and acknowledge that when one part of the model shifts, the others also shift.
So few articles focus on allostasis, the adaptive response to new situations. It's once again nice to see not just a top-down hierarchy but decentralized and local control. And all three deiodinases, not ignoring D1 and D3 like so many scientists do.
Also nice to see that in the later models the TSH-driven de novo T3 synthesis is included, and it goes hand in hand with intrathyroidal TSH-driven T4-T3 conversion at the same time.
I don't think you included any models that examine T3 dosing in complete thyroid failure. Of course, it would be hard to model. The model can't easily account for T3-driven dosing peaks and their effect on reducing TRH and TSH... research shows there is a delayed recovery of TSH secretion after a T3 dose of varying sizes. Of course, the TSH level has no feed-forward effect in a person without thyroid function ... other than cultural feedforward effects on the brain of a TSH-obsessed physician.
Your "Adaptation to Seasonality" section is interesting in light of my recently reading this new-ish paper, which has a section on "Seasonality" that reviews a lot of literature:
van der Spoel, E., Roelfsema, F., & van Heemst, D. (2021). Within-Person Variation in Serum Thyrotropin Concentrations: Main Sources, Potential Underlying Biological Mechanisms, and Clinical Implications. Frontiers in Endocrinology, 12, 619568.doi.org/10.3389/fendo.2021....
Their section on seasonality does not mention FT4 or FT3, just TSH in isolation! As a result, their conclusions are T3-blind, as they recommend "a TSH-fT4 nomogram" to personalize diagnosis and treatment. Sigh.
Your section on seasonality includes ptTSH. Interesting. Is there any evidence of ptTSH in humans? I'm not sure how ptTSH can affect T3 if it is "devoid of thyroid-stimulating activity," unless you mean it indirectly affects normal TSH production via its effect on TRH?
There is so much research on seasonality in humans that you could have reviewed... But there is no room for it here. Maybe in another paper you can look at the literature van der Spoel and team cite and do a much better job with it. I'm sure many would like to hear your response to Gullo et al's 2017 research on T4-dosed patients after a thyroidectomy losing T3 in winter in Sicily while the thyroid-healthy people gained T3 in winter.
Your "Physiological Considerations" section does a good job of emphasizing the implications of the above models for local FT3 creation from T4. It would have been more complete by mentioning the variable rate of T3 metabolic losses to two forms of T2, Triac, and T3S and T3G in tissues, and urinary losses which are higher when more thyroid hormone is free. Some people imagine that there are only increased gains, never increased losses, as if there is a constant rate of loss from our leaky T3 bucket, never an enlarged leak that compensates -- or overcompensates -- for variable rates of oversecretion (or fluctuating FT3 from T3 dosing). (I am thinking about my Leaky Buckets analogy of secretion & metabolism and my science-based concise visual map of T3 and T4 metabolic pathways.)
Incomplete models of "autoregulation" imagine that we magically always get "enough" hidden T3 from T4 produced in cells even when measurable FT3 is low or low-normal in blood, because the body just upregulates T4-T3 conversion secretly within cells. Such blind faith.
So it's true as you say that "FT3 released from organs other than the thyroid, feeds back onto TSH," but too many people forget that not all intracellular T3 gets released back to blood as FT3, due to changing T3 clearance rates.
As you know, in hyperthyroidism when there's excess T4, we also see the highest levels of RT3. Which of your models and graphs apply to the adaptations of the system in response to endogenous or exogenous hyper?
Also, there are two phases to nonthyroidal illness, and I don't think one should characterize it as one unified thing. The early acute phase is adaptive and almost inevitable, but it may pass into a chronic phase which is maladaptive. It is not the acute loss of T3 that kills, but the failure to recover T3 by TSH-driven secretion in a timely manner, in the context of a severe illness. TSH rises first in successful NTIS recovery, long before the metabolic dysregulation reduces RT3:FT4 ratio excess. In chronic NTIS the bioactive TSH does not rise high enough or the thyroid can't respond well enough and T3 remains low and tissues cannot recover.
This is why I am still angry at the way ignorant medics left me to wallow in chronic NTIS for months with daily random angina-like symptoms without the aid of a thyroid gland to help me recover FT3, and I had had low FT3 for three years before my illness elevated RT3 significantly above range. That was not adaptive. It was maladaptive to add chronic illness to the injury of chronic poor T4-T3 conversion.
