This opinion by Leese is a shocker to me in how he remains completely bewildered by the fact that some patients need more than T4 for adequate therapy, has few ideas to put forward, and clings to the present paradigm (T4 is all) + genetic add-ons as a probable solution. I thought that after his paper showing controlled T3 only treatment was an adequate therapy in those who needed it would have educated him to the bigger picture. But no; the same old story is trotted out without any reference to Ito's and our own work. It's as if we're living in different universes. In his eyes, it is like saying"we've been doing this for 35 years so it can't be wrong; it just needs a few (genetic) tweaks."
Clearly, all of his patients must be incredibly healthy on Levothyroxinine treatment! More likely he doesn't ask them about their symptoms but pronouces them cured because there lab values are somewhere in the reference range. That kind of way of assessing your success as an endocrinologist ought to be banned. This does not happen in other professions. Teachers get assessed on various things that relate directly to their ability to communicate the lesson information and on exam results. Lawyers are assessed by their bosses on convictions and acquittals. Engineers are assessed on their technology development in terms of quality and time to market. But endocrinologists are not assessed the symptom improvement of their patients (their customers!). They are simply deemed to be successful by themselves and their peers by following a broken process.
So, frustrating that nothing has changed for the better from the time I was first diagnosed 30 years ago. I would actually say that endos have got more rigid and dogmatic.
On looking at the points Leese makes here , i immediately found 9 that made me cross enough to look up counter references, and only 4 that were in any way encouraging.
And that's before i've had a cup of coffee or found my specs.
My gut feeling is that Leese is also having difficulty finding his glasses.
For example.....he doesn't mention his own paper from 2009 where adverse effects were only found with TSH below 0.03mu/l or that an even higher risk was found with TSH above 4mu/l .
THANK YOU for always having YOUR glasses on diogenes, and i sincerely hope you haven't broken them whilst continually banging your head against a brick wall on our behalf.
.......I much prefer reading your teams papers, they never fail to help me feel happier about the situation.
It was finding your work , long before i found this forum ,that gave me hope that there may be hope for better treatment, and almost more importantly for me , proved to me that i wasn't a hypochondriac .
And it was discovering your presence on this forum that gave it credibility for me.
Yes, it is an uphill struggle which one has to have plenty of stamina to keep on. Perhaps as a little tickler of encouragement we're working (early stages) on a basic mathematical model, using the reaction equations for hypothalamus, pituitary, thyroid and body response to and production of T3 from T4. The examination has immediately shown that one cannot mimic the real outcome and findings in patients, while ignoring the key role of the working thyroid to produce T3 as well as T4 and the penalties in losing the thyroid entirely.. And it does look as there may be a way to use these findings to determine appropriate dosing. If we get that far, a computer programme allied to SPINA, which Dr Dietrich has designed, may suggest optimal therapy by whatever means in the indicvidual. This would be a huge step to help doctors to prescribe, if it comes off.
a computer programme allied to SPINA, which Dr Dietrich has designed, may suggest optimal therapy by whatever means in the indicvidual. This would be a huge step to help doctors to prescribe, if it comes off.
ITT Improve Thyroid Treatment group suggested the use of SPINA in their response to the NICE draft guideline. But NICE responded: "SPINA-Thyr is an algorithm for the analysis of various tests, many of which are recommended in the guideline. The guideline did not cover the interpretation of thyroid
Which was, of course, an utterly pathetic response.
Anything which truly supports interpretation, and I have faith in SPINA being carefully and properly developed, would be better than trying to follow the incoherent guidelines.
That is excellent news about the mathematical model Diogenes. Thanks for posting the Leese item, I read some of it but the contradictions and the small sample size testing left me banging my head and my glasses are already in a precarious state held together with Sellotape as I need an eye test as well as new glasses
"On looking at the points Leese makes here , i immediately found 9 that made me cross enough to look up counter references, and only 4 that were in any way encouraging."
