A new Consensus Statement has been issued as a result of a conference between the BTA, ATA and ETA liebertpub.com/doi/10.1089/... .
This document is a mix of some detailed technical information and recommendations for a future study (it seems the use of the singular ‘a’ is intended).
It has some good points: -
The introduction of better measures of outcomes in combination therapy studies.
Selecting patients who are dissatisfied with current treatment.
With LT4 monotherapy TSH is normalised before fT3.
TH action that relies on D2 generated T3 is at risk during LT4 monotherapy.
LT4 monotherapy may cause cancer – this is something I want to write up in the future.
On the other hand, there are some problems: -
By considering genetic issues they are unlikely to find out why patients become ill, as opposed to being ill from birth.
The ethos appears to be to target TSH, in diagnosis, therapy and study outcomes.
My major concern is that there is still a lack of basic science. Hypothyroidism is a clinical condition; it must be diagnosed on a clinical basis. It is essential to observe what therapies are effective, what doses of LT3 / LT4 for various patient groups. Once effective doses are identified we can then speculate about causes. All studies so far have assumed TSH reflects clinical status (it does not) and assumed normalising serum hormone levels is an appropriate target (it is not).
There is a need to take thyroid science a step further, to acknowledge thyroid hormone action as the prime target. Most T3 comes from cells that express type-2 deiodinase (D2), these cells rely on this T3 and release it into circulation. There is a misconception that patients with impaired D2 activity can be brought back to good health by simply giving some T3 to normalise serum fT3. This is wrong! It does little to restore the T3 missing from these cells.
Whilst this document is a step forward there is still a fundamental failure to grasp basic principles of science. The theory must follow observations, normal TSH, fT3, fT4 does not guarantee euthyroidism in all cases.
Written by
jimh111
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The genetic issues strand concerns me, as I have said before.
Let us assume that you really do have a genetic basis for your issues:
If you have a test and are found to have the known DIO2 variants which cause problems, great. You have, effectively, proved your case.
If you do NOT have those known variations, where are you? Firstly, in an even smaller subset of people. Secondly, very much less likely to have your genetic cause identified and recognised. Your hope then relies on either your variation(s) becoming recognised or a genetic basis being accepted even without that recognition. Both of which seem decreasingly likely.
A few years ago I discovered that I have an extremely rare genetic deletion ( the result of this being discovered a family member) and in conversation with a geneticist I raised my Dio2/ homozygous polymorphism and my ( then) suspected RTH. I'm now convinced that a form of RTH is my problem!
His response to possible genetic links to RTH/ thyroid disorders other than the known alpha and beta receptors links and the Dio2 snp was simply " we just do not know right now". The cause may be an as yet undiscovered genetic variation but until or if that is discovered we have no answers.
So I totally agree with your conclusion!
I've been fortunate, albeit late in life, to find out what helps me otherwise I may not be here now. Medics had no answers. The well informed and experienced members here did! Like others here I've proved my case....but medics freak out when I explain my use of high dose T3. I'm risking my life.....
I'm convinced my thyroid problem is genetic and I'm convinced I was heading for the same fate as my maternal grandmother....bed bound for years with pain and exhaustion. But no medic will consider this. It must be FM CFS, IBS anxiety....I could go on!
I spent years saying to medics, "there must be an answer to my declining health and I 'm going to find it". One female GP said to me in horror, " oh no , you must listen to the doctors, they will advise you". They made a poor first of that one!
I cannot blame GPs, they can only practice what they are taught...and woe betide them if they do not!
I don't think the problem is so much "a lack of basic science" as jim suggests but more a lack of will amongst senior medics and decision makers to open their eyes and ears to what science can tell us.....even if it goes against their entrenched opinions
"The ethos appears to be to target TSH, in diagnosis, therapy and study outcomes'.
How are they ever going to extrapolate the whys and hows of thyroid disease if TSH is their target?
Rather than "a lack of science" it seems to me that a lack of understanding the science is the problem.
But I'm just an old, irritating patient so what could I possibly know!!!
Now I'll cease and go and read that Consensus Statement....hope springs eternal!
At least your geneticist was honest about ignorance.
And, if treatment were more empirical, treat until we get to a point at which you are well, the need to prove a genetic basis would not be so great.
