Just seen this paper - have not read more than the abstract so far. But it does explicitly agree that T3 can make sense - but surrounds its use with cautions.
Endocr Rev. 2021 Sep 20;bnab031.
doi: 10.1210/endrev/bnab031. Online ahead of print.
Optimal Thyroid Hormone Replacement
Jacqueline Jonklaas 1
Affiliations
PMID: 34543420 DOI: 10.1210/endrev/bnab031
Abstract
Hypothyroidism is a common endocrinopathy and levothyroxine is frequently prescribed. Despite the basic tenets of initiating and adjusting levothyroxine being agreed upon, there are many nuances and complexities to consistently maintaining euthyroidism. Understanding the impact of patient weight and residual thyroid function on initial levothyroxine dosage and consideration of age, co-morbidities, TSH goal, life stage, and quality of life as levothyroxine is adjusted can be challenging and continually evolving. As levothyroxine is a life-long medication it is important to avoid risks from periods of overtreatment or undertreatment. For the subset of patients not restored to baseline health with levothyroxine, causes arising from all aspects of the patient's life (co-existent medical conditions, stressors, lifestyle, psychosocial factors) should be broadly considered. If such factors do not appear to be contributing, and biochemical euthyroidism has been successfully maintained, there may be benefit to a trial of combination therapy with levothyroxine and liothyronine. This is not supported by the majority of randomized clinical trials, but may be supported by other studies providing lower quality evidence and by animal studies. Given this discrepancy, it is important that any trial of combination therapy only be continued as long as a patient benefit is being enjoyed. Monitoring for adverse effects, particularly in older or frail individuals, is necessary and combination therapy should not be utilized during pregnancy. A sustained release liothyronine preparation has completed phase 1 testing and may soon be available for better designed and powered studies assessing whether combination therapy provides superior therapy for hypothyroidism.
A more positive look which is great. Thanks Helvella. However until ‘tsh goal’ is removed from their treatment plan (let alone stressors and psychosocial) I fail to see what difference it makes whether they advocate t3 or not. But I suppose in time and time and more time we may catchee monkey 🤞🏻🤞🏻
There is deep antagonism to use of T3 in pregnancy.
Other than older case reports from the days of desiccated thyroid being usual, there has been precious little research into the use of T3 in pregnancy. I think it is reasonable to be concerned, but much more difficult to justify a blanket ban - which is how it appears from outside medicine.
If you would make it if your thyroid were functioning properly when pregnant, I question how can T4 only be considered safe if your thyroid is not working properly and you’re pregnant.
However, no-one is actually responsible for thyroid hormones produced in our bodies. But they are if they are prescribed.
If levothyroxine is prescribed, it follows the orthodoxy of the day so a doctor prescribing that would be blameless. But one going against that orthodoxy and prescribing liothyronine would appear to put them into the firing line for anything untoward that occurs - related or not. Worse, even knowingly allowing T3 to drop, but maintaining TSH within whatever is the current agreed standard, would likely escape all blame.
Yes I see what you are driving at but I think the logic behind refusing T3 it is flawed precisely because it goes against what nature does. I can see optimising could be an issue but it is reasonably straight forward with NDT.
Did lots of problems occur in pregnancy with NDT when it was the normal treatment for under active thyroid I wonder? You’d think someone somewhere studied it at the time and there should be some data.
One of the big problems is that old papers used old techniques of determining adequacy of dose. Whereas now we have at least reaosnably usable blood tests.
There simply is no realistic possibility of getting a doctor of today to accept any papers/case reports that were written.
And I certainly do not believe that no T3 in pregnancy is right - just putting forward how it will be perceived.
Yes, good points. Interesting that people generally felt better using the old methods of determining dose with NDT rather than blood tests and T4. I can’t believe they think knowledge began with TSH blood tests and Levothyroxine and all that went before was hokus pokus - small wonder we’re in this mess!
Thank you Helvella, that’s most interesting - at least a sustained release T3 is being trialled. It would help me to even out the doses.
I cannot ever remember my weight ever being taken into account, nor any co-morbidities, although now my age is: I have reached 70 and all of a sudden attitudes are changing. Equally my observation that I have never returned to full health and an active life is dismissed out of hand, last week I was told to just get on with it. (Fingers crossed…I am on T3 only and have been for some years now, but each new endocrinologist (they seem to come and go quite swiftly) wants to tweak things, reduce even further. Although T4 never helped, nor did a combination of T4/T3, there’s always pressure to go back to T4)
Me too Hiphypo diagnosed in 1999 and I have not seen any change in my Levo treatment from a few GP's. I have never been referred to an Endo either.
