In LT4-treated patients (blue box=ref. FT4 range), the increase in FT4 is associated with a major drop in TSH, but the increase in blood T3 is minimal. LT4 is really good at normalizing TSH; not nearly as good at restoring T3, the active thyroid hormone.
I don't think many members who have real experience will be surprised by this. Only disappointed that it has taken this long to even get here - which is not far enough.
J Clin Endocrinol Metab
. 2022 Dec 14;dgac725.
doi: 10.1210/clinem/dgac725. Online ahead of print.
Serum Thyrotropin and Triiodothyronine Levels in Levothyroxine-Treated Patients
Matthew D Ettleson 1 , Wesley H Prieto 2 , Pedro S T Russo 2 , Jose de Sa 2 , Wen Wan 3 , Neda Laiteerapong 3 , Rui M B Maciel 2 4 , Antonio C Bianco 1
Affiliations
• PMID: 36515655
• DOI: 10.1210/clinem/dgac725
Abstract
Context: Small adjustments in LT4 dose do not appear to provide clinical benefit despite changes in TSH levels within the reference range. We hypothesize that the accompanying changes in serum T3 levels do not reflect the magnitude of the changes in serum TSH.
Objective: Characterize the relationships of serum FT4 vs T3, FT4 vs TSH, and FT4 vs the T3/FT4 ratio.
Design: Cross-sectional observational study.
Setting: A large clinical database from January 1, 2009, to December 31, 2019.
Participants: 9850 participants aged 18 years and older treated with LT4.
Exposure: Treatment with LT4, subdivided by serum FT4 levelMain Outcome Measures: Model fitting of the relationships between serum FT4 vs TSH, FT4 vs T3, and FT4 vs T3/FT4. Mean and median values of TSH, T3, and T3/FT4 were calculated.
Results: The relationships T3 vs FT4 and TSH vs FT4 were both complex and best represented by distinct, segmented regression models. Increasing FT4 levels were linearly associated with T3 levels until an inflection point at a FT4 level of 0.7 ng/dL, after which a flattening of the slope was observed following a convex quadratic curve. In contrast, increasing FT4 levels were associated with steep declines in TSH following two negative sigmoid curves. The FT4 vs T3/FT4 relationship was fit to an asymptotic regression curve supporting less T4 to T3 activation at higher FT4 levels.
Conclusions: In LT4-treated patients, the relationships between serum FT4 vs TSH and FT4 vs T3 across a range of FT4 levels are disproportionate. As a result, dose changes in LT4 that robustly modify serum FT4 and TSH values may only minimally affect serum T3 levels and result in no significant clinical benefit.
Is this why people feel worse after a while when put on low dose t4 before it is eventually titrated up to optimum .Except that GPs and Endos looking only at tsh numbers going down will not increase the dose? ...For readons of my health and attempts at self empowerment I'm currently making another big effort to get my head around all of this so please forgive me if I'm a pain ... By the way I like the blue box on the graph which makes sense of so-called Range .
It is emphasising what we know are the three main issues;
That TSH doesn’t always correlate with FT4 & T3 levels , and especially in people with thyroid issues where endocrine signalling and changes may form a lower TSH base line.
That for many the amount of dosed FT4 (Levo) that TSH levels misguidedly allow is often not enough to convert adequate FT3 for wellbeing.
Where FT4 levels are high without adequate FT3, to take levels any higher (usually outside of range) risks unusable hormone being converted into inactive forms that may impair further T3 conversion. I think this is possibly the most misunderstood part of thyroid physiology.
(Free T3 edited to total as per SmallBlueThings rely below - 17.12.2022).
This last point is going to be very useful to me as I have just been officially prescribed T4 ,and will probably have to stop taking Armout NDT which I have been taking for 3 years " off the books"
So useful I understand but not sure how to deal . Maybe take lots of private tests ? and self medicate accordingly if can get t3 .Didn't they used to medicate according to clinical. s ymptoms ? But of course this would require GPs and Endos to exercise clinical judgement rather than to treat patients by computer algorithms.
I think a computer algorithm (worthy of that term) would almost certainly do better than many GPs!
It would have to be approved before use.
The reality is that most people end up on a slightly high T4 dose in order to produce enough T3 (and compensate for their reduction in thyroid hormone production).
I have been looking at one recently. It's worked out by Age, Male/Female. BMI. etc.etc. It is suppose to be 68% accurate. I tried to work it out it took me an hour and I landed up with x 1.52 kilo. Which gave the woman only 118.5 Levo she was over 12 stones in weight with a BMI of 29 and only 28 years old. Some time ago I did the simple thing my weight 63 kilos x 1.6 in Levo more or less 100 Levo dose. It does not work, there are so many other things involved in feeling well. Those poor rats. Your graphs make interesting reading thoug
There are lots of calculators. Indeed, I created a spreadsheet which implements several published formulas.