Which counter references were encouraging? Might be worth a look
i meant ...as in ..only 4 encouraging points that Leese makes in the latest paper that diogenes linked to
all towards the end :-
1 . about future research using specifically patients who DONT do well on levo,
2. 'further exploration of the differential impact of liothyronine on symptoms eg. brain fog versus fatigue , may be warranted',
3. 'the issue of pricing for liothyronine in the UK needs to be addressed.... there is a need for procurement teams to negotiate better deals'
4. 'in the future, we may need to move towards identifying if there are any subgroups of hypothyroid patients who may benefit from using liothyronine in addition to L-thyroxine, probably by identifying novel biomarkers or genetic polymorphisms'
Although i'm not sure if that's really 4, or 3 now, cos i've got brain fade from reading all these long words without coffee
I feel sorry for Dr Leese. Iv sent him an email. I think he does care - that comes over in the way he writes. But he’s been blinded by the continuing, and oppressively so, of the thyroxine/TSH paradigm that’s currently holding sway in the UK.
Let’s hope he can find his way forward because he’d be another good advocate for changing thyroidology in the UK for the better.
He needs encouragement to come out from TSH’s shadow.
His email is on the paper. You can send one too. He mentions t3 quite a few times, I got the impression he’s sitting on the fence a bit. Needs a bit of a tug (encouragement).
I too have some, but not a lot of, sympathy for Leese. It seems to me that the "establishment" doctors are each frightened to stick their necks out much beyond the accepted paradigm. In medicine it seems that all have to move in some sort of harmony or not at all. This being so, Leese is simply intellectually and viscerally unable to propose anything too far out of the party line, for fear of ostracism. Note his comment on popularism, indicating that this is a) an unadvisable and dangerous development and b) thereby implying that patient forums like TUK can therefore safely be ignored.
His ‘popularism’ comment no doubt a sentiment aka Dr Wiersinga, but he’s now retired.
Can we show Dr Leese the hand of friendship. Show him how the thyroid really works, put him out of his misery of not knowing why we like T3 and the real reasons it works?
I fear that you might eventually (or not) get a polite reply which simply restates his belief that virtually nothing is known about the underlying reason for T3 use. When by deliberately (or in ignorance) bypassing the fact that there ARE papers which precisely address his worries and puzzlement, he feigns the "more research must be done" as a way out. I don't propose to contact him as I shall probably get the two-faced reply in th same vein, without reference to our papers, which he may know of but cannot or will not understand.
But that in itself is the real problem. They keep hashing out the ambiguities in thyroid thinking. Over and over. Just to get a ‘paper’ published. Acknowledging that there is a subset of thyroid patients that don’t get on with T3 is fine, but to then ignore and dismiss them, instead of actually trying to find out why is a disgrace. This dismissiveness and undermining of patient reported symptoms, as if we are not the very best evidence of what we are feeling. They could learn so much form us and stop all this controversy if they would only but listen.
Are they building a ‘bank’ of ‘evidence’ in the form of published papers to roll out to continually dismiss T3 as a viable option? Where is the evidence of harms they talk about? Where are the facts and figures? The only evidence I can see that they use for the sweeping statement that ’the majority of patients do well on T4 mono therapy’ is the number of prescriptions for T4 issued. Based on 2014 figure (this is what KB used at a meeting in Jan this year) Presumably this is the last figure they have before stopping recording? If so why did they stop? Because that way they can always fall back on this flawed figure. Nothing more than manipulation and orchestration to fit the result they want to the ‘evidence’ the have pared down to.
So easy to say no evidence of benefit, following a systematic withdrawal to remove any evidence of benefit.
They are never going to conduct non-biased trials or studies to establish the benefits of T3. They don’t want to know.
diogenes Thank you so very much for all your efforts and for keeping us all up to date with rubbish still being published, no matter how frustrating.
