T4 has a role in the brain as well as T3

This article studying rats has shown that the brain's receptors for thyroid hormones predominate in those that are more sensitive to T4 than others elsewhere in the body. This is just to let those who have no thyroid and also take T3 only that this might not be optimal. The article is downloadable:

Frontiers in Endocrinology (Lausanne). 2014; 5: 40.

Published online 2014 Mar 31. doi: 10.3389/fendo.2014.00040

PMCID: PMC3978256

Thyroid Hormones, T3 and T4, in the Brain

Amy C. Schroeder1 and Martin L. Privalsky1,*


51 Replies

Thank you Diogenes for your post and the information contained within the link.

I am quite unwell when T4 is in my hormone replacement but improve slightly on NDT.

One finnish rogue doctor who aggressively campaigns for different treatments says that for some reason they can't explain T4 triggers conversion to rt3 for some. They can't fully explain it, but as it happens often and they see it in their clinic it doesn't matter why it happens.

He also said that sometimes patients can go to T4 only after a while on NDT or T3 only. Which he cannot explain either but seen it has happened and they only suggest t4 only because it's cheaper for the patient but if it doesn't work it simply doesn't work.

Reason why he wants to try if adding T4 would work is that on T3 only natural process of production of rt3 during illness is interfered and that can be somewhat problematic in certain cases if patient are not properly supervised. As if you look at T4 conversion to rt3 as signal for you to rest , skipping that can backfire one. But if patient cannot tolerate T4 there is no reason to torture anyone as monitoring T3 treatment is far more easier than leaving patient suffering with numerous of symptoms.

He also states that 90% of their patients feel better taking levo at bedtime.

Got a bit OT but wanted to say what he says about this matter.

As far as I understand it, levothyroxine converts to RT3 and then into T3. I shall give you a link and the doctor was a scientist and researcher too.


The reason why rT3 can be made from T4 rather than T3 being made is as follows. First, you have to be a poor converter of T4 to T3 with little or no thyroid left. Next, on a T4-only therapy, more and more T4 is given to try to get the FT3 up to normal. This fails, because of poor conversion. Then the body sees the extra T4 as a kind of toxin, so gets rid of the excess by the rT3 route. And actually giving more and more T4 makes matters worse in that T3 production is inhibited, makling the rT3 route even more effective.

Thank you diogenes, this is so interesting. Since I started tweaking my meds I have always felt that t4 had an important role in how my brain and body function, even when t3 levels are good. I did have a slightly raised rt3 when last tested but I don't really fit your description above.

I have Hashi's (my thyroid is intact). My bloods indicate that I convert well but even w optimal bloods I did not feel well and had a number of hypo symptoms (oedema, thin hair, constipation etc) on levo alone. I improved greatly for about six months when a small amount of t3 was added but became unwell again and have been chasing wellness ever since.

I finally had an rt3 test done about two months ago and I was slightly over range. I've reduced levo and increased t3 from 75/100 levo + 10 t3 to 25/50 levo + 25 t3. I can see some small improvements (my colouring looks much better for a start) but I'm still struggling w the dosage.

Every time I attempt to change the ratios to less levo and more t3 I suffer some emotional and/or cognitive SEs. I used to feel very anxious (shaking, nausea etc) on reducing doses of levo but this time around I just feel dim, almost impaired, as if I've had a few drinks. I was making dinner last night (sober I should add) and I really struggled to think through the steps of something I do daily, usually w ease. I also seem to be physically weak/wobbly/lacking coordination. My core seems particularly affected by meds and in the past I've felt like I could tell when I needed a dose increase when it became difficult to hold my posture straight.

There is a chance I am still underdosed, which could account for my symptoms but when I raise t3 I get some uncomfortable SEs so I am going slowly.

It does feel exactly like a description I read of an arctic scientist who said during winter he spent a lot of time looking for items he had just put down: spaceref.com/news/viewpr.ht...

puncturedbicycle , you are so very right . T4 plays a big role in our brain . Thyroid runs on 90-T4/10-T3 . I know that when I take more T3 that I need my concentration is not good. One can become angry assertive edgy . More T3 then needed can make one Estrogen dominant if not careful. As a matter of fact I read recently that studies where made that those committing crimes have higher levels of T3 . When my T4 are mid level my thought processes are great and so is my energy .I'm on a combo of T4 /NDT . I like both my T3 and T4 to be mid range . NDT is 80-T4/30-T3 because pigs need more T3 .

So is the paper basically saying that they have shown that in some instances T4 is acting as a direct hormone and that people on T3 only medication may need to add T4 into the mix? When reading papers like this it all sounds so complicated. But then also it makes me think how clever the scientists are and yet wonder why the intricacy of knowledge of thyroid metabolism doesn't filter down into medical practice and we are left short changed with silly illogical assumptions and simplifications that ultimately leads to a lot of unnecessary suffering. Thanks for sharing this Diogenes.

