Professor Bianco has initiated a review of hypothyroidism and its diagnosis and treatment in this upcoming Frontiers in Medicine - invitation of contributors.
Here is the background:
This collection seeks to compile research that (re)defines success in the treatment of patients with hypothyroidism beyond normalization of TSH levels. We welcome (mini)review, perspective, or original research articles contributing to this effort.
Hypothyroidism was first described in the 19th century, with effective treatment introduced approximately two decades later. Despite large experience accumulated over a century, some modern-day patients continue to experience persistent symptoms despite appropriate treatment.
While a stated goal of the treatment of hypothyroidism is to resolve symptoms, most physicians focus on normalization of serum TSH values, which is the marker used to diagnose hypothyroidism and adjust the replacement dose of levothyroxine. However, the complete physiological replacement has not been possible in other hormones deficiency syndromes, and it may be presumptuous to assume that it can easily be achieved in hypothyroidism. Given the residual symptoms and metabolic abnormalities experienced by some patients, there is, therefore, a need to question and redefine therapeutic success in hypothyroidism. Potential issues to consider are whether there are other biomarkers of thyroid status, in addition to TSH, that may be important, and whether different biomarkers are important for different tissues. In addition, the relevance of the origin of the hypothyroidism and how to balance benefit in long-term versus immediate clinical outcomes.
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Yes. T3 that has come from D2 activity in the brain or muscles and measured in the blood is not the same as T3 in the blood from tablets. Local T3 levels can be quite different to circulating T3. Bianco knows all about this but doesn't make the obvious deductions.
This makes perfect sense to me, it was only after I had been on a stable dose of T3 for about 3-4 months that my symptoms resolved, I assumed it was because it took some time for my tissues to absorb and respond to a good level of T3. An analogy might be made with watering the plants in your garden, if the soil is completely dried out a heavy deluge will result in much of the water running off the surface and little is absorbed, however with a slow and steady supply the water soaks in and replenishes the moisture in the soil to the benefit of the plants.My body was so depleted of T3 when I first started taking it I suspect much of it was not absorbed, but gradually over a few months a slow steady dose did the trick.
I know this is not the case for everyone as some people respond immediately, but we are not all the same.
I have a type of Thyroid Hormone Resistance ( RTH) which resulted in low cellular T3...and I could barely function.Endo said " levothyroxine"....not RTH!
After 20 years levo left me very ill.
I need a high dose of T3!
With help here I was able to self diagnose and self medicate.
The expected result being suppressed TSH and FT4 and FT3 high.
An annual medical check put the cat amongst the pigeons!
My GP was convinced I was killing myself.
No symptoms of overmedication!!
I tried to explain what was happening and she sent me for a heart scan..
Result....my heart is functioning perfectly!
I'm grateful to have had that confirmed.
Then, she wondered how I intended to monitor my dose ( I had explained tests are pointless on a supraphysiological dose of T3)
Reply...Signs and symptoms as used long before tests were devised.
Then....what will you do if you have to go into a care home and can't get T3?
Reply...slowly die.
Silence!
End of that conversation
She left me to self medicate
Patient Autonomy!
I don't believe my situation is unique
But I do think there are people who are suffering and dying because this problem has never been identified.
I strongly suspect both my maternal grandmother and my mother were among that number.
Based on my medical history I'm now convinced that this has been a lifelong problem and some of the damage done by cellular hypothyroidism will never be resolved.
Geneticist told me there may be an as yet undiscovered genetic variant.
After several years of recurring UTIs I've recently been diagnosed with Chronic UTI (now accepted by the NHS as a genuine illness!) and I would not be surprised if this too is the consequence of long term low cellular T3.
No doubt lots of fine words will be spoken about the " relationship between serum and tissue levels of thyroid hormones"
But I'm not convinced there will be any seismic shift in treatment in the near future because it is a relatively complex condition to translate into current tick-box diagnoses and easy treatments.
It takes a long time involving trial and error.
From LT4- only to high dose T3 -only it took me over 2 years then I had to work out my therapeutic dose of T3.
