Main Article Content
: Reference range, TSH, Antithyroid antibodies, Iran
Background: Current reference values for thyroid function tests are based on data from different ethnicities and geographical areas. Therefore, our aim was to select criteria from the guidelines proposed by the National Academy of Clinical Biochemistry (NACB) and to determine the TSH and T4 reference limits in the iodine-sufficient area of Isfahan, a metropolitan city in Iran.
Materials and methods: This study was conducted within the framework of “Isfahan Thyroid Study (ITS)” an ongoing prospective cohort that started in 2006 (n=2523) until 2011 (n=711) and included participants above the age of twenty. We measured TSH, T4, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb).
Results: Based on the NACB criteria, 1899 participants were included in 2006(58.5% male) and 377 in 2011(62.3% male). The mean± SD age was 39.66 ±12.71 and 48.96±12.35 in 2006 and 2011, respectively.
The mean± SD for TSH was 2.0±1.19 and 2.11±1.11 mU/l and T4 was 6.67±1.47 and 8.3±2.95 μg /dl in 2006 and 2011, respectively.
In 2006, the 2.5th percentile of serum TSH levels was 0.4 mU/l (males: 0.4 mIU/L, females: 0.5 mIU/L) and the 97.5th percentile of serum TSH was 4.96 mU/l (males: 4.72 mU/l, females: 5. 3 mU/l). In 2011, the 2.5th percentile of serum TSH levels was 0.7 mU/l( males: 0.6 mIU/L, females: 0.77 mIU/L) and 97.5th percentiles of serum TSH was 4.9 mU/l(males: 5.7 mU/l, females :5. 57 mU/l).
Conclusion: This study determined age and sex specific TSH and T4 reference ranges in the Isfahanian population, which could theoretically enable clinicians to classify patients more accurately.
2. Demers, L.M. and C.A. Spencer, Laboratory medicine practice guidelines: laboratory support for the diagnosis and monitoring of thyroid disease. Clin Endocrinol, 2003. 58(2): p. 138-40.
3. Klee, G.G. and I.D. Hay, Biochemical testing of thyroid function. Endocrinology and metabolism clinics of North America, 1997. 26(4): p. 763-775.
4. Chan, A.O., Y.P. Iu, and C.C. Shek, The reference interval of thyroid-stimulating hormone in Hong Kong Chinese. J Clin Pathol. 2011 May;64(5):433-6. doi(2011 Mar 21): p. 10.1136/jcp.2010.087627.
5. Yoshihara, A., et al., Reference limits for serum thyrotropin in a Japanese population. Endocr J, (2011 May 7): p. 2011;58(7):585-8.
6. Vanderpump, M., et al., The incidence of thyroid disorders in the community: a twenty‐year follow‐up of the Whickham Survey. Clinical endocrinology, 1995. 43(1): p. 55-68.
7. Guan, H., 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. Clinical endocrinology, 2008. 69(1): p. 136-141.
8. Hollowell, J.G., et al., Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). The Journal of Clinical Endocrinology & Metabolism, 2002. 87(2): p. 489-499.
9. Baloch, Z., et al., National Academy of Clinical Biochemistry. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid, 2003. 13(1): p. 3-126.
10. Schalin-Jantti, C., et al., Serum TSH reference interval in healthy Finnish adults using the Abbott Architect 2000i Analyzer. Scand J Clin Lab Invest. 2011 Jul;71(4):344-9. doi(2011 Mar 23): p. 10.3109/00365513.2011.568630.
11. Wartofsky, L. and R.A. Dickey, The evidence for a narrower thyrotropin reference range is compelling. The Journal of Clinical Endocrinology & Metabolism, 2005. 90(9): p. 5483-5488.
12. Brabant, G., et al., Is there a need to redefine the upper normal limit of TSH? European Journal of Endocrinology, 2006. 154(5): p. 633-637.
13. Aghini-Lombardi, F., et al., The spectrum of thyroid disorders in an iodine-deficient community: the Pescopagano survey. The Journal of Clinical Endocrinology & Metabolism, 1999. 84(2): p. 561-566.
14. Laurberg, P., et al., Iodine intake and the pattern of thyroid disorders: a comparative epidemiological study of thyroid abnormalities in the elderly in Iceland and in Jutland, Denmark. The Journal of Clinical Endocrinology & Metabolism, 1998. 83(3): p. 765-769.
15. Surks, M.I., G. Goswami, and G.H. Daniels, The thyrotropin reference range should remain unchanged. The Journal of Clinical Endocrinology & Metabolism, 2005. 90(9): p. 5489-5496.
16. Surks, M.I. and J.G. Hollowell, Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. The Journal of Clinical Endocrinology & Metabolism, 2007. 92(12): p. 4575-4582.
17. Atzmon, G., et al., Extreme longevity is associated with increased serum thyrotropin. The Journal of Clinical Endocrinology & Metabolism, 2009. 94(4): p. 1251-1254.
18. Bremner, A.P., et al., Age-related changes in thyroid function: a longitudinal study of a community-based cohort. The Journal of Clinical Endocrinology, 2012. 97(5): p. 1554-1562.
19. Boucai, L. and M.I. Surks, Reference limits of serum TSH and free T4 are significantly influenced by race and age in an urban outpatient medical practice. Clinical endocrinology, 2009. 70(5): p. 788-793.