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Thanks you for posting this! So much to absorb. Is Tania saying that loss of FT3 can be via weeing it out? I always thought that FT3 would always be broken down to T2 etc… Wow!!!
The references to NTIS made me think of what happened to my mother. She had lung cancer which was inevitably going to kill her (she was over 80 and too frail to cope with chemo or surgery), but doctors seemed to want to speed up the process by removing her Levothyroxine many months before she died.
As far as I'm aware what happened to my mother is standard practice in medicine in her situation.
As someone who has (voluntarily because I treat myself) stopped taking thyroid hormones a couple of times (years ago when I didn't have a clue what I was doing) I know how ill sudden withdrawal of thyroid hormones makes me feel.
This is an immense amount of information to digest. Wow thank you will have to pin this post and come back to it when move has happened and we have a study. So much amazing research coming out …
A nice commentary which covers so much ground that is always overlooked.
I'd disagree with her comment "the TSH level has no feed-forward effect in a person without thyroid function" and indeed I'd like to see some TSH obsession! To clarify. I'm sure Tania was limiting her comments to the feed-forward effects on the thyroid - she is well aware of TSH effects elsewhere and refers to them later.
Physicians are obsessed with the level of TSH (as measured by an immunoassay) but have no interest whatsoever in the various forms of TSH or their effects throughout the body. Hence, my comment welcoming some obsession.
We need TSH to regulate peripheral deiodinase and achieve normal local T3 levels. Patients without a thyroid on levothyroxine monotherapy have a lower TSH with normal serum fT3 levels. A lower TSH reduces local T3 levels. If we are to achieve normal homeostasis we need to replace the missing T3 from the thyroid. No ifs no buts.
Tania's last two paragraphs illuminate the problem. I like her use of the term "maladaptive" to describe an axis that fails subsequent to illness. Low T3 Syndrome is a response to major assault, after an illness or trauma the axis should recover. Sadly, for many people (like Tania) the axis does not recover or it even goes wrong without any obvious prior illness. This results in abnormally low TSH levels (probably with low bioactivity) that have profound effects on local T3 levels. From what I've seen on this forum these cases are some of the most severe and difficult to diagnose and treat.
It is quite true that another form of TSH has a direct effect on osteoblasts which are a source of bone formation. But I still wonder if the low TSH in hyperthyroidism is strictly comparable to apparent overdose in therapy of athyreotics. These special and probably widespread TSH effects come as a result of the different amounts and kinds of sugars that modify TSH structure and function. Thi is a special case-by-case study which is beyond our expertise.
If we give levothyroxine monotherapy to people without a thyroid we can only get normal fT3 levels by pushing TSH lower than it would normally be. This will have effects, there will be less TSH stimulation outside the thyroid than normal. A much bigger concern is where the axis is not producing as much TSH as it should do, what Tania terms ‘maladaption’. In this case not only will there be insufficient stimulation of the thyroid but even worse the peripheral adaptive mechanisms will not be triggered.
Studies into these effects will be very complex. They could start by measuring TSH bioactivity in patients who report severe symptoms with a ‘normal’ TSH.
Just to make it very clear I am advocating that we place less reliance on THS levels and devote more time to investigating why people can be severely hypothyroid with modest TSH levels. Also, put more effort in measuring TSH activity rather than how much TSH is present.
As Dr Gordon Skinner put it ‘a discotheque and a graveyard can have similar levels of presence but different levels of activity’.
The trouble with this field is that even now that the basic model is shown, it will have to be accepted by the mass of scientists so that they can chose suitable patients to test the model's working and its flexibility. This is out of our league I think, from a practical patient-gathering point of view.
Just to be clear, I was agreeing with your comment "Let's have some TSH obsession!" in the context of your preceding words like ;" Patients without a thyroid on levothyroxine monotherapy have a lower TSH with normal serum fT3 levels. A lower TSH reduces local T3 levels."
Sadly I can't see testing of TSH activity anytime soon, as long as the 'serum TSH' obsessed minions of mega vested interests rule the world, & accelerate the tombstones of thyroid patients.
The production rate (PR) of human TSH is normally between 50 and 200 mU/day and increases markedly (up to >4000 mU/day) in primary hypothyroidism; the metabolic clearance rate (MCR) of the hormone is about 25 ml/min/m2 in euthyroidism, while significantly higher in hyperthyroidism and lower in hypothyroidism (3). The PR of free alpha subunit is about 100 µg/day, increases increase approximately two-fold in primary hypothyroidism and in post-menopausal women, and decreases (about to one half) in hyperthyroidism (4). The PR of free TSH beta subunit is too low to be calculated in all hyperthyroid and in most euthyroid subjects, while is 25-30 ug/day in primary hypothyroidism (4). The MCR of the free subunits is 2-3 times faster than that of TSH, being about 68 ml/min/m2 for alpha and 48 ml/min/m2 for the beta subunit (4). The half-life of circulating TSH ranges from 50 to 80 minutes (4).
