If I haven't posted this before, here it is:Management of hypothyroidism with combination thyroxine (T4) and triiodothyronine (T3) hormone replacement in clinical practice: A review of suggested guidance
December 2017
Thyroid Research 11(1):1
DOI10.1186/s13044-018-0045-x
Colin Dayan Vijay Panicker
This paper is a useful summary but like all others it assumes T3 treatment is needed in order to supply the small amount of T3 normally secreted (note 'secreted') by the thyroid. It fails to address problems caused by imparied deiodinase in peripheral and thyroidal tissues. it also fails to address peripheral resistance to thyroid hormone resulting from endocrine disrupting chemicals, a form which usually presents with normal TFTs.
In general this is poor science. Trials are designed on the implicit assumption that the patient's hypothyroidism is unequivocally due to primary hypothyroidism and T3 requirements are due to either loss of thyroidal secretion or possibly deiodinase polymorphisms. Clinical trials should be based on clinical response, what dose of T3 is needed for treatment and does this have harmful effects? Once we know the answers to these questions then we can start to uncover an aetiology, not assume an unlikely cause and then 'prove' T3 therapy doesn't work.
Would not most trials be invalidated now, with the knowledge of polymorphisms, and in the absence of definitive, unbiased and independent trials, all options and considerations for the need for T3 and NDT, for that matter, should remain open?
The polymorphisms don't have a big effect. DIO2 polymorphisms have little if any effect on blood T3 levels and a small effect on symptoms. DIO1 polymorphisms affect blood T3 levels but don't produce symptoms. I think deiodinase polymorphisms are a bit of a red herring although a useful excuse for doctors to prescribe L-T3.
I’m surprised that you say that polymorphisms have little effect on blood T3 levels. I wondered if you meant Free T3 levels? Are there any clinical papers that suggest that there is little effect on symptoms from the polymorphisms and an explanation of why this should be?
Here is one:
Exp Clin Endocrinol Diabetes. 2013 May;
121(5):300-5. doi: 10.1055/s-0032-1331695. Epub 2013 Jan 17.
The role of type II deiodinase polymorphisms in clinical management of hypothyroid patients treated with levothyroxine.
Al-azzam SI1, Alkhateeb AM, Al-Azzeh O, Alzoubi KH, Khabour OF.
Abstract
STUDY OBJECTIVE:
Several factors can affect achieving the goals with levothyroxine (L-T4) therapy. This study investigates the clinical and biochemical response to L-T4 replacement therapy in hypothyroid patients in correlation with genetic variation in Deiodinase type || (DIO2) gene.
DESIGN AND SETTING:
This is a cross-sectional correlation study. The setting was the diabetes and endocrinology clinics at 2 Jordanian Hospitals.
METHODOLOGY:
Patients with primary hypothyroidism who are controlled on stable L-T4 replacement therapy were recruited and thyroid function test was performed. Genetic analysis to detect 4 single nucleotide polymorphisms (SNPs) rs225011, rs7140952, rs225012 and rs2839858 in DIO2 gene was carried out using the polymerase chain reaction-based restriction fragment length polymorphism assay (PCR-RFLP).
RESULTS:
There was no correlation between the 4 SNPs in DIO2 gene and replacement doses of L-T4, whereas a statistical significance was found between rs7140952 and central obesity (P<0.05), and systolic and diastolic blood pressure (P<0.05). The dose of L-T4 was associated with lower levels of TSH, fT4, central obesity, body mass index and waist circumference.
CONCLUSION:
While L-T4 dose is associated with several positive effects on hypothyroid patients, none of the examined SNPs in DIO2 is correlated with replacement doses of the drug. However, rs7140952 polymorphism is associated with components of metabolic syndrome including blood pressure and central obesity.
diogenes jimh111 This study seems to my, lay person eye, to be a) more focused on obesity and diabetes perhaps than on thyroid function. b) focused on L-T4 replacement therapy - no mention of anything to do with L-T3. It seems solely concerned with the idea that it is T4 replacement that is needed at the production level, but does this allow for the necessity for T3 at cellular level. And c) there is no attempt to evaluate the main SNP rs225014. So how does this in any way relate to the need for L-T3?
