Using a thyroid disease-free population to define the reference interval for TSH and free T4 on the Abbott Architect analyser

I don't think many of us see lab reference ranges as tight as:

TSH: 0.43-3.28 mU/L

fT4: 10.8-16.8 pmol/L

The wider ranges we so often see might suggest that some ranges were established with less attention to the possibility of thyroid disease. I'd be interested in diogenes opinion?

Clin Endocrinol (Oxf). 2016 Jun 22. doi: 10.1111/cen.13143. [Epub ahead of print]

Using a thyroid disease-free population to define the reference interval for TSH and free T4 on the Abbott Architect analyser.

Hickman PE1,2, Koerbin G3, Simpson A1, Potter JM1,2, Hughes DG1, Abhayaratna WP2, West N4, Glasgow N2, Armbruster D5, Cavanaugh J2, Reed M6.

Author information

1ACT Pathology, The Canberra Hospital, Garran, ACT 2605, Australia.

2Australian National University Medical School, Garran, ACT 2605, Australia.

3New South Wales Health Pathology, Chatswood, NSW 2067, Australia.

4Griffith University, Southport, Queensland, 4222, Australia.

5Abbott Diagnostics, Abbott Park, IL 60064, USA.

6Aotea Pathology, Wellington, New Zealand.

Abstract

OBJECTIVE:

Thyroid disease can be subtle in its presentation and TSH reference intervals may be artifactually increased by including persons with sub-clinical thyroid disease. We have therefore used a thyroid disease-free population to determine TSH and fT4 reference intervals.

DESIGN:

Apparently healthy subjects were assessed by health questionnaire, drug history, clinical assessment and measurement of thyroid antibodies.

PATIENTS:

Healthy subjects in a community setting MEASUREMENTS: TSH, free T4, anti-thyroglobulin and anti-TPO were measured on the Abbott Architect analyser. Subjects with clinical abnormalities, consumption of thyroid-active medications or with thyroid antibodies above the manufacturer-quoted reference intervals were excluded. TSH and fT4 data were log-transformed and the central 95% used to calculate reference intervals. We assessed whether these data were normally distributed. We compared samples spanning the reference intervals for both TSH and fT4 between different assays looking at biases.

RESULTS:

From a population of 1,606 subjects, 140 males (18%) and 284 females (34%) were excluded. The central population 95% for TSH was 0.43-3.28 mU/L and for fT4 10.8-16.8 pmol/L. There were no age- or sex-related differences. For both analytes the distribution was not significantly different to a Gaussian distribution (p>0.05). For 5 commonly used assays for TSH, the maximum difference in the upper limit of the TSH reference interval was 0.48 mU/L and for fT4 the maximum difference for the upper reference limit was 4.1 pmol/L.

CONCLUSIONS:

A substantial proportion of apparently healthy persons have subclinical thyroid disease. These subjects must be excluded for any thyroid hormone reference interval studies. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS:

Key terms ; Bias; Gaussian distribution; TSH reference intervals; free T4 reference intervals; thyroid antibodies

PMID: 27333057 [PubMed - as supplied by publisher]

ncbi.nlm.nih.gov/pubmed/273...

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  • When more care is taken we see narrower reference intervals, as in this study. The reference interval reports the middle 95% of the presumed healthy population. It is not a diagnostic range, if it were only 2.5% of any population would be obese.

  • Fully agree that if you make any assumption about the percentage, then that assumption itself underlies the definition that results. Hence it can be very misleading.

  • "must be excluded for any thyroid hormone reference interval studies" ... This is what Völzke did: ncbi.nlm.nih.gov/pubmed/157... getting ranges as follows:

    TSH 0.25-2.12 mIU/l - T3v 3.8-7.0 pmol/l - T4v 8.3-18.9 pmol/l

    "African-Americans with very low incidence of Hashimoto thyroiditis have a mean TSH level of 1.18 mU/liter strongly suggest that this value is the true normal mean for a normal population" ncbi.nlm.nih.gov/pubmed/161...

  • Obtaining credible ranges for thyroid analyses is not easy, because of the likelihood of hidden pathologies in the socalled normals. Looking at the figures, I do know that Abbott reads a bit low in TSH, and scaling up to more usual ranges, would come out then at about 0.6-4.5 which is a generally accepted range in other test platforms from other manufacturers. I am a bit surprised at the FT4 range. This is because the total T4 range is around 55-140 mol/L (a ratio of about 2.5/1 top/bottom). Total assays are very well controlled, much better than free thyroid hormone assays so I would expect a ratio for FT4 close to 2/1 which most other assays find. The smaller ratio here might well lie in the design of the test, which has never been particularly well regarded as an example.

  • I'm surprised the FT4 top end was so low. Shame they didn't include Ft3.

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