The combination of 50 to 200 mU/day and whatever metabolic clearance rate will result in an acceptable blood TSH and healthy bones.
Dropping the production rate and/or increasing the metabolic clearance rate drops blood TSH levels – possibly as far as undetectable – results in an impact on osteoblasts and reduced bone health.
Yet we are asked to believe that a considerable increase in production rate of TSH and/or reduction in metabolic clearance rate – possibly as high as 10 or even higher – has no impact on bone health whatsoever.
Indeed, no-one ever seems to believe that even going well above a TSH of 10 has any impact on bone health.
With the numbers quoted, that could be 4000 rather than 50 mU/day. An eighty-fold increase. (Which isn’t even identified as a maximum.)
I simply find it unlikely that the small reduction in TSH has a major impact on bone health while a massive increase has none.
This could happen, there could be a TSH receptor saturation point in bone. More importantly for patients with Tanya’s maladaptive axis who have an abnormally low TSH this will have effects on bone which will be blamed on thyroid therapy when / if patients are prescribed hormone.
I don’t understand all the very complex TSH biochemistry but just a glance at the notes shows us that just counting TSH molecules is insufficient.
So where is the evidence that TSH can regulate peripheral deiodinase activity in extrathyroidal tissues? Actually, there is just one in vitro experiment that suggests that TSH may stimulate the expression and activity of type 2 deiodinase in human osteoblast cell lines (Expression of Type 2 Iodothyronine Deiodinase in Human Osteoblast Is Stimulated by Thyrotropin, Morimura et. al, 2005; academic.oup.com/endo/artic.... But as far as I know, no one has ever confirmed the results of this study and no one has ever proven that this happens also in vivo (i.e. in living humans) and in cells other than osteoblasts.
However, there are several studies in athyreotic subjects treated with LT4 which indicate that TSH has some (mostly unpleasant) effects on tissues other than the thyroid, but doesn't seem to have any effect on 5'- deoidinase activity and T3 generation in extrathyroidal tissues.
While recombinant human TSH (rhTSH) stimulates thyroid hormone production in normal subjects with a healthy thyroid just fine (Recombinant Human Thyrotropin Is a Potent Stimulator of Thyroid Function in Normal Subjects, Ramirez et. al, 1997; academic.oup.com/jcem/artic... ), it has no effect whatsoever on thyroid hormone levels in athyreotic subjects treated with LT4., but instead just enhances oxidative stress and inflammation and reduces endothelium-dependent vasodilation (Enhanced proatherogenic inflammation after recombinant human TSH administration in patients monitored for thyroid cancer remnant, Desideri et. al, 2009, onlinelibrary.wiley.com/doi... ; Recombinant Human Thyrotropin Reduces Endothelium-Dependent Vasodilation in Patients Monitored for Differentiated Thyroid Carcinoma, Dardano et. al, 2006; academic.oup.com/jcem/artic... ).
Another study with rhTSH given to athyreotic subjects taking LT4 indicates that TSH alone, independent of thyroid hormone concentrations, has a deteriorating effect on the perfusion of the kidneys and causes the glomerular filtration rate to drop (Recombinant Human Thyrotropin Worsens Renal Cortical Perfusion and Renal Function in Patients After Total Thyroidectomy Due to Differentiated Thyroid Cancer, Saracyn et. al, 2020, liebertpub.com/doi/10.1089/... )
And yet another study with rhTSH given to athyreotic subjects treated with LT4 indicates that although TSH does seem to inhibit bone loss by effects on PTH and calcium metabolism, it doesn't raise fT3-levels in those subjects at all (The Effect of Recombinant Human TSH on Sclerostin and Other Selected Bone Markers in Patients after Total Thyroidectomy for Differentiated Thyroid Cancer, Zygmunt et. al, 2021, ncbi.nlm.nih.gov/pmc/articl... )
All this taken together with the fact that athyreotic subjects treated with LT4 have low fT3-levels when TSH is high and higher fT3-levels when TSH is suppressed (Levothyroxine Monotherapy Cannot Guarantee Euthyroidism in All Athyreotic Patients, Gullo et. al, 2011, ncbi.nlm.nih.gov/pmc/articl... ; TSH-suppressive doses of levothyroxine are required to achieve preoperative native serum triiodothyronine levels in patients who have undergone total thyroidectomy, Ito et. al, 2011, eje.bioscientifica.com/view... ) makes me believe that TSH isn't able to stimulate 5'-deiodinases in extrathyroidal tissues.