I have never been well on Levo and my GP - comparatively new to me - has constantly decreased it, as TSH rose, he cut Levo. And I wasn't converting well.
If it wasn't for TUK and this Forum I would have been none the wiser today. TUK has been a lifeline to me.
I am now on T3 only too, but because only because I couldn't live with the rotten treatment.
GP told me ladt year that I should never mention T3 to him again because it was an illegal drug. That was when I told him that I was going to trial T3 and hoped he might have keep an eye out! LoL I didn't quite expect that, but there you are.
So I trialled it and by about 4 weeks ago I dropped Levo entirely. I can't say I am totally happy, but I am 100% happier than I was on Levo.
I sourced and paid for my own T3, so no one to say anything to me at the moment.
from what I gather looks like most doctors, whether they are GP's or Endocrinologists are nutters, sorry for the rant, I have a few bones to pick with them myself.😡
I am fortunate as I take T3 only and I take one daily dose. It's not a high dose but I feel well and am symptom-free. What else could one ask for!
Whereas on levothyroxine it gave me tremendous palpitations especially overnight and cardiologist was puzzled with overnight recordings and was considering putting an implant in my heart to 'see what was going on'. Just then T3 was added to T4 - palpitations ceased and I then went onto T3 alone and it suits me fine - except if there's some change in the T3. My body will react differently if there is a change it doesn't like.
The paper describes the concept of repairing thyroids using stem cells. Which sounds fine - at least as an idea.
But I see a bit of a problem if you don't address the autoimmune processes which destroy thyroid tissue surely they will destroy any replacement thyroid tissue?
If they can arrest the autoimmune processes, and do so early in the progression, maybe thyroid tissue would regrow in anyone, even without stem cell techniques?
So we end up in the same old place, catch it early. Don't take approaches which leave people years before diagnosis. But failure to do that is the story behind so many members here.
Exactly the converse of what is being done with this absurd watch and wait nonsense - they are wantonly torturing people leaving them untreated letting TSH go up to 10+ and now I hear you need two blood tests at 10+ before any treatment is proffered. Talk about storing up problems for the future. Have they never heard of the saying a stitch in time saves nine?
I am glad to hear I belong with the lower quality animal evidence. Well it’s good enough for me - Levothyroxine no life worth living, NDT health fully restored. Give me low quality evidence every time. St Frances of Assisi has always been my favourite saint! I’d rather animals weren’t experimented on especially when we already have a medication that would suit the majority and is easy to administer. But no we ban it. 🙄 If an effective synthetic combination therapy was developed I would try it but I can’t see it ever happening the therapy might happen but access to it would be quite another matter, if the current situation is anything to go by.
But I see a bit of a problem if you don't address the autoimmune processes which destroy thyroid tissue surely they will destroy any replacement thyroid tissue?.. absolutely, you might as well give a new liver to an alcoholic and not bother telling them to stop drinking.
Am pleased to see this article from J.Jonklaas ,looking forward to reading it later.
I'm not convinced slow release/ or not is really such an issue for most people taking it , and do worry that a slow release formulation may just swap one issue of 'multiple daily doses' for another that we aren't aware of yet... but if someone has gone to the expense of making it , they will presumably be pushing hard to sell it... so it's probably still good for getting T3 use in whatever form acknowledged as 'safe' and beneficial where there is a need.
Nor am I convinced by slow release. For several reasons.
If you use one of the conventional approaches, you do several things:
Change where in the gut the T3 is released. Which might affect the microbiome, and the cells as it passes through the gut wall.
Change the amount absorbed. Few slow release formulations are accurate - they just make sure the poeak is lower and more spread out. But if that reduces the total absorbed, it might not be satisfactory.
Change the possibilities for interaction with other gut contents - including food and medicines/supplements.
Preclude any tablet splitting (depending on how it is implemented).
Despite the high price of "ordinary" liothyronine, I can see any slow release formulation being more expensive.
i hadn't thought about the implications for 'tablet splitting'.. going off peoples varying needs on here, i hope they intend to make it in many, many different doses then.... Mmm .. and if the price of 12.5mcg levo tabs is anything to go by that could be an expensive problem.They might just succeed in turning "i'm not allowed to prescribe you any T3 cos it's too expensive" into "i'm not allowed to prescribe you the right dose of T3 cos it's too expensive".