I agree Hoxo, the ability of our seemingly inert GPS and endos to understand stuff like that is quite something. I do feel so much of the treatment we get is a mixture of complacency and lack of interest. Possibly partially caused by work over load ? My Dad would still be with us if they'd thought past his mild chest problems ( ex-smoker ) and tested his heart. 18 months of symptoms before his first string of heart attacks but by that time too late to operate and died within months at the age of 74 after a life time of being very fit and healthy 😤

Thank you diogenes for that article. As it says in the text I have 'severe intellectual defects' ( as I am under medicated with t4, currently battling with my doctor over, and yet to introduce t3 ). So it was quite heavy going but informative, albeit upsetting.

I'm quite new on here and on the journey of discovery into my thyroid health or rather lack of it. Diagnosed 30 years ago, I've spent my ( stupid ) life believing doctors and thinking my problems were down to my mental health. The more I read the more I feel I've been robbed 😢 Just as I'm sure many others on here feel. Having a down day ( again ).

I am really sorry you've had such a struggle and in the past we've had members who have not been diagnosed but hospitalized and

instead were hypothyroid. It all depends upon where your TSH is or if they take a blood test for thyroid hormones in the first place.

Once you have certain diagnosis on your medical condition, it might hinder many people being treated correctly particularly if applying for jobs.

Thank you Shaws. I was very close to being hospitalised when diagnosed at 18. My gp just kept giving me fibrogel. After many months of becoming more and more poorly to the point of near comatosed, my mum ( ex nurse ) took me to a private specialist to get a diagnosis.

It just makes me soo angry that so many of us have / are suffering in relative silence and no one in the medical profession gives a stuff.

I recently saw the practice nurse and ended up chatting about my most recent results

TSH 5.9 0.35-5.5

T4 13.4. 10-20

She started off saying - oh everyone has seen the programme ( trust me I'm a doctor ) and thinks they know better. By the time I'd finished with her explaining I knew my bloods weren't right and all the knowledge gleaned for this forum and related articles she changed her tune. She seemed apologetic and frustrated on my behalf and repeatedly said 'I can't say what I want to say' !!!!!😤

I've met a hypothyroid ex-District Nurse, who was clueless about her condition.

Yep, doctors too. My current Gp fits that description. Wont listen to me, I'm just a patient. I'm about to give him the book "Tired Thyroid" by Barbara Lockheed - but I guess he will not believe her either since she is not an MD just very intelligent and an excellent observer - and a hypothyroid patient.

Does anyone understand this article sufficiently that can explain in layman terms please?

I get the gist of it - T4 has a role as well as T3, but it also talks about conversion and DIO2 (I have a faulty gene = poor converter of T4 to T3). Currently on both T3 and T4 and feeling oh so much better.

I am intelligent, but not sufficiently knowledgeable to understand all the terminology.

Basically they are saying that T4-T3 conversion in the rest of the body is not enough to supply the brain with the T3 it needs. So there have to be more active receptors that not only bind T4 better but also convert more T4 into T3 to supply the brain's extra needs. In addition, there appears to be direct action by T4 itself in the brain in addition to conversion to active T3.

Thank you so much diogenes So it seems to follow that, if like me, you have a known genetic defect that impairs conversion of T4 to T3, your brain is likely to be adversely affected.

I have been told in the past that the impact of having only one faulty gene is negligible on the brain. Since I have added T3 to my T4 a year ago however, I am like a new woman! However, the biggest change is to my mood. I am happier 😊

Next question is how does one get more active receptors in the brain to convert T4 to T3 more efficiently and to bind T4?

I'm afraid you can't do very much to have a significant effect. The only solution is to get the right T4/T3 mix to satisfy an individual's genetic makeup. The receptors in the various parts of the body will do the rest.

I've read that consumption of polyunsaturated fatty acids blocks the receptors. I don't think it was an advertorial sponsored by the Coconut Oil Marketing Board ;-)

Selenium helps with conversion . But don't exceed more than 200mcg .

T3 definatly helps with moods and depression . But more is not better . Just a small mix of T3 with T4 . I'm so happy for you that it's working for you well .

I do not fully understand the article, I will need to re read.

I am taking 1.5 grains NDT and cannot raise it further as I get hyper symptoms.

My T3 is near top of the range on this dose but my T4 is well below bottom of the range, I keep pondering whether I should add some T4 to the NDT as I am still suffering hypo symptoms.

Diogenes would you advise it?

If you do, add only a little (25 ug) say and drop the NDT by a very little to balance. If your brain is not getting enough T4 to convert, it might help, but you have to balance so as not to overdose.

