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: 04 dec. 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.
References
1. Spencer CA. Assay of Thyroid Hormones and Related Substances. In: Feingold KR, Anawalt B, Blackman MR, et al., eds. Endotext. South Dartmouth (MA): MDText.com, Inc.; February 20, 2017.
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
10. Van Houcke SK, Van Uytfanghe K, Shimizu E, Tani W, Umemoto M, Thienpont LM. IFCC international conventional reference procedure for the measurement of free thyroxine in serum: International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Working Group for Standardization of Thyroid Function Tests (WG-STFT)(1). ClinChemLab Med. 2011;49(8):1275-1281. doi:10.1515/CCLM.2011.639
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
39. Poppe K, Bisschop P, Fugazzola L, Minziori G, Unuane D, Weghofer A. 2021 European Thyroid Association Guideline on Thyroid Disorders prior to and during Assisted Reproduction [published correction appears in EurThyroid J. 2021 Jun;10(3):268]. EurThyroid J. 2021;9(6):281-295. doi:10.1159/000512790
40. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1-133. doi:10.1089/thy.2015.0020
41. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis [published correction appears in Thyroid. 2017 Nov;27(11):1462]. Thyroid. 2016;26(10):1343-1421. doi:10.1089/thy.2016.0229
42. Abeillon-du Payrat J, Chikh K, Bossard N, et al. Predictive value of maternal second-generation thyroid-binding inhibitory immunoglobulin assay for neonatal autoimmune hyperthyroidism. Eur J Endocrinol. 2014;171(4):451-460. doi:10.1530/EJE-14-0254
43. Endo K, Kasagi K, Konishi J, et al. Detection and properties of TSH-binding inhibitor immunoglobulins in patients with Graves' disease and Hashimoto's thyroiditis. J ClinEndocrinolMetab. 1978;46(5):734-739. doi:10.1210/jcem-46-5-734
44. McLachlan SM, Rapoport B. Thyrotropin-blocking autoantibodies and thyroid-stimulating autoantibodies: potential mechanisms involved in the pendulum swinging from hypothyroidism to hyperthyroidism or vice versa. Thyroid. 2013;23(1):14-24. doi:10.1089/thy.2012.0374
45. Barbesino G, Tomer Y. Clinical review: Clinical utility of TSH receptor antibodies. J ClinEndocrinolMetab. 2013;98(6):2247-2255. doi:10.1210/jc.2012-4309
46. Mariotti S, Martino E, Cupini C, et al. Low serum thyroglobulin as a clue to the diagnosis of thyrotoxicosis factitia. N Engl J Med. 1982;307(7):410-412. doi:10.1056/NEJM198208123070705
47. Netzel BC, Grebe SK, Carranza Leon BG, et al. Thyroglobulin (Tg) Testing Revisited: Tg Assays, TgAb Assays, and Correlation of Results With Clinical Outcomes. J ClinEndocrinolMetab. 2015;100(8):E1074-E1083. doi:10.1210/jc.2015-1967
48. Wells SA Jr, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567-610. doi:10.1089/thy.2014.0335
49. Trimboli P, Giovanella L, Crescenzi A, et al. Medullary thyroid cancer diagnosis: an appraisal. Head Neck. 2014;36(8):1216-1223. doi:10.1002/hed.23449
50. Bjerre Knudsen L, Madsen LW, Andersen S, et al. Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation [published correction appears in Endocrinology. 2012 Feb;153(2):1000. Moerch, Ulrik [added]]. Endocrinology. 2010;151(4):1473-1486. doi:10.1210/en.2009-1272
51. Hegedüs L, Sherman SI, Tuttle RM, et al. No Evidence of Increase in Calcitonin Concentrations or Development of C-Cell Malignancy in Response to Liraglutide for Up to 5 Years in the LEADER Trial. Diabetes Care. 2018;41(3):620-622. doi:10.2337/dc17-1956
52. Soh SB, Aw TC. Laboratory Testing in Thyroid Conditions - Pitfalls and Clinical Utility. Ann Lab Med. 2019;39(1):3-14. doi:10.3343/alm.2019.39.1.3
