This an open discussion on how and when to use combination treatment according to recent work - mainly US of course>
Thyroid Vol. 31, No. 2
Free Access
Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document
Jacqueline Jonklaas, Antonio C. Bianco, Anne R. Cappola, Francesco S. Celi, Eric Fliers, Heike Heuer, Elizabeth A. McAninch, Lars C. Moeller, Birte Nygaard, Anna M. Sawka, Torquil Watt, and Colin M. Dayan
The emphasis is on TSH, TSH, TSH in so much of this paper, and the researchers are trying to see how they can swing their results to explain TSH because TSH apparently must remain the measure of most importance.
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I came across this bit in the paper and my jaw just dropped :
Serum T3 and T4 may not have interchangeable function
Around 25% of normal children have an fT3 level above the adult reference range (87). fT3 levels in childhood correlate positively with fat mass and age of onset of puberty, whereas fT4 (or TSH) levels have no such correlation (87), suggesting that circulating T3 levels may have different functions to T4. Furthermore, in children and adults with an intact HPT axis, fT3 levels do not correlate with TSH levels (and in children they show a positive rather than the negative correlation seen with fT4) (11,87). Hence, TSH may not faithfully represent all aspects of thyroid status, especially those conferred by fT3 alone. Some of these considerations may be relevant to use of combination therapy with LT4/LT3 in adults. The relative contribution of T3 and T4 to regulating TSH levels needs to be better understood, especially during exogenous combination therapy and the greater pulsatility of fT3 levels compared with fT4 levels.
I didn't realise that any researchers believed that T3 and T4 were interchangeable. If that was the case why would the body ever try to convert T4 to T3 or create T3 in the cells of the body? All the body would need to do is to produce T4 and then excrete any excess. No complicated conversion required.
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I couldn't find any reference to central hypothyroidism or secondary hypothyroidism in the paper. No doubt it will continue to destroy the lives of (mainly) women for a few more decades.
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I don't understand why these researchers think that TSH will show similar levels in people on Levothyroxine given in the form of one "lump" a day, when compared to healthy people whose thyroids produce tiny amounts of T4 all the time. I have never seen any research comparing the amounts of T4 produced by healthy people throughout a 24-hour period compared to the amounts of T4 in people who get one "lump" a day. And along with this, TSH needs to be compared too.
I suspect that the people who are healthy, and who produce, say, 100mcg T4 throughout the day, every day, from their thyroids will have higher TSH than people who take 100mcg Levo once a day. The same experiment would also need to compare output of Free T3 as well.
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There also needs to be acknowledgement that forcing people to wait for treatment until their TSH is > 10 is actually more dangerous for the heart than treating someone with enough Levo to bring their TSH down to under the range as soon as TSH goes over range.
Taking away 50mcg of someone's Levo and replacing it with 5mcg T3 will never work. Endos in the UK (and probably elsewhere) have been setting patients up to fail with T3 for years.
Which medication
A wide range of LT3 preparations are available with tablet strengths varying from 5 to 50 μg. The ETA guidelines recommend a starting ratio of 13:1 to 20:1 (LT4:LT3), which represents a dose of 5 or 10 μg LT3 for patients taking 100 to 200 μg LT4 (55). Cutting LT3 pills with a pill cutter would allow for twice-daily dosing such as 2.5 μg twice daily. At the start, the LT4 dose is usually reduced by 12.5 or 25 μg to accommodate the addition of LT3. The therapeutic substitution of LT3 for LT4 has previously been calculated to approximate a 1:3 ratio (76).
In theory, the ratio of T4:T3 of 13:1 to 20:1 could also be achieved by a combination of DTE and LT4, an approach that has been suggested by some patient groups, possibly based on the premise that there are additional salutary effects of DTE.
I like the illustration.. makes it easier to understand some more of the possible causes of unexpected/ illogical results people sometimes get, and why they are so different from the next persons results on the same doses. both in blood tests and in how they feel.
