I really, really wish I had come across this article by Barbara S. Loughheed 3 years ago. It would have saved me much frustration and misery:
Why T4-only Treatments Do Not Work (Why We Can’t Dose by TSH and Why We Need T3)
August 7, 2014 by barb
Many thyroid patients do not feel well when taking only T4 (levothyroxine, Synthroid, etc.). There’s a reason, and it has to do with the TSH feedback loop. TSH, T4, and T3 are like the legs on a stool; there is synergy and feedback between all three hormones that keeps T3 and T4 levels balanced within a tight range for each individual. In a person who is not taking any thyroid medication, TSH rises and falls as needed, to stimulate both T4 production and conversion of T4 to T3. T3 is the more active thyroid hormone, so this feedback loop keeps T3 levels fairly constant. If the raw materials to produce thyroid hormone are not readily available (iodine deficiency), then T4 output will be lower than normal. However, an increase in TSH will cause a corresponding increase in conversion to T3, so that even though T4 levels have dropped, T3 could be maintained at a fairly constant level. TSH helps maintain optimal T3 levels.[1]
A high TSH is a flag for hypothyroidism, and most patients will be started on a T4 type of medication if their TSH is above the reference range. However, TSH is extremely sensitive to any supplemental thyroid hormone, and will drop when any thyroid hormone is taken manually. If TSH is high and enough T4 is prescribed, then TSH should drop into the normal range. But this drop in TSH also results in less T3 being produced. Multiple studies report the same results: the T4-only protocol results in lower T3 levels when compared to the same T4 levels found in people not on medication. In other words, only two (T4 and TSH) out of the three legs of the stool can be maintained at healthy levels on the T4-only protocol; T3 will be low.[2]
If T3 is prescribed (in addition to T4) to raise T3 to healthier levels, then TSH drops below the reference range. Again, only two (T4 and T3) out of the the three legs of the stool can be at healthy levels if both T4 and T3 are taken; TSH will be low. This explains why many on desiccated thyroid have a suppressed TSH.[3]
Someone on the T3-only protocol will be balancing on only one leg (T3), because both T4 and TSH are expected to be non-existent on that protocol.
TSH is part of a closed, negative feedback loop. Taking any form of thyroid hormone manually means the system is no longer closed. A feedback loop also requires input between key players. The thyroid gland is a key player, and the feedback loop cannot be expected to work well when there is no thyroid gland (RAI or thyroidectomy) or a poorly functioning one.
The graphic above illustrates these key points: manual T4-only supplementation has a negative effect on TSH. This leads to lower T3 levels than found in healthy people, which creates a lower FT3/FT4 ratio.[4] In other words, T4-only does not replicate normal thyroid gland output and creates a relative T3 deficiency. Adding T3 to compensate for this deficiency will cause an abnormal drop in TSH that is not consistent with the TSH found in healthy people with the same T4 and T3 levels. Therefore, TSH can not be used as a gauge when dosing thyroid hormone manually, because the manual dosing breaks the TSH feedback loop. It is one of those “either or” propositions: a patient cannot have both a normal TSH and healthy FT3 levels while taking only T4. If TSH is normal, then FT3 levels will be low; if FT3 is at a healthy level, then TSH will be suppressed.[5] Since T3 is the thyroid hormone that provides energy, most patients would probably choose healthy T3 levels over a normal TSH. However, doctors usually only prescribe enough thyroid hormone to maintain a normal TSH (to comply with current medical guidelines). This leaves many patients deficient in T3, and without the energy to lead a normal life.
Lack of thyroid hormone causes a cascade of other medical conditions to develop. Isn’t it inhumane to force patients to suffer because of erroneous guidelines? Hypothyroidism is treatable, yet doctors prescribe pharmaceutical drugs (statins, anti-depressants, blood pressure medications, etc.) to mask hypothyroid conditions. Is it any wonder that medical costs are so high? How big does this elephant have to be before the medical profession addresses it?
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Elisabetho
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There is a list of doctors recommended by members, because they've found them helpful. The unfortunate thing is, doctors sometimes change their minds and do a U-turn, or, they either decide - or are forced - to tow the party line.
