Standardizing Thyroid Function Tests

Awhile ago I posted a blog about an article by the American Association of Clinical Chemists on harmonizing TSH testing.

The body doing the work is the International Federation of Clinical Chemists and the committee on Standardizing Thyroid Function Tests is headed by Prof. Dr. Linda Thienpont. Diogenes mentioned her in his last epistle to the Scottish Thyroid Petition Committee. The following links are to their first reports from 2009/2010 for those who have an interest. PR

The links can take awhile before they come up.

Part 1

Part 2

Part 3

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9 Replies

  • ....methinks Diogenes is a he ? :-) :-) Thank you for your post - will read later in more depth.....

  • Is that author Graham Beastall the man who did a lot of the work on the ACB/BTA/BTF thyroid guidelines?

    (For all that we may disagree with some of those guidelines, they also contain some sense which should be taken on board by more of the medics who think they understand.)

  • Rod, I hadn't noticed that Graham Beastall is from the Dept. of Clinical Biochemistry, Royal Infirmary, Glasgow, the same as Dr. O'Reilly I believe. Wonder what their conversations are like. PR

  • FYI, Prof Thienpont and several manufacturers of FT4 tests have got together to agree on a recalibration exercise to harmonize their results with her definitive method. The manufacturers have been very reluctant to change because it will cost them millions to do it, for no return on investment -a bean counter's nightmare. However, if there is an implied threat to ban their products if they don't proceed then in a certain R Nixon's (or was it Lyndon Johnson's) words - "if you've got'em by the balls their hearts and minds will surely follow". Some however can't afford the cost of change so there'll be interesting times ahead for the regulators who might at last awake from their slumbers and do some proper regulating. Regarding FT3, total chaos with no early sign of redemption. Prof Thienpont is setting on a Ph. D. student to run this one down for standardization but it will take time obviously. Meantime, FT3 tests can differ by up to 60%! in numbers for a given sample. FT4 tests at the moment vary around the 25% mark, but TSH is generally pretty well harmonized. Accordingly, FT3 is little used, and there is as now no pressure to improve the tests. This is a key obstacle to FT3 being taken up more.

  • Diogenes, do you know if as part of their effort to standardize TFT's they are going to standardize the reference ranges? Or will reference ranges remain unique to each laboratory? PR

  • You have really hit on the big if, how and why here!. First, yes standardisation will mean two things. First after standardizing, all manufacturers allowed to sell their products will have (+ or - 5% either way, you can't get perfection in biology) the same values for the same sample (FT4 and TSH that is, FT3 is a work in progress for the future). Second they will offer a suggested reference range based on their research and development. And here we have the nub of the problem. When you make a reference range of normality, do you just use lab staff, or patients diagnosed as normal, or a mix of these (in what proportion), or friends and relations? And when the lab using the product devises its own reference range, what criteria and choice will they make; and how many subjects to get a range? 120 is the advised number, but I think this is miserably too small - nearer 1000 would be my target. If you get a couple of outliers in your 120, this can disturb the calculations significantly, but not with 1000. The healthier the subjects used, the narrower the range, especially with FT3. The reference range is to some extent a moving target, however precise and accurate the test results. This problem is never properly addressed in practical diagnosis.

  • Diogenes, why haven't they standardized TFT's before now? Did Prof. Thienpont develop some procedure that wasn't possible before? Was it simply that the regulators didn't understand there was a problem? Did no one see a problem in having wide variation between vendors and laboratories in the results that were obtained? How widespread is this problem in biochemical testing? I have found a few comments about similar problems with adrenal testing. PR

  • Diogenes,

    "This problem is never properly addressed in practical diagnosis." I couldn't agree more with that statement. That is one of the biggest problems patients face in getting a timely and accurate diagnosis. Doctors tend to equate the laboratory reference range as being equal to the patient reference range, which of course it is not, the patient reference range is much narrower (+ or -.5) and people have different set points as Anderson et al so beautifully showed. Actually the first study I have found on the 'low index of individuality' of the TFT's is from 1987, Anderson et al was the fifth study done on this. The other problem is that the Gaussian curve has always had a shelf on the right hand side which has caused much debate about why, antibodies or age. Dr. Spencer actually did some very good work in trying to point this out but I think the fact has largely been ignored. In the NACB's 2002 guidelines they say " In the future, it is likely that the upper limit of the serum TSH euthyroid reference range will be reduced to 2.5 mIU/L because >95% of rigorously screened normal euthyroid volunteers have serum TSH values between 0.4 and 2.5 mIU/L." Dr. Lee makes a similar statement in her 2003 ATA presentation, TSH Reference Range Redefined: What Should We Do. These statement were based on data from the NHANES III survey although Surks disagreed and said it was only 86% and then went off to develop an age adjusted reference range. This information has been out for years and yet doctors still treat the lab reference range as being the patient reference range. I don't know how you overcome this problem. As you said to me one time, 'one day it will be this, the next day it will be that, with no discussion about the way it was before.' I'm paraphrasing what you said. Contrary to popular belief, neither 2.5 or 3.0 have been widely adopted here in the US. The top of the ranges generally still run from 4.0 to 6.0. We will never get thyroid patients well until doctors stop treating the lab test and start treating the patient. Here in the US we do have more doctors who realize this but getting the pillars of endocrinology, ATA, AACE, Endocrine Society, RCP, BTA, BTF, to change will be a monumental task. PR

  • Legislators, regulators and medics are all involved in a never ending circular dance of passing the buck.

    While people 'just trus't them there's plenty of room for conjuring tricks.

    Fluoride in water is another scam.

    Look how long it took to get Lead and Asbestos out of the environment long after the truth about their extreme toxicity was known.

    At least the internet leaves a trail of patient knowledge and experience to fall back on- unless it gets removed, of course.

    It must be making a few collars itch somewhat, though as the case on Thyroid mismanagement tightens down- ever so slowly.

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