They don't work, they can't work. They cannot allow for variable absorption from the tablets. Varying by person, by make, even by dosage (e.g. 2 * 50 might not be identical to 1 * 100 or 4 * 25).
You have to overcome these variations before you can get anywhere.
The obvious next approach requires frequent blood tests - such as only happen in research. Cost is too great.
At best, a formula gives an idea for post-thyroidectomy dosing and might suggest significant under- or over-dosing in someone on a stable dose. But the person might need that dose!
helvella - Estimation of Levothyroxine Requirement in Adults
A discussion about the use of formulas to estimate levothyroxine dosing.
A spreadsheet with several active formulas which work out possible levothyroxine requirements including NICE NG145 guidelines. These formulas are referred to in the document above.
This is an Excel spreadsheet but is likely to work in other spreadsheet software.
I have to laugh, my adopted father was a Pick Farmer and when I was about 5 years old I found out what happened to the pigs when sent of to market. Although I have never been a vegetarian I never ate anything from the pig. Its' ironic that after my thyroid was removed 64 years later the pigs that I never ate came to my rescue in the form of NDT. Ironic, yes.
It makes me wonder if those rats were thyroidectomized for nothing. I had no idea that knowledge had been common for so long as was only introduced to T3 in 2015 and it seemed to be quite a new general addition then, or perhaps it was just my hypo head in those days getting mixed up? 🤷♀️
🙄 how long will it take them to catch up? It’s like watching a soap opera with a long drawn out, cringey story line.
GPs and many endocrinologists are simply not in possession of enough knowledge to effectively treat hypothyroidism and the panel writing the guidelines are presuming underlying knowledge, which simply does not exist. That is patently obvious from the daily posts of people landing on the site under medicated.
Some of the absent knowledge is fairly generic in nature and no doubt will be affecting other treatments and diagnoses.
If I were watching all this unfolding (painfully slowly) on the telly, I would be shouting at it 😱
😂. I used to like the Archers then it started dealing with edgy issues. We get enough of them in real life. It’s like Emmerdale - I stopped watching it when they dropped the ‘Farm’ from the title. In truth I’ve not watched soaps for well over 20 years now (could be 30). I’ve sometimes thought of donning a tee shirt saying soaps make you stupid but I fear I might get stoned in the street.😱😂👍
I can’t do any of it - I need documentaries and history, abandoned engineering and alike. I have no time for morning TV and in truth everything I watch now is not in the ‘telly’. Stopped watching terrestrial almost a year ago - it just irritated me.
Saw a brilliant interview with an economist the other day. Uncommon knowledge- the population bomb. I’ve never considered economics, but it was such an interesting programme. There were things I thought were missing from consideration, but that would have turned the programme into an all day event.🤣 😊👍
Ha! Plenty- that’s my problem radd - I’m like a cat in a tripe shop most days. So many interests! I’ve just started silk painting again- and I’m thinking of picking up a couple more mediums I used to dabble with 🤗🤣👍
I have things on the go too such as up-cycling furniture (I love painting) or sewing something but then might open an article regarding thyroid over lunch, and suddenly the afternoon has disappeared and my unfinished items remain unfinished 🤣
Glad it's not just me that finds the mainstream standard of tv offerings makes me swear, you can just feel your intelligence leaching out of you 🤬 takes a bit of digging to find something worthwhile... other half loves a bit of dross, I insist the dogs aren't allowed to watch it either🤣 generally strop off and read in the bath instead!
Awww! ❤️ we used to have a staffy that loved drinking warm bath water - no suds in you understand. She used to stand by the bath , paws on the top and wait for me to provide her with cupped hands of warm water. She was a lovely fun dog.
we have a cat 🐈⬛ that likes to get in the tub after we shower, she washes her paws and drinks from the warm water on the side of the bath, then leaves muddy footprints all over the tub 🤣🦋
Regenallotment I'm glad it's not just me that is constantly supervised by a furry friend or two 🤗... cat in the bath though... thing of nightmares like someone throwing razorblades in 😱
Mine are both utterly confused by cats as when they were pups their playmate was a kitten, which has utterly skewed their expectations of cats as most they meet now just don't play nicely at all!😂
In my documents (the ones I link to from time to time), I tried to use emojis to keep the documents small and make them simpler for me.
