Abstract
Background: Previous studies with mainly selected populations have proposed contradicting reference ranges for thyroid-stimulating hormone (TSH) and have disagreed on how screening, age and gender affect them. This study aimed to determine a TSH reference range on the Abbott Architect ci8200 integrated system in a large, nationwide, stratified random sample. To our knowledge this is the only study apart from the NHANES III that has addressed this issue in a similar nationwide setting. The effects of age, gender, thyroid peroxidase antibody (TPOAb)-positivity and medications on TSH reference range were also assessed.
Methods: TSH was measured from 6247 participants randomly drawn from the population register to represent the Finnish adult population. TSH reference ranges were established of a thyroid-healthy population and its subpopulations with increasing and cumulative rigour of screening: screening for overt thyroid disease (thyroid-healthy population, n=5709); screening for TPOAb-positivity (risk factor-free subpopulation, n=4586); and screening for use of any medications (reference subpopulation, n=1849).
Results: The TSH reference ranges of the thyroid-healthy population, and the risk factor-free and reference subpopulations were 0.4–4.4, 0.4–3.7 and 0.4–3.4 mU/L (2.5th–97.5th percentiles), respectively. Although the differences in TSH between subgroups for age (p=0.002) and gender (p=0.005) reached statistical significance, the TSH distribution curves of the subgroups were practically superimposed.
Conclusions: We propose 0.4–3.4 mU/L as a TSH reference range for adults for this platform, which is lower than those presently used in most laboratories. Our findings suggest that intensive screening for thyroid risk factors, especially for TPOAb-positivity, decreases the TSH upper reference limit.
References
1. Demers LM, Spencer CA, editors. Laboratory medicine practice guidelines: laboratory support for the diagnosis and monitoring of thyroid disease. Washington, DC: National Academy of Clinical Biochemistry, 2002.Search in Google Scholar
2. Surks MI, Boucai L. Age- and race-based serum thyrotropin reference limits. J Clin Endocrinol Metab 2010;95:496–502.10.1210/jc.2009-1845Search in Google Scholar PubMed
3. Surks MI, Hollowell JG. Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. J Clin Endocrinol Metab 2007;92:4575–82.10.1210/jc.2007-1499Search in Google Scholar PubMed
4. Friis-Hansen L, Hilsted L. Reference intervals for thyreotropin and thyroid hormones for healthy adults based on the NOBIDA material and determined using a Modular E170. Clin Chem Lab Med 2008;46:1305–12.10.1515/CCLM.2008.258Search in Google Scholar PubMed
5. Atzmon G, Barzilai N, Hollowell JG, Surks MI, Gabriely I. Extreme longevity is associated with increased serum thyrotropin. J Clin Endocrinol Metab 2009;94:1251–4.10.1210/jc.2008-2325Search in Google Scholar PubMed PubMed Central
6. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002;87:489–99.10.1210/jcem.87.2.8182Search in Google Scholar PubMed
7. Takeda K, Mishiba M, Sugiura H, Nakajima A, Kohama M, Hiramatsu S. Evaluated reference intervals for serum free thyroxine and thyrotropin using the conventional outliner rejection test without regard to presence of thyroid antibodies and prevalence of thyroid dysfunction in Japanese subjects. Endocr J 2009;56:1059–66.10.1507/endocrj.K09E-123Search in Google Scholar PubMed
8. Schalin-Jäntti C, Tanner P, Välimäki MJ, Hämäläinen E. Serum TSH reference interval in healthy Finnish adults using the Abbott Architect 2000i Analyzer. Scand J Clin Lab Invest 2011;71:344–9.10.3109/00365513.2011.568630Search in Google Scholar PubMed
9. O’Leary PC, Feddema PH, Michelangeli VP, Leedman PJ, Chew GT, Knuiman M, et al. Investigations of thyroid hormones and antibodies based on a community health survey: the Busselton thyroid study. Clin Endocrinol (Oxf) 2006;64:97–104.10.1111/j.1365-2265.2005.02424.xSearch in Google Scholar PubMed
10. Hoogendoorn EH, Hermus AR, de Vegt F, Ross HA, Verbeek AL, Kiemeney LA, et al. Thyroid function and prevalence of anti-thyroperoxidase antibodies in a population with borderline sufficient iodine intake: influences of age and sex. Clin Chem 2006;52:104–11.10.1373/clinchem.2005.055194Search in Google Scholar PubMed
11. Waise A, Price HC. The upper limit of the reference range for thyroid-stimulating hormone should not be confused with a cut-off to define subclinical hypothyroidism. Ann Clin Biochem 2009;46:93–8.10.1258/acb.2008.008113Search in Google Scholar PubMed
12. Kratzsch J, Fiedler GM, Leichtle A, Brügel M, Buchbinder S, Otto L, et al. New reference intervals for thyrotropin and thyroid hormones based on National Academy of Clinical Biochemistry criteria and regular ultrasonography of the thyroid. Clin Chem 2005;51:1480–6.10.1373/clinchem.2004.047399Search in Google Scholar
