Just for info if ever anyone can come across it, there is a chapter in a new book on hypo treatment. I don't think I can access it, but will see if any of my colleagues can extract the chapter.
Treatment of Hypothyroidism: A Comprehensive Guide for the Clinician
January 2019
DOI: 10.1007/978-3-319-72102-6_19
In book: The Thyroid and Its Diseases
Jacqueline Jonklaas
We all hope it has sensible and truthful information within it.
Thanks for posting.
Hoorah! One of my colleagues is getting the book and will scan the chapter for me to send on to TUK as a file to be obtained if wanted.
link.springer.com/book/10.1...
A little bit more information - about each chapter ...
This is the abstract from Dr. Jonklaas's chapter on treatment. At least she mentions that there may be problems with the way trials on combination therapy were conducted. It is unfortunate that they are so ignorant of the millions of thyroid patients that have only recovered their health with combination therapy. She does reference three studies from Diogenes et al, that is some improvement. PR
"Abstract
Hypothyroidism is currently a condition that can be treated, but not cured. The first routinely used thyroid hormone replacement was desiccated thyroid extract. Synthetic levothyroxine, which replaces thyroxine and relies on its peripheral conversion to the active hormone triiodothyronine, has since become standard. Levothyroxine is a well-tolerated therapy for hypothyroidism. There is a robust body of data concerning its benefits and a long duration of experience with its efficacy in reversing the symptoms of hypothyroidism. It is considered the standard of care for multiple reasons, including the fact that it is easy to administer, is an inexpensive medication, has good intestinal absorption, shows a favorable side effect profile, and has a long serum half-life. Although levothyroxine reverses most stigmata of hypothyroidism in the majority of individuals, some patients feel dissatisfied with “monotherapy.” This has stimulated interest in “combination therapy” with both levothyroxine and liothyronine. Trials of combination therapy have generally not shown benefit, although some patient preference for combination therapy exists. It is possible that the trials conducted thus far have not selected the appropriate outcome measures or targeted the appropriate populations. Monotherapy and combination therapy each carry their particular risks and safety concerns, chiefly nonphysiologic hormone ratios and inadvertent thyrotoxicosis. Research regarding which therapy fully reverses hypothyroidism at a tissue and cellular level is ongoing. In the future, regeneration of functional thyroid follicles from stem cells may offer hope for curing hypothyroidism."
Thanks you for the resume. Still a rather biaised opinion regarding combination therapy!!!
Thanks for the abstract. I think some medical (US mainly) opinion is beginning to shift in that it accepts that combination therapy may have a future. We can't expect after 30+ years of insisting on monotherapy being the only way, that the medical profession will suddenly put on sackcloth and ashes and mumble mea culpa. Like all professions seriously caught out in fundamental error, the way forward is to creep at snail's pace until the memories recalling that they thought otherwise have faded gently and blamelessly away. BTW the dating of the book indicates that the information and references probably stop in either early 2018 to late 2017. A lot has happened since then, and there's yet more to come.
Diogenes, these are the three studies referenced by Jonklaas, 2010, 2012 and 2015.
Hoermann R, Midgley JE. TSH Measurement and its implications for personalised clinical decision-making. J Thyroid Res. 2012;2012:438037.
Hoermann R, Eckl W, Hoermann C, Larisch R. Complex relationship between free thyroxine and TSH in the regulation of thyroid function. Eur J Endocrinol. 2010;162(6):1123–9.
Hoermann R, Midgley JE, Larisch R, Dietrich JW. Integration of peripheral and glandular regulation of triiodothyronine production by thyrotropin in untreated and thyroxine-treated subjects. Horm Metab Res. 2015;47(9):674–80.
This is interesting. Jonklaas still won't grasp the implications in our Frontiers papers.
What are the Frontiers papers, Diogenes?
frontiersin.org/journals/en...
Do a search for "Midgley" and you'll find the papers published by diogenes and his team.
Thanks
it certainly had a past! So darn proud - it is admirable in my opinion to admit one was wrong and accept things move on. Nothing is truly static in this existence
Diogenes, this is from the chapter on testing.
Abstract
"For thyroid function evaluation, thyrotropin (TSH) is the usual starting point. TSH shows an exponential response to changing peripheral thyroid hormone levels, thereby providing high clinical detection sensitivity. Thyroxine (T4) or triiodothyronine (T3) is frequently measured alongside, mostly as free hormones (FT4 and FT3), to assess disease severity or treatment response. Some diseases require additional testing to determine the cause of observed abnormalities or to clarify contradictory results of TSH and T4/T3 testing. Thyroid autoantibody testing is important in this context.
Testing for structural thyroid disease centers on tumor markers, mainly thyroglobulin (Tg), calcitonin, and carcinoembryonic antigen, all of which are primarily used for follow-up. Tg immunoassays are not infrequently compromised by anti-Tg autoantibody interferences, which can be partially overcome by mass spectrometry (MS) Tg measurements.