But I ended up using Apple versions of them collected as images from Emojipedia, because they were so inconsistent. (Apple because I am using an Apple machine - so they are what I would see - and they are often one of the graphically most pleasing of the options.)
The image I used is below. But on, for one example, Microsoft platforms, it shows as [GB] (or something like that).
I love pets they keep our souls topped up. Because we intend to sell and move we know it’s or fair to take on another dog at this stage - so hard to keep to!
Circumstances meant we got an 8 week old puppy when our older dog was just 10months old. It's been pretty stressful but goodness me; the joy they bring is 100% worth it.
GPs and many endocrinologists are simply not in possession of enough knowledge to effectively treat hypothyroidism and the panel writing the guidelines are presuming underlying knowledge, which simply does not exist. That is patently obvious from the daily posts of people landing on the site under medicated.Absolutely right
Regarding T3, I can't see many doctors in the UK paying any attention to this paper, even though it has Bianco in the author list. UK doctors have said some absurd things to patients on the subject of T3. The worst I heard was that it was a waste product from metabolising T4. The second worst was frightening patients into believing that T3 was going to given them heart attacks, strokes, and osteoporosis, or even kill them.
Agree and it will take simply years to filter through to mainstream practitioner training (if ever), after those at the top have finally got a grasp that this paper speaks truth.
Sadly lots of patients are still being told T3 is dangerous eg AFib etc. It's a myth that's grown and grown. And maybe as T3 became so expensive it was looked upon as something very out of the ordinary, like black magic! So treat with ultra caution. Either way it's done us all a massive dis-service. All we want is a choice. Which other conditions are allowed no choice?
The stupid thing about this supposed danger is that in the UK information has been collated on adverse effects reported about all prescribable drugs, and even a few non-prescribable drugs.
Since 1967, when this collation of adverse effects began (for drugs existing at the time - others were added as they were created), there have been zero deaths recorded as a result of taking T3.
It would appear logical, especially in current awful states, that we should maintain statistics on those who suffer adverse events due to LACK of a medicine.
Simply the other side of the coin, really. If you are recording what happens when you take something, then isn't it pike-staff plain that you should also record what happens when you don't? Especially if due to shortage, failure to prescribe, etc.
My endo dropped my Levo from 100 to 75 and added 5mg liothyronine I tried it for 6 weeks and felt much worse , liothyronine was stopped and Levo up to 125mg now a bit better but still have all the symptoms, so not sure if I need more Levo, but liothyronine certainly made me feel worse…
What we're your blood test results for t4 and t3 before intro of t3, then when you had been on the t3 for about 6 was? THEN after t3 taken away and re- replaced by t4 again ?? Is there a correlation between the blood test numbers and how you feel or should we go back to the old days when patients were treated by competant doctors observing clinical symptoms ???? Just a thought
I always use a conversion ratio of 3 to 1 i.e. 30mcg T4 is equivalent to 10 mcg T3. I'm often shocked by the number of patients who have T4 reduced by huge amounts only to be replaced by 5mcg T3.
It's as if doctors believe that T3 is explosive and will blow the patient's head off.
Being a cynic as I am, I also believe this is done to set the patient up to fail so the doctor could say, "See? I told you T3 was rubbish!"
Another way this is done is to give the patient a prescription for T3 of, say 25mcg, and the patient will be told to take all of it in one go in the morning which, if you've been ill for a long time, will probably not be tolerated.
And another way that things are screwed up by doctors is by them prescribing different doses of T3 on different days.
I too am a conspiracory theorist .My husband tells me that I'm going mad ....but I know that the flat earth society are wrong . By the way on Armour ndt leaflets they say that t3 is 3 or 4 times as powerful as t4 .
it’s taken 3 years to get to this dose, I don’t feel any better than when I started it, I’m so fed up with it all.. so many other things going on with me I don’t know what’s causing what😩
TSH 0.57 .... now higher, indicating overall reduction in thyroid hormone dose .
fT4 14.6 [12-22] ...... now lower, as a result of reduced levo dose.
fT3 4.5 [3.1-6.8] ... ALSO lower as a result of the reduced Levo dose .. less T4 to convert to T3 .
So ...it probably wasn't T3 that made you feel worse ,, it was the fact that by lowering your Levo and not adding enough T3 to compensate , you had less T4/T3 than you had on 100mcg Levo .
Then they say " Oh .. T3 made you feel worse, so we'll take you off it" .. which if you as cynical as me you might say was probably their objective . either that or they are just incompetent and very bad at maths.
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ones a ratter though and rather sees the small black cat as 'probably just a big rat'. 🫣😂
Effect of DI02 mutation on FT3 levels in athyreotic paints on T4
