Challenges in Thyroid Function Testing: Interferences and Clinical Implications
Main Article Content
Abstract
In recent decades, significant advancements have been made in the methodologies used for evaluating thyroid dysfunctions. These advancements include the development of radioimmunoassays, immunometric assays, and liquid chromatography coupled with mass spectrometry.
The main thyroid function tests include thyroid-stimulating hormone (TSH) and the measurement of triiodothyronine (T3) and thyroxine (T4), including their total and free fractions.
Over time, different generations of TSH tests have been developed, starting from radioimmunoassays to immunometric assays, and more recently, tests utilizing fluorophores and chemiluminescent molecules. The third-generation tests are currently the most widely used due to their high sensitivity and specificity. Thyroid-stimulating hormone is preferred as the initial test for evaluating thyroid function since it has a log-linear relationship with free T4 levels, enabling the identification of subclinical hypothyroidism and subclinical hyperthyroidism.
The reference range for normal TSH levels is typically between 0.45 and 4.5 mIU/L. However, there can be variations in TSH levels based on factors such as sex, age, and ethnicity. Specific reference values may be required for certain populations, such as the elderly, pregnancy, and neonates. In the elderly, an increase in TSH levels is expected. In the neonatal period, TSH levels are high after birth and take a few weeks to normalize. During pregnancy, various physiological changes occur, leading to alterations in thyroid hormones to meet fetal demands.
Laboratory interferences in thyroid hormone assays must be considered to ensure accurate results. Biotin interference can lead to falsely low TSH and falsely high free T3 and T4 levels. Macro-thyrotropin can cause elevated TSH levels with normal thyroid hormone levels. Heterophilic antibodies can also cause false results. Additionally, the evaluation of autoantibodies and markers used in thyroid cancer follow-up needs special attention.
Patients experiencing conditions like trauma, particularly in severe cases, may undergo changes in thyroid hormone levels, even without having a specific thyroid disease, which is called low triiodothyronine syndrome.
In conclusion, it is essential to be aware of potential laboratory interferences and consider individual variations to ensure accurate interpretation and appropriate management of patients.
Keywords:
thyroid function tests, hyperthyroidism, hypothyroidism, thyroid-stimulating hormone
Article Details
How to Cite
DE CARVALHO, Gisah Amaral; DROBRZENSKI, Beatriz.
Challenges in Thyroid Function Testing: Interferences and Clinical Implications.
Medical Research Archives, [S.l.], v. 11, n. 8, aug. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4340>. Date accessed: 13 may 2024.
doi: https://doi.org/10.18103/mra.v11i8.4340.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2. Matyjaszek-Matuszek B, Pyzik A, Nowakowski A, Jarosz MJ. Diagnostic methods of TSH in thyroid screening tests. Ann AgricEnviron Med. 2013;20(4):731-735.
3. Sánchez-Carbayo M, Mauri M, Alfayate R, Miralles C, Soria F. Analytical and clinical evaluation of TSH and thyroid hormones by electrochemiluminescent immunoassays. ClinBiochem. 1999;32(6):395-403. doi:10.1016/s0009-9120(99)00032-6
4. Carvalho GA, Perez CL, Ward LS. The clinical use of thyroid function tests. ArqBrasEndocrinolMetabol. 2013;57(3):193-204. doi:10.1590/s0004-27302013000300005
5. Spencer CA. Laboratory Thyroid Tests: A Historical Perspective. Thyroid. 2023;33(4):407-419. doi:10.1089/thy.2022.0397
6. Hansen PS, Brix TH, Sørensen TI, Kyvik KO, Hegedüs L. Major genetic influence on the regulation of the pituitary-thyroid axis: a study of healthy Danish twins. J Clin Endocrinol Metab. 2004;89(3):1181-1187. doi:10.1210/jc.2003-031641
7. Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004;291(2):228-238. doi:10.1001/jama.291.2.228
8. Brabant G, Prank K, Ranft U, et al. Physiological regulation of circadian and pulsatile thyrotropin secretion in normal man and woman. J ClinEndocrinolMetab. 1990;70(2):403-409. doi:10.1210/jcem-70-2-403
9. Hollowell JG, Staehling NW, Flanders WD, 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(2):489-499. doi:10.1210/jcem.87.2.8182
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11. Ramezani Tehrani F, Nazarpour S. Delivery factors and neonatal thyroid hormone levels: a systematic review. J Pediatr Endocrinol Metab. 2021;34(7):821-833. Published 2021 Apr 22. doi:10.1515/jpem-2020-0740
12. Eng L, Lam L. Thyroid Function During the Fetal and Neonatal Periods. Neoreviews. 2020;21(1):e30-e36. doi:10.1542/neo.21-1-e30
13. Vulsma T, Gons MH, de Vijlder JJ. Maternal-fetal transfer of thyroxine in congenital hypothyroidism due to a total organification defect or thyroid agenesis. NEngl J Med. 1989;321(1):13-16.doi:10.1056/NEJM198907063210103
