First, Thyroid Hormone Resistance (THR) is often totally ignored, not even considered for a moment. Despite very obviously discordant thyroid hormone test results. It's almost always presented as being rare/very rare but with little solid evidence of its incidence in all its forms.
I've long suspected that it is likely far more prevalent, at least in its milder forms, than has ever been realised.
Second, we have some known genetic variants believed to cause THR. Then along comes this new one - which should be added to the documentation/databases. But if you had been tested with one of the tests which only look at some genetic variants, this new one might not have even been tested. Even if it had been sequenced, its relevance might have been missed.
Thyroid Hormone Resistance With a Novel Mutation.
Abstract
Syndrome of thyroid hormone resistance (THR) is a rare inherited condition characterized by a reduced responsiveness of the tissues to the thyroid hormone. The syndrome is caused primarily by mutations in the thyroid hormone receptor beta (THRB) gene, leading to impaired hormone receptor function. It is a diagnosis of exclusion and often leads to delays in establishing the diagnosis. Management is usually conservative, as over-treating can be unnecessary and potentially detrimental. Our case report aims to highlight the changes in thyroid function tests and the subtle presenting symptoms of this disease so that clinicians are more mindful of this rare condition. It brings to attention the importance of follow-up to monitor the lab values and reach an accurate diagnosis. We also report a novel mutation identified in the THRB gene.
Thanks for sharing this. Your certainly correct that cellular resistance/ impaired sensitivity/ resistance to thyroid hormone is totally ignored and dismissed.
I'm still convinced this applies to myself as my thyroid journey has never been, what you'd call typical.
My endocrinologist dismisses the above yet I am on a large single dose of T3 and still have symptoms. I just wish this was taken seriously as I believe this has something to do with my severe memory issues.
I find it best to split T3 into 6 doses. Taking T3 in one dose leads to a high peak in T3 in your body which causes D3 enzyme to kick in and deactivate it in an effort to protect you from being overmedicated.
Thsmks, I've tried many times over the years to split the dose, but it results in me feeling like I'm on no medication at all. I have no over medicated signs and still show signs and symptoms of being under medicated. My endo acknowledges this and now accepts I need to take my T3 in single dose.
These are mutations of the gene that produces thyroid hormone receptors, specifically the thyroid hormone receptor beta (THRβ) gene which creates TRβ1 and TRβ2 receptors. Since the pituitary relies mainly on the TRβ2 receptors there tends to be resistance in the pituitary as well as some peripheral tissues. It usually presents with elevated fT3, fT4 and a non-sppressed TSH. So, the biochemistry looks like an over secreting pituitary adenoma but the patient is clinically hypothyroid or euthyroid. It is correctly called 'Resistance to Thyroid Hormone' (RTH) - a committee decided on the name some years ago!
This is just another mutation that has been found. As of 2021 there were 236 known mutations pmc.ncbi.nlm.nih.gov/articl... . I haven't read this paper but as it's by Sam Refetoff, the guy who discovered RTH, it should be good.
I think there is another form of RTH caused by endocrine disrupting chemicals (EDCs) which I call 'acquired RTH' or ARTH. Potential EDCs are tested in animals, if their thyroid function test is abnormal or T4 low the chemical is immediately banned. This works very well except for a tiny minority of chemicals that affect peripheral tissues but not the pituitary (because they don't affect the TRβ2 receptors). We have selected a few chemicals that disrupt hormone action whichy cannot be detected by blood tests.
As someone with an established form of RTH I had no help from medics so had to do the research my self!
Endo flatly refused to consider I have RTH and did not think I needed T3
Wrong on both counts!
So I took control, read and learned and found a few others here in a similar situation
Like others had discovered I need high dose T3-only to function but medics fear that, because they don't understand even the basic facts and assume such a dose will cause hyperthyroidism....at it's worst
To be effective T3 must reach the nuclei of the cells, attach to the various T3 receptors there, it then becomes active and can fulfil it's function.
It will only cause a hyperthyroid state if the dose is too large and too much T3 enters the cells!
I discovered this when my dose reached 212.5 mcg T3, As some of the dormant receptors "woke up" I was slowly able to reduce my dose....which is still supraphysiological!