I had to overcome the resistance and hopefully "waken up" at least some of the "dormant" T3 receptors.
I have been able to reduce my dose ( currently 112.5mcg maximum was 212.5mcg)
My dose can vary slightly depending on illness, weather for example.
My progress has also been slow because I had a lot to learn along the way and I knew I had to progress very slowly and monitor intensely.
I'm not symptom free but I now function fairly well....some of the damage done over decades remains but at 76 I'm still here to fight another day!!...
Sorry long rant again......
I realise I'm repeating myself, but...
I hope change does happen and that this cohort of thyroid patients no longer have to suffer because of misdiagnoses and wrong medication......and lack of a will amongst the decision makers to come down off their high horses and make a difference!
Hey, you did it! 💚❤️💛 Took Dr S with Armour, then Dr P re T3 use to 'save me from the clutches'! Also, sure there's a genetic component way back in my family too, esp. my paternal GG'mother - full of fluid, taking up a 2-seater sofa and couldn't walk due to obesity, just after rationing - dx'd senile dementia [mid-60's] but clearly her thyroid [myxedema madness]. Signs of thyroid issues throughout both sides of family.
I'm the same. High dose T3 and been told by a respected Endocrinologist I'm on my own with my T3 medication. I'm very angry that so many of us have been left on the TSH sacrificial slab without a caring physician to help us.
Well said Dippy Dame. Im on ndt -took me years to get nhs to fund it. ....got there in the end but only because of my sheer stubborness! I had to develop my own expertise.......my body knows best what works not these reidiculous protocols they've put in place! I call it laxy diagnosing and prescribing.....involves no brain power just a screen yo look at!! As for this research......it sounds like a double edged sword........could either improve the doctors knowledge/prescribing or end up condemming us all with stating symptoms are acceptable, justifying the ongoung incompetance and harm being done !!! Sorry I have zero faith.
Yes, Dr Skinner 2010 - after trialing me on Levo - prescribed Armour, then my GP via NHS funding did so for 5+ years, only to be removed by one of many hapless, hopeless endos. Following that, all and sundry in medicine were told that I'd 'self-dxd and self-medicated': T3 long advised by Dr P and they knew about this.
Wow, DippyDame, you are a true hero! I really admire your persistence, courage and wisdom. I have begun to suspect I might have thyroid hormone resistance as well, since I need a lot of T4 to notice any improvement, for example I need 250 mcg of T4 to sleep better, though not perfectly like I used to. I am still nervous about T3 only, but I think this might be my only option if I want to really regain my health.
TSH, FT4, FT3, vit D, vit B12, folate, ferritin and antibodies TPO and TG
Before adding T3 we are advised to optimise the above nutrients to support thyroid function
If you would like more info then start a post with your labs and dosing history and we will all have a look and try to help you work out what is going on.
Well, he seems to be opening up a more reasonable discussion.
The jury is still out but it is an interesting statement and development.
Sometimes, people do this in order to seem reasonable before they conclude what they wanted to conclude anyway. So, personally, I will wait and see and not get too excited.Thanks Diogenes!
Well summed up Paul. I think the problem is there is now such a long history of poor treatment & the powers that be not listening that, even when there might be a sign of the potential for change, we have no confidence that it won't just turn into yet another opportunity to reinforce what is either substandard or no treatment. I akin it to the story: The Emperors Clothes. I hope one day the spell will break & the medical world will see they've been fooled/foolish but I fear not in my lifetime. If I'm honest am mystified at how this sorry state of affairs continues & infact worsens. Its sheer madness.
Thank you for all the good work you do Paul. I have your first book. It helped me a lot to build my confidence up to stand up for what I really needed and seek a proper solution. It took me a long time as I found seeking a way forward wasn't through doctors but other patients - I went to doctors to get what I knew I already needed paying privately until I could get through the thick web of the NHS resistance/barriers. Not only is it hard to get the right meds but its really almost impossible to find a good doctor who knows how to properly analyse/treat as they're too bound up with set pathways & criteria. A more blinkered approach is really hard to think of & can only lead to poorer health in patients. Just what big pharma want! Wouldn't do for people to get well!
