Metin YILDIRIMKAYA, Gönül ERDEN, Ayşe Özden BARAZİ, Günay TEZCAN

Biological variation and reference change values of TSH, free T3, and free T4 levels in serum of healthy Turkish individuals

Amaç: Serum TSH, T4, T3 düzeyleri, tiroid fonksiyon bozukluklarının tanısında önemli bir yere sahiptir. Tiroid fonksiyon testleri dikkate değer düzeyde biyolojik varyasyona sahiptir. Biyolojik varyasyonun bileşenlerinin incelenmesi, topluma dayalı referans aralığın kullanılabilirliğinin değerlendirilebilmesi için gereklidir. Çeşitli yayınlarda, biyolojik varyasyon değerleri farklı bildirilebilmektedir. Biz bu çalışmada; TSH, T4, T3 düzeyleri için biyolojik varyasyon ve referans değişim değerlerini araştırmayı amaçladık. Yöntem ve Gereç: Gönüllü, 46 sağlıklı birey (yaş ortalaması 33.5 ± 9 yıl) çalışmaya alındı. Altı hafta boyunca, ikişer hafta aralıklarla, her bir bireyden toplamda dörder tane serum örneği toplandı. Serum TSH, serbest T3, serbest T4 düzeyleri imrhünoluminometrik test ile bir otoanalizörde ölçüldü. Bulgular: TSH, serbest T3, serbest T4 için birey-içi / bireyler-arası biyolojik varyasyonlar sırasıyla % 37.21/37.6, % 22.32/2.43, % 13.26/7.47 idi. Referans değişim değerleri sırasıyla % 104.0, % 63.1, % 38.8 bulundu (P < 0.05). Sonuç: TSH, serbest T3, serbest T4 anlamlı düzeyde birey-içi biyolojik varyasyon göstermektedir. TSH için topluma dayalı referans aralığın kullanılabilirliği sınırlı değere sahiptir. Tiroid fonksiyolarının takibi, incelenmesi durumunda biyolojik varyasyonun dikkate alınması gerektiği unutulmamalıdır.

Sağlıklı Türk bireylerde TSH, serbest T3 sebest T4 düzeylerinin biyolojik varyasyonu ve referans değişim değerleri

Aim: Thyrotropin (TSH), thyroxine (T4) and triiodothyronine (T3) levels in serum are important for diagnosis of thyroid dysfunction. Thyroid function tests have considerable biological variations. Evaluation of the components of biological variation is essential to assess the usefulness of reference values and to evaluate significance of changes in serial results from an individual. Published estimates may show disagreement about the values of biological variations. Not many studies exist at present that evaluate the reference change values (RCV) of these parameters. The aim of this study was to determine the biological variations of TSH, free T3, and free T4 and to calculate their RCV values in serum of healthy individuals in our population. Materials and Methods: The study group included 46 healthy volunteer subjects (mean age 33.5 ± 9 years). During six consecutive weeks, four blood samples were obtained for each subject at two-week intervals. Serum TSH, free T3, and free T4 levels were measured by an immunoluminometric assay on a random-access analyzer. Results: The intra-individual/inter-individual biological variations (defined in terms of percent coefficient of variation, CV) for serum TSH, fT3, and fT4 were 37.21/37.6%, 22.32/2.43%, and 13.26/7.47% respectively. The RCVs for TSH, fT3, and fT4 were 104.0%, 63.1%, and 38.8%, respectively (P < 0.05). Conclusions: TSH, fT3, and fT4 showed a significant intra-individual biological variation. The utility of population-based reference intervals for TSH would be of limited use. During evaluation, especially when monitoring thyroid functions, the estimates of biological variations and the RCV values should be considered.

PDF

___

1. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med 2000; 160: 526-34.
2. Fatourechi .V. Subclinical thyroid disease. Mayo Clin Proc 2001; 76: 413-7.
3. Jarlov AE, Nygaard B, Hegedüs L, Hartling SG, Hansen JM. Observer variation in the clinical and laboratory evaluation of patients with thyroid dysfunction and goiter. Thyroid 1998; 8: 393-8.
4. Andersen S, Bruun NH, Pedersen KM, Laurberg P. Biological variation is important for interpretation of thyroid function tests. Thyroid 2003; 13(11): 1069-78.
5. Fraser CG, Harris EK. Generation and application of data on biological variation in clinical chemistry. Crit Rev Clin Lab Sci 1989; 27(5): 409-37.
6. Maes M, Mommen K, Hendrickx D, Peeters D, D'Hondt P, Ranjan R et al. Components of biological variation, including seasonality, in blood concentrations of TSH, TT3, FT4, PRL, cortisol and testosterone in healthy volunteers. Clin Endocrinol 1997; 46: 587-98.
7. Harris EK, Kanofsky P, Shakarji G, Cotlove E. Biological and analytic components of variation in long-term studies of serum constituents in normal subjects. II Estimating biological components of variation. Clin Chem 1970; 16: 1022-7.
8. Harris EK. Statistical aspects of reference values in clinical pathology. Prog Clin Pathol 1981; 8: 45-66.
9. Fraser CG. Desirable performance standards for clinical chemistry tests. Adv Clin Chem 1983; 23: 299-339.
10. Ornstein DK, Smith DS, Rao GS, Basler JW, Ratliff TL, Catalona WJ. Biological variation of total, free and percent free serum prostate specific antigen levels in screening volunteers. J Urol 1997; 157(6): 2179-82.
11. Talwar DK, Azharuddin MK, Williamson C, Teoh YP, McMillan DC, O'Reilly DSJ. Biological variation of vitamins in blood of healthy individuals. Clin Chem 2005; 51(11): 2145-50.
12. Yildirimkaya MM, Bilgi C, Ozata M, Nazaroglu NK, Gundogan MA et al. Biological variation of serum lipids and lipoproteins in patients with clinically well controlled non insulin dependent diabetes mellitus. Endocrine J 1996; 43(3): 345-51.
13. Browning Margaret CK, Ford RP, Callaghan SJ. Intra- and interindividual biological variation of five analytes used in assessing thyroid function: implications for necessary standards of performance and the interpretation of results. Clin Chem 1986; 32(6): 962-6.
14. Fraser CG. Fraser CG, editor. Biological variation: from principles to practice. Washington, DC: AACC Press; 2001. pp. 1-145.
15. Harris EK. Effects of intra- and interindividual variation on the appropriate use of normal intervals. Clin Chem 1974; 20: 1535-42.
16. Lacher DA, Hughes JP, Carroll MD. Estimate of biological variation of laboratory analytes based on third national health and nutrition examination survey. Clin Chem 2005; 51: 450-2.
17. Ricos C, Arbos MA. Quality goals for hormone testing. Ann Clin Biochem 1990; 27: 353-8.
18. Andersen S, Pedersen KM, Bruun NH, Laurberg P. Narrow individual variations in serum T4 and T3 in normal subjects: a clue to the understanding of subclinical thyroid disease. J Clin Endocrinol Met 2002; 87: 1068-72.
19. Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: The Rotterdam Study. Ann Intern Med 2000; 132: 270-8.
20. 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.
21. Pearce CJ, Himsworth RL. Serum iodothyronine concentrations during introduction of thyroxine replacement therapy in hypothyroidism. Clin Endocrinol 1986; 25: 303-1.1.
22. Meier CA, Maisey MN, Lowry A, Muller J, Smith MA. Interindividual differences in the pituitary-thyroid axis influence the interpretation of thyroid function tests. Clin Endocrinol 1993; 39: 101-7.
23. Fraser CG. Inherent biological variation and reference values. Clin Chem Lab Med 2004; 42(7): 758-64.