Thyroid function tests and thyroid tumor markers have several limitations, which include (1) inaccurate immunoassay results in a subset of patients due to interferences by binding proteins, autoantibodies, heterophile antibodies, anti-reagent antibodies, or various chemicals, (2) some degree of compromised diagnostic performance due to suboptimal assay precision and inadequate reference ranges for almost all assays, and (3) poor comparability of results obtained by different assays for the same analyte.
These problems can potentially be solved by increased use of physicochemical methods (e.g., dialysis and MS), assay harmonization, improved reference ranges, and utilization of patient-specific reference intervals."
They referenced one of your studies.
Midgley JEM, Hoermann R, Larisch R, Dietrich JW. Physiological states and functional relation between thyrotropin and free thyroxine in thyroid health and disease: in vivo and in silico data suggest a hierarchical model. J Clin Pathol. 2013;66:335–42.
I think it interesting that the only studies usually mentioned on the 'low index of individuality' are Anderson's 2002 and 2003 studies. The first on the subject was done in 1980. To my way of thinking the 'low index of individuality' is a perfect example of non-ergodicity. Is this not correct? PR
I didn't mention regenerating new thyroids with stem cells. Given the individuality of people both in how their healthy thyroid works and its interaction with the body conversion, I can't see regeneration as being other than "one size fits all" in its effect which won't work adequately. We are not objects indentical on an assembly line.
Would we need to take anti rejection medication if stem cell thyroids were ever a treatment option?
The best solution would be using our own stem cells, but I don't think it would work in someone with Hashimoto's because they would be destroyed too, just like the original ones! What we need is some kind of very specific anti-antibody treatment to stop our poor thyroid cells being destroyed!
Do the antibodies stick around even if you no longer have a working thyroid? I guess there is a template in your immune system allowing instant replication if New thyroid tissue appears. I often wonder could I get primary thyroid non Hodgkins lymphoma if mine has completely atrophied several close relatives have had it and it is very rare I do have a genetic predisposition but it is very unpredictable and not screened for. Perhaps I don’t need to have any concern now my thyroid is completely defunct...except another close relative got a different NHL.
Do the antibodies stick around even if you no longer have a working thyroid?
I've always wondered about the lifespan of antibodies, and antibodies in general. For example, I had the measles as a child, over 50 years ago. I was never vaccinated against the measles - I think the vaccination may not have existed when I was born or it may not have gone into common usage until after I'd already had the disease. Do I still have detectable antibodies against measles that could still be detected after 50+ years?
Apparently the TPO antibodies do disappear if the thyroid is removed. But since nobody seems to have a clue what makes them appear in the first place, I can't see that creating new thyroid tissue would do us much good if we had TPO antibodies at any time. And what about the people who hang on to their thyroids but they get shrunken over time? Would they benefit from having new thyroid tissue?
I am in the shrunken thyroid camp - very small indeed and shrivelled and highly unlikely to have any function (endos comments during ultrasound, 3 months after starting on levothyroxine took another 6 to get me “optimised” never felt properly well on it and he did go for a Toft style optimisation).
I got malaria (p.vivax) in Africa c36 years ago. I had many attacks there but you can have different types at once so not sure if it was the same one recurring but most likely it was - vivax means lives forever! Get this I was meticulous about taking my antimalarials now I wonder how much damage those useless things did to me over the years I took them and still got malaria anyway 🙄 When I gave blood c 8 years ago I had such high antibodies to malaria it could not be used and I was advised I would not ever be able to give blood if the antibodies were that high after such a long time. I wonder if this is a strain on the body with it on red alert for decades or if it is a necessary response to keep it at bay. I was treated at London tropical school of medicine with IV quinine i was so ill I though it was curtains but that stuff worked very fast and I was amazed towake up the next day feeling pretty human again. I felt a bit dodgy on and off for about a year after but never had a full blown attack again and I felt ok from then on. It was a surprise to discover such a high level of antibodies had persisted.
P. falciparum is apparently the commonest, and most dangerous, malaria parasite. But it sounds as if your immune system was up for the challenge - a bit too much so as your thyroid got caught in the friendly fire. (Not quite accurate perhaps, but makes a good story!)
I read a fascinating article a while ago saying that the malaria parasite is very cunning when it moves from one blood cell to another. It is safe inside a blood cell but has to go in stealth mode when it moves to another. Apparently it has a way of withdrawing the marker proteins that alert the immune system, so the white cells don't detect it
Yeah falciparum causes the red blood cells to disintegrate in the brain and is the most deadly. P. vivax tends to only kill the young and infirm but if the fevers are severe giving very high temperatures like I had it is still a dangerous condition and Europeans who have had no experience of malarious areas previously are hit much harder than those who have had life long exposure with a build up of antibodies and even then it can make those in the local population who get it very poorly. They were pretty worried about me at the hospital I was hallucinating and unable to answer basic questions like DOB , next of kin etc I certainly laid there in that bed and longed to die and get release from the agony I was in. They told me I might feel worse from the quinine and I told the doc straight that if I felt any worse than this I would be dead! I was a fantastic teaching aid for the students because my symptoms were really classic. I can remember them holding their hands some distance away from my face and expressing considerable shock at how much heat was coming off me whilst I was so out of it I thought my head was a two bar electric fire 🔥 perhaps their hands were like people warming themselves on a fire hence my very strange thoughts/hallucinations. I am pretty sure if I had not got their expert help I could not have survived that bout it really was very severe in a different league to what I had suffered before - although none were a picnic the headaches were astounding the slightest movement of the head was excruciating. There have been two other times I thought it was curtains once as a young child with pneumonia and a temperature of 105F with hideous hallucinations and after my final bout of hyperthyroidism as my thyroid gave up the ghost and I plummeted into eternal hypothyroidism. I had just started on my first 20mcg (or may be it was 25mcg a tiny amount because they were worried I’d have a heart attack) levothyroxine, but I was so cold (and I had been cold for decades but this was like a cold no words could describe a deadly type cold) I honestly thought I would freeze to death. That time I looked in the mirror and saw a skull looking back it was really terrifying. I laid there and thought I have had it, and longed for death to take away my suffering. I am sure I was very lucky to survive. I am quite convinced I looked death in the face on those three occasions. Only modern medicine saved me. Oh well I still have 6 lives left!!