We've just finished a 2 year clinical trial with 100 patients before and after total thyroidectomy. We hope to be able to get a better grip on the percentage of direct T3 production by the healthy thyroid, with many more patients and no "iodine-interference" than was the case with the Pilo et al paper (now quoted as gospel on 14 controls - 20% comes from the thyroid direct in health with huge variation). Wih our number of patients we should be able to quote a mean and range for this. If as we suspect the Pilo mean was lowered because of the T3-inhibiting effect of Lugol to protect the volunteers thyroid from radiodamage the thyroid direct contribution could be significantly raised with all the implications for T4/3 treatment in athyreotic subjects. Perhaps we can enter this Bianco led review/papers study.
Professor Bianco says: 'some MODERN-DAY patients continue to experience persistent symptoms despite APPROPRIATE treatment' (capitals are mine for emphasis - I'm on a phone and can't do bold).
Isn't that part of the problem - the treatment isn't 'appropriate'?
Did HISTORIC patients, not complain of persistent symptoms? Could this be because they were treated with natural desiccated thyroid, not levothyroxine?
Full marks to professor Bianco for raising the question that TSH may not be the best marker for assessing treatment success, and that different bio markers may be needed for different tissues. I read this as meaning professor Bianco considers that TSH doesn't assess whether different tissues are replete of the thyroid hormones they need.
This statement concerns me: 'how to balance benefit in long-term versus immediate clinical outcomes'. Could this be used to limit the amount/type of thyroid hormone replacement given to patients? I'm thinking of a variation on the erroneous link between low TSH and osteoporosis in hypothyroid people with thyroid hormones fT3 and fT4 still in range. Although I'm hoping that professor Bianco means how to do what's right for patients long term but have immediate ways of determining this.
"This statement concerns me: 'how to balance benefit in long-term versus immediate clinical outcomes'. " Seems to me, they're still not interested in taking the time to get to the root cause and potentially will wish to still rely on medication to merely reduce TSH levels in the short term. Yes, high TSH can, apparently, cause thyroid cancer and all sorts of other issues, but why is it high in the first place? There is far more around what reduces TSH levels than currently meets the eye and it's not being addressed. Endos, imho, get paid to be endos - managed to gain their qualification on the information they've been 'fed'. Easy money imho. In my experience (not necessarily just around thyroid issues) doctors are quite happy to take the money and kudos and, more importantly and damaging, not be bothered to further their knowledge. Sorry! This is probably completely out of context.
When I followed the link to the research paper itself, professor Bianco had listed number of potential topics to be included. I have annotated each of these with my comments.
1. (Re)definition of successful treatment of patients with hypothyroidism
Me : Yes, let's go back to how hypothyroidism used to be diagnosed and success of treatment measured.
2. How to correctly attribute symptoms to their underlying cause
Me: I'm hoping he means tissue hypothyroidism and not fobbing people off with antidepressants etc.
3. Does the aetiology of hypothyroidism and/or the level of residual thyroid function matter?
Me: How can it not matter? If one loses all thyroid function, one is both unable to produce T3, and unable to convert T4 to T3. Surely this implies a higher T3 dose will be required?
4. Is TSH the best biomarker of euthyroidism?
Me: Many patients already know it is not.
How can it be, when patients have residual symptoms which are 'cured' when TSH is ignored, and dosing is done by elimination of symptoms?
5. The relationship between serum and tissue levels of thyroid hormones
Me: Good question, which is the root of the whole problem. Research in rats already shows there is a disconnect between the two.
6. How can thyroid-related quality of life questionnaires be adapted for routine clinical use?
Me: Why not use these questionnaires as they are currently? Or listen when patients list their symptoms and all the things they can't do, and the impact the 'residual symptoms' (aka continuing hypothyroidism) is having on their life.
7. How do we evaluate long-term outcomes?
Me: a starting point would be to look at the research prior to the introduction of levothyroxine.
8. Should T4 to T3 ratios be used to guide thyroid hormone replacement?
Me: Yes, it matters. There is no point in giving someone only levothyroxine (T4) if they poorly convert it to the active hormone T3.