T3 remains inactive until it reaches the cell's nuclei but for those of us with RTH ( genetic or acquired) a resistance exists which prevents this.
To overcome this resistance we need a supraphysiological dose of T3 to act like a "battering ram" against the cell walls. That force then allows some of the dose to enter the cells. The greater the resistance the higher the dose of T3 is required
Not a scientific explanation but an explanation none the less.
When I started to self medicate my then GP told me I would kill myself! Instead, I got my life back....albeit late in life and then in my early 70s. And, with damage from a lifetime of low cellular T3 to cope with....but still better.
Our late friend diogenes once explained this to me.
Considering their medical histories and deaths I now suspect both my parents and both grandmothers had a similar problem...but there is no way now of proving that!
WIth RTH we have to monitor the dose by symptoms alone because there is no other way to test the cellular level of T3....except post mortem!
The geneticist I saw suggested that the cause (for me) was likely to be an as yet undiscovered genetic variant
Might this new variant help provide a clue.
I absolutely agree when you say "I've long suspected that it is likely far more prevalent, at least in its milder forms, than has ever been realised."
T3 is the key factor and until that is recognised many people will suffer for years ( possibly for decades or a lifetime, as I did).
Symptoms work hand in hand with T3 and must be factored in
Medics are barking up the wrong tree and missing the correct clues to help diagnose and treat various forms of hypothyroidism.
Sidelining TSH after medication would be a start!
I had to work by a process of elimination and by trial and error from a point of little knowledge....that should not now be the case!
Without a large dose of T3 I may no longer be here.
My GP once asked me what I would do if I had to be in care/ hospital without T3. She had no words when I said, " I will just slowly die'.
She now leaves me to self medicate, and for information, has put a note on my repeat meds list which says, "Medication from other sources" and states my dose of T3
Medics must understand that adequte T3 for the individual's needs is that important!
We need better informed medics/ endos who are prepared to think outwith the established, but wrong, box!
Apologies for the long rant....it's something I feel very strongly about!
Keep fighting for change....someday the light must surely dawn.
I was listening to a podcast by vet Prof Noel Fitzpatrick who claims there should be closer co-operation/ cross over between human and animal medicine. It makes sense to me
I've often said, I'd be better off seeing the vet"!
One of my late friends was a Prof at the RVC....I would have trusted him before many of today's medics!
But the acronym EDC often means something else in USA language - every day carry - as in the gun, knife or flash-light that you choose as your default to take with you. Which rather assumes you have multiples of each of these and says a lot about the context in which it is found.
my tiny midget dog needs twice the amount about of thyroid hormones a day that I do I’ve no idea why canines have such a high requirent. I had to push to get her treated. But only a year not the decades it took to get a GP to test me so my vets would be head and shoulders above the doctors. I’ve wondered about giving her NDT but she likes her dog thyroxine very much I get prompted with the paws if I forget to give her her dose on time. She’s massively better on it.
I've posted this before but it keeps seeming to be relevant!
To the Editor:
A 33-year-old veterinarian with Hashimoto's thyroiditis and hypothyroidism, stable with a levothyroxine replacement dosage (thyroid-stimulating hormone, 0.9; normal, 0.4-5.0 mIU/L) of levothyroxine 50 μg/d, presented with mild anxiety, jitteriness, and insomnia. Repeat thyroid-stimulating hormone was undetectable. Serum total T4 was 15.4 μg/dL (normal, 6.0-10.0 μg/dL), and free thyroxine index was 14.9 (normal, 6-10). On further questioning, the patient realized she had recently run out of her prescribed levothyroxine tablets and had been taking levothyroxine “dog tabs” 0.5 mg/d, thinking that would be the same as the 50-μg tablets she had been prescribed, inadvertently taking 10 times the prescribed dose. Her levothyroxine therapy was discontinued, and repeat thyroid function studies 2 months later revealed a thyroid-stimulating hormone level of 5.1 mIU/L. The patient was restarted on levothyroxine 50 μg/d, and repeat thyroid-stimulating hormone level 2 months later was 1.0 mIU/L. The patient was instructed to take her prescribed levothyroxine tablets and not use her levothyroxine “dog tabs” in the future.
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Thyroid Hormone Resistance