I summarise the evidence for TSH stimulating peripheral diodinase in this page of my website ibshypo.com/index.php/tsh-r... .
High levels of fT4 will suppress TSH and increase type-1 diodinase which takes place at the cell membrane and converts T4 to T3 and reverse T3. I'm really thinking of type-2 deiodinase as this dominates at lower hormone levels, takes place close to the cell nucleus and is thought to regulate local T3 levels as well as being the main source of T3 in healthy individuals.
TSH has a number of isoforms of varying bioactivity and it would appear to have differing roles. Consequently I'm wary of experiments using recombinant human TSH because presumably this substance was developed with the objective of stimulating the thyroid to secrete hormone. It's quite possible therefore that rhTSH may not have the peripheral deiodinase activity of TSH.
Ideally we would have an experiment where subjects without a thyroid on (mainly) levothyroxine would be given TRH to stimulate secretion of TSH. We could then compare tT3 and tT4 levels before and after TRH stimulation.
A very important issue is the bioactivity of the TSH. Bioactivity is assessed by measuring TSH stimulated activity in the thyroid. I assume increased TSH bioactivity will lead to increased deiodinase also but have no evidence.
I'm in the process of posting a brief forum topic on TRH and TSH bioactivity as it is relevant to this topic.
Thanks for your answer and for the link to your website. But I'm sorry, I don't see any convincing evidence for TSH stimulating peripheral deiodinases there, either.
In your thought experiment, you completely ignore the fact that there are several other factors that can up-regulate or down-regulate the expression and activity of deiodinases in a tissue specific manner and in different situations (Deiodinases and the Metabolic Code for Thyroid Hormone Action, Russo et. al, 2021, europepmc.org/article/MED/3... and Metabolism of Thyroid Hormones, Peeters et. al, ncbi.nlm.nih.gov/books/NBK2... )
For example, when it's cold, D2-activity in BAT (brown adipose tissue) is stimulated by the sympathetic nervous system via noradrenaline and cAMP-generation via the ß3-adrenergic receptor as you can see in this figure: ncbi.nlm.nih.gov/pmc/articl...
>High levels of fT4 will suppress TSH and increase type-1 diodinase <
High levels of fT4 suppress TSH, because the D2 expressed in the tanycytes near the PVN of the hypothalamus and the D2 expressed in the thyrotrophs of the pituitary is quite different from the D2 expressed in other tissues. It's not ubiquitinated as much as the D2 in other tissues and is thus not deactivated as much after its reaction with T4. Which is why the central D2 - unlike the D2 in other tissues - doesn't slow down making T3 from T4 when the T4-concentration in the cells is high (see: Differences in hypothalamic type 2 deiodinase ubiquitination explain localized sensitivity to thyroxine, Werneck de Castro et. al, 2015, ncbi.nlm.nih.gov/pmc/articl... ; Atypical expression of type 2 iodothyronine deiodinase in thyrotrophs explains the thyroxine-mediated pituitary thyrotropin feedback mechanism, Christoffolete et. al, 2006, academic.oup.com/endo/artic... ).
This difference between central D2 and the D2 in peripheral tissues is exactly the reason why LT4-mono-therapy fails to restore both normal TSH levels AND normal fT3 levels in athyreotic patients. Because the level of fT4 that is able to normalize TSH through D2-derived T3-production in the hypothalamus and the pituitary is much lower than the level of fT4 those patients need to compensate for the missing thyroid (including the missing TSH-stimulated thyroidal deiodinases) and to be able to normalize their fT3 levels. So the only way they can raise their fT3 levels with T4-only-therapy is to suppress TSH by raising fT4 to a high normal or even slightly elevated level.
By the way, high levels of fT4 do not increase type-1-deiodinase, because unlike D2, D1 is not posttranscriptionally regulated by T4. Instead the DIO1-gen is positively regulated by T3, which means T3 stimulates D1-expression and activity in D1-expressing tissues like thyroid, liver and kidney. Which is why low levels of fT3 in athyreotic patients treated with not enough LT4 further contribute to low levels of fT3, because D1-activity in their liver and kidneys is decreased.