It seems lacking in relation to what is being discussed? I don't mean to be rude by that, but would like to understand the relevance.
Is there written evidence of this jimh111 ?
Evidence of what? The polymorphisms do have effects but they do not reflect the major health problems we see on this forum. The effects in terms of signs and symptoms are comparatively minor.
What I'm asking is where are you getting your information from, how are you making this decision, I would like to read to see if I can see why you say this.
Do we really know the full effect of the polymorphism at this stage? How can you be sure that they do not reflect the major health problems being seen on the forum?
I'm interested and trying to understand where you are coming from.
OK. You can look at these studies: -
ncbi.nlm.nih.gov/pubmed/?te... and
ncbi.nlm.nih.gov/pubmed/?te... . I've looked at half of them. We are only intested in studies that relate to treatment of hypothyroidism. Whislt some show effects these effects are minor, they don't lead to the life changing conditions we see here. I think polymorphisms are not that important.
These studies have looked at common polymorphisms, it may be that rare polymorphisms produce greater effects but even so restoring blood T3 levels back to normal should eliminate any non-congenital effects of the polymorphism. Most patients who have difficult to treat hypothyroidism end up requiring higher than normal fT3 levels. Thus their treatment problem is not a consequence of a polymorphism. (Assuming they have not had the problem since birth).
Polymorphisms produce comparatively minor problems that resolve when blood fT3 levels are normalised.
Thank you for the links, I will have a good read. And tag linda96 in too.
May I ask who 'we' is?
Sorry I may be being a bit dim, but in the interest of not misunderstanding, when you say 'Whilst some show effects these effects are minor...' when some what? Polymorphism? What I'm trying to establish is how can we be certain that they don't lead to the life changing conditions we see here?
No offence but if Polymorphisms are or are not important I want to know for sure.
I haven't looked at the studies you have linked, and may not have time now tonight, but I will do. However, the study diogenes posted earlier, did not include the most common and significant polymorphism of rs225014.
With genetics being in it's infancy, how can we know that these 'common' polymorphisms are actually the most common? Surely that cannot be defined as yet? Do we know the % of population that has been DNA tested? I'm not sure I have seen it noted anywhere.
The difficulty is actually getting the T3 levels back to normal when so many are being refused T3 and are finding T4 ineffective. Plus the idea of those who need higher T3 levels being allowed to have them is as yet a dream in the current climate.
In this case by 'we' I meant you and I, although I guess I really meant to say since we are looking at hypothyroidism the only relevant papers are ones that address polymorphisms in hypothyroid patients.
Yes there may be other polymorphisms, particularly more rare ones. I'm guessing as I'm not certain but they have looked at the genes for DIO1 and DIO2 and identified the common ones, thus there won't be any more common ones. Regardless, the issue at hand is that the thyroid has failed, some patients with polymorphisms miss the T3 from the thyroid (arising from secretion and deiodinase within the thyroid). Therefore if you replace this missing T3, i.e. bring fT3 levels back to normal with L-T3 then you have fully compensated and so the effects the polymorphisms have on hypothyroidism have been corrected. When this is done by precribing a little L-T3 patients feel a bit better but a large number of patients on this forum with severe symptoms do not recover. Hence their problem is not due to deiodinase polymorphisms.
I think I am understanding what you are saying. I'm just working my way through the links you posted. But may have to come back to it tomorrow with fresh eyes and clearer head.
I'm awaiting my DIO2 gene results with interest, as I've been on T3 only for some years and know I feel tons better than I ever did on T4. Maybe it will all make more sense when I get my own results back.
I'm also getting confused about the effect of the polymorphisms in deiodinases DIO1 and DIO2.