14. American Academy of Pediatrics, Rose SR; Section on Endocrinology and Committee on Genetics, American Thyroid Association, et al. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics.2006;117(6):2290-2303.doi:10.1542/peds.2006-0915
15. Visser WE, Peeters RP. Interpretation of thyroid function tests during pregnancy. Best Pract Res Clin Endocrinol Metab. 2020;34(4):101431. doi:10.1016/j.beem.2020.101431
16. Korevaar TIM, Medici M, Visser TJ, PeetersRP. Thyroid disease in pregnancy: new insights in diagnosis and clinicalmanagement. Nat Rev Endocrinol. 2017;13(10):610-622.doi:10.1038/nrendo.2017.93
17. Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum [published correction appears in Thyroid. 2017 Sep;27(9):1212]. Thyroid. 2017;27(3):315-389. doi:10.1089/thy.2016.0457
18. Pop VJ, Broeren MA, Wiersinga WM, Stagnaro-Green A. Thyroid disease symptoms during early pregnancy do not identify women with thyroid hypofunction that should be treated. Clin Endocrinol (Oxf). 2017;87(6):838-843. doi:10.1111/cen.13433
19. Lazarus J, Brown RS, Daumerie C, Hubalewska-Dydejczyk A, Negro R, Vaidya B. 2014 European thyroid association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur Thyroid J. 2014;3(2):76-94. doi:10.1159/000362597
20. Cappola AR, Auchus RJ, El-Hajj Fuleihan G, et al. Hormones and Aging: An Endocrine Society Scientific Statement [published online ahead of print, 2023 Jun 16]. J ClinEndocrinolMetab. 2023;dgad225. doi:10.1210/clinem/dgad225
21. Waring AC, Arnold AM, Newman AB, Bùzková P, Hirsch C, Cappola AR. Longitudinal changes in thyroid function in the oldest old and survival: the cardiovascular health study all-stars study. J Clin Endocrinol Metab. 2012;97(11):3944-3950. doi:10.1210/jc.2012-2481
22. Bremner AP, Feddema P, Leedman PJ, et al. Age-related changes in thyroid function: a longitudinal study of a community-based cohort. J ClinEndocrinolMetab. 2012;97(5):1554-1562. doi:10.1210/jc.2011-3020
23. 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(12):4575-4582. doi:10.1210/jc.2007-1499
24. Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frölich M, Westendorp RG. Thyroid status, disability and cognitive function, and survival in old age. JAMA. 2004;292(21):2591-2599. doi:10.1001/jama.292.21.2591
25. Stott DJ, Rodondi N, Kearney PM, et al. Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism. N Engl J Med. 2017;376(26):2534-2544. doi:10.1056/NEJMoa1603825
26. Rodondi N, den Elzen WP, Bauer DC, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010;304(12):1365-1374. doi:10.1001/jama.2010.1361
27. Gencer B, Collet TH, Virgini V, et al. Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts. Circulation. 2012;126(9):1040-1049. doi:10.1161/CIRCULATIONAHA.112.096024
28. Chaker L, Baumgartner C, den Elzen WP, et al. Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis. J ClinEndocrinolMetab. 2015;100(6):2181-2191. doi:10.1210/jc.2015-1438
29. Collet TH, Gussekloo J, Bauer DC, et al. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. ArchIntern Med. 2012;172(10):799-809. doi:10.1001/archinternmed.2012.402
30. Blum MR, Bauer DC, Collet TH, et al. Subclinical thyroid dysfunction and fracture risk: a meta-analysis. JAMA. 2015;313(20): 2055-2065. doi:10.1001/jama.2015.5161
31. Guo J, Hong Y, Wang Z, Li Y. Analysis of the Incidence of Euthyroid Sick Syndrome in Comprehensive Intensive Care Units and Related Risk Factors. Front Endocrinol (Lausanne). 2021;12:656641. Published 2021 Jun 9. doi:10.3389/fendo.2021.656641
32. Mebis L, Debaveye Y, Visser TJ, Van den Berghe G. Changes within the thyroid axis during the course of critical illness. EndocrinolMetabClin North Am. 2006;35(4):807-x. doi:10.1016/j.ecl.2006.09.009
33. Fliers E, Boelen A. An update on non-thyroidal illness syndrome. J Endocrinol Invest. 2021;44(8):1597-1607. doi:10.1007/s40618-020-01482-4
34. Adler SM, Wartofsky L. The nonthyroidal illness syndrome. Endocrinol Metab Clin North Am. 2007;36(3):657-vi. doi:10.1016/j.ecl.2007.04.007
35. Biegelmeyer E, Scanagata I, Alves L, Reveilleau M, Schwengber FP, Wajner SM. T3 as predictor of mortality in any cause non-critically ill patients. Endocr Connect. 2021;10(8):852-860. Published 2021 Jul 28. doi:10.1530/EC-21-0080
36. Fliers E, Bianco AC, Langouche L, Boelen A. Thyroid function in critically ill patients. Lancet Diabetes Endocrinol. 2015;3(10):816-825. doi:10.1016/S2213-8587(15)00225-9
37. Economidou F, Douka E, Tzanela M, Nanas S, Kotanidou A. Thyroid function during critical illness. Hormones (Athens). 2011;10(2):117-124. doi:10.14310/horm.2002.1301
38. Mariotti S, Caturegli P, Piccolo P, Barbesino G, Pinchera A. Antithyroid peroxidase autoantibodies in thyroid diseases. J ClinEndocrinolMetab. 1990;71(3):661-669. doi:10.1210/jcem-71-3-661
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