Gullo's 1990 research showed that the amount of T3 produced by a person's thyroid varies from 6.5-42%.
9. Update on restoring native thyroid function by generating thyroid follicular cells from stem cells or immunotherapy.
Me: Ooh, this is interesting. Let me know when I can sign up to a research project.
10. The role of exercise, sleep, and diet in reversing residual hypothyroid symptoms.
Me: Exercise sleep and diet aren't a replacement for the hormones one's body is supposed to be producing.
11. Design of a combination therapy trial
Me: the crucial thing would be to NOT limit doses by using TSH as a marker of euthyroidism. The resolution of symptoms should be the goal, not TSH within range.
Exercise, sleep and diet - wouldn’t object if this focusses on stomach acidity and levels of vitamins.But not if anyone starts to treat Hashi’s as a new kind of ME which might just all be in the mind.
6. How can thyroid-related quality of life questionnaires be adapted for routine clinical use?
Me: Why not use these questionnaires as they are currently? Or listen when patients list their symptoms and all the things they can't do, and the impact the 'residual symptoms' (aka continuing hypothyroidism) is having on their life.
Personally, I think medical questionnaires are deliberately designed to be traps for the unwary.
The questions are usually very vague, and allow for different interpretations from patients, doctors, and therapists, etc.
The possible answers are also vague and frequently don't cover the situation the patient wants to describe.
Patients are usually not allowed to take questionnaires home, nor can they see all the questions and possible answers before they start.
Doctors use questionnaires on their PCs in the surgery to just fill it in themselves as they quiz their patient. There isn't the time for the patient to consider their answers.
I've read anecdotes from patients where they were asked questions, and when the doctor was finished the questionnaire they would declare "You're depressed. You need anti-depressants." There is often no discussion or choice and loads of symptoms are dismissed.
If the patient disagrees with the doctor they are told that people don't know when they are depressed. The doctor thinks he knows better on the basis of a 3 minute questionnaire.
The idea that someone in pain might be depressed because of that pain is often ignored. Instead, to save money, the medical profession has decided to switch cause and effect and tell patients that depression causes pain.
Switching cause and effect is common in many branches of medicine when it saves money.
I think this is the standard questionnaire used by the NHS in GP surgeries :
It's appalling, in my opinion. I cannot see how it helps when someone has a thyroid disease, or endometriosis, PCOS, low B12, or iron deficiency, or a thousand other possible conditions.
The sad thing is, the person is probably clinically depressed, because their body has got into this state from a badly performing thyroid. There is such an overlap of symptoms. These people are just so ignorant. They are downright dangerous.
By the way, thank you for posting this Diogenes, it's really encouraging to see that someone else is beginning a conversation to question the status quo.
Time for a reassessment of the treatment of hypothyroidism
"In the treatment for hypothyroidism, a historically symptom-orientated approach has given way to reliance on a single biochemical parameter, thyroid stimulating hormone (TSH)."
If the medics listened to the scientists and acted on their findings then patients would benefit.
But...
First, the medics must admit that they have been wrong!
To alter the status quo the decision makers in high places must open their eyes, ears and minds!
But...
How might they make the necessary shift without losing face.
As someone who has had to "work it out" more or less by myself and to self medicate, I despair for patients with complex thyroid issues in general, and with cellular hypothyroidism in particular.
To quote linda96 "they have been left on the TSH sacrificial slab without a caring physician to help."
I totally agree with her...
Forgive me everyone if I sound annoyed at this madness!
I've often wondered why it's a given that we're expected to just live with thyroid issues (it's a lifelong illness, allegedly) and therefore be dished out with FREE run of the mill thyroid medication for the rest of our lives. Is the FREE medication to keep us quiet and not dig too deeply? I know it sounds silly. But what is it they don't want us to know?
Our Wonderful Dr Skinner set up a World Thyroid Register - even suggesting taking this to Law if £$ could be found to fund that. He was effectively 'silenced by the system'... those still doing this to us! He died, late 2013, likely due to the stress of being hounded by these types. Not enough around with his 'b*lls' to take on the wicked system they've put together.