20. Boucai, L., J.G. Hollowell, and M.I. Surks, An approach for development of age-, gender-, and ethnicity-specific thyrotropin reference limits. Thyroid, 2011. 21(1): p. 5-11.
21. Amouzegar, A., et al., Reference limit of thyrotropin (TSH) and free thyroxine (FT4) in thyroperoxidase positive and negative subjects: a population based study. J Endocrinol Invest. 2013 Dec;36(11):950-4. doi(2013 Jul 15): p. 10.3275/9033.
22. Aminorroaya, A., et al., Incidence of thyroid dysfunction in an Iranian adult population: the predictor role of thyroid autoantibodies: results from a prospective population-based cohort study. European Journal of Medical Research, 2017. 22(1): p. 21.
23. Aminorroaya, A., et al., The TSH levels and risk of hypothyroidism: Results from a population based prospective cohort study in an Iranian adult's population. European journal of internal medicine, 2017. 41: p. 55-61.
24. Adibi, A., et al., Normal values of thyroid gland in Isfahan, an iodine replete area. Journal of Research in Medical Sciences, 2008. 13(2): p. 55-60.
25. Li, C., et al., An epidemiological study of the serum thyrotropin reference range and factors that influence serum thyrotropin levels in iodine sufficient areas of China. Endocr J, (2011 Sep 30): p. 2011;58(11):995-1002.
26. Kim, W.G., et al., Thyroid Stimulating Hormone Reference Range and Prevalence of Thyroid Dysfunction in the Korean Population: Korea National Health and Nutrition Examination Survey 2013 to 2015. Endocrinology and Metabolism, 2017. 32(1): p. 106-114.
27. Mariotti, S., et al., The aging thyroid. Endocr Rev, 1995. 16(6): p. 686-715.
28. Valeix, P., et al. Thyroid hormone levels and thyroid dysfunction of French adults participating in the SU. VI. MAX study. in Annales d'endocrinologie. 2004.
29. Hubl, W., et al., Reference intervals for thyroid hormones on the architect analyser. Clinical Chemistry and Laboratory Medicine, 2002. 40(2): p. 165-166.
30. Wartofsky, L. and R.A. Dickey, The evidence for a narrower thyrotropin reference range is compelling. J Clin Endocrinol Metab, 2005. 90(9): p. 5483-8.
31. Volzke, H., et al., Reference intervals of serum thyroid function tests in a previously iodine-deficient area. Thyroid, 2005. 15(3): p. 279-85.
32. Völzke, H., et al., Reference levels for serum thyroid function tests of diagnostic and prognostic significance. Hormone and metabolic research, 2010. 42(11): p. 809-814.
33. Surks, M.I. and J.G. Hollowell, 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 Oct 2): p. 2007 Dec;92(12):4575-82.
34. Fontes, R., et al., Reference interval of thyroid stimulating hormone and free thyroxine in a reference population over 60 years old and in very old subjects (over 80 years): comparison to young subjects. Thyroid research, 2013. 6(1): p. 13.
35. Oliveira, J.H., et al., Investigating the paradox of hypothyroidism and increased serum thyrotropin (TSH) levels in Sheehan’s syndrome: characterization of TSH carbohydrate content and bioactivity. The Journal of Clinical Endocrinology & Metabolism, 2001. 86(4): p. 1694-1699.
36. Estrada, J.M., et al., Thyrotropin isoforms: implications for thyrotropin analysis and clinical practice. Thyroid. 2014 Mar;24(3):411-23. doi(2013 Dec 13): p. 10.1089/thy.2013.0119.
37. Jensen, E., et al., Establishment of a serum thyroid stimulating hormone (TSH) reference interval in healthy adults. The importance of environmental factors, including thyroid antibodies. Clinical Chemistry and Laboratory Medicine, 2004. 42(7): p. 824-832.
38. Kratzsch, J., 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(8): p. 1480-6.
39. Tunbridge, W., et al., The spectrum of thyroid disease in a community: the Whickham survey. Clinical endocrinology, 1977. 7(6): p. 481-493.
40. Spencer, C.A., et al., National Health and Nutrition Examination Survey III thyroid-stimulating hormone (TSH)-thyroperoxidase antibody relationships demonstrate that TSH upper reference limits may be skewed by occult thyroid dysfunction. J Clin Endocrinol Metab, 2007. 92(11): p. 4236-40.
41. Boucai, L. and M.I. Surks, Reference limits of serum TSH and free T4 are significantly influenced by race and age in an urban outpatient medical practice. Clin Endocrinol (Oxf). 2009 May;70(5):788-93. doi(2008 Aug 25): p. 10.1111/j.1365-2265.2008.03390.x.
42. Hamilton, T.E., et al., Thyrotropin levels in a population with no clinical, autoantibody, or ultrasonographic evidence of thyroid disease: implications for the diagnosis of subclinical hypothyroidism. The Journal of Clinical Endocrinology & Metabolism, 2008. 93(4): p. 1224-1230.
43. Mirjanic-Azaric B, I.S. and, and S. N., The Impact of Serum Triiodothyronine to Thyroxine (T3/ T4) Ratio in Euthyroid Subjects. Annals Thyroid Res, 2016. 2(2): p. 66-68.