Half of the T4 produced by the thyroid gets converted via these deiodinases to roughly half/half rT3 and T3. If you have problems of low food intake, say strict dieting, stress or ill health then more rT3 gets produced than T3. So if all the T4 HAS to deiodinate to either rT3 or T3 and if you are homozygous for polymorphisms in the deiodinases this has to cause more problems than you are suggesting, surely?
Thyroid hormone production is also 'downstream' from other polymorphisms say in MTHFR (methyltetrahydrofolate reductase) so the process of thyroid hormone production is already compromised before it starts, possibly adding to the 'strain' on the deiodinases?
You say that 'most patients who have difficult to treat hypothyroidism end up requiring higher than normal fT3 levels. Thus their treatment problem is not a consequence of a polymorphism.' Can I ask please what proof there is that higher than normal fT3 levels are NOT a consequence of a polymorphism? And 'difficult to treat hypothyroidism' did you mean higher than normal T3 medication levels?
Of the second link you posted I picked the 4th paper at random, it's by Castagna MG et al 'DIO2 Thr92Ala Reduces Diodinase-2 Activity and Serum-T3 levels in thyroid-deficient Patients'. from May 2017. doi.org/10.1210/jc.2016-2587 The Results: The DIO2 genotyping revealed an association between low FT3 values and Thr92Ala..... (rs225014)
There has to be a more than a low level response from DIO1 and DIO2 because they are supposed to have a significant effect to control the level of circulating bound and unbound T3 and T4. Polymorphisms must, as a consequence, also make a significant difference.
I'm in danger of getting too deep into deiodinase polymorphisms and drifting away from this thread. Just to clarify DIO1 converts T4 to T3 and fT3, DIO2 converts T4 to T3 only. DIO2 takes place deep within the cell and is thought to regulate local tissue T3 levels, it is also the major contributor to circulating T3 levels.
My comment about patients with difficult to treat hypothyroidism needing higher fT3 levels is based on what I see on these forums. Although early studies found no difference in fT3 levels between patients with and without the DIO2 polymorphism this paper did. Those without the polymorphism had an average fT3 of 3.4 and those who had the polymorphism from both parents had an fT3 of 2.9 (2.9 - 4.2). Thus, if the polymorphism was the cause of the sort of serious hypothyroidism we see on this forum we could make all the patients better by giving a little L-T3 and upping their fT3 by 0.5. This doesn't happen.
I'm saying that T4 deiodinates to approx half/half rT3/T3 [Reverse T3 (rT3)] but you are saying fT3, meaning free T3. Which of us is correct, please? I think this is what is confusing me.
Sorry a typo. should read 'DIO1 converts T4 to T3 and rT3, DIO2 converts T4 to T3 only'. Just to complete the picture DIO3 converts T4 to rT3 and T3 to T2. So, rT3 comes from DIO1 and DIO3. rT3 has a very short half life, T3 stays around longer.
I know this thread is a few moths old, but I needed to bring up the Reverse T3 issue. Deodination must also have a place in the conversion of T4 to rT3. Stress was mentioned in one post and as stress is accumulative, I think more and more rT3 is made. The wrong iodine atom is knocked off hence the rT3. I have had my DNA tested for polymorph in D102 but it was alright, so it must just be the stress is making my body work wrongly. The ratio of rt3 to T3 is different to half and half, there is more T3.
The Endo I saw was aghast that I was on 50mcg as this is way above what he said the body made. 4-9mcg per day. Though this is true it is not the whole story, there is direct manufacture of T3 in the Thyroid, there is then also conversion of T4 to T3 in the Thyroid and there is also peripheral conversion, with a total amount of 30 mcg approx. being made per day. So my 50 does not look so bad.
Thanks for posting Diogenes. I have tried to make sense of the paper but I am struggling today! Maybe I need to add a bit more T3 to my T4. I have experienced some positive effects of adding 12.5mcg T3 to my 100 mcg T4. So all I can say is you have to try it (T3) to see if it works for you- improves symptoms- and you need to go slowly and give it a fair trial.
