We've gone a long way to matching what actually happens in patients with a theory of integration of the HPT axis. This needs five simultaneous solutions: 1) stimulation of the pituitary by TSH-releasing hormone from the hypothalamus, 2) Effect of released TSH on the thyroid, 3) production of both T4 and T3 by the thyroid under the influence of TSH, 4) conversion of T4 to T3 in the body and 5) the whole feedback mechanism of FT4 and FT3 on hypothalamus and pituitary. Mind boggling maths, but matching theory to reality rather than theorising first and hope it matches reality seems to throw up better fits and new relationships we hadn't thought of before. This is NOT for thyroid medics directly, but a step to laying the groundwork to see if the idea can counsel a doctor through a mathematical algorithm like Dr Dietrich's SPINA as to the best treatment modality for any individual patient. So the next step of course is to relate the mechanism to real results. Sorry if this sounds a bit esoteric, but it is a necessary beginning to understand better how the system works and how it responds to pressure.
Trying to match theory and reality: We've gone a... - Thyroid UK
Trying to match theory and reality
linda96 ?
Thanks. You like a challenge!
I really like that approach and its potential for development. Your efforts give many of us hope that there’s light at the end of the tunnel!
Can this be applied to the athyreotic, those suffering hypopituitary, etc.?
(Obviously a full description would cover everyone. I am meaning, can you switch off all contribution of the thyroid and see a meaningful result?)
What we do is first consider and develop the whole model, then take out one of the relevant parameters at a time to see what changes there are to smoothness of data and fit of reality. This is especially important for the T3 production of the thyroid direct and, it seems for hypothalamus signalling to the pituitary. It just may be that the best solution includes a push me/pull you feedback control for the hypothalamus-pituitary interaction which we've never thought of before.
Hi, I'm really fascinated by the sound of this aspect of the modelling as my Endocrinologist has very recently suggested that I may have Central Hypothyroidism. She also suspects it may be Tertiary (Hypothalmic) rather than a pituitary issue and I wonder what the best treatment options would be. As far as I'm aware, there is very little research on aspects of treatment protocols for Central Hypothyroidism and particularly between the HPA control and related TSH, fT4 and fT3 blood parameters. I'd certainly be very interested in any additional readings if you could perhaps recommend as we're really in the darkness and I'm not sure if there are any experts in Central Hypothyroidism around? It's been a long journey for me already to get here after over 15 years of different types of investigations from a range of specialists although I realise that many Endocrinologists have a limited understanding of the complexity of the the feedback systems in the HPT and HPA axes. Grateful for any insights you may have, including any Specialists in this area of research. Many thanks in advance. Kindest regards.
Sorry havent read all replies yet but got very excited about your low tsh/t3/t4 because that's my story for many years and medics all say the as "in range" dispite being low, so"youre fine".... Actually no I'm not bxxxxy fine Im feeling shit is what I wanted to say but instead Iwent away. And I Started reading and also found this site which is very very supportive and better still it is empowering. Thats what we want isnt it, to be believed and taken seriously. Do you have antithyroid antibodies? Have you ever had very very overactive thyroid (I think its called something like "sub-accute thyroid storm" or something. Have you ever read the Professor Toft "counterblast" article?.. Watch this space x
Sorry I forgot Id responded once before... Brain fog etc. I would really like ti know how you get on
Many thanks. I'll try and have a look at the Toft Counterblast article and let you know. My real concern is that so little seems to be known about any of the issues related to Central Hypothyroidism. In fact, knowledge about the Thyroid feedback loops in general seem to be dominated by the "TSH" mantra and most of us will go through life undiagnosed, despite suffering a plethora of symptoms that are indicative of a poorly functioning HPT axis and/or Thyroid gland issues. More often than not, strange blood results are not followed up in real time but dismissed or rescheduled for another 6 months - or more in these current Covid19 times. Most of the research I've read suggest that it's either/or HPT/Autoimmune whereas I think it can be both, or perhaps a more dynamic interaction between TPO Antibodies, the TSH, fT4 and fT4 feedback and the HPT axis. I'll keep watching for sure. Kind regards and very best wishes.
google.com/search?q=thyroid...
This might save you some time.