Thank you Diogenes,

my last tests were early February and results were,

TSH 1.5 range 0.35 - 4.7

T4 6.5 range 7.8 - 21.0

T3 5.2 range 3.8 - 6.0

last dose of NDT was taken 17 hours before blood test, as you can see T3 is at a good level and T4 below bottom of the range.

Not sure if I should drop the NDT by 0.25 or 0.5 grains.

Any other advice would be really appreciated.

Thank you.

I would lower your NDT you are already experiencing hyper symptoms. and add T4 .You have to wait six weeks to do labs with T4 . T3 is a faster acting hormone .Chart your symptoms as you go along .

Many thanks jgellis,

I got the hyper symptoms when I tried to increase to 1.75 grains so reduced back to 1.5 grains, but on this dose I still feel hypo. symptoms.

I have posted my recent results to diagnose (please see above) who has suggested to maybe add 25ug T4 and reduce the NDT.

If you could offer any further advice after seeing my results I would really appreciate it.

Also do you mind me asking how much NDT and T4 you take.

Thank you.

You could try 1.25 NDT and 50mcg T4 . Any NDT or T3 must be split 2/3x a day . and labs must be done 6-7 hours after the last dosing or just before the next dose .

I dose with 75mcg T4 and 1g NDT . NDT I dose 3x/day .

Many thanks,

did you work your dosage out yourself or do you see an endo. who prescribes and advises you?

I have been looking at tiredthyroid.com and the lady who runs the site also advises to combine NDT with T4 as she says the ratio in NDT does not suit everyone.

No, I'm a cautious old Hector. The golden rule: if you change anything, do it in small amounts and slowly and assess the results carefully before you go one way or the other

Diogenes, not sure if you have answered my question which was for jgellis.

Think our posts have crossed.

I replied to you above with my recent results.

If you have time do you mind commenting on my levels.

Many thanks.

My advice is still the same. If you add any T4 do it gently and slowly, and leave enough time to see if anything changes for good or bad. Any advice is strictly try it and see but don't rush to judgement.

Many thanks, I am going to give it a go.

Lucy I tried so many different variations . My last labs showed that I wasn't yet mid range with T4 . So I raised my T4 by .25mcg and lowered my NDT by 1/4.

I finally found an Endo who LISTENS and goes by symptoms first labs last . I wish all Endo/Dr would practice the same way .

We learn a lot from one another and that is very inspiring . This forum is GREAT .

The ratio of human thyroid and NDT (porcine )Human thyroid has more T4 and less T3 90/10 and the opposite is in porcine 80/30 .


Not sure that we are comparing the right things here.

The ratio 80/30 is based how much thyroid hormone is present in processed porcine thyroid. Not how much a pig releases into its bloodstream. (I think the ratio is actually more like 84/20 - or near 4.2:1 in most desiccated thyroid medicines.)

What is the 90/10 human ratio based on? Our respected diogenes has suggested that is not now thought to be the amount directly produced by the thyroid (he suggests 20% has been considered likely but suggests that more T3 might actually be produced).


Also, remember that these are weight ratios. Although 100 molecules T4 convert to 100 molecules of T3, 100 micrograms of T4 actually convert to 84 micrograms of T3.

[ Corrected above sentence which, as originally typed, was complete rubbish. ]

In treatment, the ratios of T4 and T3 offered don't matter so long as the FT3 blood level is adequate as a result. If the T4 is doing relatively little, then the fact it is in different relation to T3 is irrelevant. The body's conversion mechanisms will simply intervene as needed and if there is any conversion from T4 required will simply convert a little T4 to augment the T3 offered if by itself the T3 so offered is inadequate. After all whatever the T4/T3 ratio in such products as NDT, they aren't any less physiological than T4 only- which is about as unphysiological as you can get.

I'm with you Musicmonkey 😊 it pretty much gave me a headache lol. I'm yet to try t3 so still in bad brain fog land. But hearing that it is possible to feel better cheers me up and gives me hope

I've not yet read the article, but troubled by my decline in performing simple arithmetic I came across: file.scirp.org/Html/7-13303...

(I'm no longer adolescent!)

Thanks for that one SmallBlueThing ( Suzanne Vega ? Great tune ) May I ask when you were diagnosed ? I was 18 and for a long time have suspected my problems really started years before. So that makes very interesting reading.

I wasn't diagnosed until my 50s, when I had one of the -- I think -- half dozen hyper swings I've had through my life, after several years of blood tests and inaction when I was hypo. For a variety of reasons I didn't get treated and then 18 months later I'd gone severely hypo and then hyper, thanks to an iodine dressing. I was pleading with my GP to start treatment for hypo, but it took a couple of months for my TSH to climb back into the "orange zone", and treatment started when it was obvious it was heading back over 10.