A good example of biassed thinking based on the belief that TSH is the best diagnostic comes from the huge NHANES database. The writers of this paper, which is assumed by the thyroid world to be irreproachable targets TSH as a predictor of thyroid dysfunction and relates TSH to some likelihoods of ill health eg AF. However, we have re-examined this data and found that rather than TSH controlling such matters, the patient cohort actually showed statistical signs of nonthyroidal illness which could be an equally acceptable way of determining an outcome. Therefore the changed TSH could be a passive result (causation) by NTI, rather than TSH causing the NTI. Interpretation of data to support TSH as a cause rather than a result is thus questioned. An opinion paper based on this argument is shortly to be in print. It seems to have caused a lot of foot dragging - especially when someone's data conclusions can be re-analysed to show a conclusion different from theirs.
Look forward to the opinion paper diogenes . Science is suppose to be fluid. This over reliance on the biased opinions of decades ago has to stop. I question just what keeps them alive? It seems immoral.
diogenes , are there any papers that talk about lower T3 being a cause of Afib as well as high T3? I've found a couple, but they are very brief. I am in the position of having the Dio2 gene defect from one parent, and now being stuck in Afib. They blamed the 12.5mcg of T3 I was taking with my Levothyroxine at the time the Afib started and frightened me into stopping it. But my blood test at the time showed that by dropping Levo dose a little and adding in the T3 my T3 level had gone done to bottom quarter of the range. I certainly wasn't over medicated on any scale - TSH, T4 or T3 but they still blamed it.
Now I have to start the fight to be recognised again. My GP looked at the gene test result and just said he knew nothing about it and my problems were not my thyroid because my results were in range.
Well, I copied the paper into a Word document and added highlights and footnotes. Nearly finished reading and have nearly 30 notes, most of them negative!!!
Hopefully the main ones can be summarised in an email
In Windows 10, use the white "Windows" key (usually between [Ctrl] and [Alt]), keeping that pressed, touch the full-stop (to the right of "M"), release both keys.
That should display the emoji picker. Click on 🤍 (the heart at the bottom), and scroll down to find the question mark. Click on it and it should get "typed" for you.
Some of them do not work in HU - like !? (as a single emoji).
In Windows, if you hover the mouse pointer over any emoji character in the emoji picker, it displays a tiny bit of text saying what it represents. Things like "red square", "orange square", etc.
🟥🟧🟨🟩🟦🟪🟫⬛⬜◼◻◾◽▪▫🔲🔳
You have to divine the meaning from the context! They do not have any absolute meaning - like bullet points are just conventional marks.
*Sigh* Sometimes the language barrier gets to me. I could not figure out what a "full stop" key might look like. I studied the keys to the right of "M". They are <>? when capitalized, and ,./ in lower case. Finally, it struck me. When reading aloud, you would pause briefly at a comma. and drop your voice and STOP briefly at a period. So I finally got it to work in Windows 10 by holding down the "Windows" key which has a (sort of) picture of a window on it...located between the Ctrl and Alt keys, and then pressing the period (.) key.
I already knew what a lorry and a lift were, but I still have a lot to learn.
The full stop (Commonwealth English), period (North American English) or full point is a punctuation mark. It is used for several purposes, most often to mark the end of a declaratory sentence (as opposed to a question or exclamation); this sentence-terminal use, alone, defines the strictest sense of full stop.
If you have the PDF saved on your computer, and have Microsoft Word on Windows, you can open the PDF using Word. (Might have to use "Open with ..." - right-click on the PDF, Open with... > maybe Choose another app - choose Word.)
Allow Word to open the document, allow it to convert it, eventually (it can be slow) it will open in Word. It can be very good, or medium good, or just about usable. Save as a Word document and do with it as you please.
That often does a better job of making a Word document that is similar to the PDF than copy and paste does.
Thank you, will have a look. Maybe I've been going about it wrong.
Diagrams don't seem to come out, but I thought you have to pay to convert a PDF. At least in the past, payment has been asked for, so I gave up trying!