Two (picky) points:
It looks to me like you have changed your train of thought from calculating equivalence for 100mcg Levo .... to calculating for 125mcg levo half way through the text at this *//* point.
"Then use the 3.33:1 ratio. That means we would need to absorb 26.7 micrograms of T3 to be equivalent to 100mcg of T4."
*//*
"In order to absorb 33.33 micrograms, assuming an absorption of 95% of a dose of T3, that would need a tablet of just over 35 micrograms."
( not sure if you changed trains here, or if i just got lost at the station ? )
The other point, if i'm being pedantic, is that there is a blue bar for 10% T4:T3 conversion %... but there is not a corresponding table for results at 10%, which makes it slightly confusing at first , for the 'logically challenged' like me.
But otherwise.. a very helpful illustration. Thank you for 'doing the maths'
@humanbean you are spot on. I was dosed with 150 mcg T4 and my Endo at the time lowered my T4 from 150 to 100 mcg T4 with 5mcg T3. I felt if this is what T3 feels like don't need it. I later realized that He lowered my T4 so low for me . I felt edgy lethargic and just couldn't function. Adding back some T4 I felt the difference. Yes I most definitely felt that I was set up for failure.
Thank you. Nothing changes then…. What is wrong with those researchers’ minds? Could it be they are funded by big pharma? Forgive me for being suspicious…
Gosh! That's quite a heavy paper to wade through. As a patient, I find it encouraging that there is an interest in doing more research on combination therapy. However, I feel that the needs and experiences of patients get lost in the ever more complicated findings.
We have, of course, seen previous effects of thyroid treatment being defined according to the "consensus" of a room-full of specialists.
Thyroid physiology is clearly extremely complicated, and it is understandable that doctors want to have clear guidance derived from the evidence. But I don't think they will ever achieve it in my lifetime!!
For example, assuming that each of us can take the same dose per kilogram, to get the same effect, is surely naive. We are all different in too many ways to allow simplistic formulas to work. For the same reason, any strictly controlled studies, based on naive assumptions, will surely not give us truly workable conclusions.
On the other hand, many of us, who source our own T3 medication, have found simple ways to establish the appropriate dose to improve our health and well-being. Perhaps endocrinologists should start listening and learning from us????
They don’t understand and never will their minds are closed book. I could get better results treating people with NDT and dosing until symptoms are gone. They make something simple seem very complex - it justifies their grotesque salaries for keeping people ill. Where would there cudos be if it were known that we don’t really need them at all. There will be a tiny number here that will need specialist help if say they need T3 only but most of us could self medicate on combination therapy and feel a lot better than these fools could ever achieve for us. We are just TSH numbers that they toy with and what we have to say about our condition is simply ignored. How could anyone like that ever hope to help their fellow human beings with thyroid problems to a condition where they enjoy good health.
Don’t be silly… they’re the ‘exspurts’! Defined as “Ex - a has-been and spurt - a drip under pressure”!
I am so glad my old endo, who put me on the combo treatment in the first place, worked with me and monitored my adjusting my dosages until I felt optimal. It resulted in a very unconventional 25mcg T4 and 45mcg T3 regime today. My TSH is so low it’s unmeasurable and just comes back as 0.01 each test, my FT4 at only 4.8 is way below the range of 12-21, and my FT3 is at 6.8 right at the top of the range.
But the important thing is that I feel well, the DEXA scans have consistently shown no signs of osteoporosis and I can record an ECG every day on my watch which shows no evidence of atrial fibrillation!
Subsequent endos (mine sadly retired) have tried to reduce my T3, (in fact one tried to take it away altogether but living in Wales saved me from that terror) and I have always managed to ‘persuade’ them to leave me to sort myself out…
The only reason I have anything at all to do with them is to ensure they sign me off for the next twelve months’ prescriptions of T3!