13. Zöphel K, Wunderlich G, Grüning T, Koch R, Döge H, Kotzerke J. Where does subclinical hypothyroidism start? Implications for the definition of the upper reference limit for thyroid stimulating hormone. Nuklearmedizin 2005;44:56–61.10.1055/s-0038-1623926Search in Google Scholar
14. Zöphel K, Wunderlich G, Kotzerke J. Should we really determine a reference population for the definition of thyroid-stimulating hormone reference interval? Clin Chem 2006;52:329–30.10.1373/clinchem.2005.060111Search in Google Scholar
15. Laiho J, Djerf K, Lehtonen R. Sampling design. In: Heistaro S, editor. Methodology report, Health 2000 Survey. Helsinki: National Public Health Institute, 2008:13–5. Available from: http://www.terveys2000.fi/doc/methodologyrep.pdf. Accessed on 7 June, 2014.Search in Google Scholar
16. O’Leary PC, Boyne P, Atkinson G, Mileham KJ, James I. Longitudinal study of serum thyroid hormone levels during normal pregnancy. Int J Gynaecol Obstet 1992;38:171–9.10.1016/0020-7292(82)90125-4Search in Google Scholar
17. Kurioka H, Takahashi K, Miyazaki K. Maternal thyroid function during pregnancy and puerperal period. Endocr J 2005;52:587–91.10.1507/endocrj.52.587Search in Google Scholar
18. Kundra P, Burman KD. The effect of medications on thyroid function tests. Med Clin North Am 2012;96:283–95.10.1016/j.mcna.2012.02.001Search in Google Scholar
19. Wiegratz I, Kutschera E, Lee JH, Moore C, Mellinger U, Winkler UH, et al. Effect of four oral contraceptives on thyroid hormones, adrenal and blood pressure parameters. Contraception 2003;67:361–6.10.1016/S0010-7824(03)00006-4Search in Google Scholar
20. Bjoro T, Holmen J, Krüger O, Midthjell K, Hunstad K, Schreiner T, et al. Prevalence of thyroid disease, thyroid dysfunction and thyroid peroxidase antibodies in a large, unselected population. The Health Study of Nord-Trondelag (HUNT). Eur J Endocrinol 2000;143:639–47.10.1530/eje.0.1430639Search in Google Scholar PubMed
21. Guan H, Shan Z, Teng X, Li Y, Teng D, Jin Y, et al. Influence of iodine on the reference interval of TSH and the optimal interval of TSH: results of a follow-up study in areas with different iodine intakes. Clin Endocrinol (Oxf) 2008;69:136–41.10.1111/j.1365-2265.2007.03150.xSearch in Google Scholar PubMed
22. Spencer CA, Takeuchi M, Kazarosyan M, MacKenzie F, Beckett GJ, Wilkinson E. Interlaboratory/intermethod differences in functional sensitivity of immunometric assays of thyrotropin (TSH) and impact on reliability of measurement of subnormal concentrations of TSH. Clin Chem 1995;41:367–74.10.1093/clinchem/41.3.367Search in Google Scholar
23. Chan AO, Iu YP, Shek CC. The reference interval of thyroid-stimulating hormone in Hong Kong Chinese. J Clin Pathol 2011;64:433–6.10.1136/jcp.2010.087627Search in Google Scholar PubMed
24. Eskelinen S, Suominen P, Vahlberg T, Löppönen M, Isoaho R, Kivelä SL, et al. The effect of thyroid antibody positivity on reference intervals for thyroid stimulating hormone (TSH) and free thyroxine (FT4) in an aged population. Clin Chem Lab Med 2005;43:1380–5.10.1515/CCLM.2005.236Search in Google Scholar PubMed
25. Jensen E, Hyltoft Petersen P, Blaabjerg O, Hansen PS, Brix TH, Kyvik KO, et al. Establishment of a serum thyroid stimulating hormone (TSH) reference interval in healthy adults. The importance of environmental factors, including thyroid antibodies. Clin Chem Lab Med 2004;42:824–32.Search in Google Scholar
26. Surks MI. TSH reference limits: new concepts and implications for diagnosis of subclinical hypothyroidism. Endocr Pract 2013;19:1066–9.10.4158/EP13246.COSearch in Google Scholar PubMed
27. Statistical Yearbook of Finland 2012. Helsinki: Statistics Finland, 2012:97. Available from: http://www.stat.fi/tup/julkaisut/tiedostot/julkaisuluettelo/yyti_stv_201200_2012_6270_net.pdf. Accessed on 7 June, 2014.Search in Google Scholar
28. Varo P, Saari E, Paaso A, Koivistoinen P. Iodine in Finnish foods. Int J Vitam Nutr Res 1982;52:80–9.Search in Google Scholar
29. Lamberg BA, Haikonen M, Mäkelä M, Jukkara A, Axelson E, Welin MG. Further decrease in thyroidal uptake and disappearance of endemic goitre in children after 30 years of iodine prophylaxis in the east of Finland. Acta Endocrinol (Copenh) 1981;98:205–9.10.1530/acta.0.0980205Search in Google Scholar PubMed
30. Bülow Pedersen I, Laurberg P, Knudsen N, Jørgensen T, Perrild H, Ovesen L, et al. A population study of the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure. Clin Endocrinol (Oxf) 2005;62:713–20.10.1111/j.1365-2265.2005.02284.xSearch in Google Scholar PubMed
Supplemental Material
The online version of this article (DOI 10.1515/cclm-2014-0287) offers supplementary material, available to authorized users.
©2014 by De Gruyter