53. Favresse J, Burlacu MC, Maiter D, Gruson D. Interferences with Thyroid Function Immunoassays: Clinical Implications and Detection Algorithm. Endocr Rev. 2018;39(5):830-850. doi:10.1210/er.2018-00119
54. Ylli D, Soldin SJ, Stolze B, et al. Biotin Interference in Assays for Thyroid Hormones, Thyrotropin and Thyroglobulin. Thyroid. 2021;31(8):1160-1170. doi:10.1089/thy.2020.0866
55. Sedel F, Papeix C, Bellanger A, et al. High doses of biotin in chronic progressive multiple sclerosis: a pilot study. MultSclerRelatDisord. 2015;4(2):159-169. doi:10.1016/j.msard.2015.01.005
56. Elston MS, Sehgal S, Du Toit S, Yarndley T, Conaglen JV. Factitious Graves' Disease Due to Biotin Immunoassay Interference-A Case and Review of the Literature. J ClinEndocrinolMetab. 2016;101(9):3251-3255. doi:10.1210/jc.2016-1971
57. Li D, Ferguson A, Cervinski MA, Lynch KL, Kyle PB. AACC Guidance Document on Biotin Interference in Laboratory Tests. J ApplLab Med. 2020;5(3):575-587. doi:10.1093/jalm/jfz010
58. Mills F, Jeffery J, Mackenzie P, Cranfield A, Ayling RM. An immunoglobulin G complexed form of thyroid-stimulating hormone (macro thyroid-stimulating hormone) is a cause of elevated serum thyroid-stimulating hormone concentration. Ann ClinBiochem. 2013;50(Pt 5):416-420. doi:10.1177/0004563213476271
59. Hattori N, Ishihara T, Yamagami K, Shimatsu A. Macro TSH in patients with subclinical hypothyroidism. ClinEndocrinol (Oxf). 2015;83(6):923-930. doi:10.1111/cen.12643
60. Haddad RA, Giacherio D, Barkan AL. Interpretation of common endocrine laboratory tests: technical pitfalls, their mechanisms and practical considerations. Clin Diabetes Endocrinol. 2019;5:12. Published 2019 Jul 24. doi:10.1186/s40842-019-0086-7
61. Koshida S, Asanuma K, Kuribayashi K, et al. Prevalence of human anti-mouse antibodies (HAMAs) in routine examinations. Clin Chim Acta. 2010;411(5-6):391-394. doi:10.1016/j.cca.2009.12.006
62. Graf H, Carvalho GA. Laboratory Interfering Factors in the Diagnosis of Hyper and Hypothyroidism. Arq Bras Endocrinol Metabol. 2002;46(1):51-64. doi: 10.1590/S0004-27302002000100008
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
10. Van Houcke SK, Van Uytfanghe K, Shimizu E, Tani W, Umemoto M, Thienpont LM. IFCC international conventional reference procedure for the measurement of free thyroxine in serum: International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Working Group for Standardization of Thyroid Function Tests (WG-STFT)(1). ClinChemLab Med. 2011;49(8):1275-1281. doi:10.1515/CCLM.2011.639
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
39. Poppe K, Bisschop P, Fugazzola L, Minziori G, Unuane D, Weghofer A. 2021 European Thyroid Association Guideline on Thyroid Disorders prior to and during Assisted Reproduction [published correction appears in EurThyroid J. 2021 Jun;10(3):268]. EurThyroid J. 2021;9(6):281-295. doi:10.1159/000512790
40. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1-133. doi:10.1089/thy.2015.0020
41. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis [published correction appears in Thyroid. 2017 Nov;27(11):1462]. Thyroid. 2016;26(10):1343-1421. doi:10.1089/thy.2016.0229
42. Abeillon-du Payrat J, Chikh K, Bossard N, et al. Predictive value of maternal second-generation thyroid-binding inhibitory immunoglobulin assay for neonatal autoimmune hyperthyroidism. Eur J Endocrinol. 2014;171(4):451-460. doi:10.1530/EJE-14-0254
43. Endo K, Kasagi K, Konishi J, et al. Detection and properties of TSH-binding inhibitor immunoglobulins in patients with Graves' disease and Hashimoto's thyroiditis. J ClinEndocrinolMetab. 1978;46(5):734-739. doi:10.1210/jcem-46-5-734
44. McLachlan SM, Rapoport B. Thyrotropin-blocking autoantibodies and thyroid-stimulating autoantibodies: potential mechanisms involved in the pendulum swinging from hypothyroidism to hyperthyroidism or vice versa. Thyroid. 2013;23(1):14-24. doi:10.1089/thy.2012.0374