It is basically that they will not let go of the TSH story (that must be right, we've thought so for so long after sensitive TSH came about) but want to hang the T3/T4 dosage situation on to that as a combined add-on. That is, we weren't basically wrong re TSH , but simply know a little more about T3's importance than we did. So we can just add that on without changing what we thought.
Geez .. they don't call it a 'blinded' trial for nothing do they.....
they seem determined to only ask one very blinkered Question , ie:
..... "how many people on full dose levo will see an improvement if you replace 25mcg(ish) of their levo with somewhere between 5/ 8 (ish) mcg T3 for 6 months ?"
.. but they could find the answer to that question for free , by simply reading this forum every day for 6 months.
Answer:
a very few people will say .. "wow, brilliant improvement just by adding 5mcg T3"
the majority will quite possibly feel worse, or no better.
But.... what they WON'T learn from a 6 month , fixed dose study is :
A lot more people will need to play around for a year and a half, and will finally end up saying "wow brilliant improvement" when that are taking at least 15mcg T3 with only very slightly reduced levo, (or no reduction at all) and have also improved some other dietary/supplementary factor they found was not optimal.
A few people will find they are improved with 30mcg T3 and a MUCH lower dose of Levo.
A few people will eventually find they don't like T3 at any dose and say "wow , i'm so much better now i've tried NDT"
A few will be improved by optimising Levo dose properly and realise they didn't need to try T3, they just needed a better doctor.
A very few will realise they feel better without any levo at all and can manage on T3 only.
And a few will go off to buy a celery juicer.
Why are THEY so determined to find a fixed 'normal' formula that works for everyone, when there is no such state of 'normality' to be found in the TFT's of any healthy population anywhere on the planet, and there never has been ?
What is so hard about the concept of INDIVIDUALITY ?
.....is it too hard for them to spell ?
I'm no expert , but i'm sure what i've just written above will be more accurate than the results of a 'blinkered' trial done at great expense .. so i'm going to unilaterally award myself a small G&T and go and watch the sunset with a blackbird.
Thanks for posting - I haven’t managed to read the entire document as yet but having skimmed through the basics, I see that they haven’t actually carried out the research only on “dissatisfied” patients and are now considering that this might be a good idea. All that so called brain power in the room and they chose so many sub clinical patients that do not suffer symptoms to include. It beggars belief.
Hmm, 'All that so called brain power in the room...' - let's stop there, eh? 😅 Notwithstanding their supposed 'oath', some of them see the evidence before their very eyes yet choose to ignore you/us... it takes a special kind of *&%$* to do that and then glibly cash their pay cheque. 👺
Certainly NOT those amazing doctors and medical researchers out there... I refer to the 'chronic-plodders' who seem to be duping so many of us. Think this meme is more apt.
I think I’ve said this before- a bright young NHS Endo I saw told me that my pituitary gland didn’t know my thyroid was dead that’s why the TSH is a very important test, also, he has managed to get the TSH in range even those on T3, to which I replied “but are they well “. He laughed and said “I don’t know”. He also said he couldn’t step outside his guidelines for fear of his job and career!! Those men in grey suits have a lot to answer for. And I still won’t get T3 on the NHS but he’ll monitor me if I buy my own.
Eek, dreadful for you/patients and even pretty sad for some of them... not for long though... because it's NOT them. At least he'll monitor you... could be worse; I was told that but UN_dx instead! Yes, I've sourced mine for > a decade via Dr P, said to be better than the then NHS stuff.
I wonder if this preoccupation with tsh and most of the papers I have read means it doesn’t matter how much they ‘discuss’ treatment they will never get positive results that can be possible.
Perhaps they start off wanting to help people but once they start seeing you as a machine and not as a person, realise you aren’t running as well as you should be but it’s not imminently fatal, off you trot. I’ve checked your fuel injection system, your valves, your onboard software and it’s passed. We could get you running almost like new but it’s complex, time consuming and expensive and the only person that will appreciate it is you, my colleagues definitely won’t.
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