Difference in Reference Ranges ~ reading matter... - Thyroid UK

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Difference in Reference Ranges ~ reading matter for a rainy day .

tattybogle profile image
14 Replies

(see list of other posts further down page) .

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"FREE THYROXINE MEASUREMENT IN CLINICAL PRACTICE: how to optimize indications, analytical procedures, and interpretation criteria while waiting for global standardization."

Federica D’Aurizio , Jürgen Kratzsch, Damien Gruson ,Petra Petranović Ovčariček & Luca Giovanella

Critical Reviews in Clinical Laboratory Sciences | Received 28 Mar 2022, Accepted 03 Sep 2022, Published online: 13 Oct 2022

doi.org/10.1080/10408363.20...

tandfonline.com/doi/full/10...

Just posting this cos i stumbled across it and i want to read it one day (a rainy day ~ it's very long) and i'll forget otherwise.

It references 4 of        diogenes publications (and one from R Hoermann , JW Dietrich , R Larisch)

Also contains this table of Reference Ranges for several assays in current use .

Table 2.

Main analytical characteristics of the most used FT4 immunoassays as quoted by the manufacturers.

Manufacturer/assay ... Principle of immunoassay ... Assay range ... *Reference Interval (pmol/L)

Abbott ARCHITECT Free T4 ... CMIA two-step ... [5.15–64.35] ... [9.01–19.05]

Abbott Alinity i Free T4 ... CMIA two-step ... [5.41–64.35] ... [9.01–19.05]

Beckman Coulter Access Free T4 ... CLIA two-step ... [3.22–77.20] ... [7.86–14.41]

Roche cobas Elecsys FT4 IV ... ECLIA one-step, 2 sequential incubations ... [0.5–100] ... [11.9–21.6]

Siemens Healthineers Centaur FT4 ... CLIA one-step, labeled analog ... [1.3–155] ... [11.5–22.7]

Siemens Healthineers Atellica IM FT4 .. CLIA one-step,labeled analog .. [1.3–154.8] ... [11.5–22.7]

(*Reference intervals were calculated in a population of apparently healthy adult males and females. Information correct to May 2022).

"Standardization: facts, problems, and perspective.

Despite some improvements over time, FT4 measurements of the same specimens by different immunoassay platforms continue to differ . Assay variations affect FT4 RIs with potential clinical implications in reporting and interpreting results. In fact, patients are often referred to more than one laboratory, as laboratories use different methods for their FT4 assay, and physicians working in separate facilities may discuss the results of clinical cases without realizing that different methods have been used. In addition, over time, new measurement methods are introduced, and laboratories may change the method they use, for example, when technical supplies are replaced. The common assumption that laboratories can eliminate method differences by adjusting their reference intervals according to the method used has not been confirmed. RIs vary substantially between laboratories, and there is no clear correlation between the measurement procedure used and the suggested RIs. The most likely reasons are that laboratories use different sources of information and different study designs when establishing and validating their RIs. The diversity of the RIs can influence the interpretation of the results and have implications for the clinical treatment of patients."

"The International Federation of Clinical Chemistry and Laboratory Medicine Committee for Standardization of Thyroid Function Tests (IFCC C-STFT) developed and established a reference measurement system for FT4 standardization and is now working with national partners on implementing it ...... "

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Some other posts discussing different fT4 lab ranges :

healthunlocked.com/thyroidu... varying-lab-ranges-accroos-the-counry

healthunlocked.com/thyroidu... tsh-range-altered-from-last-time

healthunlocked.com/thyroidu... a-critical-need-for-ft4-test-standardisation

healthunlocked.com/thyroidu... free-t4-reference-intervals-ft4-ranges

healthunlocked.com/thyroidu... nhs-bristol-changed-their-t4-range-to-7.9-14.4pmol-l?

healthunlocked.com/thyroidu... thyroid-function-test-comparisons

healthunlocked.com/thyroidu... what-tsh-test-is-used-affects-diagnosis-of-hypothyroidism

healthunlocked.com/thyroidu... /the-range-of-ranges

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tattybogle profile image
tattybogle
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diogenes profile image
diogenesRemembering

I also replied to a shorter communication by these authors

Global FT4 immunoassay standardization.

Response to: Kratzsch J et al. Global FT4 immunoassay standardization: An expert opinion

February 2021

Clinical Chemistry and Laboratory Medicine 59(6)DOI: 10.1515/cclm-2021-0036

helvella profile image
helvellaAdministrator in reply todiogenes

Link to the first page only of diogenes' reply here:

degruyter.com/document/doi/...

tattybogle profile image
tattybogle in reply tohelvella

just found this ~ diogenes' gave us the full text of his letter to Kratzsch here :

healthunlocked.com/thyroidu... (a long awaited letter)

tattybogle profile image
tattybogle in reply totattybogle

plus this related post .. about how differences in TSH testing can affect diagnosis .

healthunlocked.com/thyroidu...? (What TSH test is used affects diagnosis of hypothyroidism)

tattybogle profile image
tattybogle in reply totattybogle

The paper contains this interesting snippet on newborns and changes in their thyroid hormone levels over time :

"At birth, a newborn quickly adapts to extrauterine life by developing a state of relative overactivity of the thyroid gland .

