New research Nov 2015 showing TSH to T4 NOT linear link but multi loop systems involved creating huge variants TSH over rated.

[waveylines]

New research published November 2015 showing that TSH to T4 is not a linear link. TSH been over rated. Far more complex systems at interplay with the body setting new set points and individual systems becoming more known could explain the huge variation -  Is there hope for a new way forward to be evolved? 

ncbi.nlm.nih.gov/pmc/articl...

[diogenes Remembering]

This review was the culmination of all we had discovered over the last 4 years of work. However there is more. We have two papers in press. One shows that separately measuring FT4, FT3 and TSH and looking at each measurement one at a time, is not the most accurate way of doing diagnosis. First , all three measurements have to be done. None is optimal on its own. Then one uses a statistical analysis to combine all three into an interlocking measure that takes account of the variation of each setpoint measurement within its reference range. Then we can plot the numbers obtained and show a better discrimination between healthy, hypo and hyper subjects. This is easily attainable for routine diagnosis, by a simple computer  programme, but it does need all three measurements to get the best most accurate answer. The second paper describes all the various models that have been developed to determine optimal treatment for hypothyroid patients. Again using a simple computer graph can easily determine this for an individual, and also show whether or not someone is sufficiently treated by T4 alone. Finally we have  a paper for consideration (not yet accepted) which shows that in health, before the onset of disease, patients in the reference range for FT3 have different prognoses for the adequacy of later T4 mono therapy, depending on where their set point is in the range. For example, those high in the FT3 range are more stressed than the average, because the thyroidal conversion of T4 to T3 is greater and therefore because the body's T4-T3 conversion is less efficient. Thus even before one becomes ill, there are indications of who might more readily benefit from T3 addition in therapy if disease strikes later just by looking at their position in the healthy reference range. This promotes my long held notion that everyone ought to be tested when healthy for FT4 and FT3 at least e.g. when say 18 years old or earlier and the results archived for targeting therapy if and when a patient later becomes ill.

[waveylines in reply to diogenes]

Diogenes -this is wonderful! For those of us  who  already have existing hypothyroidism will there still be a way of working out the type of treatment most effective?  Can the set point keep changing thereby causing further issues of inbalance? Bear in mind am no scientist so have limited understanding but am keen to learn!! Expect my comments are showing my huge ignorance.... Lol 

[diogenes Remembering in reply to waveylines]

Re your first question, I think this is now possible. And in addition before you become ill, it will help if routine prescreening and archiving of healthy thyroid results becomes acceptable.  Secondly, yes. Imagine that a hypothyroid patient (random choice) starts on T4 alone. Then we know that for EVERYONE, this is not natural. The thyroid when healthy produced both T4 and T3, and the tissues have, according to the individual relationships between thyroid and body, cooperated in producing the optimum levels of each hormone for  health. Thyroid better at T3 production to compensate for poorer T4/T3 conversion in the whole body for example. The consequences for unnatural therapy when disease strikes  therefore depends on who you were, biochemically-wise, by that I mean the balance between what your thyroid gland could do and your body's response, before it they happen. Furthermore, wrong treatment over a long time can have bad effects. Your body "wants" to be as healthy as possible given the circumstances, good or bad. So if you have been given suboptimal treatment over a long time, it adjusts to try to give you the best possible outcome. Now perhaps after this time you try to give yourself better treatment. Too late: your body has adjusted to the "insult of sub optimal  treatment" genetically, so you can never get back to who you were when well. This is why detecting and treating dysfunction asap on diagnosis is essential.

[RedApple Administrator in reply to diogenes]

Diogenes, Thank you so much, not just for this, but everything you and your colleagues are doing to bring about hope that there can be an end to the thyroid treatment madness.

In particular, I'd love to be able to print the following excerpt from your post, onto a huge A1 size sheet of paper and pin one up in every GP consulting room. It expresses exactly how I feel about my own situation.

Furthermore, wrong treatment over a long time can have bad effects.

Your body "wants" to be as healthy as possible given the circumstances, good or bad.

So if you have been given suboptimal treatment over a long time, it adjusts to try to give you the best possible outcome. 

Now perhaps after this time you try to give yourself better treatment.