At the end of the day I am doing my own small scale research which is infinitely better than being wedded to "TSH only results" so favoured by 99.9% of medics. I have an appointment with endo who will consider T3 but have already been told in my appointment letter that I won't be given any T3 even if they agree I need it! needless to say I have an apt with my MP to protest. Keep up the good work Diogenes.
The remark about T3 in your appointment letter is shocking. I feel, more and more, that we must challenge the ethics of withholding T3 prescriptions, rather than trying to challenge medical professionals on the current science, which they ignore. It might be harder for the NHS to ignore individual and group complaints based on the ethics - or otherwise - of current medical practice.
He seems to have a big downer on NDT implying it is not to be trusted despite its long and successful use. It is the simplest way to get a combinaron therapy and it certainly suits me a lot better than Levothyroxine on which I felt dire despite being optimised to a low TSH. I have the DIO2 mutation that causes poor T4 to T3 conversion.
I was never even told about let alone offered T3 combination therapy on the NHS despite making it quite clear I still felt very unwell on levothyroxine. Antidepressants were happily dished out like dolly mixtures to me. Since taking NDT my depression has completely vanished and antidepressants have no place in my life.
I know which medication I trust for its efficacy.
It should be a matter of freedom of choice for the patient and provided as an option on the NHS which I have paid into all my working life. Now I am ill through no fault of my own the NHS can offer me nothing but a life of illness, suffering and a plethora of ineffective medications that just mask the real problem
Yes TSH110, and it also annoys me the way the NHS Drs carry on as if we're ungrateful wretches when we try to refuse the myriad of damaging and unnecessary drugs ~ which they continue to insist are an adequate alternative to optimal and appropriate thyroid treatment.
They seem to forget we've paid in as a collective as part of an INSURANCE system and we're not getting these medications for free! We're paying their wages and in return they're wasting OUR money and time, keeping us ill, and getting paid bonuses from Big Pharma for doing it!!
Corruption on a grand scale ~ of which the end result is that many of us end up having to give up our careers and then make further demands on an already over stretched system! A waste of time, money and most importantly, our lives! I've lost years of mine ~ hence the rant.😕 x
I saw your comment about myriad and damaging drugs, and getting paid bonuses by Big Pharma, and I was coming to that conclusion myself.
I do regular Temp Pulse BP during the day. I can see when my T3 is wearing off as my BP goes up and pulse goes up. My Blood pressure used to be Borderline 'needing medication' I do not need it now.
I also have skin discoloration on my lower left leg, it was all the way round and inflamed at times, I can now see normal skin colour appearing, a brown area is slowly lightening. T3 decreases peripheral resistance and increases contractility of the heart.
So T3 could save costs on Blood pressure medication, and on dressings and potions for treating a leg ulcer.
Yes, it's not difficult to come to that conclusion is it? T3 also lowers cholesterol levels, and stops GPs forcing statins on you! It's just so annoying that we have to source it ourselves like criminals ~ well I do anyway. 😕 What a crazy system. x
I believe patients with depression should have a complete, competent thyroid workup and their situation remedied before antidepressants enter into the picture. BTW it would be interesting to know the ratio of women to men who are prescribed antidepressants before checking out their thyroid! My money is on more women, particularly older. JMO.
TSH110 thanks for explaining re NDT, think that is where I "lost the plot" when reading the paper. As you say freedom of choice is vital with respect to what hormone treatment we choose to keep us well.
I am just about to start reading "inflamed mind" by Edward Bullmore . He is looking at effects of auto immune disease on depression etc. Quite "off the wall thinking" but very interesting in the context of those of us with Hashi's and docs determined to prescribe anti depressants.
Waiting for that one to come into the library. How are you getting on with it?
Thanks for the book info-will look it up. Sounds like the author thinks outside the box.My kind of person.
