Abstract
Our aims were: 1) to analyze the effect of the methodology used to derive clinically feasible cut-off values for thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb), which exhibit highly skewed distributions; and 2) to describe the influence of thyroid antibodies on thyroid stimulating hormone (TSH) and free thyroxine (FT4) reference intervals among thyroid disease-free aged subjects. The reference population consisted of 1086 individuals with a mean age of 73years. The impacts of TPOAb and/or TgAb positivity on the reference intervals of TSH and FT4 were evaluated by both including and excluding subjects with elevated thyroid antibodies. The exclusion of subjects with elevated thyroid antibodies had no effect on the FT4 reference interval in either gender or on the TSH reference interval in men. Among women, the exclusion of 196 (34%) thyroid antibody-positive subjects resulted in lowering of the upper reference limit of TSH from 7.2 to 5.8mIU/L. When the more stringent “mode-method” by summing mode+(mode–2.5th percentile) was used, 334 women (58%) were excluded and the upper reference limit of TSH remained essentially identical. Regardless of the statistical methodology used to derive cut-off values, the effect of antibody positivity was found to be less than expected.
References
1. Faulkner WR, Demers LM. Importance of age-dependent reference values in biochemical testing: are we including the elderly population? Clin Chem 1994; 40:855–6.10.1093/clinchem/40.6.855Search in Google Scholar
2. Bjoro T, Holmen J, Kruger 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
3. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med 2000; 160:526–34.10.1001/archinte.160.4.526Search in Google Scholar
4. 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
5. Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf) 1995; 43:55–68.10.1111/j.1365-2265.1995.tb01894.xSearch in Google Scholar
6. Sawin CT, Castelli WP, Hershman JM, McNamara P, Bacharach P. The aging thyroid. Thyroid deficiency in the Framingham Study. Arch Intern Med 1985; 145:1386–8.10.1001/archinte.1985.00360080056006Search in Google Scholar
7. Hueston WJ. Treatment of hypothyroidism. Am Fam Physician 2001; 64:1717–24.Search in Google Scholar
8. The International Statistical Classification of Diseases and Related Health Problems, 10th revision. Geneva: WHO, 1997.Search in Google Scholar
9. Classification of Medicines (ATC) and Defined Daily Doses (DDD). Helsinki: National Agency for Medicines and Social Insurance Institution.Search in Google Scholar
10. Lopponen MK, Isoaho RE, Raiha IJ, Vahlberg TJ, Loikas SM, Takala TI, et al. Undiagnosed diseases in patients with dementia – a potential target group for intervention. Dement Geriatr Cogn Disord 2004; 18:321–9.10.1159/000080126Search in Google Scholar
11. Linjakumpu T, Hartikainen S, Klaukka T, Veijola J, Kivela SL, Isoaho R. Use of medications and polypharmacy are increasing among the elderly. J Clin Epidemiol 2002; 55:809–17.10.1016/S0895-4356(02)00411-0Search in Google Scholar
12. Kairisto V, Poola A. Software for illustrative presentation of basic clinical characteristics of laboratory tests – GraphROC for Windows. Scand J Clin Lab Invest 1995; 222(Suppl):43–60.10.3109/00365519509088450Search in Google Scholar PubMed
13. Lazarus JH, Burr ML, McGregor AM, Weetman AP, Ludgate M, Woodhead JS, et al. The prevalence and progression of autoimmune thyroid disease in the elderly. Acta Endocrinol (Copenh) 1984; 106:199–202.10.1530/acta.0.1060199Search in Google Scholar PubMed
14. Huber G, Staub JJ, Meier C, Mitrache C, Guglielmetti M, Huber P, et al. Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies. J Clin Endocrinol Metab 2002; 87:3221–6.10.1210/jcem.87.7.8678Search in Google Scholar
15. Sundbeck G, Eden S, Jagenburg R, Lundberg PA, Lind-stedt G. Prevalence of serum antithyroid peroxidase antibodies in 85-year-old women and men. Clin Chem 1995; 41:707–12.10.1093/clinchem/41.5.707Search in Google Scholar
16. Ligthart GJ, Corberand JX, Geertzen HG, Meinders AE, Knook DL, Hijmans W. Necessity of the assessment of health status in human immunogerontological studies: evaluation of the SENIEUR protocol. Mech Ageing Dev 1990; 55:89–105.10.1016/0047-6374(90)90108-RSearch in Google Scholar
17. 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 (www.nacb.org), 2002 (Thyroid 2003;13:3–126).Search in Google Scholar
18. 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
19. Roberts CG, Ladenson PW. Hypothyroidism. Lancet 2004; 363:793–803.10.1016/S0140-6736(04)15696-1Search in Google Scholar
20. Taimela E, Kairisto V, Koskinen P, Leino A, Irjala K. Reference intervals for serum thyrotropin, free thyroxine and free triiodothyronine in healthy adults in Finland, measured by an immunoautomate based on time-resolved fluorescence (AutoDELFIA). Eur J Clin Chem Clin Biochem 1997; 35:889–90.Search in Google Scholar
21. Keffer JH. Preanalytical considerations in testing thyroid function. Clin Chem 1996; 42:125–34.10.1093/clinchem/42.1.125Search in Google Scholar
22. Surks MI, Sievert R. Drugs and thyroid function. N Engl J Med 1995; 333:1688–94.10.1056/NEJM199512213332507Search in Google Scholar PubMed
©2005 by Walter de Gruyter Berlin New York