TSH-receptor autoantibodies in patients with chronic thyroiditis and hypothyroidism

[helvella]

So you thought you have just about understood antibodies in hypothyroidism?

Sorry, but back into class again.

Don't worry if you don't understand. The authors of the paper have simply reported their observations and made a suggestion that these antibodies might be relevant. It clearly requires more research to get to the meaning.

Open Access Published online by De Gruyter May 5, 2022

TSH-receptor autoantibodies in patients with chronic thyroiditis and hypothyroidism

Mariella Giannone, Miriam Dalla Costa, Chiara Sabbadin, Silvia Garelli, Monica Salvà, Stefano Masiero, Mario Plebani

, Diego Faggian, Nicoletta Gallo, Fabio Presotto, Loris Bertazza, Davide Nacamulli, Simona Censi, Caterina Mianand Corrado Betterle

From the journal Clinical Chemistry and Laboratory Medicine (CCLM)

doi.org/10.1515/cclm-2022-0162

Abstract

Objectives

The reported prevalence of TSH-receptor (TSHR) autoantibodies (TRAb) in patients with chronic thyroiditis (CT) range from 0 to 48%. The objective was to study the prevalence of TRAb in patients with CT and hypothyroidism and to correlate it with gender, age, thyroid dimensions, TSH levels, and autoimmune diseases.

Methods

The study comprised 245 patients with CT and hypothyroidism (median age 42 years, 193 females, 52 males) and 123 Italian healthy subjects matched for sex and age as controls. TRAb were tested with ELISA using a >2.5 IU/L cut off for positivity. TSHR blocking (TBAb) and TSHR stimulating autoantibodies (TSAb) were measured in 12 TRAb-positive patients using bioassays with Chinese hamster ovary (CHO) cells expressing wild-type or R255D-mutated TSHR.

Results

TRAb positivity was found in 32/245 (13.1%) patients and significantly correlated (p<0.05) with TSH levels. TRAb positivity was significantly higher in males vs. females (p=0.034), in females 16–45 years of age vs. >45 years of age (p<0.05) and in patients with reduced vs. normal/increased thyroid dimensions (p<0.05). Linear regression analysis showed a correlation between TRAb concentrations with age (p<0.05) and TRAb concentrations with TSH (p<0.01). In bioassay with TSHR-R255D all 12 patients tested were TBAb-positive while 33% were also TSAb-positive suggesting the presence of a mixture of TRAbs with different biological activities in some patients.

Conclusions

TRAb have been found in patients with CT and hypothyroidism. A mixture of TBAb and TSAb was found in some patients and this may contribute to the pathogenesis of thyroid dysfunction during the course of the disease.

Keywords: autoimmune thyroid diseases; chronic thyroiditis; hypothyroidism; TSH-receptor autoantibodies; TSH-receptor blocking antibodies; TSH-receptor stimulating antibodies

Open Access to full paper here:

degruyter.com/document/doi/...

[tattybogle]

Ooh . goody it's about time somebody got more interested in this , especially the 'blocking' ones.

12 out of 12 of the study subjects tested had blocking ones ... strongly suggests (TBAb) should be checked more often, but testing for them in isolation is obviously tricky ....seems you might need some Chinese hamsters to help.

"TSHR blocking (TBAb) and TSHR stimulating autoantibodies (TSAb) were measured in 12 TRAb-positive patients using bioassays with Chinese hamster ovary (CHO) cells expressing wild-type or R255D-mutated TSHR..... In bioassay with TSHR-R255D all 12 patients tested were TBAb-positive...... while 33% were also TSAb-positive , suggesting the presence of a mixture of TRAbs with different biological activities in some patients."

I'm off to read it properly . Thanks for posting it helvella

Interesting how TRab are more common in males .... curiouser and curiouser

[radd]

helvella,

Is this paper for real? 🤣

‘Consequently, TRAb testing may be a useful diagnostic tool in TPOAb/TgAb negative patients with hypothyroidism and normal echogenic pattern to exclude rare causes of hypothyroidism such as TSH-R gene mutations.’ That may be so but it’s blatantly not going to happen imminently when auto-antibodies are deemed seemingly so irrelevant by our dear medical establishment.

When we read credible articles we are told having multiple groups of antibodies is common but for many of us Hashi peeps, TRAb’s only become a realisation once our gland has been atrophied.

A mixture of both TBAb and TSAb can cancel each other out resulting in normalised TFT’s and so no outward evidence of the inner autoimmune turmoil. Our poor bodys☹️. If they have all these new super-duper assays, why don’t they use them!

[helvella in reply to radd]

Many times I have read that Hashimoto's flares are due to the destruction of the thyroid gland - and individual follicles rupturing. That releases excess thyroid hormone.

While there might well be some truth in that as a process that can occur, it just doesn't seem likely to explain flares. (Very simplistically, the total thyroid hormone that could be release - possibly over years - would be just the quantity that can be stored in a thyroid. I don't think that can account for flares happening over many years.)

