"If, for example, your thyroid has been under-producing for a long time, the receptors on the outside of those cells may for various reasons alter their function with the result that insufficient amounts of hormone manage to get inside where they are needed. The unused hormones will accumulate in the bloodstream where the levels will eventually return to within the reference range but since those in your cells will be low, the blood test results will not line up with the clinical picture. "
Can anyone explain what is meant by this quote on the Thyroid UK site - what non-genetic factors cause receptors to stop functioning? I'm assuming from the way it's phrased the meaning of this is organic causes within hypothyroidism itself, rather than environmental toxins affecting receptors. But what within the disease itself affects receptors, and do you have any literature on this please?
also if you have any medical literature on endocrine disrupting chemicals affecting thyroid receptors specifically that would also be helpful.
and... has anyone else been in this position where their hormone levels began low, and over time (untreated) they crept higher in range while you were severely sick on a cellular level. I've conversed with members who've had cellular hypothyroidism here with normal/high normal bloods but I'm interested to know if you were tested first with out of range hormones.
Written by
perardua
To view profiles and participate in discussions please or .
Don't know what it is about. Thyroid hormone receptors are in the cell nucleus. T3 and T4 are actively transported to the cell nucleus by intracellular transporters, not via receptors. If there was a problem getting thyroid hormone to the cell nucleus this would result in a very high TSH as thyroid hormone would not get to the receptors in the pituitary.
Give a link to the article on the Thyroid UK website.
further down it states sufficient cortisol is needed to 'open' the receptors(?)
would you by any chance have an insight on what might be going on with a patient like me who started with a normal TSH and low free hormones, and then (untreated) the blood levels began to raise into the range (TSH still the same) while being severely hypo? is that not an instance of less being transported out of the serum and into the cells? what are your thoughts on the below?
Hey DippyDame, always love talking to you here as we've spoken a few times. Yes I do know how low that FT3 is, but I'm still in a very complicated situation with endocrinologist and I can't self treat. Do you have any corroborating medical literature on % of RR for thyroid health (for endo not me)? I remember finding some studies on Thyroid Patients Canada a while back so I'll try and dig them out.
T3's biological activity is initiated by binding to its nuclear receptor within target cells. There are two major receptor types, alpha and beta in differing proportions around the body, and research evidences genetic mutations to have been found on the beta receptor that impairs how thyroid hormones can react with that cell.
However, more common reasons for cellular hypothyroidism on the forum is when the receptors become ineffective from insufficient use due to reasons such as nutrient deficiencies (particularly Vit A and iron) to elevated/insufficient cortisol that is unable to raise enough glucose to meet the mitochondrial demands in producing ATP, or the way the deiodinases (enzymes) are working which may activate or deactivate thyroid hormone.
Thyroid hormones transport proteins called thyroid binding globulin (TBG) and others carry T4 and T3 to the tissues to be cleaved becoming ‘free’. Different deiodinases (D1, D2, D3) serve different body parts and their activity, determined by differing physiologic conditions and TBG that together predict thyroid hormone tissue levels.
These mechanisms are further mediated by the amount of available hormone and other hormones levels such as oestrogen that influences the amount of TBG. This is why it is important to have a balance as all hormones work together and as a rule an excess of one will cause a deficiency in another somewhere down the line, and vice versa.
If hormones aren’t working correctly or we accumulate excess inflammation or stress, D3 may convert an excess of thyroid hormone into inactive forms that risks impairing further good conversion. Therefore, lab serum levels may not match that of what is going on within the cell that may have become cellular hypothyroid.
thank you very much for this very informative reply. I knew that lab values do not necessarily equate to cellular levels for various reasons but I’m trying to find the details to show to an endocrinologist in a very complex situation. Would you by chance have any literature on the topics mentioned in your second paragraph? Since literature is all they’d consider
hi thanks, i'll have a look at Dr. Myhill's site. Yes I've seen the Restorative medicine article and was of the view it was the saving grace until jimh111 debunked quite a bit of it on another user's post - ie we all agree on the sentiments expressed but the science and referencing is apparently not up to scratch and having over 100 refs is apparently a red flag
Thanks for the link to the Thyroid UK article, it now makes sense. As radd notes when we talk about thyroid receptors we usually think of thyroid hormone nuclear receptors, there are three in humans TRα1, TRβ1 and TRβ2 (only in pituitary / hypothalamus in adults). T3 binds to these hormones along with 'cofactors' and this causes DNA expression which releases mRNA which creates proteins to do things. This is called 'genomic action' and is the main way thyroid hormones work.
Thyroid hormones also have 'non-genomic' actions, they can act in other ways including binding to receptors on the cell membrane. These are the receptors Peter Warmingham is referring to. I don't know about these receptors down-regulating during hypothyroidism, I would expect the opposite effect. These receptors work in very complex ways with cellular transport proteins (MCT8, OATP1C1 and others) to convey T3 and T4 from the cell membrane to the nucleus. This is an incredibly complex process which I don't understand. You can get a feel for it from this diagram researchgate.net/figure/Non... .
The essential point is correct, blood levels of T3 and T4 do not reflect cellular (nuclear) levels of hormone (or activity). Local T3 levels are regulated by deiodinase enzymes that convert T4 to (T4 and reverse T3) and T3 to T2. When all is well and in simple primary hypothyrodism blood TSH, fT3 and fT4 give a good reflection of thyroid status. However, in serious trauma local T3 levels can fall even when blood levels are normal. Tissue T3 levels (or activity) can fall for a number of reasons, not all of which are understood.
The moral is that blood TSH, fT3, fT4 don't always reflect thyroid hormone activity. The blood tests are very useful but don't always show what is going on. You can be hypothyroid with normal blood tests.
Thank you very much @jimh111 for responding to the Thyroid UK article. I am too far along in severe brain fog to grasp the complex concepts fully, but I wanted to know if that quote was useful to bring forward or whether endocrinologist would also make no sense of it, so you've answered that for me.
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.
Do high levels of T3 have to potential to shut down T3 receptors?
thyroid / vitamin results 
Iron and Thyroid Hormone Replacement
Thyroid levels and heart failure
Peripheral Thyroid Hormone Conversion and Its Impact on TSH and Metabolic Activity: 