My ignorant understanding is that there are circumstances in which the HPT axis/pituatory (?) can "downregulate" the production of thyroid hormones (I think of a fuse or a trip-switch or, if you are Old School, a ballcock in a toilet cistern) So that, if the body has had an accute hyperthyroid episode (I had accute post partum thyroiditis which needed pharmacutical controll), in such a situation the bodies production of tsh gets stuck on low (like using a very fine fuse-wire or a jammed-down ballcock) So it will never get overelevated again (thus preventing another hyperthyroid episode) but at the same time keeping T4 etc low in all circumstances thereby precipitatung Hypothyroidism but just about "in range" as "they" say. In such a situation the measurement of tsh is meaningless... forget about it as it will never get above the low position as it is "Downregulated". In such a situatiin the person, for example me, will have years and years (me. over 15 years before I took unilatteral action) of low tsh low t4 and low t3. Mine were consistently never above 10% in range and very slowly the t4/3 was slipping down furtherbut at a glacial pace. With depression /sluggishness/brain fog /constipation/slow weight increase (3 stone in about 20 years) etc etc. JOY! Medics refused pharmacutical help because of The Range Protocol.
I emphasise that Im not a medic (I'm a lawyer as a matter of fact and accept that I am often wrong BUT also totally fed up with Hypothyroidal symptoms whatever the cause.
Note that I also have elevated Anti TPO antibodies and a family history of thyroid problems.
Anyway, Ive started on Armour Thyroid which I get from America without prescription. I feel like Im an illegal drug user and am scared ti tell my GP but Im fed up with feeling ill.
Im telling you this incase it helps you.
I check my resting heart rate from time-to-time, its in the 60's and oxygen sat is 97 so I believe that Im not in the Heart Attack zone.
Good luck and let me know how you get on
Incidentally Im expecting Diogenese/Grey Goose/Hellava etc to tell you (and me) if they disagree. As a court lawyer Im used to healthy criticism and actually welcome it as its how we learn.
Many thanks, much appreciated! I think we've had remarkably similar experiences. How are you doing on NDT? My Endocrinologist has said she may be open to trying a T4/T3 synthetic combination but seemed much more averse to the Armour option, which she won't consider at all! I'm really interested in your experiences and dosing protocols - assuming 2 grains or more? Thanks again. The parallels are amazing. 15 years, low or normal TSH and low fT4 and fT3 which should be clear markers for CH unless you're only interested in TSH - as most NHS protocols seem to dictate, despite symptoms that cry out (sometimes quite literally, expletives deleted) Hypothyroidism! Please do keep in touch and happy to message direct, although I would never have got up to speed on my research without seeing some of the earlier exchanges of posts on this fantastic open resource for Thyroid related issues. I hadn't realised at the time the extent of our suffering - in silence! How few of us recognise the need to become our own advocates when we start out on the Thyroid rollercoaster ride. Apologies in advance for the lame reference here to the legal profession but great to know there are some keen legal minds amongst us. Slainte!
I used Armour reluctantly as no other options. Can let you have source. I am currently taking 1 grain as scared to take more, I did take 1 3/4 grain for a while but t3 went abobe protocol range so got scared. Planning to do a meddicheck test in next week or so. I understand that Armour was the treatment in the 60's 70"s and 8o"s..so what my Dad and aunties must have taken. I dont know why tje experts object to it now when it was the stsndard NHS Medication for many years (see Toft) I would like to know why it was ok tjen and not now? People take it in the litigious USA and I havent heard of any big damages (cf:Thylidimide)
Maybe Diogenese et all can shed light on problems with Armour. I would love to know.
Also how an I suposed to get other help? I address this question to the Universe.
Asto how I am... well its early days but i get really really bad seasonal affective disorder, most obviously in Jan/Feb/March so too early to tell but I am functioning at present and feeling more warm than usual but I guess that this might be a "girl thing" as Im in my early 60's.
Many thanks. When did you start the NDT Armour? Did you ever try the T4/T3 combination. I'm leaning towards the Natural option as I think there are also T1 and T2 in the mix as well as the long historic use prior to the synthetic Thyroxine that has become the accepted dogma for the NHS protocols in response to TSH moderation. It's meaningless for anyone with CH? Slainte!
Never had any other option because no help from GP/NHS. Started very very low last Feb when stsying with retired GP friend incase of adverse reaction (1/4 grain) Then after test (Medicheck) showed little change I increased bit by bit.. I dint like going it alone under NHS radar but dont like Hypo symptoms either. I kind of feel that learned people like Diogenese and formerly Toft would say if this was totally bad (although Im not going ti blame anyone if I drop dead tomorrow!)
I'm not due for an Endocrinologist appointment until early next year - only 1 appointment in 2020 due to Covid 19 restrictions but last year I only had 2 appointments almost 6 months apart! It's tediously slow! And equally frustrating ,which is why I'm now looking for alternatives and self advocacy but still finding my way through all the research, guidance and real practical experience from a knowledgeable and sympathetic group of fellow sufferers. Surprised at our numbers but I'm becoming less surprised as I read more about our shared suffering. A medical profession that seems ambivalent to the growing streams of evidence to the contrary, that monitoring TSH alone in bloods is a poor substitute for most patients, and inadequate to effectively control their range of symptoms! I'm sure that I'm already preaching to the converted! Ciao for now! Hasta la vista!