WHO say death occurs at at rate of 3.1% vivax vs 11.6% falciparum in indigenous populations from hospital records, and travellers from non malarious areas have a 10% chance of dying of vivax compared to falciparum. No idea why the values are so much lower for travellers. They reckon it is actually a pretty serious condition that can be very severe and even deadly, although not as statistically deadly as falciparum it is not the harmless/benign illness it is often made out to be. Having had/having it I would totally agree. Small wonder my blood had to be binned.
I had measles 60 years or so ago! In theory you could only get it once. But if your immune system is compromised you might get it again. But my mother said she actually managed to get it 3 times!
And of course shingle is the chicken pox virus, which lurks in our nerves, kept at bay by the immune system, until we are weakened for some reason
Yes I got shingles about 10 years before being diagnosed with hypothyroidism although I had suspected i had it not long after the shingles. My mother had shingles too and later on hypothyroidism and thyroid cancer.
My mother managed to get Chicken Pox twice, instead of shingles, once as a child and once when she was 60! And Mumps twice, though that's another thing you're only supposed to be able to get once! Crazy immune system. She had hypothyroidism when she was about 12 but apparently recovered and never took any medication afterwards. I would love to know what her thyroid levels were.
Have you read this
humanbean and Hidden ?
ncbi.nlm.nih.gov/pmc/articl...
It is very fascinating.
This is what is says about immune system memory:
One of the most significant features of the immune response is its ability to retain a memory of previous infections. This both protects individuals from reinfection and limits the spread of infection in a community. Immune memory can be very long-lasting; when adults were studied, their memory for the measles infection was decaying so slowly, it would have taken over 3000 years to decrease by half. This goes well beyond life-long protection. These robust durable changes are the reason that, when we vaccinate, the protection this produces delivers long-term benefits.
3000 years?!? Wow!
I've never had an identifiable disease more than once, apart from the obvious things that everyone gets, like colds and respiratory infections. At least I'm unlikely to get measles again, even if it isn't guaranteed. 
I still wonder how my mother managed to get it 3 times!
Antibodies get faster to act with repeated exposure to the disease so perhaps this was key?
cold and flu viruses change all the time, which is why they have to develop a new vaccine every year.
Thank you. Brilliant, but very complicated (the actual immune system is even more complicated - which just goes to show...!) Hope I can get my brain around it. But not tonight
It is an involved read isn’t it?! But still fascinating and quite
mind boggling to discover the ever evolving disease prevention strategies employed. Makes you realise how dynamic it had to be and what a fine balancing act our immune systems must tread to keep it all in check yet not damage us too severely by over reacting. With autoimmune thyroiditis mine went overboard along the way!
"mind boggling to discover the ever evolving disease prevention strategies employed"
That's one reason I don't believe in Evolution! 
But that's best for private discussion.
Week have to beg to differ on evolution 😉
The complexity proves to me just the opposite. Anyone intelligent would never have made the mess that describes the working of the human organism.
Diogenes and TSH110 any "Mess" is evidence of the (mostly genetic) deterioration of what was originally perfect. Genetic bottlenecks and the effects of entropy are some of the likely destructive processes involved.
I read a fascinating article on why the "Backwardly wired" vertebrate retina is actually an extremely efficient design, capable of detecting a single photon of light. There are reasons for it having to be backwards, and the Mullerian cells (if I remember rightly) act as fibre optic channelers of light to where it needs to be.
But, as said, it's not a topic for discussion here. Though I would love to 
Not very positive about NDT - the original combination therapy - despite the millions it helped long before Levo ever got a foothold. All conveniently omitted ☹️
Weird set of dangers to list: 1) nonphysiologic hormone ratios and 2) inadvertent thyrotoxicosis.
I doubt many patients would agree 
I do rather well on non physiological hormone ratios 😂🤣😂 i say bring them on! & a whole lot better than on T4 monotherapy
And what is T4 mono therapy other than non-physiological? In health the thyroid produced both T4 and T3. That's physiological!
linda96 FYI
Thanks for posting this @Diogenes, will be interesting to see the chapter when you get it to TUK.