Click on Diogenes' name and go to his profile. You will see his various posts announcing the publication of papers by his research group. Alternatively, contact Louise Roberts at TUK and she will let you have links to all the relevant papers.
I have tried to read all of them, but still not too sure! 😂
• in reply to
I can usually get the gist of the biology/biochemistry parts and some of the diagrams and graphs. But not the maths and statistics - which may be most of it at times!
Is this true of the NICE guidelines? "Some patients do not feel well on L-thyroxine despite a serum TSH in the reference range. Key issues to consider in such patients include establishing whether the patient had established hypothyroidism initially, and whether the Lthyroxine has been titrated carefully enough, possibly using small increments, to achieve a careful balance between symptoms and serum TSH concentrations."
How would you establish, possibly years after the fact, whether the patient had hypothyroidism initially? I was diagnosed years ago and never told what my TSH was. I wouldn't know where to start to try to track down that data.
Do the NICE guidelines really recommend that the doctor consider the patient's symptoms? That would be a good thing, but from what I have read in this forum, it seems that many, if not most, doctors totally ignore symptoms and just rely on TSH "in range."
This paper should do the trick - title, authors, abstract
Specific nuclear binding sites of triiodothyronine and reverse triiodothyronine in rat and pork liver: similarities and discrepancies.
Wiersinga WM, Chopra IJ, Solomon DH
Endocrinology, 01 Jun 1982, 110(6):2052-2058
DOI: 10.1210/endo-110-6-2052 PMID: 7075548
Abstract
The specific binding of [125I]T3 and [125I]rT3 to nuclear extracts of rat and pork liver was studied. The Ka values of the binding of T3 and rT3 to nuclear extracts were similar (0.65 +/- 0.12 vs. 0.68 +/- 0.10 x 10(9) M-1; P = NS), but the maximal binding capacity for T3 was smaller than that for rT3 (333 +/- 36 vs. 1209 +/- 338 fmol/mg DNA; P less than 0.05). The amount of nonradioactive T4 required to cause a 50% displacement of [125I]T3 from the nuclear binding sites was, on a molar basis, 27 times greater than that of T3 in the case of pork liver and 110 times greater than that of T3 in the case of rat liver. Similarly, rT3-binding sites were highly specific. Relative to rT3, 16- and a 100-fold greater molar excesses of T4 were required to cause a 50% displacement of [125I[rT3 from the nuclear binding sites in pork and rat liver, respectively. Similarly, 700--2150 times more rT3 than T3 was required to obtain a 50% displacement of [125I]T3; in contrast, 50--250 times more T3 than rT3 was needed to displace 50% specifically bound [125I]rT3. Reduced glutathione and other sulfhydryl (SH)-reducing agents increased, whereas oxidized glutathione and SH-oxidizing or -binding agents decreased the binding of [125I]T3 and [125I]rT3 to nuclear extracts, with one exception. Dithiothreitol, a potent SH-reducing agent, reduced the binding of rT3 whereas it increased the binding of T3 to the nuclear binding sites. A 48-h fast was associated with a significant reduction in the maximal binding capacity of nuclear extracts for T3 (control vs. fasting rats, 589 +/- 92 vs. 339 +/- 50 fmol T3/mg DNA; P less than 0.05) and rT3 (1620 +/- 162 vs. 693 +/- 102 fmol rT3/mg DNA; P less than 0.005) without changes in affinity. The data suggest that 1) there exist specific high affinity, low capacity nuclear rT3-binding sites in rat and pork liver which are distinct from the nuclear T3 receptors, and 2) rT3- and T3-binding sites are reduced in parallel during starvation.
I have so much trouble understanding this 'if it ain't broke, don't fix it' attitude. How many people need to tell those like Leese that it is indeed 'broke' before he takes it on board?
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
.......something else i have to thank this forum for 
The cheesy grin I just did is : plus - plus D by the way. And 
is : plus- plus O . And 
