Serum thyroglobulin (Tg) monitoring of patients with differentiated thyroid cancer using sensitive (second-generation) immunometric assays can be disrupted by false-negative and false-positive serum thyroglobulin autoantibody misclassifications

Journal of Clinical Endocrinology and Metabolism

Volumn 99, Issue 12, 2014, Pages 4589-4599

  Spencer, Carole A ^a   Petrovic, Ivana ^a   Fatemi, Shireen ^b   LoPresti, Jonathan ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b KAISER PERMANENTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

THYROGLOBULIN; THYROGLOBULIN ANTIBODY; AUTOANTIBODY;

ANTIBODY BLOOD LEVEL; ANTIBODY DETECTION; ARTICLE; DIAGNOSTIC TEST ACCURACY STUDY; DIFFERENTIATED THYROID CANCER; FALSE NEGATIVE RESULT; FALSE POSITIVE RESULT; HUMAN; IMMUNOASSAY; IMMUNOLOGY TEST KIT; INTERMETHOD COMPARISON; LIQUID CHROMATOGRAPHY; MAJOR CLINICAL STUDY; RADIOIMMUNOASSAY; SECOND GENERATION IMMUNOMETRIC ASSAY; SECOND GENERATION IMMUNOMETRIC ASSAY KIT; SENSITIVITY AND SPECIFICITY; TANDEM MASS SPECTROMETRY; THYROGLOBULIN BLOOD LEVEL; THYROID PAPILLARY CARCINOMA; BLOOD; CLASSIFICATION; LABORATORY DIAGNOSIS; ONCOCYTOMA; PAPILLARY CARCINOMA; PROCEDURES; STANDARD; THYROID TUMOR;

ADENOMA, OXYPHILIC; AUTOANTIBODIES; CARCINOMA, PAPILLARY; FALSE NEGATIVE REACTIONS; FALSE POSITIVE REACTIONS; HUMANS; RADIOIMMUNOASSAY; REFERENCE STANDARDS; THYROGLOBULIN; THYROID NEOPLASMS;

EID: 84916620171     PISSN: 0021972X     EISSN: 19457197     Source Type: Journal    
DOI: 10.1210/jc.2014-1203     Document Type: Article

References (69)

1. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19:1167-1214.
2. Spencer CA, Takeuchi M, Kazarosyan M, et al. Serum thyroglobulin autoantibodies: prevalence, influence on serum thyroglobulin measurement, and prognostic significance in patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab. 1998;83:1121-1127.
3. Görges R, Maniecki M, Jentzen W, et al. Development and clinical impact of thyroglobulin antibodies in patients with differentiated thyroid carcinoma during the first 3 years after thyroidectomy. Eur J Endocrinol. 2005;153:49-55.
4. Spencer C, Fatemi S. Thyroglobulin antibody (TgAb) methods - strengths, pitfalls and clinical utility for monitoring TgAb-positive patients with differentiated thyroid cancer. Best Pract Res Clin Endocrinol Metab. 2013;27:701-712.
5. Verburg FA, Luster M, Cupini C, et al. Implications of thyroglobulin antibody positivity in patients with differentiated thyroid cancer: a clinical position statement. Thyroid. 2013;23:1211-1225.
6. Spencer C. Commentary on: Implications of thyroglobulin antibody positivity in patients with differentiated thyroid cancer: a clinical position statement. Thyroid. 2013;23:1190-1192.
7. Ringel MD, Nabhan F. Approach to follow-up of the patient with differentiated thyroid cancer and positive anti-thyroglobulin antibodies. J Clin Endocrinol Metab. 2013;98:3104-3110.
8. McLeod DS, Cooper DS, Ladenson PW, et al. Prognosis of differentiated thyroid cancer in relation to serum thyrotropin and thyroglobulin antibody status at time of diagnosis. Thyroid. 2014;24:35-42.
9. Spencer C, LoPresti JS, Fatemi S. How sensitive (second-generation) thyroglobulin measurement is changing paradigms for monitoring patients with differentiated thyroid cancers, in the absence or presence of thyroglobulin autoantibodies. Curr Opin Endocrinol Diabetes. 2014;21:394-404.
10. Spencer C, Petrovic I, Fatemi S. Current thyroglobulin autoantibody (TgAb) assays often fail to detect interfering TgAb that can result in the reporting of falsely low/undetectable serum Tg IMA values for patients with differentiated thyroid cancer. J Clin Endocrinol Metab. 2011;96:1283-1291.
11. Clarke NJ, Zhang Y, Reitz RE. A novel mass spectrometry-based assay for the accurate measurement of thyroglobulin from patient samples containing antithyroglobulin autoantibodies. J Investig Med. 2012;60:1157-1163.
12. Grebe SKG. Diagnosis and management of thyroid carcinoma: a focus on serum thyroglobulin. Expert Rev Endocrinol Metab. 2009;4:25-43.
13. Spencer C, Fatemi S, Singer P, Nicoloff J, LoPresti J. Serum basal thyroglobulin measured by a second-generation assay correlates with the recombinant human thyrotropin-stimulated thyroglobulin response in patients treated for differentiated thyroid cancer. Thyroid. 2010;20:587-595.
14. Malandrino P, Latina A, Marescalco S, et al. Risk-adapted management of differentiated thyroid cancer assessed by a sensitive measurement of basal serum thyroglobulin. J Clin Endocrinol Metab. 2011;96:1703-1709.
15. Chindris AM, Diehl NN, Crook JE, Fatourechi V, Smallridge RC. Undetectable sensitive serum thyroglobulin (<0.1 ng/mL) in 163 patients with follicular cell-derived thyroid cancer: results of rhTSH stimulation and neck ultrasonography and long-term biochemical and clinical follow-up. J Clin Endocrinol Metab. 2012;97:2714-2723.
16. Trimboli P, La Torre D, Ceriani L, et al. High sensitive thyroglobulin assay on thyroxine therapy: can it avoid stimulation test in low and high risk differentiated thyroid carcinoma patients? Horm Metab Res. 2013;45:664-668.
17. Giovanella L, Clark PM, Chiovato L, et al. Thyroglobulin measurement using highly sensitive assays in patients with differentiated thyroid cancer: a clinical position paper. Eur J Endocrinol. 2014;171:R33-R46.
18. Giovanella L, Treglia G, Sadeghi R, Trimboli P, Ceriani L, Verburg FA. Unstimulated highly sensitive thyroglobulin in follow-up of differentiated thyroid cancer patients: a meta-analysis. J Clin Endocrinol Metab. 2014;99:440-447.
19. Kushnir MM, Rockwood AL, Roberts WL, Abraham D, Hoofnagle AN, Meikle AW. Measurement of thyroglobulin by liquid chroma-tography- tandem mass spectrometry in serum and plasma in the presence of antithyroglobulin autoantibodies. Clin Chem. 2013;59:982-990.
