Tina at Thyroid Patients Canada has published a new article.
Initial glance is as promising as ever for her work.
Gullo: LT4 monotherapy and thyroid loss invert FT3 and FT4 per unit of TSH
By thyroidpatientsca on November 12, 2020 • ( 0 )
thyroidpatients.ca/2020/11/...
An ancient post here by me!
healthunlocked.com/thyroidu...
A slightly less old post by Airmed :
healthunlocked.com/thyroidu...
And Gullo is referred to by diogenes in this post:
Thanks for posting helvella. I think it it absolutely disgraceful that, on this forum, we read from researchers similar statements.
Is it not surprising (shocking) that our experts seem to be completely unaware that the active hormone is T3 but they keep patients very unwell, losing jobs, difficulties in relationships or just not improving at all on T4 (levothyroxine). We also know that many patients seem to be o.k. on levo so wont be on this forum.
It's about time they had an 'about turn' and prescribe what the patients' bodies require to enable them to have a pain-free, happy, life.
Why are the professionals so ignorant????? They seem not to keep up with scientific evidence. Neither do they listen to their ailing patients and dispense anything but T4/T3, or T3 alone and through misinformation, removed NDT.
thyroidpatients.ca/2019/04/...
She is very good and very well worth following
Thanks for this one helvella
For those who appreciate Tania, I suggest signing up and giving a Like to her blogs.
Just been looking at their site and finding the lack of Likes depressing. I know how many here have said positive things. Have they not signed up as needed? Or simply not clicked the Like button?
Good point...and I'm guilty as charged!!!
It was only supposed to be gentle encouragement! 
Have mentioned signing up for her Blogs several times. 🙃
me to , guilty as charged . So i've signed up and liked it , despite my fear of all things internet.
I've also just noticed you can leave a comment without signing up, so i did that
too.
There's a speech bubble just under the title of the article, with a number in brackets after it. Click there.
Right , so i've just gone back and "liked" the things i liked but hadn't "liked"..... it's taken about 40 minutes to press that many "likes".
No idea how she finds time she to write so much good stuff , but I wouldn't have properly understood any thyroid science without her pictures to explain it
Thanks for posting. I fear there is a danger in over-analysing this information which is more 'interesting' than helpful. It's certainly true that the thyroid is a dynamic source of T3 which responds to events ranging from iodine deficiency to non-thyroidal illness. The thyroid in response to TSH is able to maintain steady T3 levels or help lower them during severe illness.
If we lose the thyroid we lose this dynamic response, this is mitigated to large extent by a steady supply of thyroid hormone tablets. The Gullo study shows us that for optimal therapy some T3 is necessary. It also shows us that if T3 is not given the TSH, T3, T4 system will be abnormal.
The question is how relevant or important is this? Millions of patients are doing fine on levothyroxine monotherapy. The science tells us that they will not be optimal but they are happy and feel fine - a state most of us aspire to. Research shows us that about 15% of these patients may have minor coginitive impairment and have mildly adverse lipid profiles. This patient group is not optimal but their plight is trivial compared to that of other thyroid patients.
If we consider patients who are not doing well we could theoretically restore their fT3 and fT4 to the levels seen in the healthy population. Using Gullo's data corresponding to a TSH around 1.0 would give us e.g. an fT3 of about 4.4 and fT4 of 14.2. We can do this with levothyroxine plus liothyronine or NDT in multiple doses. Will these patients then be hunky dory? Experience shows us it ain't gonna happen.
We need to bite the bullet and accept that the reason so many patients fail to recover is not because they can't achieve what was their normal hormone levels. The problem is not the thyroid. There may be a thyroid problem as well but the real problem lies elsewhere. This raises the question of how much of the iceberg is under water. Such patients whose thyroid fails are lucky because they get a mildly elevated TSH and persuade a doctor to start treating them. The other group of patients with the same illness and a normal TSH are forgotten.
One such group is patients with subnormal TSH secretion. Consider a patient with TSH 1.0, fT3 3.7, fT4 12.5. If you put an 'x' on Gullo's graphs you will see that their fT3 is worse than L-T4 treated patients and their fT4 worse than euthyroid controls. They are doubly worse off yet considered euthyroid. They additionally suffer from impaired type-2 deiodinase (D2) which regluates local T3. And of course they have a near perfect fT3:fT4 ratio!
Beware that many studies (not the Gullo one) study thyroid patients with good TSH response - only patients with a TSH > 10 are selected.
(I have no evidence whatsoever but I suspect that tissues that use D2 to regulate local T3 levels are more sensitive to changes in T3, tissues which derive T3 from the blood may be less fussy about T3 levels).
Tania's notes about T3 in mitrochondria and integrin seem to be of little relevance. It's accepted that the prime role of thyroid hormone is 'genomic', action via nuclear receptors activating DNA expression. There are non-genomic actions for various thyroid substances, these seem to be less important. T3 has little action in integrin but patients on L-T3 monotherapy don't seem to miss the T4. This suggests non-genomic actions are not so important or not dependant on thyroid hormone.