The possibility of various TSH-receptor antibodies having a war seems very likely a better explanation. Of course, both could be happening at once - and continually varying.

[radd in reply to helvella]

helvella,

I have thought the same when thyroid hormone levels have gone sky high. Where can it all have come from? However, I feel the felt effects of the amount released from ruptured follicles must be tripled or quadrupled by some up-regulated enzymes or mechanisms as well as perhaps rushes from TSI's.

My gland has gone and I don't suffer the attacks of days gone by but am still horrified that such an internal war continues in others whilst doctors offer anti-depressants for unusual mental and physical symptoms.

I can't remember, are you a Hashi peeps too hel?

[helvella in reply to radd]

No - I am unexplained. ⁉️

[radd in reply to helvella]

😳 .

😊

[radd in reply to helvella]

Just realised you must be interested in TSHR gene mutations then?

Genes behaviour can changes are we get older so perhaps some sort of congenital hypothyroidism with delayed onset. Have you ever had TRAb's tested or your gland scanned?

[helvella in reply to radd]

I did get an ultrasound scan - nothing significant noted.

As I titrated my dose of levothyroxine, various symptoms resolved. And I did so over a long period of time - and included the 2012 "old" Teva issue which delayed things further.

Even my GP was amazed at the differences he could see as well as things like cholesterol looking like that of a young athlete!

I felt that I was lucky to have found out and started treatment. Cause didn't seem to be very important.

I suspect that antibodies are an unlikely cause as I am pretty stable over years.

Also, at the time, I was even more ignorant than now.

[tattybogle in reply to radd]

. If they have all these new super-duper assays, why don’t they use them!

TRab tests seem easy enough to do ( as do TSI tests) so i think it's a real shame they don't test TRab more often at initial hypothyroid diagnosis... just think how much interesting data they would now have if they'd done all of 'us' .....and how this record might help explain some people's fluctuating / inexplicable results.

Mind you if they did, they might have to stop blaming anything interesting on "patient might not be taking their tablets regularly" .. and that is soooo much easier than actually thinking about it .

But the testing to differentiate blocking /stimulating TRab function seems to still be a bit of a problem .... on seeing what they had to do here to find out TBAb... looks like it's still a bit of a head f*** .... i got lost , but did they need two tests and then compare them to work out the difference ? ..... not quite sure where the chinese hamster ovaries come into it , but they are in there somewhere too....... and they only did it for 12 subjects ... perhaps it's a bit pricey? .

If it was affordable / simple i would have expected them to have done more than 12 people.

I will have to read it again another day and try a bit harder to get my head round how exactly you go about isolating and counting "a TBAb" .... i do find the actions of TBAb /TSAb fascinating .... i only wish more endocrinologists did .

helvella , i have also thought that the often used explanation of "Hashimoto's chucking the thyroids contents out during an autoimmune attack" can't account for all the fluctuations we see, especially ones that last for months .... because how long could that 'dump' really last for ?

I had fT4 going over range to a pretty nuts level (200% 240% 180% ) all by itself over a period of at least 9 months (more likely a year and a half in reality but not tested properly) and i find it hard to believe my thyroid was being attacked and consistently 'dumping' T4 for that long ....it seems way more likely to me that some TSAb were playing about with it.

.... of course my GP thought i had increased my dose instead of reducing as requested, so he doesn't have to be curious and actually think about it ,cos he can just write "?compliance " and think he's solved the puzzle, and move on.

I never realised you were 'unexplained '.....

[radd in reply to tattybogle]

tats,

Yes, I wondered why only 12, and I thought it interesting TRAB’s were more prevalent in males. Everyone should be routinely checked for all thyroid antibodies for any thyroid related issues except cancer.

Chinese hamster ovaries bought ‘normal’ (wild-type) and genetic impairment to the assays. They’ve been using CHO for years but I’m not very knowledgeable on the workings of assays. They use lots of animal stuff and human too.

I liked the bit about ‘patients with CT and hypothyroidism and 123 Italian healthy subjects matched for sex and age …. .’ A bit presumptuous 🤣🤣🤣 …. Like a dating agency!

[tattybogle in reply to radd]

i'd quite like to be part of a study where they tested my TBab /TSab / TPOab /TGab / did an ultrasound/ and then matched me with a healthy attractive Italian male.... why do i never get invited to these dating parties ?

[radd in reply to tattybogle]

🤣

[tattybogle]

just linking this member Bhattinsami to this post as it seems she was previously hypothyroid on Levo (has some TRab antibodies (TBII positive) and TPOab )... then stopped levo.... and now taking low dose carbimazole . radd

PurpleNails

( Ex111 i thought this post might interest you too, as you have also switched from Hypo/Levo to Hyper /carbimazole )

[PurpleNails Administrator in reply to tattybogle]

I’ve come to the conclusion antibodies MAY help with diagnosis but might not conclusively. It’s likely why lots of doctors don’t “bother” and go by TSH (and hopefully FT4 & FT3).