Too late: your body has adjusted to the "insult of sub optimal treatment" genetically, so you can never get back to who you were when well. 

[waveylines in reply to diogenes]

Thanks Diogenes for the explanation. 😊😊

I do feel depressed though that long poor treatment leads to setting that can't be changed back up? Though based on my own experience I have to agree. For example prior to developing hypothyroidism (that in my case wasn't diagnosed for several years, then followed about six years to get best treatment  balance for me) I still struggle with energy & weight. I have recently found that reducing my carbs has helped enormously -ie finally my weight & waist size is dropping. Before being ill I was slim & active. I was hoping that I would be able to build my active levels up & to some degree I can but NOT back to where I was. Maybe it's age too!! Lol... 

However am puzzled if the body can reset to a lower level to survive why can't it rest back up again.....or have I misunderstood? 

[diogenes Remembering in reply to waveylines]

The short answer is "epigenetic". This is a phenomenon now proven in mice for thyroid function effects (T3). After a significant length of time of inadequate treatment, the body's genes are chemically altered so that the "readout"  is changed - often interfering with starting reading the code that translates into the appropriate protein. If better treatment is restored, this situation does not completely change back to the original state. You are in a new state with a new setpoint which will be difficult to alter again.

[diogenes Remembering in reply to waveylines]

The relevant paper to read on epigenetic effects of T3 on mice is:

Obha K, Leow, M K-S, Singh BK, Sinha RA et al.  Endocrinology, April 2016, Vol 157, issue 4, pp 1660-1672.

[waveylines in reply to diogenes]

Thanks Diogenes - 😊 Will nosey on pub med...

[ITYFIALMCTT]

I particularly like this summary from that paper: "The ease of [TSH] measurement was translated into simplicity of interpretation, ignoring the fact that TSH is both an indirect measure reflective of thyroid hormone homeostasis and a controlling element. Thereby, this concept obscured the intricate relationship of the TSH response with the underlying change in the hormonal milieu. By separating TSH from its physiological roots and primary role as a controlling element (Figure ​(Figure1),1), not only did it become a statistical parameter in its own right, but also it thereby gained the role of the dominant thyroid function test".

[humanbean]

For those who don't already know this, diogenes   (who replied above) is one of the authors of the paper under discussion. He is John E.M. Midgley, and we are very lucky to have him in our corner.

[Justiina]

I feel like crying as most of it was blah blah to me, words never seen it is frustrating that my English skills only applies to certain point and then poof. 

Tho I got the point of the study,  but couldn't get all details. 

[waveylines in reply to Justiina]

Justina -I don't understand all the science behind all of this -only the overview as I am not a scientist. So please don't feel disheartened. Just know that there are very clever scientists out there exploring further and finding new information about how the body works which has shown up the inadequacy of  using the TSH as the main test of assessment and treatment for hypothyroidism. It is good news! 😊

[Justiina in reply to waveylines]

You are right!  I  am sometimes very frustrated as I would really want to understand everything   I know,  impossible!

[helvella Administrator in reply to Justiina]

Justiina,

I spend half of every day saying "Thank you" that by far the majority of thyroid papers are in English - my native tongue.

The odd time I have seen a paper in a language other than English (German or French, Italian or Russian), even with the help of Google Translate, I get almost nowhere.

Your English is so good it is easy for us to assume you can wade through complex scientific papers.

My second thanks, occupying the other half of the day, is that most papers are not in Finnish.

[waveylines in reply to helvella]

Here....here -didn't realise Justine. I would stand no chance in another language -can't entirely follow the scientific papers in my own language....lol 

[Justiina in reply to helvella]

 

Well I once had to translate four papers in german to understand what I have eaten.  Ordered stool test from Germany and thought I would get the results in English, because I got cortisol saliva test results in English. 

I do not speak any german.  

Eventually I managed to understand it. To make it hard it was easier to translate it to English first as couldn't find matching word in finnish.  It could sound complete jibberish! 

I am way too stubborn to ask help... 

[waveylines]

 I didn't know that about Diogenes 😊😊 but am delighted we have such a clever man in our midst who  on a personal note has already given me wonderful advice over the years -thankyou. 