As I read your post, I started to think of medicine as being a bit like a map. Some roads exist, even some motorways, where we can get from our current position at "Illness" to "Wellness" at 70mph in half an hour. There are smaller roads which do get there, but sometimes a bit slow. There are even footpaths and bridleways. But if your "Ill" is on the Isle of Wight, and your desired "Well" is outside Belfast, there is no way of getting there. And if your personal "Well" is at the top of Snowdon, and your current "Ill" isn't even marked on the map...
Hmmmm! That sounds like the endo I saw. When I insisted I was going to carry on withT3 only he shrugged and said, " Oh well its like getting into a car.....you don't always arrive safely at your destination".
I guess his opinion would have been that I'd never see the top of Snowdon let alone reach there!
I liked the geneticist, he talked a lot of sense....though I'm not convinced genetic testing is vital for thyroid issues although, for me, it did help point me in the right direction.
Some things frighten the life out of a patient who is doing well on 'options' but then being told they will no longer be able to source the ones that restored their lives/health.
The rs225014 (Thr92Ala) DIO2 polymorphism is associated with mild symptoms, for example being less able to remember six digits in reverse order. And it only really shows up these symptoms if the polymorphism is inherited from both parents. Logically, if we replace the small amount of T3 the thyroid used to provide (when TSH is lowish and fT4 average) the effects of the polymorphism will be overcome. Another feature is that people with this polymorphism get a little more T3 from their thyroid and a little less from D2. Thus, they are LESS dependent upon D2 and so can be expected to suffer less from poor conversion issues. Finally, overstating the relevance of the polymorphism will make it more difficult for the majority whose need for T3 is just as great.
The studies into DIO2 polymorphisms have looked at common variations. There may be rare variations that have a greater effect, although we might expect these to have life-long effects. i.e. they would not explain why someone had good thyroid health which deteriorated at some time.
Genetics will play a part in susceptibility. I strongly suspect that genetic makeup makes someone susceptible to endocrine disruption. RTH caused by endocrine disrupting chemicals (EDCs) may be linked to genetics but not arising out of one's genes.
It's important to find out what levels of TSH, fT3, fT4 groups of patients are hypo at and what levels they need to get better. We can then seek to find why they are hypo and how these results reflect thyroid hormone action.
“There is a misconception that patients with impaired D2 activity can be brought back to good health by simply giving some T3 to normalise serum fT3. This is wrong! It does little to restore the T3 missing from these cells.”
I have not yet read the full article and believe I am just barely grasping what is being said in your post, as I have limited understanding of the complexities involved in TH action. However, the above statement was concerning, considering that in this forum, achieving proper serum T3 levels (in the context of individual variability and subjective well being) is considered key. Can you please expand on that statement?
Also, despite the current lack of proper science around this as you point out, would love your thoughts on what you would imagine possibilities to be (perhaps in the future if not now) to address the missing T3 in cells/impaired D2 activity. Thanks!
Essentially type-2 deiodinase converts T4 to T3 close to the cell nucleus and regulates local T3 levels in tissues such as the brain and skeletal muscle. D2 is also the main source of circulating T3. If D2 activity is impaired you will see reduced serum fT3 levels. You can normalise serum T3 by giving a little liothyronine but this will not replace the T3 that usually comes from D2 activity.
The only ways to correct this is to restore normal D2 activity (if you can) or supply sufficient T3 that it compensates for the cellular T3 that would have come from D2 activity. I believe this is why patients such as myself need to take around 50 mcg liothyronine which is far more than needed to restore normal serum T3 levels.
A little more info as I'm back on my PC now. Some patients have a TSH that is lower than your would expect for their fT3, fT4 levels. Their pituitary is not producing as much TSH as it should, not quite central hypothyroidism which is usually associated with pituitary damage but a TSH that is what I call 'subnormal'. This can happen if they have previously been hyper for some time (months +) either from taking too much hormone or perhaps during the early stages of autoimmune hypothyroidism. This can down-regulate their 'axis', they produce less TSH which usually has less bioactivity. As well as stimulating the thyroid to produce hormone TSH also promotes T4 to T3 conversion, so if there is too little TSH T4 to T3 conversion will be reduced.
Most patients will have autoimmune hypothyrodism diagnosed by a high TSH and low fT4. Ideally these patients will be given a little liothyronine which will restore a normal fT3 and they will do well on it. It is a smaller group of patients with a subnormal TSH that I am adressing above. These patients are often not diagnosed because their TSH may be normal with low normal fT3 and fT4. Even if they are diagnosed they are rarely given the doses of liothyronine that they need because there is a false assumption that restoring a normal fT3 is sufficient.
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