Thyroid hormone receptor resistance

[Tanyaking]

Has anyone suffered or have knowledge of this? What causes it and how is it treated? Many thanks in advance for any help.

X

[jimh111]

There are rare genetic forms. One affects the TRAlpha1 receptor of which there are about 14 cases worldwide that is associated with severe disability. The other form affects the TRBeta1 receptor and usuall presents with high fT4 and a non-suppressed TSH. I think there are a little over 1,000 cases worldwide.

The 'correct' term is 'resistance to thyroid hormone' and it can cover other causes as well as mutations of the receptors. These conditions occur from birth and so wouldn't explain onset of hypothroidism during later life.

[Tanyaking in reply to jimh111]

Do you know how it is diagnosed and then treated jimh111?

[jimh111 in reply to Tanyaking]

The genetic form of TRBeta1 RTH is diagnosed when a patient has a high fT4 and non-suppressed TSH with no hyperthyroid symptoms. A blood test can be done to confirm a genetic mutation, but not all patients have a mutation. Treatment is with levothyroxine if the patient has hypothyroid symptoms or a goitre. Otherwise if the patient is clinically euthyroid treatment is to leave them alone (rather than mis-diagnosing as hyperthyroid based on blood tests).

[shaws Administrator]

I cannot answer myself but this is from an archived site as Dr Lowe has died but there are other topics at the top of the page. Links within these topics may not work as all are archived.

web.archive.org/web/2010112...

[PR4NOW]

If you want to dig deeper into the subject I would suggest,

thyroidmanager.org/

The column on the right lists topics related to your question. Although the first paper was written in 1967 by Dr. Refetoff, I suspect there is much yet to be discovered. PR

[jimh111]

My earlier response was a bit literal and brief, apologies. In the thyroidmanager website you can look at the Impaired Sensitivity to Thyroid Hormone section, this is very heavy going though.

More generally speaking there are a number of disorders where there is resistance to thyroid hormone. Most of these are detected by blood tests of one sort or another. They are generally very rare and very serious. Clearly there are lots of patients with very obvious signs and symptoms of thyroid hormone underactivity and perhaps normal thyroid hormone levels. This suggests there is resistance to the hormone in the peripheral tissues but not in the pituitary (which controls TSH, fT3 and fT4 levels). Many endocrinologists will say that this can't be so. However, the patients exist and they respond to thyroid hormone, thus it is the endocrinologists' theory which is wrong. In fact the pituitary responds to thyroid hormone differently to other tissues, in terms of receptors, deiodinase and other mechanisms. Thus it is quite reasonable that the peripheral tissues may not be responding correctly whilst the pituitary is.

I hope this helps, I've kept it a little vague as it's a very complicated subject and I don't want to get into really technical issues as it would confuse and take too much time. Dr John Lowe wrote a lot of good stuff on these basic issues.

Jim.

[helvella Administrator Thyroid UK in reply to jimh111]

There is also the suggestion of specific pituitary resistance to thyroid hormone, as here:

Endocrine. 2011 Dec;40(3):366-71. doi: 10.1007/s12020-011-9538-2. Epub 2011 Sep 29.

Pituitary resistance to thyroid hormones: pathophysiology and therapeutic options.

ncbi.nlm.nih.gov/pubmed/219...

Just to make an already complicated area even more complicated.

That can cause excess thyroid hormone as the pituitary carries on making TSH when there is already adequate thyroid hormone.

My point really being - I agree wholeheartedly that the pituitary operates differently and, therefore, there can be a mismatch between what the pituitary "sees" and does and what the rest of the body needs.

[SAMBS in reply to helvella]

Oh dear Helvella and Jim, this makes my own research very much more complicated given my TB infected gland removal when I was a baby and fact my dad had TB, almost same time if not before or after, though I have pictures of me in my school uniform aged 5, standing beside him with my grandfather at a TB Sanitorium in Kent in 1953! I also know my parents separated when I was 18 months old, and then again again at 3yrs old and it was my paternal grandparents who took me the 2nd time. The only family I knew growing up was my dads family.

Where was I between 18months and 3yrs old? I don't know and there is no one to ask. I was born in Taplow, Buckinghamshire in England, where my mothers family had lived.

All my father's family lived in Scotland - being Scottish - but he was in a Sanitorium in Kent! (Perhaps he was demobbed from the Airforce after ww2 at Manston in Kent, having been stationed in Africa & Egypt in the war ).

Still in Kent - My first childhood memory was of being in a gypsy type caravan with both my mum and dad one day. She used to picks Hops!

We had a paraffin stove heater in the caravan - the smell of paraffin burning still evokes memories of the day I was forced to eat mince in that caravan, I hated it then - as did my younger son when he was a child and also refused to eat it, when I was eating it quite happily by then in my 20's. Bizarre!

So much could be genetic inheritance or not! Jim my younger son is married with no children. My oldest, collapsed at Uni aged about 19/20, with what they called a viral infection. They tested his blood in Bradford Hospital, looking for the cause, even HIV. I was told they couldn't find the cause but did treat him with a variety of anti-biotics till they found the right one.when we saw him there, he wasn't in isolation, but did have an oxygen tent round top half of his bed! Which also reminds me, my dad and I both had a collapsed lung at same age of 29. My dad married at age 27, when my mum was pregnant with me! my baby history came from my paternal grandmother and memory jogging from me with the paraffin, and photos I still have. However dad told me about his collapsed lung just after I'd had mine!

My eldest son and his wife had two healthy boys in quickish succession, her third pregnancy a girl, died in the womb at 6 months gestation, if they know the cause they haven't said, but I thought preeclampsia was mentioned! She fell pregnant again within 3 months and gave birth to a another but healthy baby girl, which I put down to the mothers immune hormones normally passed through feast feeding to a baby, going instead to the newly conceived foetus.

So, as you see Jim, know my biology! Yes it is also assumption and conjecture when the only provable facts I have. with me is a scar on my neck under jawbone, and family health history. My father had a recurrence of TB in the 90's, it was mentioned on his death cert., his actual cause was given as Hematemisis and stress related ulcers which burst in his stomach or oesophagus causing his death.

I do know he suffered from ulcers a lot in his older life before and after retirement. He was always taking something bought OTC or prescribed for them! This may account for my dislike of taking so many prescribed meds and only occasional supplements in my later adulthood, till I even stopped them. I was never a sickly as such child, but yes have have had what could now be called underlying infections with my bone shape irregularities in my foot and I in my wrist, plus my health over the last 3 years starting with the blood test diagnosis, aneurysm and brain haemorrhage! If you have any thoughts Jim on the above, I'd be interested to read them!

[SAMBS in reply to helvella]

I think I looked at that before Helvella, it was too much information for my brain to process unfortunately. Perhaps now I'm on month 2 of my Arko supplement, I'll be able to take it some of it in better!

[Tanyaking]

Bless you...is it treatable? Is there hope? ...I'll pm you my email now.x

[StarFlower2 in reply to Tanyaking]

Tanyaking...I have ISTH (impaired sensitivity to thyroid hormone) it seems to be rare. I'm interested in hearing from others who are suffering from this to compare symptoms and possible treatment 

[Tanyaking in reply to StarFlower2]

Can I ask how you was diagnosed with this Lynn,and how you've treated it's? X

[StarFlower2]

Thank you helvella.  Yes, I downloaded the Ebook last week and found it very informative. I'm currently struggling to find the right dosage of t3. I'm up to 100mcg daily and still suffering with hypo symtoms.