20. Hoofnagle AN, Roth MY. Clinical review: improving the measurement of serum thyroglobulin with mass spectrometry. J Clin Endocrinol Metab. 2013;98:1343-1352.
21. Zöphel K, Wunderlich G, Smith BR. Serum thyroglobulin measurements with a high sensitivity enzyme-linked immunosorbent assay: is there a clinical benefit in patients with differentiated thyroid carcinoma? Thyroid. 2003;13:861-865.
22. Heilo A, Sigstad E, Fagerlid KH, et al. Efficacy of ultrasound-guided percutaneous ethanol injection treatment in patients with a limited number of metastatic cervical lymph nodes from papillary thyroid carcinoma. J Clin Endocrinol Metab. 2011;96:2750-2755.
23. Iervasi A, Iervasi G, Ferdeghini M, et al. Clinical relevance of highly sensitive Tg assay in monitoring patients treated for differentiated thyroid cancer. Clin Endocrinol (Oxf). 2007;67:434-441.
24. Miyauchi A, Kudo T, Miya A, et al. Prognostic impact of serum thyroglobulin doubling-time under thyrotropin suppression in patients with papillary thyroid carcinoma who underwent total thyroidectomy. Thyroid. 2011;21:707-716.
25. Wong H, Wong KP, Yau T, et al. Is there a role for unstimulated thyroglobulin velocity in predicting recurrence in papillary thyroid carcinoma patients with detectable thyroglobulin after radioiodine ablation? Ann Surg Oncol. 2012;19:3479-3485.
26. Hay ID, Lee RA, Davidge-Pitts C, Reading CC, Charboneau JW. Long-term outcome of ultrasound-guided percutaneous ethanol ablation of selected "recurrent" neck nodal metastases in 25 patients with TNM stages III or IVA papillary thyroid carcinoma previously treated by surgery and 131I therapy. Surgery. 2013;154:1448-1454; discussion 1454-1455.
27. 131I-negative lesions. Nucl Med Commun. 2014;35:176-181.
28. Spencer CA, Bergoglio LM, Kazarosyan M, Fatemi S, LoPresti JS. Clinical impact of thyroglobulin (Tg) and Tg autoantibody method differences on the management of patients with differentiated thyroid carcinomas. J Clin Endocrinol Metab. 2005;90:5566-5575.
29. Schlumberger M, Hitzel A, Toubert ME, et al. Comparison of seven serum thyroglobulin assays in the follow-up of papillary and follicular thyroid cancer patients. J Clin Endocrinol Metab. 2007;92:2487-2495.
30. Baloch Z, Carayon P, Conte-Devolx B, et al. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid. 2003;13:3-126.
31. Krahn J, Dembinski T. Thyroglobulin and anti-thyroglobulin assays in thyroid cancer monitoring. Clin Biochem. 2009;42:416-419.
32. Taylor KP, Parkington D, Bradbury S, Simpson HL, Jefferies SJ, Halsall DJ. Concordance between thyroglobulin antibody assays. Ann Clin Biochem. 2011;48:367-369.
33. Pickett AJ, Jones M, Evans C. Causes of discordance between thyroglobulin antibody assays. Ann Clin Biochem. 2012;49:463-467.
34. Nygaard B, Bentzen J, Laurberg P, et al. Large discrepancy in the results of sensitive measurements of thyroglobulin antibodies in the follow-up on thyroid cancer: a diagnostic dilemma. Eur Thyroid J. 2012;1:193-197.
35. Latrofa F, Ricci D, Montanelli L, et al. Thyroglobulin autoantibodies in patients with papillary thyroid carcinoma: comparison of different assays and evaluation of causes of discrepancies. J Clin Endocrinol Metab. 2012;97:3974-3982.
36. Clark P, Franklyn J. Can we interpret serum thyroglobulin results? Ann Clin Biochem. 2012;49:313-322.
37. Crane MS, Strachan MW, Toft AD, Beckett GJ. Discordance in thyroglobulin measurements by radioimmunoassay and immunometric assay: a useful means of identifying thyroglobulin assay interference. Ann Clin Biochem. 2013;50:421-432.
38. Algeciras-Schimnich A, Lasho MA, Ness KM, Cheryk LA, Grebe SK. The Roche Elecsys and Siemens-Centaur thyroglobulin autoantibody assays show comparable clinical performance to the recently unavailable Beckman-Coulter access thyroglobulin autoantibody assay in identifying samples with potentially false-low thyroglobulin measurements due to thyroglobulin autoantibody interference. Thyroid. 2011;21:813-814.
39. 125I-labeled human thyroglobulin preparations. Clin Chim Acta. 1985;151:121-132.
40. Netzel BC, Grebe SK, Algeciras-Schimnich A. Usefulness of a thyroglobulin liquid chromatography-tandem mass spectrometry assay for evaluation of suspected heterophile interference. Clin Chem. 2014;60:1016-1018.
