Thyroid hormone resistance index and mortality in euthyroid subjects: [e-mail] study

[helvella]

Acquired resistance to thyroid hormone has been discussed quite a few times on forum. Good to see a paper recognising the possibility.

Thyroid hormone resistance index and mortality in euthyroid subjects: [e-mail] study

in European Journal of Endocrinology

Authors:Silvia Patricia Alonso1, Sergio Valdés2, Cristina Maldonado-Araque3, Ana Lago4, Pilar Ocon5, Alfonso Calle6, Luis Castaño7, Elias Delgado8, Edelmiro Menéndez9, Josep Franch-Nadal10, Sonia Gaztambide11, Juan Girbés12, Felipe Chaves13, Sara García-Serrano14, Eva García-Escobar15, Jose Carlos Fernández-García16, Gabriel Olveira17, Natalia Colomo18, and Gemma Rojo-Martínez19

DOI: doi.org/10.1530/EJE-21-0640

Online Publication Date: 01 Nov 2021

Objective: It has been proposed that a mild form of acquired resistance to thyroid hormone may occur in the general population. Its clinical significance remains largely unknown. The objective was to explore whether a newly described thyroid hormone resistance index is associated with the risk of mortality in a sample of community-dwelling euthyroid subjects representative of the adult population of Spain.

Design: Longitudinal observational study including 3750 individuals, free of thyroid disease, TPO Abs negative (<50 IU/mL) and with TSH levels within the euthyroid range (≥0.5 and ≤5.0 mUI/mL) participating in the nationwide study [e-mail] (2008-2010).

Methods: We used the Thyroid Feedback Quantile-based Index (TFQI) as a marker of resistance to thyroid hormone. The study population was grouped into categories according to their TFQI values at baseline. Fatal events were ascertained from the national death registry (end of follow-up December 2016).

Results: 231 deaths were recorded during an average follow-up of 7.3 years. Compared with the category with the highest sensitivity to FT4 (TFQI≤p5) (reference), the Relative Risk of mortality in the categories with TFQI>p5 and ≤p25; >p25 and ≤p50; >p50 and ≤p75; >p75 and ≤p95; and >p95 were 1.01, (0.47-2.19), 1.42 (0.68-2.97), 1.54 (0.74-3.22), 1.47 (0.70-3.11) and 2.61 (1.16-5.89) respectively (p for trend 0.003). The association remained significant after multivariate adjustment of the data (p for trend 0.017).

Conclusions: A thyroid hormone resistance index focused on deviations of the average pituitary response to thyroid hormones may be associated to all-cause mortality independently of other conventional risk factors and comorbidities.

Full paper is behind a paywall.

eje.bioscientifica.com/view...

jimh111

[LindaC]

Fascinating! Thank you helvella! Where would we be without researchers?

AND Diogenes and You! 🍀 And so many other wonderful contributors xox

[Gismo333]

Please also refer to scientist Dr JC Lowe. He was my doctor and has written many papers on this. I had thyroid receptor resistance, it’s not uncommon

[helvella Administrator in reply to Gismo333]

I have done so many times! And...

A PDF Conversion of Dr Lowe’s Thyroid Science Website

A conversion of some of Dr Lowe’s website into a PDF to help make it accessible.

From Dropbox:

dropbox.com/s/w7cjut689r1w1...

From Google Drive:

drive.google.com/file/d/1Rl...

[Thyroid17]

Looks very interesting, I'm going to make the time to read this soon. Thanks

[jimh111]

Thanks for posting. I'm very much into acquired resistance to thyroid hormone (ARTH as I call it). I believe this is caused by endocrine disrupting chemicals (EDCs). I will have to wait to see the full paper but there seems no reason why the authors should claim there is RTH or that it is acquired. They would have to show that the RTH is acquired and not genetic. i.e. the subjects developed RTH at some stage in their life.

This study care.diabetesjournals.org/c... seems to be the one associated with the invention of the TFQI index. If I understand TFQI it appears to be a measure of TSH response to fT4, when fT4 and TSH are higher TFQI is higher. This index deliberately ignores fT3!

RTH usually refers to impaired T3 binding, genetic RTH caused by mutations of thyroid hormone receptors is the usual recognised form although I believe an acquired form is caused by EDCs. The term 'impaired sensitivity to thyroid hormone' (isth) is usually used to describe multiple causes of impaired thyroid hormone action such as RTH, deiodinase problems or cellular transport defects.

I think the study you posted should refer to ISTH because (I assume) they have not identified the locus of impaired thyroid hormone action. The obvious possibility is a deiodinase problem but these teams seem to go out of their way to avoid considering this option, they refuse to measure fT3. Another potential answer is TSH is high because these subjects produce TSH with reduced bioactivity. TSH is higher in the elderly and reduced TSH bioactivity is thought to be an explanation. Again the endocrinologists avoid finding out by not doing a trial that measures TSH bioactivity.

This could be vital research, there could be some mechanism that reduces sensitivity to thyroid hormone but I find it very annoying that they don't even bother to measure fT3. Perhaps they are worried that the result would render their study worthless?

I'm not shooting the messenger here, I appreciate you letting us know about the study - I'd like to shoot the study team. Maybe they are scared that if they find a low fT3 increases mortality it would lead to increased demand for liothyronine.

[helvella Administrator in reply to jimh111]

I definitely don't take that as criticising me!

We need to be able to discuss, even disagree, but when it comes to T3 measuring, how can their curiosity not lead them to look?