45. Barbesino G, Tomer Y. Clinical review: Clinical utility of TSH receptor antibodies. J ClinEndocrinolMetab. 2013;98(6):2247-2255. doi:10.1210/jc.2012-4309
46. Mariotti S, Martino E, Cupini C, et al. Low serum thyroglobulin as a clue to the diagnosis of thyrotoxicosis factitia. N Engl J Med. 1982;307(7):410-412. doi:10.1056/NEJM198208123070705
47. Netzel BC, Grebe SK, Carranza Leon BG, et al. Thyroglobulin (Tg) Testing Revisited: Tg Assays, TgAb Assays, and Correlation of Results With Clinical Outcomes. J ClinEndocrinolMetab. 2015;100(8):E1074-E1083. doi:10.1210/jc.2015-1967
48. Wells SA Jr, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567-610. doi:10.1089/thy.2014.0335
49. Trimboli P, Giovanella L, Crescenzi A, et al. Medullary thyroid cancer diagnosis: an appraisal. Head Neck. 2014;36(8):1216-1223. doi:10.1002/hed.23449
50. Bjerre Knudsen L, Madsen LW, Andersen S, et al. Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation [published correction appears in Endocrinology. 2012 Feb;153(2):1000. Moerch, Ulrik [added]]. Endocrinology. 2010;151(4):1473-1486. doi:10.1210/en.2009-1272
51. Hegedüs L, Sherman SI, Tuttle RM, et al. No Evidence of Increase in Calcitonin Concentrations or Development of C-Cell Malignancy in Response to Liraglutide for Up to 5 Years in the LEADER Trial. Diabetes Care. 2018;41(3):620-622. doi:10.2337/dc17-1956
52. Soh SB, Aw TC. Laboratory Testing in Thyroid Conditions - Pitfalls and Clinical Utility. Ann Lab Med. 2019;39(1):3-14. doi:10.3343/alm.2019.39.1.3
53. Favresse J, Burlacu MC, Maiter D, Gruson D. Interferences with Thyroid Function Immunoassays: Clinical Implications and Detection Algorithm. Endocr Rev. 2018;39(5):830-850. doi:10.1210/er.2018-00119
54. Ylli D, Soldin SJ, Stolze B, et al. Biotin Interference in Assays for Thyroid Hormones, Thyrotropin and Thyroglobulin. Thyroid. 2021;31(8):1160-1170. doi:10.1089/thy.2020.0866
55. Sedel F, Papeix C, Bellanger A, et al. High doses of biotin in chronic progressive multiple sclerosis: a pilot study. MultSclerRelatDisord. 2015;4(2):159-169. doi:10.1016/j.msard.2015.01.005
56. Elston MS, Sehgal S, Du Toit S, Yarndley T, Conaglen JV. Factitious Graves' Disease Due to Biotin Immunoassay Interference-A Case and Review of the Literature. J ClinEndocrinolMetab. 2016;101(9):3251-3255. doi:10.1210/jc.2016-1971
57. Li D, Ferguson A, Cervinski MA, Lynch KL, Kyle PB. AACC Guidance Document on Biotin Interference in Laboratory Tests. J ApplLab Med. 2020;5(3):575-587. doi:10.1093/jalm/jfz010
58. Mills F, Jeffery J, Mackenzie P, Cranfield A, Ayling RM. An immunoglobulin G complexed form of thyroid-stimulating hormone (macro thyroid-stimulating hormone) is a cause of elevated serum thyroid-stimulating hormone concentration. Ann ClinBiochem. 2013;50(Pt 5):416-420. doi:10.1177/0004563213476271
59. Hattori N, Ishihara T, Yamagami K, Shimatsu A. Macro TSH in patients with subclinical hypothyroidism. ClinEndocrinol (Oxf). 2015;83(6):923-930. doi:10.1111/cen.12643
60. Haddad RA, Giacherio D, Barkan AL. Interpretation of common endocrine laboratory tests: technical pitfalls, their mechanisms and practical considerations. Clin Diabetes Endocrinol. 2019;5:12. Published 2019 Jul 24. doi:10.1186/s40842-019-0086-7
61. Koshida S, Asanuma K, Kuribayashi K, et al. Prevalence of human anti-mouse antibodies (HAMAs) in routine examinations. Clin Chim Acta. 2010;411(5-6):391-394. doi:10.1016/j.cca.2009.12.006
62. Graf H, Carvalho GA. Laboratory Interfering Factors in the Diagnosis of Hyper and Hypothyroidism. Arq Bras Endocrinol Metabol. 2002;46(1):51-64. doi: 10.1590/S0004-27302002000100008