I feel I was hypo pre-school and during primary school, and went hyper at the age of 12 when my dad died after a brief illness. Other major stress events have affected me similarly, but none were tested for and diagnosed until recently, when it was a minor symptom I went to my GP about. I'd brushed the major ones under the carpet!

At school, I think I used food restriction and lack of warm clothing to keep me on the edge, living on stress hormones, when I was hypo.

Those that take a lot of T3 have a hard time to do arithmetic .

I've not taken any for five months. My TSH has risen to 3.0 and I felt hypo at 0.89.

I can tell you with absolute certainty that I have absolutely no T4 in my body at all and am functioning well now i am taking just T3 medication. I cannot take T4, nor will my body produce any T4 as i have pituitary damage and do not produce any TSH which drives the thyroid and many other systems. The conversion of T4 to Reverse T3 or active T3 is dependent on the value of TSH in the body. This has been known for some time so why academics waste cash on worthless papers like these is an absolute nonsense!


I'm afraid you are wrong. The swing between rT3 or T3 production by the body from T4 is nothing to do with TSH at all, but is to do with either T4 overload in therapy or the onset of severe nonthyroidal illness otherwise. Absence of T4 is not necessarily bad if your T3 dosage is sufficient to adequately supply both brain and body. But having some T4 helps the brain to achieve its higher T3 requirement at lower T3 dose.

Thank you for sharing the article. For some of us taking T4 is not an option. I cannot tolerate even the smallest amount of synthetic or swine T4. Both make me very unwell. I'm afraid my brain will have to cope with T3-only for the rest of our days.

Sorry you are off track with that. Try reading Paul Robinson's books who explains the role of TSH very clearly, when the TSH is very low T4 is all converted to Reverse T3 which blocks the receptor cells. It has nothing to do with the amount of T4 - this is detected by the variation of TSH. Its a clever feedback system. When the TSH is low or non existant, like mine, any T4 is actually detrimental because it all converts to Reverse T3 and blocks receptor cells which other wise would be linking to active T3 and being used by the body especially in the brain. As I have Hypothyroidal Dementia its very important to keep my T3 levels high for my brain to function better and in fact my Dementia has actually improved since starting on T3, and is now relatively stable.


I don't rate Paul Robinson as a scientist. If he was right then in hyperthyroidism when TSH is negligible T4 would be converted to rT3. But it isn't - it's converted to T3 mostly. Secondly the idea that rT3 blocks receptor cells is no longer believed. The Robinson idea simply doesn't hold water.

I am living proof that you do not need T4 in your body! I have been on just T3 for well over 6 years now and have not had any T4 in my body in that time. I have gone from living a miserable existence -asleep most of the time and totally confused the rest with chronic Dementia symptoms, to a busy active live playing tennis 3 times a week, walking, driving and cycling regularly. More importantly my brain has woken up and some of my Dementia symptoms have disappeared although there is clearly a great deal of damage due to the incorrect thyroid medication(ie T4). I can categorically tell you that if I take any T4 I become extremely ill very quickly and only return to my current state when I take just T3 medication.

Its totally clear that we are all different and therefore need different solutions to our thyroid problems but some of us thrive on just T3. Would it not be appropriate to find out why rather than waste public money trying to force people to believe that T4 is a universal requirement?

I am not advocating that T3-only is an impossible or bad way to treat, only that if you can tolerate T4 at all, that helps brain supply of T3 and so the required overall T3 dosage to the body is not as high. I do not as you will see from this forum advocate T4 only as the cure all - far from it. Our group is actually trying to discover why some patients need T3, and who they might be. There are all sorts of problems with T4 only - bioavailability differences from product to product, immune reaction to fillers in tablets and much more. But out of interest are you sure you have no thyroid left at all - i.e. if you were to take a blood test, do you get no FT4 result or a little (which might indicate you have a remnant still ticking over). I only go by certificated, peer-reviewed evidence not unsupported assertions, however often and by however many they are made. So that re the rT3 receptor blockage idea, see the website on tired thyroid.com which also casts doubt on that idea.

Many thyroid patients need both T3/T4 to be well and balanced to feel their optimum . Our own thyroids make/ made both . Except in higher levels of T4 and small amounts of T3 . When we need to dose because our own thyroids either don't function right or some have had to have thyroidectomy . I'm not saying that there are no patients that do very well with T3 only . I'm sure there are many .But then there are those that do very well on T4 because they are great converters to T3 . And some of us who are not good converters and don't do well with whole lot of T3 we need to dose with the combination of higher T4 with a small mix of T3 . As many patients are on thyroid meds that's how many different needs are to get to our "SWEET SPOT". We need to learn to respect and accept one another's different needs . IT'S NOT ONE SIZE FITS ALL ...

Yes that's the one, I took from it that t4 does have some direct action in parts of the brain rather than needing to be converted to t3 first.

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