Report of an interesting study where T3 (liothyronine) was used to treat mice with medulloblastoma. The treatment reprogrammed the cells so they became normal rather than cancerous.
We will need to wait for a human trial to know if it will work. One difficulty I see is that the brain doesn't readily accept T3 so high than normal doses may be needed.
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jimh111
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They were looking at the 'genomic' action of thyroid hormone. This is how we think of thyroid hormone action - T3 binding to receptors and triggering DNA expression. It is usual in these types of studies to use T3 to cut out all the complexity of T4 to T3 conversion etc. in theory at least T4 might also work although many severe illnesses cause 'low T3 syndrome'. I don't have knowledge of the actions of cancers on T4 to T3 conversion, it seems that different cancers can have different effects.
As an aside I love this statement: 'In the study, they treated mice that had medulloblastoma with T3, a synthetic form of the thyroid hormone triiodothyronine, which is often used to treat hypothyroidism'. If only liothyronine was often used.
By the way, this study has nothing to do with the non-genomic effects of T4 binding to cell surface receptors, a mechanism that proliferates cancers.
Thyroid hormone is mainly active after T4 is converted to T3. The T3 binds to receptors (and 'cofactors') onto the 'thyroid response element (TRE)' on DNA. This is called genomic action and it releases RNA which produces proteins that 'do stuff' (I express it this way because I don't understand what goes on at this stage). This is the principal way thyroid hormone works.
However, like any substance in the body T4 can have other activities. T4 also binds to receptors on the cell membrane particularly the 'intergrin αVβ3 receptor'. This is called non-genomic action and is fast acting, because there is no need for DNA expression (which takes several hours).
In simple terms thyroid hormone action is effected by T3 action on DNA but there are other minor actions that T4 (and T3) can have without binding to DNA.
We keep being told that T3 cannot get through the blood-brain barrier into the brain. (Untrue.)
We keep being told that T4 is all we need as the body simply converts as needed. We know how that is not the whole picture.
The brain does perform a fair amount of its own T4 to T3 conversion and appears able to manage some degree of variable T3 levels in different parts of the brain.
I'd expect a number of endocrinologists to insist there is no justification for using T3. Though Jim has replied with some good thoughts.
I had way sufficient T4, given Levo [trialed, Dr S] to find that it led to me being 'speedy', getting up dancing/kicking my height [as I used to be! ], until I realised that feeling was 'too wired'. Finally, Dr P = T3 alone, most of the time fine for more than a decade... T4 # always very low: I must ignore that.
The brain prefers T4 using D2 to convert it to T3. This allows it to regulate local T3 levels independent of blood T3. It also means that if there is a peripheral conversion problem giving enough T3 to restore serum fT3 will not deliver adequate T3 to the brain.
jim111, did you mean the brain prefers T4 using D2 to convert T4 to T3, thereby self-regulating the amount of T3 independent from serum T3 levels?
Sorry if I'm misunderstanding the point you were making - my own brain seems to be quite clogged (presumably due to low levels of both hormones) so harder to wrap my head around things these days
Interesting! Thank you for clarifying. Does this mean taking T3 only would put one at a disadvantage in terms of brain functioning, or alternately that hypos on T3 monotherapy may have to take higher levels than needed by the body (effectively overmedicating?) in order to get enough T3 to the brain? Or, does the brain somehow work around lack of T4 in that situation and work just fine when serum levels of T3 are adequate despite low/absent T4?
I think the question is too complex for anyone to give a precise answer. The body and in particular the deiodinases adjust to hormone levels so it's likely there will be some compensation. However, my judgement going from my knowledge and personal experience is that T3 monotherapy will lead to 'asymmetric' (can't find a better term) therapy, that sone tissues will be a bit hypo and some hyper. This is why I always suggest people stay on the lowest effective dose and not aim for perfection. I take up to 50 mcg liothyronine. I also take 50 mcg levothyroxine. The levothyroxine doesn't have much effect on symptoms but it seems a good idea to haven't some in case there are effects we are not aware of.We should also bear in mind that many people are severely hypothyroid, or can't function normally without above average T3 levels. There are risks on both sides. This is why endocrinologists should get off their backsides, establish which groups need what dose and urgently identity the underlying causes. By finding treatments for the underlying causes patients can be taken off thyroid hormone or put on doses that mimic thyroidal secretion. Levothyroxine monotherapy is not a safe option.