Indeed he did. Dr Skinner picked me up more or less from the floor after the effects of nhs incompetance left me undiagnosed for three years then left on a dose of 50mcg of levothyroxine for over a year despite my TSH shooting ever higher and ft4 floored. No ft3 of course -deemed unnecessary. Dr Skinner noted in his notes "A very poorly Lady." I had all the classic physical features of hypothyroidism that he spotted the minute I walked in. Am eternally grateful to lovely Dr Skinner who restored my health.......I saw him for 6 years until sadly we lost him. Greatly missed....
Good to hear - me also - he said, "I could tell just by looking at you" [left for 7 years with heart issues, then becoming a creature from the deep] - I'm sure many of us can spot our former selves in others!? Those endos with notions of their expertise would and have [to me] scoffed at Gordon Skinner... not fit to wipe his boots down!
Me also - a fine man - last time I saw him at his Glasgow Clinic [his home town], I danced a jig with him and we sang a rather funny song about the English. What a compassionate, kindly, humane character. The World is a Way Worse Place Without Him. I've just tried to post his Obituary... but it won't load. Hope you've seen it.
I have. I also went to his memorial day. The last time I saw him I'd bought him a bottle of Highland whiskey as a small token of my thanks. It turned out to be his favourite and he literally hugged it in awe & said how did you know. I didnt of course but was chuffed Id clearly picked the perfect pressie. Lovely, lovely man with a fab dry humour. Miss him.
Awww How Lovely! I bet he was delighted! (I used to love whiskey - which one - so that when I have one, very occasionally these days, I can lift a glass to him?) A Veritable 'Health Prince' Among 'Thieves of Wellbeing'! Yes, so funny and cheeky with it: the Obituary; summing him up wonderfully. Don't much make them with such integrity in these debased [endocrinology] times.
Travelling was difficult then in 2010, feeling so ill after being ignored for seven years with even their silly, scrappy TSH being only 0.14 and then 0.11 within range. Clearly no clue about statistics and populations - let alone individual differences. I only saw Dr S, first in Birmingham and then twice in Glasgow; that's all it took to begin some recovery, where using Armour had enough T3 to make a significant difference!
Dr P I saw once in Northumberland [closer to home] for info on reducing all of the supplements I'd added over years to try to 'fix myself' - he added a couple more and advised that I'd need T3 for life + an adrenal supplement. Much better but I've never fully recovered. Still, coming back from the dregs of semi-existence [never me!], so I owe much to those two fine men.
Dr P another great man. I saw him once he put me on adrenal supplements too. I took them for a while but weaned off after a year or so. I was lucky my adrenals recovered. Am so sorry youve never fully recovered, thats such a shame. B12 jabs and finally gluten free were two big finds for me. Im loads better but my energy is finite if I do a lot one day am exhausted the next. Am sure age is a factor in this too but not the whole picture. There is much still not understood.....
Yes, another lovely man who was adamant re T3. Seems my adrenals have been OK, since the CT scan said fine!? Perhaps time for me to wean right down - I'm much less now - but they were great at the time, Dr P saying he'd never seen a 'heel reflex'?? quite so bad. I do take supplements which have helped so much... what's to be done when they have nothing but sneering on offer? I say below in the event anyone reads to, hopefully, be even more AWARE than usual.
Thank you for that, yet I fully acknowledge there are some waayyy worse than me... not diminishing my own stuff but appreciative that I've at least found something to work. CFS seemed to come [always an issue from EBV in 1979] but I manage everything > well enough ] in 2015 with my being 'punch-drunk', stumbling, uncoordinated with FREEZING SHINS. I thought thyroid issues... this led to my reluctantly seeing an endo who UN-Dx'd me after 5+ years of treatment and said I'd likely never been hypothyroid! So I lost Armour prescription, with all and sundry within medicine being told how I 'self-diagnosed + self-medicated'!
