Pregnancy disrupts the accuracy of automated fT4 immunoassays

[helvella]

This paper includes:

Indeed the International Federation of Clinical Chemistry working group for Standardization of Thyroid Function Tests acknowledged the need for standardization of the fT4 assay.

Have to say, in my facetious moments, I have wonder what the IFCCSTFT group do when they are not stating the obvious.

However, acknowledging an issue and discussing if the same sort of issue could occur due to contraceptive pills or HRT - and in thyroid disease.

The paper also identifies a limit being that if you don’t have an out-of-range TSH, you are unlikely to have an FT4 test!

And it points out that if the assays are biased, they need to use assay-specific reference intervals. Which is like using a ruler that is known to be too short or too long and adding/subtracting every time you measure something. Far better use an accurate ruler?

Pregnancy disrupts the accuracy of automated fT4 immunoassays

in European Thyroid Journal

Authors:

Heleen I Jansen, Antonius E van Herwaarden, Henk J Huijgen, Rebecca C Painter, Jacquelien J Hillebrand, Anita Boelen, and Annemieke C Heijboer

Correspondence should be addressed to H I Jansen; Email: [e-mail]

DOI: doi.org/10.1530/ETJ-22-0145

Volume/Issue: Volume 11: Issue 6

Article Type: Research Article

Article ID: e220145

Online Publication Date: 31 Oct 2022

Copyright: © The authors 2022

Abstract

Objective

Thyroid hormone measurements are often performed in pregnant women, as hypo- and hyperthyroidism during pregnancy can severely affect the fetus. Serum free thyroxine (fT4) measurements are well known for their analytical challenges, due to low serum concentrations and the subtle equilibrium between free and bound T4 (to thyroid-binding globulin (TBG), transthyretin and albumin). Pregnant women have high TBG concentrations due to an increase in human chorionic gonadotropin (hCG) and estrogen and lower albumin concentrations which change the equilibrium and may affect the validity of fT4 measurements in their samples. As accurate serum fT4 measurements in pregnant women are important for the long-term health of the fetus, we aimed to evaluate the accuracy of several fT4 immunoassays in the serum of pregnant women.

Methods

FT4 was measured in healthy controls and pregnant women using a candidate-reference method (LC-MS/MS) and five commercially available automated immunoassays (Alinity (Abbott), Atellica (Siemens), Cobas (Roche), Lumipulse (Fujirebio) and UniCel DXI (Beckman Coulter)). Method comparisons (Bland Altman plots and Passing and Bablok analyses) were performed.

Results

Serum samples from both healthy controls (n= 30) and pregnant women (n= 30; mean gestational age, 24.8 weeks) were collected. The fT4 immunoassays deviated +7 to +29% more from the LC-MS/MS in serum samples of pregnant women than healthy controls (falsely high).

Conclusions

Our results indicate that immunoassays overestimate fT4 in pregnant women, which might lead to an overestimation of thyroid status. Physicians and laboratory specialists should be aware of this phenomenon to avoid drawing false conclusions about thyroid function in pregnant women.

Keywords: pregnancy; free thyroxine; immunoassay; LC-MS/MS

Open access here:

etj.bioscientifica.com/view...

Figure 3

Passing and Bablok regression analyses for the five automated immunoassays in pregnant women and healthy controls. On the x-axis, the fT4 concentrations were measured using LC-MS/MS and, on the y-axis, the fT4 concentrations using the respective immunoassays are shown. (A) Alinity; (B) Atellica; (C) Cobas; (D) Lumipulse; (E) UniCel DXI.

[shaws]

Thanks for posting and I think this is an important statement:-

"Physicians and laboratory specialists should be aware of this phenomenon to avoid drawing false conclusions about thyroid function in pregnant women".