>Ideally we would have an experiment where subjects without a thyroid on (mainly) levothyroxine would be given TRH to stimulte secretion of TSH. We could then compare tT3 and tT4 levels before and after TRH stimulation.<
What would be the point in that? We already know that high TSH levels in athyreotic patients do absolutely nothing to boost conversion of T4 to T3 in peripheral tissues, because fT3 levels are even lower in athyreotic patients with an elevated TSH than in patients with a normal or suppressed TSH (see links in my previous post)
Besides, Synder and Utiger tried something like this already in 1972 and repeatedly administered TRH (every 4 hours) to some normal subjects with a healthy thyroid and to some patients with primary hypothyroidism (i.e. thyroid failure). While TRH caused a small rise in both T3 and T4 levels in the normal subjects, T3 and T4 levels in the patients with primary hypothyroidism didn't rise at all, but remained the same as they had been before the administration of TRH (Repetitive Administration of Thyrotropin-Releasing Hormone Results in Small Elevations of Serum Thyroid Hormones
This experiment also showed that TRH supplementation in symptomatic patients with a subnormal TSH (as you suggest on your website) would be absolutely useless. Because when TRH is administered repeatedly (which would be nessesary, since TRH has a very short half life of just a few minutes), it doesn't stimulate TSH secretion anymore, but inhibits it. So you can't restore a normal TSH with TRH as it would only cause the exact opposite after several TRH-doses.
Besides, TRH can't be taken orally (it's a peptide and thus must be injected into the blood or applicated by nose spray) and also has some unpleasant side effects like flushing, dizziness, nausea, increased heart rate, strange taste in the mouth and the need to pass urine, so I don't think patients who already don't feel well would want to supplement TRH. Especially not, when there is the option to normalize fT3 levels so much easier by taking T4 and T3.
My website topic ‘Subnormal TSH Secretion’ describes how lower serum hormone levels and reduced peripheral type-2 deiodinase (D2) with low local T3 levels causes severe hypothyroidism. Many factors alter deiodinases, a wider discussion is not specific to the topic and would add distracting complexity.
The models developed by Diogenes and his team demonstrate T3 homeostasis and allostasis (adaption to events). They include feedback by fT3, fT4 and feedforward by TRH including stimulation of thyroidal secretion and deiodinase. Most T3 (including serum T3) comes from peripheral deiodinase. The axis and peripheral deiodinase maintain relatively stable serum fT3 levels most of the time doi.org/10.1111%2Fcen.12538 .
In cases of serious illness or major trauma there are adaptations that reduce local and circulating T3. For example, during major burns or a heart attack. In some cases, there is ‘low T3 syndrome’, serum T3 levels are reduced during illness. The hypothalamus responds by secreting less TRH which reduces thyroidal secretion and deiodinase. In normal circumstances peripheral tissues respond by increasing deiodinase activity in order to restore T3 levels. This is undesirable, remember most T3 comes from peripheral deiodinase. At the same time the hypothalamus tells the thyroid (via the pituitary) to lower T3 it must also send a message to other tissues to act likewise. Of course, it is possible there is another as yet undiscovered hormone that sends this message but my view it that TSH has this function.
In the webpage I linked to I show that there are TSH receptors in tissues that express D2 and that TSH stimulates D2 activity in the thyroid, brown fat, osteoblasts and parts of the brain. Ideally, more studies will be carried out.
I think the loss of thyroidal T3 secretion and deiodinase is the major cause of lower levels in athyreotic patients on levothyroxine monotherapy. This accounts for 20% - 30% of T3 which corresponds to the experimental data ncbi.nlm.nih.gov/pmc/articl... . (The major source of T3 at these levels is D2 not D1 doi.org/10.1172%2FJCI25083 ).
“We already know that high TSH levels in athyreotic patients do absolutely nothing to boost conversion of T4 to T3 in peripheral tissues, because fT3 levels are even lower in athyreotic patients with an elevated TSH than in patients with a normal or suppressed TSH” TSH is high because fT3 is low! Higher fT3 will suppress TSH through the feedback mechanism. This doesn’t stop a more vigorous TSH, a higher set point, promoting peripheral deiodinase.
I proposed a TRH study as an experiment not a therapy as we don’t know the long-term safety of TRH therapy. The Synder and Utiger study is interesting.