Turns out this was due to < 2013 right lower leg pain [waking me out of sleep, sometimes 'dragging' when I was using a gym]. GP largely ignored but biometrics!?? consultant twice dx S1/L5 spinal issue - GP ignored twice - no referral. By end 2018 severe turbulence did something to disturb also LEFT leg. Had to 'fight' for an MRI... discovered pretty much whole of spine is F*d. As always, I set about doing for myself... specific exercises [I do to this day] and with huge physiotherapy costs... so little via NHS. No one would ever know that I have these issues - assimilated into my gait - until I recently saw a new podiatrist [first time NHS!] who said that holding my leg in such a way from 2013 has led to 'retraction' [and describes this as 'deformity', FFS! ]. As I say, no one would ever know - amazing what the human body and can do for itself - just as well, eh? Just escaped death in January from 'ruptured appendix'... staff couldn't believe that I was walking around, exercising, laughing n joking before op! All of this stuff has sure toughed me up! Yes, AGE is certainly a factor. Best xox 💚🍀
Oh flip Linda thats awful! I was deteriorating fast with dreadful wide ranging neurological symptoms I could barely walk which turned out to be b12 related. My GP could see I needed b12 but couldn't prescribe jabs as it was low but in range & referred me to neurology (CCG protocol) 6 month wait so went off piste again and self injected b12 - judging by GPs face much to her relief. The neurologist backed me but wanted me to carry on buying it myself to save NHS money! I had to beg! Agreed in the end like a big favour to me. Unbelievable. He never bothered to see me again or do any investigations. 6 months wait for a ten minute consultation. Keft a bad taste in my mouth. The gems are out there but boy are they hard to find!
Wow - my B12 has been fine and I do supplement - quite honestly, with sooo much having gone on, I just haven't had time for everything. Maybe I need to look at this... in my spare time Thank you - this could be an issue for me - several others on here have said. Looks like you got on top of that one too - well done, again! xox
At last. I have had so many battles with my GP's and would hope that the future holds a much more nuanced response to the needs of patients with hypothyroidism. T4 is such a blunt instrument. I have had this so long I cannot remember what well looks like and now with co-morbidities, the picture is very confused.
And are these other co-morbidities that you have developed due to poor treatment for your hypothyroidism? Being under treated, not treated or given the wrong treatment, wreaks havoc on the body long term. Something the vast majority of medics seem to have completely forgotten. The long term. consequences of under treating for a long time are huge.
Having seen your latest post about Professor Bianco 's reply, it's obvious he's not yet changed his spots. He is adamant there's no benefit from T3 treatment 'if serum thyrotropin (TSH) levels are maintained within the normal range'. It is 'resolution of symptoms' not 'maintaining TSH in normal range' that is the crux of the matter. I can't believe medics and researchers have lost sight of the fact that it is resolution of symptoms that is important.
Indeed.......the myth of the TSH has spread further afield.... I had the mis fortune to see a cardiologist due to consequences of sucessful cancer treatment resulting in cardiotoxicity (their teminology not mine!) and this was at a hospital where a well known notorious Endo is. My cardiologist was firmly of the believe that it was due to over treatment of hypothyroidism. (It wasnt!!) We had several very long discussions where I politely fought my corner. I was under a lovely endo elsewhere but instead of consulting him he went straight and took advice from this notorious one then wrote to my GP & copied my endo in! Unbelievable!!! My endo managed the situation & wrote to my GP explaining that I was appropriately medicated and why and that resolved it. I managed to get away from the cardiologist.....think we were both relieved not to see each other any more! I dont think Id mamaged to change his mind. Its like brain washing of the medical fraternity.......that is what we are up against - brain washing.
Is it appropriate to send this link to Bianco's questions to our Endocrinologists? I posted on another thread about my recent consultation with my Endo and I would love to send him this and invite him to submit my case history.
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]. As I say, no one would ever know - amazing what the human body and can do for itself - just as well, eh? Just escaped death in January from 'ruptured appendix'... staff couldn't believe that I was walking around, exercising, laughing n joking before op! All of this stuff has sure toughed me up! Yes, AGE is certainly a factor. Best xox 💚🍀
Finally being treated for Hypothyroidism. 
Diagnosed, treated but still unwell