NDT in any guise and from any producer is not a licensed medicine in the UK. It is permitted still in USA. Other countires like Australia also forbid its use. The original reason, which has persisted until now, is that NDT products were 1) not sufficiently well controlled as to batch-to-batch consistency of T3 and T4 amount and 2) in any case had the wrong relative amounts of T4 and T3, compared with what happens in the average healthy human body. These, plus the adoption of T4 only therapy, led to stoppage in official use. (NB T4-only therapy has never been justified by a clinical trial). The two problems above can be dismissed. In 1) the products are now strictly controlled as to content by superior quality control and 2) the T3/4 product ratio is an irrelevance as the body will adjust automatically by altering its T4/3 product (if there is any). Also using this argument should also be applied to T4-only therapy as this is even more physiologically different from what the healthy thyroid supplies - the therapy relies totally on a patient's ability to satisfactorily convert the appropriate amount of T4 into T3. As to central hypothyroidism, low TSH, FT4 and FT3 are indeed symptoms of it. There is a direct test called the TRH stimulation test. This involves injecting the hypothalamus hormone TRH, and taking blood samples to find if TSH is indeed stimulated. If not, then central hypothyroidism is confirmed. Unfortunately the test is rarely done these days because of its cumbersome protocol compared with just measuring TSH. Unfortunately just doing a TSH measurement and not probing further leads to misdiagnosis.
Many thanks. Much appreciated! Please do let me know if you have any additional reading that you could recommend and I'm really interested in your modelling work on the Dynamics of interactions amd feèdback between the Thyroid hormones and the HPA Axis. It sounds like T3 may be a key factor in this feedback and control. I'm also interested in the T4 and T3 conversion issues as my T3 has always been at the lower end of the range. Grateful for all your insights. Thanks again! Slainte!
We have in review at the moment a theoretical paper which has investigated how the HPT axis works and its connection to body T4/3 conversion. The outcome is that the link between hypothalamus and pituitary and between pituitary and thyroid is in both cases controlled by balancing feed forward and feed backward actions The body's T4//T3 conversion is feedback only. This means that where endocrine glands are concerned, it is absolutely important to regulate and control them closely in all situations (because any failure in this close control has disproportionate effects elsewhere). The body supplies enough T3 by conversion of T4 in health, so this produces only a feedback system (because the body is not a gland but a convertor) to communicate with the the endocrine system. Hope it will appear in J Theoretical Biology as we await reviewer response.
Many thanks and it sounds really exciting! I have always suspected that we have oversimplified a more fluid and dynamic system and that all the diagnostic testing is very static in nature, hence the focus on more static "storage" hormones in the treatment protocols monitoring TSH as a proxy for the status of the HPA Axis and fT4 as a proxy for the status of hormone levels. Appointments that are typically at 3-6 months intervals in between blood tests all point towards more static approach to managing a more dynamic and complex system and probably, to a large extent, accounts for the poor outcomes in more complex cases and little scope for more tailored treatments beyond the standard protocols of TSH and fT4. Looking forward to seeing the review when it's available. Muchas Gracias! Kind regards and very best wishes. Slainte!
I was also wondering if there were perhaps any additional insights or considerations of any alternative treatment protocols proposed. My concern is that there seems to be even less research available on Central Hypothyroid from either the Hypothalamus or Pituitary and the relative treatment perspectives. The implicit assumption appears to be broadly similar- replace the.missing hormone (fT4) and the body will do the rest. As we know, that's not necessarily the case for a range of conditions, particularly where fT4 is not optimally converted into fT3 and at a cellular level. I wondered if there are any additional implications for Central Hypothyroid from either perspectives in the modelling? Thanks again! I really value your work, research and insights. Much appreciated! Groetjes!
Current medical opinion seems to be that central hypothyroidism is rare compared with Autoimmune problems. Unfortunately, I don't think you can cleanly separate those with central hypo problems and those without. There is probably an overlap, with mixed central and autoimmune patients having the central part missed in diagnosis, but being able to stagger along with just an AIT diagnosis and T4 therapy. Usually docs think they have succeeded with a patient if the patient gets benefit from T4, never mind the underlying reason(s).