However, if you email
dionne.fulcher@thyroidUK.org
she will send you the list. Chose one that appeals to you and then ask for PM feed-back from members on here. That's about the best you can do. But, I have to say that, apart from poor dear Dr P, doctors that know anything about thyroid are as rare as hen's teeth.
Dr Peatfield. He's not a GP anymore, but he knows more about thyroid and adrenals than any GP or endo. Unfortunately, he's over 80, and in bad health, so I doubt he'll be taking patients on much longer.
If you want to know more details about him, start a new post with his name in the title, and those in the know will respond to you.
Believe me I read and read, on here and elsewhere, and really appreciate all the info, but something clicked when I read this today. Maybe my brainfog in the past prevented me from connecting the dots 😋
Yes, could be. It does make a difference seeing it all in one place, rather than different post talking about different bits. But, beware of that article, there are niggling little bits that don't ring quite true. For example :
If the raw materials to produce thyroid hormone are not readily available (iodine deficiency), then T4 output will be lower than normal. However, an increase in TSH will cause a corresponding increase in conversion to T3, so that even though T4 levels have dropped, T3 could be maintained at a fairly constant level.
I believe that what actually happens when iodine is in short supply is that the gland increases its production of T3 (3 iodine atoms), and reduces its production of T4 (four iodine atoms), in order to use less iodine. It would be silly to produce T4 with 4 atoms, only to have to removed one atom in the body to make T3. That would be uneconomical. It's just a detail, but it niggles.
Hi Elisabetho. I was so intrigued by your info on barbara loughheed's article, I googled her and found she has a website called tiredthyroid.com. Wanted to share this because it looks like she has written much more on this subject which I know will be helpful to me and hopefully others. God bless Dr. Google! (LOL) Thanks. irina
I enjoyed reading your post, particularly as I have no brain fog today 😉I like the stool analogy. Have also picked up Dr Peatfield's book again and only this afternoon been reading about negative feedback. Cheers for that 👍🏻
Whilst interesting this blog tiredthyroid.com/blog/2014/... overstates its position and has several errors. Feel free to skip this if you can't be bothered with a load of detail!
‘TSH rises and falls as needed, to stimulate both T4 production and conversion of T4 to T3.’
‘an increase in TSH will cause a corresponding increase in conversion to T3’.
This is a bit embarrassing as I believe TSH does stimulate type-2 deiodinase but can’t find strong proof. The reference [1] cited in this blog does NOT show TSH increases conversion to T3, it wrongly presumes the increased D2 activity is due to a higher TSH rather than a lower fT4 (D2 increases as fT4 falls). As greygoose noted the increase in T3 is primarily due to increased T3 secretion by the thyroid. Reference [1] refers to increased thyroidal T3 secretion and although it also refers to ‘increased efficiency of D2-mediated T3 formation’ it does not ascribe this to TSH. (Although D2 activity increases when fT4 falls, I suspect it also increases as TSH rises – that TSH has an independent effect. However, reference [1] does not demonstrate this.)
‘However, TSH is extremely sensitive to any supplemental thyroid hormone, and will drop when any thyroid hormone is taken manually.’ This is not true. The pituitary responds to circulating hormone levels, it does not know whether the hormone has come from the thyroid or a tablet.
‘If T3 is prescribed (in addition to T4) to raise T3 to healthier levels, then TSH drops below the reference range.’ This is not true. Patients treated with L-T3 and L-T4 at doses that give average hormone levels do not in general have a suppressed TSH.
When discussing L-T3 therapy it is stated ‘if FT3 is at a healthy level, then TSH will be suppressed. [5]’. This is not confirmed by reference [5] which gives two examples: -
The first compares two groups of subjects with autoimmune thyroiditis: untreated euthyroid controls v L-T4 treated hypothyroid patients.
TSH 2.93 1.49
fT3 4.9 4.6
fT4 13.8 16.8
The difference between the fT3 figures is statistically significant. However, TSH at 1.49 is a long way from being suppressed.
The second example compares treated thyroid carcinoma patients with controls.