The comment 'Notice that in the healthy FT3 distribution, two bars at the mid-point of range almost achieve 25%. This means that almost 50% of the healthy population attains mid-range FT3. In the TSH-driven healthy controls, low and high FT3 is rare' is incorrect. This seems to reflect a direction in perception, a desire to see an abnormality rather than an objective examination. The peak bars show 24/204 subjects, as noted on the graph. If you extract this graph and the Gullo one into Word and reformat them to the same vertical and horizontal scale it becomes clear they are similar.
In attempting to simplify this article I fear I have made it more complex. In short the Gullo study shows that there are different fT3, fT4 levels in levothyroxine monotherapy and this affects TSH. However, I would argue that even if we restore optimal hormone levels it will do very little for patients who are not doing well. If we focus on these fine details and try to achieve optimal fT3, fT4 levels we are wasting out time. We need to look elsewhere. For many of us the problem is not the thyroid, it lies in the pituitary / hypothalamus or in peripheral hormone activity.
I agree with you about the error in writing 25% instead of 24/204. 2x 24 subjects is not 50% of 204. and yes , it does make you wonder about the objectivity.
But i wonder if you are falling into a different trap of saying optimal normal healthy levels of Ft3 is around 4.4 and fT4 14. 2, and if you restore levels to this and person doesn't get better the problem lies else where........ what about the >50 (approx) people on that same Ganslmeier et al graph who have FT3 of greater than 5pmol/L and in particular the 5 subjects who had FT3 between 6 and 7 pmol/L....... how can we assume these folk would be back to their normal selves with an FT3 of around 4.4
Having said that i'd better shut up now , because , for example, i have absolutely no understanding of the word 'genomic'.... yet.
and it's also possible that i'm no better at working out how many people had which FT3 levels according to that graph than Tania was..
(and it's possible i'm not being objective either, since i have FT3 around 4/5 on Levo and still don't function correctly, so if i used to have more than that in health it would explain why i'm still not OK )
You are right, an fT3 of 4.4 would be an average with some people having a higher natural fT3 and some lower. Some patients on the forum do get better with an fT3 of e.g. 5.8 but a lot of us need a much higher fT3 which is clearly not natural. My case history is complex but I know my normal fT3 was 4.9. Also, some patients leave a long time between their last dose of T3 and taking the blood, often for good reasons but nonetheless it gives a misleading fT3 figure.
‘genomic’ is the mode of T3 action. T3 binds to receptors which attach to a region of DNA, this triggers’DNA expression’ which means the DNA eventually makes proteins for growth, repair, metabolism etc. This is the main function of T3 and it takes several hours. It’s called genomic because it acts on the genome or DNA
Thyroid hormones also have other minor actions called ‘non-genomic’ actions, they act via direct mechanisms and tend to happen quickly.
The Gullo study is important because it shows that patients need T3. If you push fT4 high fT3 will increase but this will be associated with increased reverse T3 which can reduce the amount of T3 converted from T4 within cells that are using the T3.
It's a shame more of us don't know our pre problem FT3 level, it might simplify the options when looking for the solution.
Thanks for the clarification of how the 'Gnomes' work, i'll file it in my memory next to 'Goblins' (TGab)
It does seem logical that increased rT3 ,as well as being a method of removing excess fT4 , might also reduce conversion from fT4 to fT3... but i'd read (probably also from Tania) that rT3 doesn't fit on T3 receptors inside cells, but fit's on different receptors on the outside of the cell wall, and on the basis of this i've been disagreeing with folk who say "rT3 blocks T3"
I'm not clear what mechanism would cause rT3 to reduce T4 to T3 conversion in cells? Is this known?
( or am i oversimplifying the whole issue ? which is very likely since my natural area of professional expertise is constructing dwellings out of sticks and string)
I can't remember Tania's notes about rT3 binding to receptors on the cell wall. I fear this just creates confusion. Thyroid hormone binds to genomic (sorry for bringing in the Gnomes again) receptors and this is the purpose of thyroid hormone. Other actions as far as we know are minor and not relevant to treating our hypothyroidism. rT3 does not block T3, it doesn't bind to thyroid hormone receptors.
Type-3 deiodinase (D3) converts T4 to rT3 and so it is competing for T4 with D1 and D2, especially D2 which converts T4 to T3 near the cell nucleus. So, if rT3 is high (it varies a lot normally) we can guess that some tissues which express D3 may have received less T3. In this sense rT3 impairs the availability of T3 in tissues with high D3 activity. Although rT3 is reducing T3 availability in these tissues I don't like the term 'block' because it might give the wrong impression.
It seems that rT3 reduces T4 to T3 conversion, especially D2 activity. How much this happens and to what extent it affects pateints is unknown. I describe it in a topic I recently added to my website ibshypo.com/index.php/rever... . WARNING this is a very difficult subject, you may want to ignore it and have a cup of tea instead!
Thanks, yes you're right , that's quite enough of that sort of thing for a Saturday afternoon. I'd rather go down the garden and discuss sloe Gin recipes with the Gnomes.
This is the most British thing I've ever read in my life 🤣
Can anyone explain how and why the practice guidelines have selected 10 as the magic number for a TSH being too high? It is well outside the standard reference range, and even that is too wide for determining health.
TSH/FT3/FT4 Test Results 
Low FT4 With Normal FT3 and TSH?
TSH ft3 ft4
TSH, FT4 & FT3 normal! (?)
Relating FT4, FT3 and TSH values to various chronic nonthyroidal illnesses