In normal subjects TSH returned to base levels after each TRH dose. Two hours after the first dose T3 increased from 81 to 106 (31%) and T4 from 6.7 to 7.4(10%). It’s difficult to interpret this data because of serum stores of T3 and T4. Note that TSH remained the same even with higher serum hormone levels, indicating a possible axis reset.
“T3 and T4 levels in the patients with primary hypothyroidism didn't rise at all, but remained the same as they had been before the administration of TRH”. Baseline TSH in these patients was 148, their thyroid was being thoroughly whacked and they had little scope for more TSH stimulation of T4 to T3 conversion (and not much T4 to convert).
“This experiment also showed that TRH supplementation in symptomatic patients with a subnormal TSH (as you suggest on your website) would be absolutely useless. Because when TRH is administered repeatedly (which would be necessary, since TRH has a very short half-life of just a few minutes), it doesn't stimulate TSH secretion anymore, but inhibits it.”. One patient (M.J.) had pituitary insensitivity to TRH. The other two responded with substantially increased T3 and T4. Again, we can’t draw conclusions about peripheral deiodinase due to large, stored quantities of T3 and T4 in the blood. TSH was substantially reduced to normal levels – not by TRH but in response to increased T3 and T4 levels.
Beck-Peccoz carried out an interesting study nejm.org/doi/full/10.1056/N... that showed that patients with idiopathic central hypothyroidism of hypothalamic origin secrete TSH with reduced bioactivity. This cohort is similar to the group I describe as suffering from subnormal TSH secretion. TRH treatment led to TSH with increased bioactivity and higher T3, T4 levels. Six patients received oral TRH and one subcutaneous TRH. The paper is behind a paywall (I have a copy) so here are a couple of figures that illustrate the effects: -
Figure 1 nejm.org/na101/home/literat... shows how TRH stimulation increases TSH bioactivity. B/I is the ratio of TSH bioactivity divided by TSH as measured by immunoassay.
This study shows TRH restored TSH bioactivity and thyroid hormone levels. “It's not the TSH in my life that count, it's the life in my TSH.”
My proposed placebo-controlled study would assess the response of patient signs and symptoms of hypothyroidism to TRH.
The option to normalize fT3 levels with L-T3, L-T4 combination therapy doesn’t work as a large number of patients will testify. We find we need larger doses of liothyronine, e.g. 40 mcg daily to restore normal cognitive function. I ascribe this to insufficient D2 activity in the brain caused by low levels of TSH with low bioactivity. The brain gets most of its T3 from D2 conversion of T4, restoring serum fT3 and fT4 does not compensate for the loss of locally derived T3.
Incomplete models of "autoregulation" imagine that we magically always get "enough" hidden T3 from T4 produced in cells even when measurable FT3 is low or low-normal in blood, because the body just upregulates T4-T3 conversion secretly within cells. Such blind faith.
That blind faith - (on the part of medics, and when I also had blind faith in them!) - left me, after decades of deteriorating health, barely able to function.
Additionally -
- the belief that an apparently adequate/ high level of serum T3 is enough to ensure sufficient T3 for the body's need. If FT3 level is considered at all!
- the apparent lack of understanding that T3 does not become active until it enters the nuclei of the cells
So an apparently adequate FT3 level does not mean adequate tissue/ cellular level
- that low cellular T3 causes ill health
- and so on
And finally-
-the understanding that some of us need a little T3 while others need T3 in supraphysiological doses, to allow us to function
I'm angry too, but how do we persuade the medics to listen to the scientists.
My brain is also a victim of this thyroid mess ....and, of that early blind faith!
Hi, I’ve been trying to follow all of these posts but my brain fog and lack of medical knowledge just can’t take it all in. I’m beginning to think that us poor thyroid sufferers will never be properly treated as it all seems so complicated. The more I read the more I’m scared that the medics will never ‘crack’ the body’s very clever code. On a personal level I wonder if having another autoimmune disease causing high inflammation has doomed me by blocking my absorption of any thyroid hormone I take. I’m really hoping that taking T3 along with T4 will help me but only two weeks in so we’ll see in six week blood tests 🤞
Diogenes, thanks for the post. Unfortunately, due to Covid brain I only understood a small proportion. Have at last tested negative after 10 days since positive. I wasn't ill with Covid but had a terrible time with Hay fever, now reducing too.
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Sorry no link, it's from an ad site, but still a good read: Improving Thyroid Hormone Conversion
How much T3,t4 body still produce when on NDT?