And it is time thyroid treatment was given a though shaking  up -there are too many of us out there who do not respond to mono therapy well or are treated by TSH readings alone thereby resulting in poor response to treatment. 

The allegation that it is all in the mind for those of us who complain about still feeling ill despite so called adequate thyroid treatment  has been offensive to many patients and a real stumbling block -personally one that I think has prevented medicine from looking at the problem more constructively sooner. 

So it is really refreshing to see this piece of work and another that I saw talking about the multiple complex feedback systems which all interplay with the thyroid that anyone break in these systems can wreak havoc. Such investigations surely in the end have to lead to much better and effective treatment for patients. And I hope will stop the hounding of doctors who dare to treat outside the TSH regime which is a simplistic narrow approach leading to inadequate care for a significant percentage of patients. 

With summer in the air it is always wonderful to see research breaking through new barriers. 😊😊😊😊

[linlow in reply to waveylines]

Late as I am to this discussion (see what taking time out does to you ) you might enjoy this one that I love to link to then nahypothyroidism.org/thyroi... - another paper that explains why the current system of tests fails sufferers. One that everyone should copy to their doctor/endo when they struggle to get support.

I love that it explains 'why T4 preparations are often associated with poor clinical response and continued residual symptoms that the unknowing physician assumes is not due to low thyroid'.

[helvella Administrator]

eljii,

Wrong percentage, as I see it.

You are working on the weights of the two substances. I consider the number of molecules to be more appropriate. After all, if we secrete one molecule of T4 and that gets converted to one molecule of T3, the fact that the T3 is lighter is not relevant.

Molecular weight of levothyroxine = 776.87   

Molecular weight of liothyronine = 650.9735

So T3 is 83.79% the weight of T4, molecule for molecule.

If my working out is right (and please, anyone, do check it) that means about 34% T3 on a molecule by molecule basis (rather than 29% T3 on a microgram by microgram basis).

[waveylines in reply to helvella]

Interesting  concept.  Has anyone ever been able to find out what is really needed? Or has it all been hidden  by the proproganda/belief that we can survive well medicated on t4 only?  I find it really interesting as whenever it is mentioned there are wide variants in what is a good ratio. Maybe it's an individual thing once more and depends how are bodies have adapted which loop/s is/are broken and how are bodies adapt? 

Maybe it's also a difficult area to assess as the conversion is going on all over our bodies -maybe different parts of our bodies require a greater ratio then others...

Just thoughts...!!! 

[Hillwoman]

I'm glad to have caught this discussion, though I'm rather late! (Have had awful relapse since summer 2015, so don't get on the forums very often now.) However, Diogenes' comments seem to indicate that there isn't much one can do to improve health after a period of non-diagnosis or under-treatment. It would certainly explain my own current situation, but it seems there isn't much hope for the future either.  

[linlow in reply to Hillwoman]

Hillwoman you need to read the nahypothyroidism 'Thyroid hormone transport' document that I linked to in my comment above. Depending on your current treatment, if you search for the piece I quoted as liking, it might explain why you are failing to respond and provide ammunition to get that corrected.

Hope it helps.

[Hillwoman in reply to linlow]

Thanks for that, I'll have a look.

[waveylines]

Hillwoman I don't think he meant it like that. There are plenty of people out there who's lives have improved dramatically after lack of or poor treatment including people who ended up in wheelchairs because of that. It does take time for the body to recover though and to find the right treatment dose, Vits mins etc that is right for you. I've also noticed that I've never quite got back to where I was before I became ill but I am heaps better from my lowest point. So please take heart.....don't give up.  You can improve.... Do you know what's caused your relapse? 

[Hillwoman in reply to waveylines]

I've obviously misunderstood something. I'll have to re-read and see if I can make more sense of it. My comprehension has been greatly affected by this condition and others.

Thank you for asking about the relapse. I wish I knew what caused it. I've been working with Dr Peatfield for several years and more recently with Dr Myhill, and I think most bases have been covered. It seems likely that I have peripheral insensitivity to thyroid hormone, on top of poor conversion from T4 to T3, and Hashimoto's. Certain treatments aimed at my overall health bring improvements for 2 or 3 weeks, then it reverts to its previous state, then slides down further. Currently, we're checking for chronic virus infections like EBV. I haven't been tested for Lyme yet - too expensive!