Thank you so much for sharing this, Helvella! So much to consider when reaching a perfect dosage and combination. And sustained release T3 - the sweetest phrase for many patients. I read that in the US there is a trial of one developed on a zinc molecule and will last 12 hours - that would be an answer for so many of us.
Thanks for this, it took some time to study. Jacqueline Jonklaas is one of the 'better' endocrinologists (just about!). There is some very good information about thyroid hormone mechanisms, tips on getting better levothyroxine absorption and an accurate summary of combination studies. It is otherwise quite depressing, repeating a number of invalid assumptions and a general lack of scientific method.
The statement that combination therapy should not be used in pregnancy has no supporting evidence. Firstly, combination therapy has been used in pregnancy for over one hundred years in the form of NDT. Secondly, the 'recommended' doses of 5 to 10 mcg liothyronine would produce very little variation in fT3, indeed fT3 and fT4 would remain closer to normal than with levothyroxine monotherapy. It is possible that high doses of T3 might lead to an increased adverse outcomes (small enough not to be noticed anecdotally) - this has not been investigated.
She claims the goal of treating hypothyroidism is to achieve normal biochemistry and later refers to 'optimization' of therapy. This is a fundamental mistake, the goal is to make the patient well, this may sometimes require abnormal biochemistry.
When discussing TSH she fails to mention it's second role, regulation of deiodinase activity. This is universally ignored by the endocrine community.
When comparing symptoms with biochemical 'euthyroidism' on page 8 she cites studies that used controls that were not healthy, they were under investigation for symptoms! This is nonsense, studies must use healthy subjects as controls. In any event if there is a lack of correspondence between hypothyroid symptoms and biochemistry it more than likely indicates the biochemistry is an inadequate marker.
The document only considers primary and secondary hypothyroidism. There are many other causes such as a down-regulated axis, endocrine disruption, low T3 due to a chronic illness and other unknown causes.
She refers to reference intervals as decision limits. This is wrong, if this applied prevalence of all diseases would be 2.5%.
She states that TSH is a good marker for primary hypothyroidism because of the log linear relationship between TSH and fT4. (I know it's better described by a complex polynomial). This is mathematical nonsense. In healthy subjects TSH and fT4 exit their reference interval limits at around the same time. TSH responds exponentially but it also has a much wider reference interval. TSH is a good marker because as the thyroid starts to fail the pituitary has to work harder to stimulate the same level of thyroidal secretion. The 'sensitivity' of TSH is nothing of the sort, it's just an exponential curve. This ignorance of school arithmetic leads to obsessive faith in TSH.
She does point out that reliance on TSH assumes that the pituitary is functional, and there is no non-thyroidal illness.
We have the absurd statement that total T3 (she doesn't like fT3) below the lower reference limt is not sensitive or specific for hypothyroidism due to enhanced conversion and also because T3 falls due to illness, starvation and drugs such as beta blocker and glucocorticoids. These conditions are causing low T3 and hypothyroidism, either correct the underlying condition if possible or else give T3 to compensate. We have this nutty idea that if low T3 is caused by a chronic condition or treatment it isn't really hypothyroidism and we should do nothing.
Claims that 'diagnosis is simple', TSH can be used to predict dose for euthyroidism (after quoting studies that show TSH does not correspond to symptoms) and adjusting dose until 'TSH is at goal' - signs and symptoms have been ditched.
Inconsistent TSH / fT4 levels are put down to 'non-adherrence' without checking for fT3 or that the axis is intact.
There is a detailed analysis of combination studies, all of which have failed to identify suitable cohorts (mainly by insisting on an elevated TSH for diagnosis) and made no attempt to determine effective T3 doses. This is like writing a book on using tealeaves in the teapot to analyse thyroid status.
p. 40 states that combination therapy should not be undertaken in pregnant women for fear of insufficient T3 crossing the placenta. I'm aware of studies that suggest T3 does not cross the placenta but this is contradicted by women on T3 monotherapy having normal pregnancies and by the use of NDT for over a century.
Finally, the statement 'LT3 should be utilized in a physiologic ratio'. I see very few patients on the forum who recover with physiologic doses of T3, they usually require much more. This is why the studies are worthless, they assume instead of determining the dose and then findout out why such doses are needed.
This is a quite depressing document, it reveals a complete lack of appreciation of the need for scientific method, the sort of stuff we are taught at school.
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