Another paper that raises the problem of unsuitable T4 treatment and the value of combination therapy. It's behind a paywall, but the summary here I feel is very encouraging. Combination therapy is becoming if not respectable at least worthy of examination. We definitely have progress here.
The relevance of T3 in the management of hypothyroidism
•February 2022
•The Lancet Diabetes & Endocrinology
DOI: 10.1016/S2213-8587(22)00004-3
•Domenico Salvatore
•Tommaso Porcelli
•Matthew D Ettleson
•Antonio C Bianco
Levothyroxine monotherapy has been the standard of care for treatment of hypothyroidism for more than 40 years. However, patients treated with levothyroxine have relatively lower serum tri-iodothyronine (T3) concentrations than the general population, and symptoms of hypothyroidism persist for some patients despite normalisation of thyroid-stimulating hormone (TSH) concentrations. The understanding that maintenance of normal T3 concentrations is the priority for the thyroid axis has redirected the clinical focus to serum T3 concentrations in patients with hypothyroidism. This Personal View explores whether it is currently feasible to identify patients who could be considered for liothyronine supplementation in combination with levothyroxine. Genetic profiling stands out as a potential future tool to identify patients who do not respond well to levothyroxine due to suboptimal peripheral thyroxine (T4) activation. Moreover, new slow-release liothyronine preparations are being developed to be trialled in these symptomatic patients, in an attempt to restore T3 concentrations and provide conclusive results for the use of T4 plus T3 combination therapy.
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diogenes
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I do worry that "they" will come up with some way of identifying patients which is incomplete. For example, using their suggestion, some feature of their genetic profile.
That might identify a proportion of those who would benefit. However, it could also be used to deny those who do not have that feature.
Surely the fundamental is the empirical: Does the person in front of me feel better with some T3? (Which can, of course, only be assessed by trialling T3.)
" Genetic profiling stands out as a potential future tool to identify patients who do not respond well to levothyroxine due to suboptimal peripheral thyroxine (T4) activation. "
Why do some people insist on over complicating everything ?
I can think of a 'tool' to identify this group of patients...... a doctor ...... one who is allowed to order fT3 and fT4 tests ... and can also read out the following words :
" Do you feel better now you've been treated with Levo ? "
I think we're already seeing this. Some have privately tested for DIO2 snps and been successful in getting T3 prescribed on that basis. But there are wild types* who would benefit from T3 and can't make that argument.
There is no possible criticism of an individual who gets a test for a DIO2 SNP. Nor that they use the test to justify requesting a prescription for liothyronine.
Not having that SNP is not in itself reason to deny liothyronine. In reality, we simply do not have the knowledge to deny anyone. (Might never be possible to determine in advance that an individual would, or would not, benefit from liothyronine. It's arrogant to assume we can ever reach that point.)
Absolutely. I don't begrudge anyone who successfully obtains treatment on that basis (although it shouldn't be necessary to do so). One's ability to pay for testing or lack of the SNP shouldn't be used to deny treatment. As you say, the more pertinent question is Does the person in front of me feel better with some T3? (Which can, of course, only be assessed by trialling T3.)
I also worry about Bianco et al's connection to the new T3 drug that keeps FT3 levels stable. Stable FT3 levels may not work at all patients - especially if these 'stable levels' have to be held within the standard ranges designed for healthy people or people on T4 monotherapy.
Thank you so much for updating us on what is happening Diogenes.
It is interesting to see so many of these types of less negative papers coming out regarding T3 usage.
I would like to be much more optimistic but I've been there in the past and don't want to make myself too positive only to be dragged down once again.
What would be so wrong with them learning how to get good results using T3 'as it is' , before they go meddling with it and potentially ending up with something that doesn't work the same way .
Rather like nice fresh milk .. OK, there are some issues .. it goes off too quick in the summer without a fridge , but people have already figured out acceptable ways to deal with that ...... but nobody really likes UHT do they.
Of course, the elephant in the room re use and testing of T3 or a T3-derivative is that we don't know the pharmacokinetics of NDT's T3 and T4. It would be ironic if, as I suspect, the kinetics of the T3 in NDT might be similar to Bianco's derivative. I suspect NDT/DTE contains protein-bound T4 and T3 which will also take time to degrade and thus soften the dose peak. All at once, a costly derivative becomes prey to a cheaper and well known alternative. Though pigs will fly - it will be another reason to protect a pharmaceutical and its value to a company, and weigh even further against NDT.
Such a dreadful coincidence that your positive suspicions about desiccated thyroid, and the seeming "rehabilitation" of T3, have coincided with an all-time low in the number of available desiccated thyroid products. (That is, prescription standard. There are vast numbers of "glandulars".)
Don't knock the 'glandulars' - they saved me when I became allergic to levothyroxine (both tablets and oral) and porcine NDT! They definitely have their place. It's not that hard to dose if you use resting heart rate as a guide.