[linlow in reply to Hillwoman]

Hillwoman Do you think your setback could be associated with the change from Cynomel to Tiromel? Tiromel is weaker according to this site thyroidrt3.com/which.htm

[Hillwoman in reply to linlow]

linlow, I think that might be one reason. I wasn't doing very well on Cynomel, but I had stabilised at a low level while on 56.25 mcg daily. Drs P & M advised me to increase the T3 slowly, and start hydrocortisone and pregnenolone (my cortisol is very low). This I've been doing, but on Tiromel. I'm now up to 137.5 mcg.

The way I try to even out differences between T3 brands is to crunch up the tablets and swallow as a powder on waking. The Tiromel is nearly finished, and I have a stock of Greek Unipharma T3, which I will start tomorrow.

[linlow in reply to Hillwoman]

I think that that site says that Unipharma is even weaker. I hope that my memory is too bad to remember that there is more than one Unipharma (no sleep last night so the brain is rather on its last legs )

[Hillwoman in reply to linlow]

Oh crikey, I'll have to watch the Unipharma carefully then! I get mine from Cyprus, and it has Greek and English script on it.

Do you have insomnia too? I sympathise. I have apnoea and there are too many nights without any sleep. Thanks for responding to my Qs when you're so tired.

[linlow in reply to Hillwoman]

no probs, its not insomnia as such, I have cfs so my sleep time, as a rule, is very short. On top of that my circadian rhythm is longer than 24 hours so I keep getting out of sync and once a month (or there abouts) I have one night that I get no sleep at all. Life's wonderful innit

I checked the link again and it says 'UniPharma T3 is VERY weak'. I think I recall one of the admins on here saying something very similar when someone mentioned that they had sourced UniPharma. Looks like you had better start researching your next supply already

[Hillwoman in reply to linlow]

Will do! Unipharma isn't cheap, but the only Tiromel I could find expires this August. Yet again, I reflect on the fact that none of us, absolutely none, should be in this position. Grrr....

[linlow in reply to Hillwoman]

I am fortunate that my endo will prescribe them but I totally agree with you. You need to print out the research doc from the OP and the nahypothyroidism link I posted to take to your doctor and see if you can't use them to support your case for a more thorough investigation. Don't hold your breathe though.

[waveylines in reply to Hillwoman]

Hill woman so sorry to hear of your struggle to heal from CFS -it's a really difficult condition and many people still mistakenly think it's all in the mind. I was once formerly diagnosed with it but luckily made a more or less full recovery with time and thyroid medication. I was lucky. It will be interesting as the research in unfurls in multiple pathways to maintain our equilibrium whether anything comes up for CFS sufferers. It could be that there is a fault/s in one of the pathways that hasn't been discovered yet.... Of course this is pure speculation!

You've done well to get onto Dr Myhills books -she often closes her books as she is so busy. Hope she is able to improve things for you. Hugs

[Hillwoman in reply to waveylines]

Waveylines, thank you for your support. The whole CFS/ME debate can get so fractious on thyroid and other forums. My own ill-health started at 14 with some exotic vaccinations, followed by severe enteritis that lasted 3 years without treatment before my appendix perforated (all in my head, you see). A family propensity to auto-immune conditions was triggered at this time and Hashi's and PA developed - also undiagnosed and untreated for many years. It went on from there. Now I'm 51!

I used to be monitored by Dr Irving Spurr, the ME researcher, until his retirement from his private clinic in 2014. He diagnosed ME after finding evidence of long-term viral infection and poisoning by agricultural pesticides. Dr Peatfield looks after the thyroid and adrenal aspects. Dr Myhill I've known for a very long time, but there was a long hiatus in contact after she and I moved to opposite ends of the country over 20 years ago. I was never really off her books, so I was able to resume with her care two or three years ago. It all costs a packet though!

All the best. xx

[linlow]

to quote chriskresser 'The thyroid produces T4 in significantly greater quantities (in a ratio of 17:1) than T3, which is approximately 5x more biologically active than T4.' So 20mcg of T3 will be equivalent to 100mcg of T4 (though most people seems to consider the potency closer to 4:1).