DIAGNOSIS OF ENDOCRINE DISEASE: How reliable are free thyroid and total T3 hormone assays?

[helvella]

We see a steady stream of people with FT4 (Free T4) and, if done, FT3 (Free T3) results which appear questionable.

This paper emphasises that the common assays do indeed have problems.

The paper's suggestion of getting an assay performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) is fine and might be "the answer" in some ways. But how on earth do you get off the starting blocks?

We all know that TSH-only testing is the rule. FT4 is lucky. And FT3 only if especially privileged! What are the chances of your doctor, especially a GP, pushing to get an LC-MS/MS assay? I can imagine going into an appointment and saying that you don't think your results reflect your actuality so, please do an LC-MS/MS assay. Unfortunately, I can also imagine a GP's response. (Not to blame the GP as they are likely unaware of the issues and cannot order such an assay even if they believe it appropriate.)

DIAGNOSIS OF ENDOCRINE DISEASE: How reliable are free thyroid and total T3 hormone assays?

in European Journal of Endocrinology

Authors: Kerry J Welsh 1 and Steven J Soldin 1

Abstract

Hypothyroidism is a very common disorder worldwide, for which the usual treatment is monotherapy with levothyroxine (L-T4). However, a number of patients treated with L-T4 continue to report symptoms of hypothyroidism despite seemingly normal levels of thyroid-stimulating hormone (TSH), free-T3 (FT3) and free-T4 (FT4) measured by immunoassay. This review summarizes the limitations of the immunoassays commonly used to measure thyroid hormone levels and emphasizes the advantages of the role of liquid chromatography-tandem mass spectrometry (LC-MS/MS). Immunoassays for free thyroid hormone are affected by alterations in serum binding proteins that occur in many physiological and disease states. Multiple studies show falsely normal values for T3, FT3 and FT4 by immunoassay that are below the reference interval when measured by (ultrafiltration) LC-MS/MS, a reference method. We suggest evaluation of thyroid hormone levels by ultrafiltration LC-MS/MS for patients who continue to experience hypothyroid symptoms on LT-4. This may help identify the approximately 20% subset of patients who would benefit from addition of T3 to their treatment regimen (combination therapy).

Freely available here but, as it is an XML link, might not work on all platforms:

eje.bioscientifica.com/view...

Also, the full paper is in PubMed Central:

ncbi.nlm.nih.gov/pubmed/277...

[diogenes Remembering]

I'm sorry, but Soldin is a guy I wouldn't trust with my silverware or anything else for that matter. He has an agenda, pushing MS as his discovery and the "gold standard" for assays like FT4 and FT3. I pointed out to himin a published paper that his method was bogus (not the MS but the method of separating FT4 from total T4, likewise FT3 and total T3). He merely mumbled about in a reply without addressing his problems, but then without telling anyone changed his method, but still used his bogus data as a supporting backup for new studies. That's the kind of scientist he is. His method is prone to all kinds of potential artefacts which I won't go into here, but suffice it to say that his group and the defining analytical group in Ghent under Linda Thienpont and Katleen van Uytfanghe do NOT see eye to eye. And do not get the same results.

[helvella Administrator in reply to diogenes]

Thank you for letting us know.

[diogenes Remembering in reply to helvella]

If you'd like to see our short (polite but damning) criticism of his work:

Inaccuracies in Free Thyroid Hormone Measurement by Ultrafiltration and Tandem Mass Spectrometry

October 2009 Clinical Chemistry 55(12):2228-9; author reply 2229-30

DOI: 10.1373/clinchem.2009.134593

SourcePubMed

Nic D Christofides, John Edward M Midgley

It's readily accessible

[helvella Administrator in reply to diogenes]

I remember you mentioning the temperature issue some time ago.

[diogenes Remembering in reply to helvella]

Here is another in more detail:

"All that glisters is not gold": Ultrafiltration and free thyroxine measurement With apologies to W Shakespeare

November 2010 Clinical biochemistry 44(2-3):151-3

DOI: 10.1016/j.clinbiochem.2010.11.001

SourcePubMed

John Edward M Midgley

[JGBH in reply to diogenes]

Thanks for letting us know about such a charlatan... We patients need all the help we can get and FT4 and FT3 are important tests to have done. Obviously this guy is trying to discredit their importance. So fortunate you knew about him and his unethical practice and make us aware.

Very difficult for us to recognise when a "scientific paper" is not really what is should be.

Obviously Helvella does not have your professional knowledge of this man's behaviour and was genuinely trying to inform us.

[helvella Administrator in reply to JGBH]

But I am delighted when we have discussions which add to overall understanding.

I have no problem with being told I am wrong!

[JGBH in reply to helvella]

Agree, it’s stimulating and it points out that all “research “ papers can’t be trusted when written by someone more concerned with his ego and moment of glory rather than the true outcome from genuine research.

You are not wrong, simply trusted this man to be serious in his research and honest.

However I wonder who actually checks the validity of research papers? Had it not been for Diogenes who knows him we would be none the wiser. Rather concerning.

It is perhaps best to stick to well-known research work and avoid the more obscure papers?

[Hidden in reply to diogenes]

You are lucky to have any ( silverware )

[diogenes Remembering in reply to Hidden]

All heirlooms which are a pain to polish. Great grandads were rather entrepreneurial people, some things only kept for their memories.

[Hidden in reply to diogenes]

I understand, I was only joking.