Thank you so much for sharing your thoughts and insights, Jim - super interesting. Apologies for my very delayed response. I recall reading that T4 and T3 both have direct and differing impact on hair follicles ( this miggt be the article: academic.oup.com/jcem/artic... so figure it’s quite likely that T4 may have other direct impacts on the body as well as you say. And helpful to hear of your dosages - haven’t heard of those kinds of numbers too often but I seem to be headed in that direction as well and hearing this makes me feel a bit more comfortable with that.
Not sure I’m understanding what you mean by treating underlying causes (such as tackling autoimmunity and / or triggers of autoimmunity like viral infections, toxins, microbiome, etc, ?)
Couldnt agree more that we need better, more physiologically aligned treatment options and protocols. Think about that all the time.
Edit: I’m curious if you think T4 monotherapy isn’t a safe option eve n in those who covert very well?
By tackling underlying causes I'm thinking of other causes of insufficient thyroid hormone action such as endocrine disruption or subnormal TSH secretion. Rather than just dosing T3 and T4 to resolve symptoms it is better to try and get rid of the root cause.I always supported levothyroxine monotherapy for those who did well on it but changed my view when I came across the cancer proliferating effects of higher fT4 levels. I now feel monotherapy should not routinely be used.
Unfortunately here in the U.S. where corporate money pretty much runs the show we’re a very long ways from where we need to be in terms of even acknowledging the harm caused by so many of the toxins including the many endocrine disrupters we’re now perpetually exposed to, let alone properly regulating them or providing legitimized medical assistance to evaluate or treat the effects. At least the UK does better in terms of regulations than we do. Hopefully there’ll be a radical shift in thinking about these things some time in the foreseeable future.
I saw you’d mentioned t4 playing a role in proliferating cancer above as well, don’t think I’d ever heard that before so this is new to me, will look into it more. Thank you.
Thank you for the link and for putting together the information! Read through a couple pages, look forward to the rest.
In addition to PBDEs and PCBs we're also chronically exposed to pthalates, BPA and BPS (which has been found in the coating of thermal receipt paper at up to 1000 times the level found in cans!), pesticides, PFAS, parabens, etc - not sure to what what degree those effect thyroid hormones in particular, but broadly speaking endocrine disruptors are ubiquitous!
Very much so. The difficult bit is identifying which one(s) is causing the problem. I take the approach that it's unlikely to be ones with short half-lives because they won't accumulate much and more importantly we would notice their effect. For example, if we only had symptoms at home or when having drinks from plastic bottles we would spot the connection. So, I think most problems involve EDCs with long half-lives. At least this narrows it down a bit.Endocrinologists completely ignore endocrine disruption, probably because they would have to think and carry out a proper examination of the patient.
Ha, no that won't be happening in any endo's office anytime soon.
PFAS are definitely among the most concerning EDCs for the reason you state - and they are EVERYWHERE, at least in the U.S. - including in our drinking water. Now thankfully there are filters available for PFAS but they're expensive and variably effective.
I actually tend to think about EDCs rather differently, even short-lived ones - seems to me that they are SO ubiquitous (if ubiquitousness can have levels) that trying to isolate the effects of a particular exposure would be nearly impossible (though admittedly with limited hypo mental capacity, a lot feels impossible to me) - for instance, repeatedly walking barefoot on vinyl flooring that may be in one's home, the perpetual contact with plastic cases on phones, handling receipts when we go shopping, the various personal care products we put on our bodies daily (especially in the case of women, who tend to use many more products than men), the water we drink, the electronics we're constantly handling, the absorption into food from various food packaging as well as contaminants in food (like microplastics in seafood), medical implants, etc. And a lot of that is unknown and undisclosed exposure (e.g., manufacturers who claim BPA-free cans sometimes just replace BPA with BPS).
I try to avoid exposures as much as possible but even with being vigilant seems to me a reduced exposure is the best we can hope for in this day and age. I'm actually less careful now than I used to be because I realize how futile the efforts are.
Was thinking about this again and wondering if things might be different in the UK and EU which tend to have tighter regulations than the US so looked it up and came across this - thought you may be interested if you haven’t seen it already
Revealed: scale of ‘forever chemical’ pollution across UK and Europe
It can’t help I’m sure, it causes so many problems. It’s fundamental to good health and well-being. I wish endocrinology would wake up to this fact and stop starving us of it. I’m beginning to think other areas of medicine will be the ones to move things forward whilst endocrinology lazily slumbers on in undeserved contentment oblivious to what everyone else is discovering about T3. They would, of course, when they think TSH is the only thing that matters….a false idol if there ever was one.
