US-based, Prospective, Blinded Study of Thyrotropin Receptor Antibody in Autoimmune Thyroid Disease

[helvella]

A rather disappointing paper. First, the full paper is, as so often, behind a paywall.

Also, because the the paper doesn't come out with a clear "Yes, the tests are wonderful and reliable."

It is quite clear that there is sufficient uncertainty to question all results from these tests.

We have had a few posts recently mentioning TSH receptor antibodies and/or TSI - so likely to be of some interest.

US-based, Prospective, Blinded Study of Thyrotropin Receptor Antibody in Autoimmune Thyroid Disease

The Journal of Clinical Endocrinology & Metabolism, dgae448, doi.org/10.1210/clinem/dgae448

Published: 19 July 2024

Abstract

Context

Bioassays provide information on the functionality of thyrotropin receptor antibodies (TSH-R-Ab) and thus may offer more clinical utility than binding assays.

Objective

In this prospective, blinded, US-based study, the clinical performance of several TSH-R-Ab assays was compared.

Setting

US endocrinology clinic.

Subjects

One hundred sixty-two unselected, consecutive, well-documented patients with various thyroid diseases and healthy controls.

Intervention(s)

Blinded TSH-R-Ab measurements.

Main Outcome Measure(s)

Sensitivity and specificity of 4 TSH-R-Ab assays.

Results

The 4 TSH-R-Ab assays were negative in all 42 patients without autoimmune thyroid disease (AITD). In 104 patients with Graves’ disease (GD), irrespective of the disease duration, TSH-R-Ab positivity was present in 65 (63%), 67 (65%), and 87 (84%) for the Cobas and Immulite binding assays and stimulatory TSH-R-Ab [thyroid-stimulating immunoglobin (TSI)] bioassay, respectively (TSI vs Immulite P < .0025, TSI vs Cobas P < .0009). Fifteen newly diagnosed GD patients were all positive in the TSI bioassay, but only 11 (73%) were positive in the Cobas and Immulite binding assays. Nine GD patients with biochemical subclinical hyperthyroidism were TSI-positive but Immulite- and Cobas-negative. Two GD patients were blocking TSH-R-Ab [thyroid-blocking immunoglobin (TBI)]-positive and TSI-negative, and the Immulite and Cobas were positive in both. Additional serum samples from AITD patients that consisted of 30 TBI-positive and 10 TSI-positive samples were blindly tested in the binding assays. Only 6 of the 10 TSI-positive samples were positive in both binding assays, and 30 and 28 of the TBI-positive samples were positive in the Cobas and Immulite assays, respectively.

Conclusion

Binding TSH-R-Ab assays are less sensitive than TSI bioassays and are not specific for stimulating antibodies. Measuring the function of TSH-R-Ab in a bioassay can provide useful information to clinicians.

Keywords: thyrotropin receptor antibody, binding assay, bioassay, autoimmune thyroid disease

Paper is behind a paywall - only this abstract is accessible:

academic.oup.com/jcem/advan...

[Rainbow-Lover]

Thank you for posting

[HealthStarDust]

I’m still trying to get my head around trab and tsi antibodies. I can’t even tell if their the same think or a 2 things part of 1 thing. See? That’s how confused I am!

[helvella Administrator Thyroid UK in reply to HealthStarDust]

TSH-R-ab come in three forms:

❖ Stimulating

❖ Blocking

❖ Neutral

TSI is effectively another name for the stimulating form of TSH-R-ab.

TBI is effectively another name for the blocking form of TSH-R-ab.

TSI occurs in Graves' Disease. TSI stimulates the TSH receptor and that results in excessive production and release of thyroid hormones. Effectively TSI acts like a more powerful and uncontrolled form of TSH.

TBI is associated with Hashimoto's Thyroiditis. TBI blocks the TSH receptor and can prevent TSH stimulating the receptor.

The naming is not helpful to ordinary people like us.

[HealthStarDust in reply to helvella]

Thank you.

It certainly isn’t helpful for the lay person. Is there a blood test to find out which type of trab people have?

[helvella Administrator Thyroid UK in reply to HealthStarDust]

Yes. The TSI test!

This is why many replies here say Graves' must be diagnosed by a TSI test.

Not sure what the statistics are, but historically, Graves' was often diagnosed without any TSH-R-ab test at all, or only the TSH-R-ab test that does not differentiate between the types.

I don't remember anyone having a specific TBI test for diagnosis - might be research-only.

[HealthStarDust in reply to helvella]

I think tattybogle was just explaining to me on another post that the test for the blocking type of trab are probably only tested in research settings.

[HealthStarDust]

Just to add more confusion (or hopefully clear it up)

TRAB which can be broken down to:

TSI (stimulating antibodies)

TBI (blocking antibodies)

And they also go by other names too? For example, when I read on thyroidpatients.ca/2020/04/... and see this image (above) they are named TSAB and TBAB respectfully?

Honestly, just down them the lay person at all!

tattybogle helvella

Graphic of overlapping antibodies in thyroid disease.

[helvella Administrator Thyroid UK in reply to HealthStarDust]

I don't remember seeing those acronyms before. But people who write scientific papers, and others who write documents based on them, might use unusual choices or make up new acronyms.

I think in this case, Tania has tried to avoid introducing the word "immunoglobulin" as a synonym for antibody. And it would likely have been much better if no-one had introduced it in the first place!

TSAb = TSI

TBAb = TBI

(And there is much confusion about capitalisation as well! Which of these should we choose - "AB", "Ab" or "ab"? It is inconsistent and potentially confusing. I prefer "ab" - even if it goes against other conventions - because I see the change of case and it highlights that they are "ab" to whatever comes before. I might be wrong!)

[HealthStarDust in reply to helvella]

Thanks. Most obliged.

[tattybogle in reply to HealthStarDust]

This image helped me understand the action of stimulating vs blocking forms of TRab

Stimulating ( Agonist) fit into the TSH Receptors (on the thyroid) and act on the thyroid in the same way that TSH does ... even if there is no TSH)

Blocking (Antagonist) cap off the TSH Receptors on the thyroid (preventing TSH from having any effect on the thyroid)

As for all the different names /abbreviations in research papers .... you just have to understand that there are 3 kinds of TRab (stimulating / blocking / neutral) and then play "guess what abbreviation they used/made up this week "... it's good fun for all the family.

.

[HealthStarDust in reply to tattybogle]

Thank you. I prefer catchphrase with the family.