The point that is made in the paper about NDT is that the ratio of T4 to T3 is higher than some research has indicated may be “normal”. What of course we don’t know is whether the levels each individual had before they developed thyroid problems were “normal”.
This argument about the "wrong" T4/T3 ratio in NDT is about the biggest red herring in thyroidology. If dosing by controlling the T3 is the main objective, then if T4 is the inactive hormone it doesn't matter how much or little there is, so long as the combination of T3 given direct + T4-T3 conversion together produce the right FT3 for the patient. Furthermore, if you allege that the ratio in NDT is non physiological, how about pure T4, where there's no T3 at all and you make the unproven assumption that an adequate conversion to T3 is made in all cases, without testing that statement out in practice. Double-think, a practice rife in thyroidological thinking.
It is great having your expertise on this site Diogenes. Helps to de-bunk the assertions made in papers like this one. This paper also talks about a lack of long term studies on the use of T3/T4 combination therapies and possible detrimental effects. As someone who started adding a small amount of T3 a week ago, is this true? Maybe we should crowdfund some research if there hasn’t been any or not enough ?
There's a paper by Graham Leese et al showing that well controlled patients on T3 only do not even after many years, develop serious effects on heart and bones. So T4/T3 should be exactly the same.
I've been on T3 only for about 8 years now, and no heart problems. Being checked for arthritis at the moment (OsteoA but not osteoporosis)
I'm fairly sure that I saw a statement last year, and I'm pretty sure it was BTA or such, that stated that overmedication of L-T4 had the same adverse effect as overmedication with L-T3. But can I find that document now!!
It makes sense that this be the case. Yet the scaremongering about effects of use of L-T3 do not extend to the effects of too much L-T4. Any drug is going to be 'dangerous' if not needed. But if needed that is a different matter.
I know of a young lady (mother of 4 children) who was told she had terminal bone cancer and only a year to live as they couldn’t figure out why it was decreasing at such a rate.
They then apologised and said they got it wrong- it was too much t4!
Crazy
Yes, I had a bone density (bd) scan about 10 years ago. A couple of years ago I accidentally got two appointments for a followup bd scan, I am on NDT btw. I thought I was due for one so I arranged a private one - then, a week later my doc said it was about time I had a bd scan. I did both of them just so as not to upset anyone! One result said that my bd had INCREASED by 10% and the other said it had DECREASED by 10% - I just said OK, took an average (zero, no change) and stopped worrying about it.
IMO "Sorry" just doesn't suffice with this kind of medical error. JMO-as always.
After radiation for larynx cancer in 1984 affected my thyroid function I was placed on 300 mcg (yes 300) of levothyroxine . Was on it for years. The reasoning at that time seemed to be it would lessen my chances of thyroid cancer down the road. When I was diagnosed with atrial fibrillation in 2011, three cardiologists and an endocrinologist were in my room. All agreed that years at the 300mcg dose greatly contributed to my a-fib!
I wonder if this and the previous case was reported to the Yellow Card system?
No. I live in the states. And I'm willing to bet that what was told to me in my hospital room never made it into a chart. I was a nurse for 40 years and one thing I do know is how the healthcare system works here.
Hidden And how it works here too, I'd guess!
I think our 2 healthcare systems start with different treatment guidelines but end up accomplishing agendas which are similar (more money in the pockets of the system) We just get there by different routes. My understanding of the NHS is they want to save money by denying treatment & meds they deem too costly. Here (US) because we have insurance companies that fork over money to practitioners and health institutions we can get treatments and meds we need and in a timely matter as long as the doctor's documentation of need is worded to fit their guidelines. Proper documentation is an artform here. The glitch comes when we have a problem (like thyroid issues,etc) that are not big moneymakers for those involved. Effective thyroid care can be difficult to obtain here, IMO, because it doesn't generate enough income. Few expensive tests (labs are usually cheap). No patented meds to order (read expensive) as thyroid drugs have been around long enough to be cheap. And many docs aren't up on proper care because it's not worth their while to pay for seminars and the like to stay informed. Also sometimes, since our symptoms can be so vague and overlap with other illnesses, it's possible patients with thyroid issues may get fobbed off and sent to be treated by a specialist whose expertise also treats the same symptoms but generates more money. We can find ourselves being referred to more specialists for our symptoms because everyone gets a piece of the pie and everyone is happy. If the patient feels well that's a happy accident. Sorry to be so negative and harsh but that's how I have seen our system evolve. Often we not only have to fight for correct, appropriate treatment but we have to fight to refuse tx we know isn't going to help us and that wastes our time and well-being. Whew! Thanks for listening.
