It's clear that the cells in our bodies have different local requirements for T4 to convert to T3. This paper looks at indirect possible markers from cells to discover if any have diagnostic possibilities aside from direct TSH, FT4 and FT3 measurements. If so, then specific organs could display their responses.
Biomarkers indicating tissue thyroid hormone status: ready to be implemented yet?in Journal of Endocrinology
Authors: Heleen I Jansen1,2, Eveline Bruinstroop3, Annemieke C Heijboer1,2, and Anita Boelen1
I have started reading and am delighted by what I have seen so far.
There are, surely, many benefits to come from a deeper understanding of how thyroid hormones actually have their effects.
Some of the eventual outcome of this sort of analysis (metabolomics and proteomics) might eventually provide a way of assessing thyroid hormone status without relying on TT4/FT4/TT3/FT3 and TSH.
Without the clarity of though that people such as the authors and you - diogenes, it has long appeared to me that use of markers than actual hormones might be a route to more frequent, even more of less continuous assessment of thyroid hormone status. Even if thyroid hormone measurements are also needed.
Thanks for highlighting this paper. This is really very interesting! I see that one of the bio markers is ferritin. My ferritin was bouncing along the bottom of the range for years before I was officially diagnosed with hypothyroidism. Might be a reason why! Now looking through my medical records for other bio markers!
Hi suztango , that would also account for why my Ferritin shot up once I was on the correct thyroid medication for me. Not a bigger increase in dosage, but a different type - NDT.
Let's hope this starts to raise the profile of cellular hypothyroidism.
I've had to exercise trial and error, self medication and much reading to work out that this could only be the answer to a lifetime of numerous illnesses which became more debilitating as I grew older!
I'm not alone in this!
I wish I'd known 50 years ago what I now know.....
but, no internet or TUK back then!
Given that I tolerate 100mcg T3 ( + occasionally) with no symptoms of overmedication I then concluded that RTH must be causing cellular hypothyroidism
This high dose has eased or resolved many symptoms.
Medics have viewed my approach with scepticism ....and horror!
I've tried to explain my reasoning and they now leave me to it....a bit less convinced that I'm killing myself!
But, I'm now aged76 and still here to tell the tale!
A bit broken by this insidious disease, but not defeated!
I'm no expert but reading many posts on the forum I suspect this problem may be less rare than thought.
How are these people currently treated?
not with the best understanding....or any understanding
I might be accused of constantly ranting about the possibility of low cellular T3, so it is reassuring to read ( or now be in the process of close reading) this review.
Fingers crossed that the future is brighter for those who suffer this problem, than the past has been for many of us.
But...will the medical profession listen to the scientists!!
This is interesting - i cant say i understand all the details. Very broadly this does give me hope for future profiling and then individual treatments. I have the DIO2 gene and non responsive coeliac disease maybe there is some overlap between the conditions - it mentions gut/thyroid axis and i do have fatty liver (despite being very slim and also an active runner & cyclist) i take folic acid as I’m often deficient and i have osteopenia. Thank you too all those involved it does sound incredibly complex - and teasing out all the various strands of this must be painstaking work.
Thank you diogenes, that was really interesting. I read it from beginning to end, and have forgotten most of it already, but did I note that quite a few of the discussed bio-markers that were excluded, were excluded because they remain outside 'normal' for thyroid patients even after being considered adequately medicated?
Many of us have experienced (or are experiencing) the typical chronic symptoms of hypothyroidism .. elevated creatinine & other liver function changes, high cholesterol, osteoporosis, cardiac issues, pre-diabetic state, low GFR and/or protein in urine, slow gut motility, low gastric acid and/or other gut issues, etc, etc , .. all incredibly reversed (or to some degree or another) with adequate and effectively working thyroid hormone replacement meds. Perhaps the authors should confer with the forum 😁.
I also think most of the forum has been to that awful soul destroying ‘cellular hypothyroidism’ place where perfect thyroid hormone levels (not dictator-doctors ranges, but our own real forum levels) still don’t alleviate hypo symptoms.
I liked the reference to …. ‘The MCT8 mutation causes the inability to transport T3 and T4 into cells that express MCT8. Cells that do not express MCT8 but a compensating transporter are subject to high T3 and, therefore, hyperthyroid, likewise cells that express MCT8 without compensating transporter are hypothyroid (Friesema et al. 2010).’
and '‘Mutations in the THRA and THRB genes cause distinct genetic diseases called RTHα and RTHβ. RTHα causes hypothyroidism in TRα-dominant tissues (intestine, bone, heart and brain), whereas serum TH concentrations are relatively normal.’
I’ve often wondered why we don’t hear more about genetic testing beyond that of the D1 & D2 deoidinases. THRA and THRB gene impairments were being discussed at least since 2011 and probably earlier and there is so much research since.
Anyhow, a wonderful paper in that these associated issues are at least being recognised, but someone please enlighten me (in laymen’s language) if there really is anything new here.
The thing that worries me most about all this interesting research is the apparent lack of curiosity in the actual medics who are treating us. Lots of valuable information with no facilitation to the patient. I understand that they can’t read everything but why are protocols being set up (eg annual health checks for those with heart problems) if they over-ride the experience and curiosity of the genuinely interested doctor and patient. They were probably set up for ease of administration and with good reason to attempt to ensure ‘good practice’. I am pretty sure where hypothyroidism is concerned ‘protocols’ do not necessarily work in our favour.
I can only assume that the medical students who were naturally of a curious/ intelligent/ questioning nature , sidestepped their GP/Endocrinology career path early on, and went off to do something where they weren't going to be spoon fed a lifetime of "computer says~ blood tests indicate patient is well now " (patient on floor)
More or less says there are no reliable markers except in unusual circumstances such as RTH.
They are rather obsessed with blood letting. Two easy and specific markers spring to mind.
Ankle reflex time is highly specific to hypothyrodism and can be accurately measured. I was so hypo. I didn't have an ankle reflex but most patients do.
The other marker requires a brain wave - literally. Sleep is shallower and interupted in hypothyroidism. They could use an EEG and sleep monitoring to measure the brain's response to liothyronine and establish the dose required to achieve brain euthyroidism.
Looking further it should be possible to find some way of measuring the effects of hypothyroidism on skin, hopefully by a non-invasive technique.
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... metabolite , metabolic, metabolomics..... 
New dose of thyroxine
New blood results show very small improvement in T3 and free Thyroxine
Active T3 test and 24 hour urine test.
perplexed- new results -‘ T3 - 4.4
Is T3 from conversion within the cell shown in fT3 blood result?