Luck had nothing to do with it, I researched and picked the one developed by Dr John C Lowe who was the adviser to thyroiduk. I also had fortnightly blood tests for fT3 and fT4 run by my NHS GP, which would have quickly picked up if it hadn't got thyroid hormones in.
I meant luck in the most general sense. It is lucky there is something that appears to be of good quality. It is lucky that it is available (there have been problems with supply).
I always ensure I have 2 years supply in hand! Concern over possible supply issues and over whether NHS would continue it if I went in hospital, are the reasons I pursued getting T3 on NHS.
Thank you for posting this, Diogenes, this is encouraging news indeed! However, I am not sure how genetic testing will tell who needs T3? It is a fact that thyroid hormone carries out metabolic activity in cells, not in blood. So, unless there is a way to actually measure how much T3 is available at cellular level, I am not sure they will be able to tell who needs T3 and who doesn´t. After all, many patients on T4 only with "optimal levels" according to doctors have become symptom-free on T3, even though nobody diagnosed them with T3 deficiency. So, unless they develop a method to measure T3 at cellular level - or revert to going by symptoms - I am not sure how they will be able to tell who is T3 deficient...
I suspect we’d all be better with some - after all that is what our thyroids once gave us in health.
If that were the case (and it might well be so), we'd have to go through a period of time in which they selectively prescribe T3, very likely adding another genetic variation or whatever from time to time, and only getting to "all" in fifty years or so.
And genetic testing isn't cheap, or certainly not as cheap as Levo/T4 that gets dished out with alacrity. Indeed, who'll be 'deserving' of the testing, what testing and how many might be missed out/overlooked again...
Why don’t they just reinstate NDT and ask us how we feel on it and titrate the dose until we feel well again - back to the future. They’ve enough poor excess pigs being destroyed all for naught to make an immediate start! Perhaps not the fortunes to be made as with synthetic T3 and many layers of complexity to allow lots of creaming off profit and keeping it controlled so the price can be artificially pumped up by limiting supply. Good that T3 is trending tho….
Thanks for posting this. The fact that they want to establish who would benefit by genetic testing is worrying. Surely patients who are not regaining their well being with poor quality of life on Levo only would be excellent candidates.
Very encouraging but how long would this take to gain approval and then be rolled out, possibly not in my lifetime - would be truly great if we could all try slow release T3 or even NDT and go by how we feel as most of us on T4 alone do not have the quality of life they deserve!! Not rocket science is it!!
I do have a genetic issue, DIO2 heterozygous. I'm pretty sure that's why I have been much better on combination T3/T4. But blood tests are not able to reflect the level of T3 in the blood and my TSH is never within in the range. It's encouraging to see more studies and articles of this kind, but until more knowledge and understanding is reached patients will remain unable to access effective diagnoses and treatment. It's getting closer though
As far as I can see they see they already have the answers they simply won’t let us take them and prefer to pontificate and pretend there isn’t any evidence to support combination therapy when millions have taken it since c.1889. And many of us are doing a lot better on it than t4 monotherapy. How can they seriously believe one hormone only is better for us than the two a functioning thyroid makes. How much evidence do these scientists need before they treat us properly?
thanks for posting diogenes. At the end of the day the medics need to listen to and look at their patients rather than tapping on their computers. A half hour session with a patient (I know that is not what's allowed in the current system) really understanding their symptoms and really understanding what thyroid disease is would save many subsequent appointments from a patient that never feels well because of the obsession with TSH.Medical schools need to offer proper training/ more hours learning about Thyroid issues. They might find that the overall NHS treatment bill will eventually reduce because patients are being treated properly !
Thanks for sharing this, diogenes . It’s good that the argument for T3 and combination therapy is gaining more traction.
I do however think it will take a long time for grassroots practitioners to understand it. I have a new GP who I had to speak to last week to review my repeat prescription for Levothyroxine. He wanted me to do blood tests to check levels and when I said I’d rather not as I’d had them done recently by my (private) endo who had written to him, he went online and read my endo’s most recent letter to him.
I get Levothyroxine via the NHS and have to pay privately for T3. “Ah, you also have T3,” he said as he read the letter. “We don’t prescribe it much here. We don’t see any evidence that it works.” I laughed out loud. “Well, it’s been a game changer for me,” I said.
He put Levothyroxine back on my repeat list with no further hassle. I was happy enough with that.