[diogenes Remembering]

This analysis of late pregnancy FT4 values in 5 widely used assay platforms comes as no surprise to me. Commercial production of FT4 assays has shown up their basic lack of knowledge as to the care that needs to be taken to validate their methods. However, I've two criticisms of the paper. 1) by measuring these assays, they make a generalisation which they apply as a universal given to condemn the whole field. However, there are assays that have been proven to be unaffected by TBG or albumin (Vitros -ECi) by test and publication of results. These seem not to be frequently used, possibly owing to pathetically poor marketing by the company concerned. I note that from this study the LC-MS gold standard method gives a mean ratio of 13/19.5 = 68% pregnant value/healthy control values). Our first FT4 assays in 1981 gave a ratio of 70-75% (very near the gold standard method ratio shown by the paper). All our assays since then gave the same ratio to a close approximation. 2) As part of our eBook this gives me an opportunity to discuss the widespread failure of companies to produce adequate assays and their apparent failure or indifference to showing insensitivity to TBG and albumin before the assays were launched. This is a unique case where FT4/FT3 assays should come from one well-resourced producer who has done the extensive work needed to validate the assays. It also shows up the fact that in spite of Dr Thienpont's team's work to harmonise such assays with the gold-standard method, the companies have made no discernible effort to apply the appropriate revisitation of their assays' validity. Other tests which aren't so subject to exact measurement can be got away with. Yes/no as to drug actions, diabetes etc. It's only really in the thyroid free hormone and TSH tests that numbers within the reference range are essential for diagnosis and treatment, and the normal diagnosis by Yes/No in other fields has been wrongly applied to the thyroid - ie if within range anywhere, that's OK. I thank you for drawing this paper to my notice. Finally, it is less than amusing that several papers quoted in this paper are themselves invalid.

[helvella in reply to diogenes]

Apologies, diogenes, I had meant to mention you in my post so you were alerted to it. Glad you found it anyway!

I'm well aware that you have profound understanding of the issues.

Thank you for your reply.

Does the IFCCSTFT group actually achieve anything at all? Or, by existing, do they deflect criticism from the assay manufacturers?

[diogenes Remembering in reply to helvella]

The problem I see is that the companies make soothing noises about re-calibration and then do nothing about it. There is no extra money in recalibrating and it costs them So no dice in actuality. The IFCCSTFT group don't seem to have the power to actually legally stop companies marketing poor assays. As I've said many times, the regulators who have the power have failed to use it and this then passes to the above organisation which has no such power.

[helvella in reply to diogenes]

That would be the MHRA in the UK, the FDA in the USA?

[diogenes Remembering in reply to helvella]

Correct

[humanbean]

My bolding and underlining

Thyroid hormone measurements are often performed in pregnant women, as hypo- and hyperthyroidism during pregnancy can severely affect the fetus.

I may have dreamed this but I'm sure some hypothyroid members who got pregnant have complained that they only had a TFT once during pregnancy, or had to really beg to get more than one.

Others have complained that only TSH was measured. And I very rarely see a Free T3 being quoted by anyone who is pregnant.

[helvella in reply to humanbean]

Remember the frequently repeated fallacy that T3 cannot cross the placenta?

Hence, yet again, T3 doesn't matter. (Even if it were true, the mother could be suffering severely while the foetus did well. But I think that entirely impossible to imagine.)

[humanbean in reply to helvella]

Oh yes - I never believed that. It implies that nature and evolution created two entirely different ways for humans to make use of thyroid hormones, firstly as an embryo and a fetus, then - hey presto - the instant they are born they can make and use T3?

An absolutely daft idea.

I have never read an explanation as to why doctors ever believed that.

I like this case report :

endocrine-abstracts.org/ea/...

Click on the poster or "View ePoster" to see more. I just wish they had given the reference ranges for the numbers that were quoted for the TFT results.

[helvella in reply to humanbean]

These pregnancies may challenge current dogma regarding thyroid hormone treatment during pregnancy.

Really means, drives a coach and horses through the unwarranted, non-evidence based, wholly unjustified assumptions which have resulted in a false dogma.

Effectively there has been a perpetuation of lies by those who should be most trusted - medics.

[Hidden in reply to humanbean]

But even if you do get a TFT in pregnancy you need a medic who understands it.

I didn't have a diagnosis yet but had a TSH of 8.something at around 12 weeks pregnant and they just said it was fine! Less than the scared '10' so off you pop.

Didn't know then what I know now, I'm just grateful my son was delivered at term and healthy.

[humanbean in reply to Hidden]

I'm sure that poor levels of thyroid hormones must lead to an increase in miscarriages for many women. But the medical profession seems not to care at all.