Well anecdotally, I for one feel that some of the physical effects of being T3 deprived for so long are permanent. I don't read or write as well as I used to, for just one thing. I've been told off today for missing things at my volunteering job. It's cognitive. I hope cancer isn't also one of those things T3 deprivation predisposes me to.
Unfortunately there is at least anecdotal info on this. However there are a number of posts on here that tell us that improvement (on optimal dose) goes on for months, even years. I am holding on to those ones.
My reading and writing have been badly affected too and my once meticulous attention to detail can be deeply suspect. Ask for a reasonable adjustment at the volunteering job as they should be enabling you to work with this horrible illness not not telling you off like a naughty child for something that’s happened as a result of the disorder. It’s a poor show treating a volunteer like that.
The person I report to has tried to be understanding and there's a lot I don't do, as the main problem is my concentration is poor (sometimes I keep falling into daydreaming) and I can literally have a sort of cognitive blindness, where I don't see things that need to be done.
In this situation what happened was for various reasons I can't disclose, I had a sudden interruption of my meds, and whilst I communicated this to the manager (with whom I have done many lengthy explanations of the impact of having the right meds, vs. not having them) she still doesn't quite get it. She is good, caring and I likely wouldn't receive the same support in a paying job. The thing is only someone whose been there can understand fully. I can't blame anyone for not getting it at all.
And then I feel like a moaner for having to keep explaining and so sometimes just accept the tongue lashing for 'not concentrating on tasks better' it's a small organisation and a mistake can be a big problem.
It’s not moaning, it’s explaining and educating your boss and trying to get her support to do the job well. They should be doing it by law it’s not a kind favour they are deigning to give you out of the charity of their hearts, but a right they need to put in place not to be breaking equalities law. As for being reprimanded, I find that awful management on the part of your boss. No one should be tongue lashed at work - she needs some management training! I bet others don’t like being treated like that either well no one does, surely.? You’d concentrate on it if you could but her expectations are not realistic. I’d be looking at how I could make it work for you not absolving my responsibility by blaming you, even more so if a mistake can have large implications.
Well I hope you can get more support I know how awful it is trying to work when you have this disorder. I became utterly incompetent and was working when my hypothyroidism was very overt and I was still useless after two years of Levothyroxine. NDT was my saviour I retrained in gardening and have never looked back. It’s a more forgiving vocation and I got a sole gardener job so I am my own boss more or less. I had to work hard to get there doing exams and training and the like but it paid off. Not sure I’d have managed to on T4 monotherapy though. You keep soldiering on. This disorder affords us great insight, like you say it’s hard to know it unless you have had it. It allows you to empathise with and help others when things have gone decidely pear shaped in your own life. It’s the one good thing that comes out of it - greater compassion for human suffering.
Yes, it certainly has given me greater compassion for human suffering, that I can say!
I can also relate so much to what you're saying regarding diminishing competency when ill with this disease. It has been an awful confidence sapping experience. I do think perhaps this post isn't a good fit as truthfully, it needs a lot of attention to detail.
Your work sounds ideal, I am trying to think of things I can do on my own, at a pace that works for me. I really want to get well enough to do that. Unfortunately jumping through certain hoops recently has put me back a fair bit.
I really appreciate your posts, they've really helped me feel better about it all♥️
Wow!!! This can be a tremendous breakthrough. Because the heart the brain muscles have a big receptive sights for T3. Thank you so much for sharing such a valuable information. Lets hope it works even better on humans. After all T3 is proving to have a very valuable place in our well-being. 🙏 . Now let's hope that Dr's except it too.
If their own thyroids were still producing T3, then surely any supplementation would become ‘higher than normal doses’? I have followed some of these kiddies on social media and contributed to their various fundraisers for treatments and it’s heartbreaking to watch them fight so hard and still end up losing. I’m sure the parents would want to try any treatment that might just save their child when ‘thoughts and prayers’ have run out.
It sounds promising but we must wait for human trials before we know.
I should have mentioned it earlier but this study shows benefits of T3 for one specific cancer. We can't assume it would be effective for other cancers
The STAR study on people with fast cycling bipolar were given T3, I think at quite high doses, but it did not cause elevated levels and it did alleviate symptoms in a high number of subjects. It is a highly intractable condition with a very poor treatment response so this was an interesting result.
It may be the same if it were given for brain cancer in children and anything that could assist there would be hugely welcome.
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], until I realised that feeling was 'too wired'. Finally, Dr P = T3 alone, most of the time fine for more than a decade... T4 # always very low: I must ignore that. 
Useful study on effect of central hypothyroidism on T4 and T3 production
John Dommisse interview by Mary Shomon with contrasting idea about T3 only.