LOL! I suspect you are very right. And think the same here about the lack of interest in thyroid problems because the general 'training' promotes it as easy to treat with just one small pill a day. How naive! How narrow minded and unscientific! How stupid! Considering Dr's are suppose to to be the 'more intelligent' in our society, what chance do we have?
I wonder how many others conditions could be eradicated or better controlled with balanced hormone etc. But I suspect the pharma companies and the private sector would not actually want us well.
I don't think it is just our two countries either, a worldwide issue. Much of it through pure greed, the rest through disinterest and ignorance.
Right on. I believe our solution involves educating ourselves (like with specifics found on this site)and bringing our finds with written documentation when possible-perhaps even a copy to leave with the doc. From what I know after having my recent labs evaluated here I am bringing a very specific request to my June 6th Endo appt re exactly where I want my T4, T3, and TSH to be in the guideline scale. I also have an appt for May 21st with my Electrophysiologist who works with me in so many ways. He has agreed to put in writing on my online chart that the problem of possible heart problems from very low TSH is no longer applicable to me as I have a pacemaker. This way, tho my new endo so far appears to be working out (one previous visit) he is covered when I tell him my TSH goal is to be below 1. I'm looking at my 'road to thyroid health' now like a chess game. Stay as many moves as I can ahead of possible recalcitrance. Also, we have to believe in our ability to copartner our care and not back down from 'medical skirmishes' when needed. We may not be doctors but we are intelligent people who can understand what we read. And doctors who like to caution us about "Dr Google" don't understand the internet is just a huge visual library. Telling patients not to research and educate themselves about their illnesses is like saying " Don't read this information. You might learn something I don't want you to know." Also, a word about lab tests and results. Some docs schedule me to come in a week before my appt to have labs drawn so we can discuss them during my visit. About 2 days after they are drawn the results appear on my online patient portal and I have access to them. Other docs prefer to wait til the visit to draw labs. Sometimes a test may need to be added. But generally I don't like this approach and speak up to strongly request results be available for the visit. The one doctor who gives me grief about this is the one who has ignored my thyroid situation for so long. This approach allows her to send the results to me online with no chance of a dialogue about possible dose or med changes. Slick but I don't allow it anymore. What a tear I'm on today!😡 Thanks for reading my novelette! irina
Hidden Oh how very true. And yes we do need to learn how to 'play' these doctors the same way they think they are playing us! And it does help to stand up for yourself. Trouble is so many are feeling so tired and low that they struggle to 'fight back' and stand up for themselves. Why it helps to have someone else there, and to go in knowing what you want, making sure the supporting adult knows too - so can insist if patient not getting anywhere. I think it helps to have an 'unknown' friend there. That way Dr does not know who that person is so will be careful what they say and often treat patients better. Good luck.
I like the idea of the 'unknown advocate'-esp if they are involved in healthcare!. Kind of like a 'ringer' in sports.
Yes, a good retrospective study. I believe this outcome is due to the excellent care of the doctors who prescribed L-T3. I like to make an analogy with a blunt knife and a sharp knife. Although inherently more dangerous in the hands of an expert, e.g. a surgeon, the sharp knife is safer. L-T3 is inherently more dangerous, it bypasses protective deiodinase mechanisms but due to the skill and care of the L-T3 prescribing doctors the risks are fully mitigated. In addition patients lives are restored. L-T3 is generally safe provided the patient is monitored carefully.