TSH 0.21 1.64
fT3 5.0 5.0
fT4 20.2 14.1
In this case the patients’ TSH is suppressed, but we should consider that a suppressed TSH is targeted in carcinoma patients and that the high fT4 levels will reduce D2 activity. It’s perfectly feasible that a lower dose of L-T4 would have given a similar fT3.
Thus, based on this evidence we can’t draw the conclusion that fT3 cannot be normalised on L-T4 therapy without suppressing the TSH, even if we stretch the meaning of ‘a healthy level’ to mean precisely the same level.
The general thrust of this blog is good with essential points such as TSH is a poor guide for many patients and some T3 is required to normalise both fT3 and fT4. It’s important to read these articles with a critical view and check the references confirm any claims.
We can dose by TSH (and fT3) for some patients (no choice if we want to avoid congenital hypothyroidism) and not all patients need T3.
TSH does stimulate D2 deiodinase activity as we've repeatedly shown in articles in Frontiers in Thyroid Endocrinology. In the working thyroid there is direct TSH stimulation of deiodinase within that organ to produce on average about 1/5 of the total T3 found in the body (this is an average, some will produce less others more). This is a fine control of T4-T3 conversion by body deiodinases. As the thyroid activity declines, increasing TSH stimulates more and more conversion of what T4 is being produced in the thyroid to T3 (both within the organ and elsewhere) to try to keep the whole body as healthy as possible in adverse circumstances. This can go on for quite some time, until when the thyroid has lost about 90% of its activity, the whole thing collapses and there is no longer any thyroidal control of body T4-T3 conversion. This is why oral therapy with an absent thyroid is not the same as the natural system. Then we rely on body conversion only.
Sorry Elizabetho I'm drifting away from your post, please ignore the following if you wish.
Diogenes. This is helpful information. I'm quite convinced TSH stimulates D2 but I'd like to be able to prove it, particularly outside the thyroid and especially in the brain which is dependant on D2 to convert T4 to T3. Thyroidal D2 contributes to circulating T3 and this can be replaced by taking T3 in tablet form. However, replacing brain T3 is much more difficult since brain T3 levels are independantly regulated by D2. Blood T3 levels differ from brain T3 levels.
If D2 is reduced by a lower TSH brain T3 levels will be low and this will not be reflected in blood assays. Higher blood fT3 levels are required to compensate for reduced brain D2. Since the heart has less D2 we have the problem that if we take sufficient T3 to overcome reduced brain D2 activity it will be too much for the heart. This will presumably lead to an increase in long term cardiac risk. I need 20 mcg L-T3 to restore brain function, I appreciate there may be cardiac risk and so I try to mitigate any risk by exercise. The ideal solution is to restore normal thyrotrope function.
TSH stimulation of D2, if it occurs (I believe it does) presents a major challenge as we see many patients on this forum who have a down-regulated hypothalamic pituitary thyroid axis. They have low normal TSH, fT3 and fT4. I assume this is because at some time they were thyrotoxic, either as a consequence of taking high dose thyroid hormone (mea culpa) or more likely a period of thyrotoxicosis during the progression of their autoimmune hypothyroidism. Patients may not have noticed a period of hyperthyroidism which may not be sufficiently severe for them to seek medical treatment. Other conditions can also down-regulate the HPT axis leading to reduced TSH with reduced bioactivity.
(There has been a study using human recombinant TSH to observe the effect of TSH on D2 which showed no effect. The problem with this type of study is that TSH has many isoforms with differing bioactivity. Presumably human recombinant TSH has been developed for its ability to stimulate thyroid secretion and not its effect on D2.)
I hope that a paper in submission will answer your query. It clearly shows that as the active thyroid mass declines, FT3 overall in the body is maintained as close to normality as possible until the last possible moment. This must mean that whatever T3 is still produced by the failing thyroid, even if it is stimulated on its own account, cannot account in full for the maintenance of FT3 as a whole in the general circulation by corporeal T4-T3 conversion. Thus there has to be a general TSH-mediated stimulation of conversion. As you point out, TSH has many isoforms and probably the internal T3 production by the thyroid is stimulated in a feed-forward manner by one of them.
Thanks, very useful. I was planning to write to you and Ruldolf on this topic in a few weeks time (if I may) as I have some of my own data. I will drop this topic now as it's Elisabetho's thread.
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