Doctors were quite keen to test me for antibodies- why? Perhaps to confirm my hyper wasn’t autoimmune and suggest immediate RAI as (nodules don’t remit).

[tattybogle in reply to PurpleNails]

i suppose , at the end of the day , they have to just interpret what is actually happening to T4 /T3 levels at each point in time and deal with that phase the best they can.

Presumably a big part of the 'diagnosis ' has to be about observing any swings in function over several years... and whether they know there are some sort of TRab at play , or not .

and if not, then they are looking for a hot nodule etc .

[SmallBlueThing]

A few years ago my GP told me she couldn't order a TSH-receptor autoantibodies test, in relation to my eye problems; yet I've never been offered a referral to an endocrinologist.

I'm currently in a flare, since COVID-19 in February last year. The vacutainer shortage meant no thyroid test until this February, when I requested one because tachycardia was more noticeable. Trainee GP for appointment, who may have put my double vision down to thyrotoxicosis, yet I've had it since 2019 when my TSH was 1.2 miu/L.

[radd in reply to SmallBlueThing]

SmallBlueThing,

Thats terrible. Poor you. Do you think you have TED? Are they dry, itchy, gritty, swollen? You could get an appointment with an ophthalmologist who specialises in TED.

What were TFT results from feb?

[SmallBlueThing in reply to radd]

My eyes aren't noticeably swollen, but have been causing me problems for about 12 years now, including a period where I couldn't rotate them upwards, when tired. One optician suggested posterior blepharitis, for which I use a USB-powered heated mask and drops. I'm wondering if blocked tear ducts contribute to my nasal cavities drying out, worsening my sleep apnoea. The double vision gives me a second image displaced higher and at an angle, robbing me of confidence when crossing the road.

February results were free T4 24 pmol/L [9.0 - 25.0] and TSH <0.05.

As my tachycardia was usually most apparent at about 9pm, I did a mail order test at that time, which came as a bit of a shock with:

TSH <0.01 mu/L [0.27 - 4.2]

FT4 29.2 pmol/L [12 - 22]

FT3 7.4 pmol/L [3.1 - 6.8]

No tachycardia when I had an ECG, and I've subsequently dropped 25 mcg levothyroxine to 100 mcg + 1 grain Thiroyd, which I now take at midnight rather than on waking. I was still experiencing savage temperature drops at the time of my out of range test results.

[helvella in reply to SmallBlueThing]

I did have a couple of periods of double-vision. Oddly, it was only on one side. I coudl stop it by simply putting my hand in front fo the right eye.

It is concerning and disconcerting.

The first time, I went out of the back door and looked up to see a flock of red kites whirling round. But somehow, there were twice as many in my right eye than my left.

[SmallBlueThing in reply to helvella]

My neighbour worried that our red kites might swoop down and take her terrier

[radd in reply to SmallBlueThing]

SmallBlueThing,

Yes, you looked over medicated so good you have reduced. You may even need to drop another 12.5 or 25mcg T4 as medicating the NDT most don't need T4 so high in range. Your 'savage temperature drops' can be a symptom of cellular hypothyroidism that can happen when we have excess circulating thyroid hormone.

As 9pm tachycardia happens regularly just before taking thyroid meds at midnight have you tried split-dosing the NDT for better hormonal spread over 24 hours?

If you are worried about your eyes write a new post with a title something like 'Suspected TED, Can Anyone Help Please'. Others with TED experience might have missed your reply tacked on the end of helvella's post.

[SmallBlueThing in reply to radd]

Thanks. I've experienced temperature drops since before treatment started. I was always the cold one in the family, but kept it at bay by being active, when younger. I've kept an eye on my temperature over the past eight years of treatment. I usually drop to 35.3°C, but sometimes lower than 35.0°C . Having a sleep for two to four hours under a blanket brings my temperature back to a more normal level.

My evening tachycardia was experienced with morning dosing, and I wondered whether a rise in blood glucose level after my main meal may have triggered it, so tried (and maintain) midnight dosing to avoid the potential for a double trigger.

I've been taking 100 mcg Teva levothyroxine for the past fortnight, and feeling quite dopey, though without the side effects others have reported for that brand. My GP wrote Eltroxin on the second line of the prescription, so it's been ignored by all the big chain pharmacists I've tried over the past few years since the independent I was using consistently failed to source another, equally vital, medicine.

[helvella in reply to SmallBlueThing]

In some parts of the UK the high street opticians/optometrists can refer people directly to ophthalmology units. It could be worth trying one of them?

It is ludicrous when doctors are unable to order tests. I can see that they might not order tests on a scattergun approach. But if they order a test, or try to, it might be acceptable for the lab to question the rationale. It is NOT OK for them to refuse without finding out more.

[SmallBlueThing in reply to helvella]

I did get a letter for my GP from one. With others, I got the the impression they knew nothing about TED.