Reference Ranges

[Ginny52]

Dear people

Why are reference values for thyroid hormones set locally whereas values for (say) creatinine are set nationally (or even internationally!)?

Thank you very much!

[jimh111]

Each assay is a little different so the reference intervals reflect the individual assay. Thyroid hormones are present in minute quantities and so levels are estimated indirectly via immunoassays. That's the limit of my technical understanding.

[Ginny52 in reply to jimh111]

Thank you for the prompt reply Jim! So- the answer is because it’s harder to measure them than other biochemical substances? G

[Ginny52 in reply to Ginny52]

Or because they can’t get it together to use a standardised assay? Not being frivolous- I have to speak to the endo on Thursday, and I realise that if I haven’t understood this, I haven’t really understood anything. For instance- each lab seems to set its own reference range- can that be right? G

[Marz in reply to Ginny52]

My understanding is that ranges are set based on the levels of say 1000 people tested in a particular lab - hence the differences. Whether this includes people without a thyroid problem I am not sure. It is only knowledge gained from reading here 🤔

If you scroll down and down you will come to 10 more posts similar to yours - under the heading Related Posts. Could be something helpful there !

[helvella Administrator Thyroid UK in reply to Marz]

Since I became involved in thyroid issues, we have seen a widespread change in the ranges for TSH. The most obvious thing is that the top of the range has dropped. Used to be that many went up to 6 or 7 or so. Now most go up to around 4.5, or 5.5.

I was aware that there was increased care to ensure that the reference ranges for thyroid tests were done on people who do not suffer any thyroid issue, including having raised antibodies without any apparent effect. Or, indeed, any illness which could affect results.

There is also greater awareness of the need to exclude those who have antibodies to TSH itself (which antibodies bind to TSH and form macro-TSH - some TSH tests are sentitive to the presence of macro-TSH and read high if present).

I wonder, though, whether labs check for interference by biotin which has become quite an issue over the past few years?

Some labs appear to follow the ranges set by the test manufacturer. Even if all labs did so, we would see distinct differences between the manufacturers. They have not put the work in to fully standardising ranges.

Tests with widespread standardisation require the availability of high accuracy reference samples. I don't think they are available for thyroid hormones.

I'll add that antibody tests have had extremely disparate ranges. Some standardised their results so that 0 to 1 is negative, 1 to 2 is suspect, over 2 is positive. Others used actual results in IU/mL.

Given all the uncertainties, it really does mean that we have to use the laboratory's reference ranges.

Also, the 1000 samples story, whilst having some truth, is likely not to be 100%. For example, they might use 1000 or some other number of subjects. And I would expect them to re-run this range-setting if anything significant changes - updated testing kits, new analyser machines, etc. It all too often reads as if someone ran the range-setting process in 1981 when they first got an automated analyser and never looked again!

[Marz in reply to helvella]

Like everything thyroid related - it can appear confusing ! Then of course there are so many Drs ignoring the ranges or saying your TSH needs to be 10 before considering treatment .... sigh !

[helvella Administrator Thyroid UK in reply to Marz]

I purposely didn't allow myself to go in that direction!

[jimh111 in reply to Ginny52]

Much more difficult to measure. I've put some details here ibshypo.com/index.php/refer... .

If you click on the colourful picture it takes you to Wikipedia and if you click on the same picture in there and keep clicking you get an enlarged picture where you can see the throid hormones are on the extreem LHS.

You can also use the first link on my webpage to find the individual reference intervals and calculate (if you wish!) the relative amounts.

I don't understand it in detail but economic thyroid assays get the hormones to attach to antibodies and then use some sort of calculation to estimate their concentration. Thus each lab will use a slightly different technique leading to different reference intervals. This paragraph should not be taken as truth! Just giving a vague feel for how its done.

[Hidden]

Maybe for practical purposes the only thing you might want to discuss with your endo is your own personal range.

Unless you had a full thyroid test when you were healthy this is impossible to know. But the fact is that we each have our own personal "Metabolic set point" with a rather narrow range above and below it where we feel well.

This means that yours could be near the top or the bottom of any lab test range, anywhere in between or even below or above!

The endo needs to allow for that fact in deciding how to treat you. This might help to guide the fine tuning of your treatment

[diogenes Remembering]

There are two sources of trouble. The first is that different manufacturers produce tests that don't agree with each other fundamentally. For example Abbott's FT3 test has a range way below what all the others claim. So a range of say 3.5-6.5 in one test could be 2.0-4.8 on another. This scandal arises because the manufacturers don't do their development of the test properly and the regulatory authorities let them get away with it. The second cause of variability using the same machine is that different hospitals want to use the test according to their local population. By random chance the various ranges don't exactly agree with each other and the choice and number of subjects to produce the local range is often questionable. It's usual to test 100 socalled euthyroids to get a range. But choice of say lab staff as a means of getting the range locally can lead to distortions.

[tattybogle in reply to diogenes]

Do you have any insight into why the FT4 ref range in NW England has narrowed so much from [8-18] down to [7.9-14] in 2017 ?

I cant get a straight answer as to whether this is to do with the machines , or a local 'policy' change .

[diogenes Remembering in reply to tattybogle]

The 8-14 range you quote is frankly a nonsense because it is both too low and too narrow. I wouldn't give houseroom to any diagnosis based on this test. If it is machine-based I suspect again the Abbott test which is truly a poor one. I cannot see why the pathologists can't see the rubbish they are using.

[tattybogle in reply to diogenes]

Thank you diogenes, you have made my day! I have suspected something amiss for the last few years, since allegedly i am nowadays 200% through the range on a reduced dose, with a similar TSH and no other pertinent changes.

Predictably , the Gp seems to assume i increased my dose by loads without permission (at the same time as the lab changed the range!) and hasn't yet seen that it's a curious coincidence.

[Ginny52 in reply to tattybogle]

That’s extraordinary!