I put it more simply and bluntly - any medication is dangerous if not needed or not being processed correctly.
The essential point is levothyroxine is inherently safer than liothyronine because the body has deiodinase and other mechanisms that protect against thyrotoxicosis. If you bypass these safety mechanisms (and you may have to) then you are taking greater risk and so should take greater care. The study shows that this has been done successfullly.
Please can I trouble you to supply me a link to a paper or article where it says that deiodinases protect against thyrotoxicosis? I wasn't aware of this aspect to their talents.
This paper joe.endocrinology-journals.... by Graham Williams and Duncan Bassett is excellent if rather technical. 'In thyroid hormone deficiency, DIO2 expression and activity are increased, whereas its expression and activity are reduced in thyrotoxicosis. ' The 'Thyroid Disease Manager' has an excellent section on deiodinase under the title 'metabolism of thyroid hormone' in particular this diagram thyroidmanager.org/chapter/... (you will need to register to view this). Also, Tony Bianco's website is superb as he runs the major deiodinase research facility deiodinase.org/ .
Deiodinase is a very complex subject, make sure you refer to accredited sources, there are some quack articles on the web written by people who fail to understand the subject. It's difficult enought without being confused by wrong information.
Was reading today what happened when a chap went to an Endo recently. Was told that several of his patients, whom had been on T3 for 10-15 years had had symptoms return so T3 didn't work and there was clinical trials proving this. Mind you, he also said he would be struck off if he issued NDT. When patient said no you wouldn't Endo said well, he didn't know about NDT so was not prepared to take the risk of issuing it. Last Oct I attended an Endo appointment with a friend and Endo then said he didn't know what NDT was?? The history of thyroid treatment?? How can Endo's 'not know'. An excuse not to issue? And Surely it is the patient taking the 'risk' and they should have the option. It is the lies that annoy me! Just avoidance of the real issue.
My GP and endo have both told me that I have been slightly overmedicated with T4 and that this is putting a strain on my heart for the last 3 years. They only looked at my TSH level though which was down well below 1. From private blood tests my T4 and T3 levels were within range. So the medical profession certainly does warn about too much T4 as well as T3.
Yep blatant bias against the use of T3. Rife! There are too many of us actually getting our lives back using it - who needs trials...we are living proof! Question who is paying for the trials, what the criteria they are using etc, too many of them are geared towards a specific outcome. i.e, wasn't there a study of over 65's, published last year. they gave a number of >65's up to 50mcg of T4 and when there was not enough benefit evident they concluded that over 65's don't need T4 therapy. And that was published!!! Apparently cohort had been chosen as having A symptom of hypo in previous 12 months. NO consideration for the fact that they may have needed more, or NDT or T3!! Are the existing studies worth the paper they are printed on? (Or the digital space)
The answer seems to be largely "no". This paper by the arch denouncer of bad practice Dr J Ioannidis indicates that in medicine only about 3% of meta-analyses and randomised clinical trials are worth anything at all. Thyroidology will not be immune from this. And these are the papers and studies that NICE will be relying on for deciding the "new" guidelines to come.
Intensive Care Med
doi.org/10.1007/s00134-017-...
EDITORIAL
Are systematic reviews
and meta‑analyses still useful research?
We are
not sure
Morten Hylander Møller1*, John P. A. Ioannidis2 and Michael Darmon3,4
How do those of us who have no thyroid due to RAI fit into this sort of survey? What are we called?
janveron1
Check this isn't cellulitis, which often shows itself in a collapse of peripheral capillaries and veins above the ankle. If the patch feels hot and tight, then this is a sign. Antibiotics then needed immediately.
T4 Monotherapy Versus T4/T3 Combination Therapy
T4 & T3 combination therapy... day 9... awesome! 
Studies on TSH for those on combined T3 T4 therapy 
Advice about combination of T4/T3