A sudden burst of thyrotropin-releasing hormone and TSH release, reaching up to 70–100 mIU/L within 30 min of birth, leads to a two- to six-fold increase in circulating T4 and T3 concentrations.

TSH significantly decreases to within normal infant concentrations in the first 3–5 days of life, while FT3 and FT4 serum levels remain elevated for several days and act on tissues.

Thus, the interpretation of RIs of TSH and FT4 for newborns must take into account the gestational age and postnatal age up to one month old.

Thyroid hormone concentrations then decrease slightly during childhood and adolescence.

There is also a progressive decrease in thyroid T4 production, iodine turnover, and absorption with age, which produces an overall progressive decrease in thyroid function. The concomitant drop in TSH during this period suggests that it is the primary mediator of these effects.

Serum TBG concentrations increase up to age 5 years; this increase contributes to the gradual dissociation between FT4 and T4 .

Subsequently, the TBG concentration, which decreases between 15 and 16 years of age, results in a gradual decrease in serum concentrations of total T3 and T4."

Santolina profile image
Santolina

Thanks VERY much for this. This is an important piece of research as it's from institutions which are highly regarded. Plus, in order to be published in a T&F journal, the peer review process is more stringent than most. Here, they're discussing the iodine component which after decades of thyroid issues, I've only just begun using. Three drops of Lugol's 15% in a small glass of water before bed.

helvella profile image
helvellaAdministrator in reply toSantolina

Always remember that T4 contains 63.54% iodine. So more than 60 micrograms of iodine in a single 100 microgram levothyroxine tablet.

Santolina profile image
Santolina in reply tohelvella

thanks but presumably not in glandulars, like Metavive ?

helvella profile image
helvellaAdministrator in reply toSantolina

We cannot comment on the content of Metavive or other glandulars.

But, in general terms, all thyroid tissue will contain iodine. Bear in mind that the thyroid gland has a specialist mechanism for taking up iodine from the bloodstream (sodium iodide symporter). Then, within the thyroid, it forms monoiodotyrosine (MIT) and diiodotyrosine (DIT). These are the amino acid tyrosine which contain one and two atoms of iodine (respectively).

See en.wikipedia.org/wiki/Thyro...

How much MIT and DIT? I have no idea. And it could vary considerably from batch to batch within a product line as well as between products.

radd profile image
radd in reply toSantolina

Santolina,

I agree with helvella. Most iodine is contained within the thyroid gland but not just within the hormones as is up taken by the glands epithelial cells (via the sodium iodide symporter - both Na+ and I- ions) for the making of the hormones.

The tolerance of supplemented iodine is very much to do with deficiency but also autoimmune activity on any remaining gland. It also has to be balanced with selenium to neutralise the resulting hydrogen peroxide. Glutathione is also good for reducing oxidative damage.

Santolina profile image
Santolina in reply toradd

Sorry to be so long in replying - work difficult. Much of the information about iodine is promoted by the pharmaceutical industry and is simply wrong. I & my fellow academic editors have been through the research and there are layer upon layer of misinformation. I've also worked as a consultant with various charities - mostly in Africa - and here, iodine is used for just about everything as many countries can't afford medicines. Malaria has been rife because it hasn't been profitable enough to research ... until it comes to Europe.

The western world is consumed and being eaten by drugs - antibiotic resistance is a huge factor today - look at the work being done at Nottingham Uni - almost re-inventing the wheel by looking, again, at plants /herbal remedies and solutions. Covid/vaccines and the power of the corporates are not concerned about health - only about profit. Many here won't believe this - rely instead on the medical treadmill for support.

radd profile image
radd in reply toSantolina

Santolina,

Iodine deficiency is huge in parts of Africa. We have iodine deficiency within pockets of the UK but at least we have thyroid meds to offset a proportion of it.

Covid/vaccines and the power of the corporates are not concerned about health - only about profit. Many here won't believe this - rely instead on the medical treadmill for support.

Do you refer to forum members, as the majority have been well let down by the medical profession on multiple levels. Hence the high numbers here ... 131,071 members  and 153,108 posts!

tattybogle profile image
tattybogle in reply toSantolina

Santolina if you want to discuss lugols and iodine supplementation (or covid / vaccines/ malaria/ corporates / profit .. etc) please would you start your own post about it ?

I'd prefer to keep this post on track .... it was about FT4 testing ,

tattybogle profile image
tattybogle in reply toSantolina

Santolina , you should probably read this one too then ~ healthunlocked.com/thyroidu... iodine-a-collection-of-useful-information-because-the-search-facility-on-health-unlocked-is-totally-pants

(preferably before you take additional iodine, as the potential effects of too much iodine with thyroid conditions are complex).

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