Fyi under NHS I never got an AIT diagnosis,only when I paid for my own private blood test (BlueHorrizon) did I know that I had high anti TPO antibody count,I'd never heard of antibody-thing until then ! I took the test result to GP whose exact words were "we could have dont that for you" .My silent reply was "....but you didn't" How could I have asked for something I didn't know existed . And why didn't NHS GP do it if I'd a history of Thy problems ( which I had with post natal hyperthyroidism).My guess is that thyroid issues are an NHS blind spot and maybe should be looked at in every case of clinical depression ,
Many thanks! I think one of the problems may also be that the sole reliance on the TSH blood test, often in the absence of any requests to test fT4 and/or fT3 will clearly miss most diagnoses of Central Hypothyroidism, where the typical combination of low/normal TSH, fT4 and fT3 - often at the lower ends of the "normal" range should suggest at the very least some further investigations. In my case, I was almost constantly told my blood tests were 'normal' or at worst 'marginal' or 'subclinical', despite having high levels of TPO Antibodies, typical of Hashimotos cases, as well as an unusual combination of low/normal TSH, fT4 and fT3. I was fortunate enough to have my first blood tests taken in the Netherlands, where there is less emphasis on TSH in blood tests alone and more consideration of the full range of hormones, severity of symptoms and patient well being. Unfortunately, I had to return to UK before my next consultations and ended up in the NHS system with it's unerring focus on the TSH and a general reluctance to test anything else without a "clear" rationale. I wish I'd known then what I know now and I'm sure I would have been a more persuasive and "informed" patient, capable of advocating for my own health and armed with the evidence to help with the friendly persuasion. We really do need to become our own advocates, to keep up to date with the latest research, as well as encouraging more research of the kind you are leading in an area of medicine and practice that seems to be lost in the scramble for "pharmaceutical" silver bullets, or golden linings, dressed up in "value for money" metrics, cost cutting and a race to the bottom of the private healthcare pyramid. I'm really looking forward to your paper and review when it's available, and please keep up your valiant work and vital research in this important area, lest we are all forgotten! Slainte!
Ref you persuading/arguing with your GP for better thyroid testing/support... god luck with that. A few reads of pists here will confirm my experience which is not to bother with GP or even consultant. You just cant get them to diverge from The Protocol. Make sure you read Toft and you will see what Imean. The Proticol and Ranges are writtenin stone as far as UK is concerned.
Many thanks, Tythrop. I've just read the Toft paper that you provided links to and I had an "Aha" moment, particularly on the issues of suppressed TSH and inadequate or "under-replacement" with Levothyroxine due to reluctance to push TSH below 0.1. This is a real problem with Central Hypothyroidism, which is so often missed due to the TSH over-reliance when it's low/normal in conjunction with low/normal fT4 and fT3, as well as suspected "conversion" problems. It's a perfect storm and explains so much of my misery over the past 15 years, when CH was such an evident call (or at least justified further investigation) to anyone with even a basic understanding of the Thyroid feedback systems, controls and interactions. How I wish that I'd known then, what I now know about the HPA and HPT axes and an apparent lack of basic medical knowledge of Thyroid and HPA disorders amongst our NHS Health Professionals, as well as some of the Endocrine "Specialists and Experts"? I'm now trawling back through all the comments on Toft's earlier paper in 2017 for any additional insights. Thanks again. Kind regards and very best wishes.
You're welcome.The next problem is how to get anyone to treat you or even to take you seriously.Toft has retired,I emailed him once and had a very nice reply but as retired he can't do anything .There are people in ,I think Bristol University (I'll check this) who do a lot of research .I want you to succeed so that I can jump on your band wagon.
It should also indicate what will happen with the thyroid destroyed completely. That is, is someone more or less likely to need combination treatment.
Just to say my thyroid was ablated with RAI in 2005 - diagnosed Graves 2003 - and finally gave up completely some 7/8 years later whereupon I became very unwell with symptoms akin to Sjogren's Syndrome though negative upon investigation.
I started reading Elaine Moore's first book and read of all my symptoms that appear to happen to some people following RAI thyroid ablation.
My thyroid had then finally given up, my feedback loop was now broken and I am definitely more improved since on a T3/T4 combo and even feeling more well when I started supplementing with NDT some 2 years ago, as it feels feels softer on my body.
So, just adding, a little bit of reality to all the theory.
This helps my peace of mind, Thankyou
It sounds brilliant but fiendishly complex! Good luck!
Thanks D,this is what I want to know. I need to understand what's going on rather than just moan and feel impotent. Ta x100.
I will put here a link to an article I saw on net (Lockdown = research time for me) which I thought made sense.
pituitary.org.uk/news/2017/...
Unfortunately, this author still sticks to the now discredited story about normalising TSH in therapy. People with TSH in the normal range, especially the higher end, are mildly hypothyroid (undertreated). Patients with TSH from about 0.2-1 are correctly treated (with T4 only) and those with TSH less than this don't necessarily need dose reduction but should be properly assessed from symptoms and presentation. If the patient is well then TSH is irrelevant.
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