I felt awful after 7 years on T4 monotherapy and my TSH never went below 4.59 even on 200mcg/day. Thankfully, my old endo (sadly now retired) decided to try me on a trial of T3/T4 combination and over the next 3 years allowed me, under his supervision, to adjust my dosages to where I felt well. As soon as I added the T3, I felt as though my brain had been switched back on and I could suddenly cope with life again. I’m now on 25mcg T4 and 50mcg T3 ( split into 2 doses) and I feel well. I recently did a DIO2 test through Regenerus for curiosity’s sake, and it turns out I don’t have any anomalies and yet without my T3 I’d be reduced back to being a zombie, so if genetic testing became a pre-condition for being prescribed T3, I’d be right up the Suwannee without a paddle…
Yeah there could be a miriad of yet unknown reasons why T3 is needed as well asT4 apart from the fact it’s blatantly obvious to me that approximating what a healthy thyroid makes has to be better for health than just giving one hormone some of which needs to be converted to T3 leaving the person short. Small wonder many of us don’t feel good on T4 alone. I’d like to know if anyone is really optimal health wise on just T4 - this is the real research that should be happening, justifying T4 monotherapy with combination. Therapy as the default and T3 only for those who needed it, like it once was before this utter folly we have now was embarked upon, destroying many lives along the way.
Regenerus only test for Dio2 genetic mutations. Dio1 genetic mutations also cause significant T4 to T3 conversion problems.
If on levothyroxine monotherapy, one's conversion rate can be estimated by the equation fT3 ÷ fT4. Then using Midgley et al's research 'Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion ' one can identify whether one has conversion issues and would be better including T3 in one's thyroid medication.
Replying to myself. The basic problem with all this sort of work is that it relies on statistics to diagnose an individual. The saying is "statistics includes the individual, but the individual cannot be diagnosed by statistics". A pseudo logic has now become engrained - that the individual can be so diagnosed, even when simultaneously it is acknowledged that they are an anecdote within the general population of ill people. This has come about because using the incorrect approach to diagnosis and treatment simplifies the search for the "correct" treatment. - look at the numbers, not the patient. Until this attitude changes and the diagnosis of thyroid malfunction is again admitted to be a multifactorial and tricky problem to solve rather than a computer readout, one can't progress. It is a whole rethink of the logic that is needed. Even this paper falls into the statistical trap as do virtually all.
This explains so much diogenes. It’s mathematical training that’s needed and how to correctly apply statistical methodology. Until it changes I guess it’s lies, damn lies and statistics holding things back.
This is really encouraging. I have had the sense that lots of research (not all obviously 😉) has had the aim and result of backing up flawed science, not being critical and testing their fragile theories, but more an exercise in shoring up weak foundations. Having more than one group questioning mono-therapy as the mono-option for treatment is going to move things on tremendously.
I’m ok on just Levothyroxine at present, but I would not be so naive as to think this will last forever. I still get high antibodies in my blood results and whilst I may have answered the question ‘Do I have Hashimoto’s’ I still want to monitor the ‘level’ of activity (for want of a better explanation).
If they factor symptoms into the diagnosis. All will be well the fact they mention wellness at all suggests a more holistic approach 🤞😊
Thank you diogenes for keeping us all in the loop 😊👍
Thank you diogenes for posting this. Hopefully we are going in the right direction but how long before the endos and doctors get up to speed? had a Blue Horizon thyroid DNA test done some years ago. Both endos I have seen have dismissed this as no relevance to treatment but probably also because they do not know the differences in types of hypothyroidism. My test showed a signalling problem from the hypothalamus (tertiary hypothyroidism). This is probably congenital but exacerbated by the loss of half my thyroid. Regarding the slow release T3, I used 20mcg of this from Germany for 4 years. I have just started 2x 5mcg T3 tablets and presently (although it’s early days) feel much better on this, probably because more of this gets absorbed through my poor digestive system. I have a friend who had/has hyperthyroidism. She manages perfectly well on 75mcg levothyroxine despite no thyroid whatsoever. I find this intriguing and wonder whether her secret is a better performing liver where I understand most of the T4 to T3 conversion is made. I think it’s true to say that whatever the type of hypothyroidism, the lack of hormone impacts on all one’s organs to their detriment. Therefore if testing is done on ‘healthy’ participants the outcome as to the efficacy of the hormone/drug is likely to be different.
Thank you for posting. I agree, it's definitely a step in the right direction. Now all we need is them to stop dosing T3 by TSH! And accept that other categories of patients need T3.
For example, me.
I have normal Dio2 genetic mutations so under their criteria I would not be prescribed T3. However, using your research 'Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency', I calculated my T4 to T3 conversion rate, it was 0.16. This puts me most definitely in the category of poor converter (personally I think you need a new category of 'abysmal converter' for me 🤣 ).
I am homozygous for Dio1 genetic mutation, which may explain this poor T4 to T3 conversion rate, however this genetic mutation isn't considered by this research.
So instead of selecting patients who would benefit from T3 therapy, by genetic mutation, why not select them on the basis of T4 to T3 conversion rate? Or by ongoing hypothyroid symptoms and a trial of T3 (for a year).
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Here we are again. Hashimoto's and levothyroxine intolerance 
Go home its just psychological. We are A & E. GPS have no control here we say what goes 
Wondering Where To Go From Here
Results are in but where to go from here please?