41. Rodbard D. Statistical estimation of the minimal detectable concentration ("sensitivity") for radioligand assays. Anal Biochem. 1978;90:1-12.
42. Schneider AB, Pervos R. Radioimmunoassay of human thyroglobulin: effect of antithyroglobulin autoantibodies. J Clin Endocrinol Metab. 1978;47:126-137.
43. Feldt-Rasmussen U, Rasmussen AK. Serum thyroglobulin (Tg) in presence of thyroglobulin autoantibodies (TgAb). Clinical and methodological relevance of the interaction between Tg and TgAb in vitro and in vivo. J Endocrinol Invest. 1985;8:571-576.
44. Weigle WO, High GJ. The behavior of autologous thyroglobulin in the circulation of rabbits immunized with either heterologous or altered homologous thyroglobulin. J Immunol. 1967;98:1105-1114.
45. Feldt-Rasmussen U, Petersen PH, Date J, Madsen CM. Sequential changes in serum thyroglobulin (Tg) and its autoantibodies (TgAb) following subtotal thyroidectomy of patients with preoperatively detectable TgAb. Clin Endocrinol (Oxf). 1980;12:29-38.
46. Feldt-Rasmussen U. Serum thyroglobulin and thyroglobulin autoantibodies in thyroid diseases. Pathogenic and diagnostic aspects. Allergy. 1983;38:369-387.
47. van der Laken CJ, Voskuyl AE, Roos JC, et al. Imaging and serum analysis of immune complex formation of radiolabelled infliximab and anti-infliximab in responders and non-responders to therapy for rheumatoid arthritis. Ann Rheum Dis. 2007;66:253-256.
48. Latrofa F, Ricci D, Grasso L, et al. Characterization of thyroglobulin epitopes in patients with autoimmune and non-autoimmune thyroid diseases using recombinant human monoclonal thyroglobulin autoantibodies. J Clin Endocrinol Metab. 2008;93:591-596.
49. Spencer CA. Clinical review: Clinical utility of thyroglobulin antibody (TgAb) measurements for patients with differentiated thyroid cancers (DTC). J Clin Endocrinol Metab. 2011;96:3615-3627.
50. Latrofa F, Ricci D, Montanelli L, et al. Lymphocytic thyroiditis on histology correlates with serum thyroglobulin autoantibodies in patients with papillary thyroid carcinoma: impact on detection of serum thyroglobulin. J Clin Endocrinol Metab. 2012;97:2380-2387.
51. Heilig B, Hüfner M, Dörken B, Schmidt-Gayk H. Increased heterogeneity of serum thyroglobulin in thyroid cancer patients as determined by monoclonal antibodies. Klin Wochenschr. 1986;64:776-780.
52. Sabra MM, Grewal RK, Ghossein RA, Tuttle RM. Higher administered activities of radioactive iodine are associated with less structural persistent response in older, but not younger, papillary thyroid cancer patients with lateral neck lymph node metastases. Thyroid. 2014;24:1088-1095.
53. Nascimento C, Borget I, Troalen F, et al. Ultrasensitive serum thyroglobulin measurement is useful for the follow-up of patients treated with total thyroidectomy without radioactive iodine ablation. Eur J Endocrinol. 2013;169:689-693.
54. Ibrahimpasic T, Nixon IJ, Palmer FL, et al. Undetectable thyroglobulin after total thyroidectomy in patients with low- and intermediate-risk papillary thyroid cancer - is there a need for radioactive iodine therapy? Surgery. 2012;152:1096-1105.
55. Nixon IJ, Ganly I, Patel SG, et al. The results of selective use of radioactive iodine on survival and on recurrence in the management of papillary thyroid cancer, based on Memorial Sloan-Kettering Cancer Center risk group stratification. Thyroid. 2013;23:683-694.
56. Tuttle RM, Sabra MM. Selective use of RAI for ablation and adjuvant therapy after total thyroidectomy for differentiated thyroid cancer: a practical approach to clinical decision making. Oral Oncol. 2013;49:676-683.
57. 18F-FDG PET/CT scan in patients with biochemical recurrence of differentiated thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2013;40:874-880.
58. Angell TE, Spencer CA, Rubino BD, Nicoloff JT, LoPresti JS. In search of an unstimulated thyroglobulin baseline value in low-risk papillary thyroid carcinoma patients not receiving radioactive iodine ablation. Thyroid. 2014;24:1127-1133.
59. Chung JK, Park YJ, Kim TY, et al. Clinical significance of elevated level of serum antithyroglobulin antibody in patients with differentiated thyroid cancer after thyroid ablation. Clin Endocrinol (Oxf). 2002;57:215-221.
60. Durante C, Tognini S, Montesano T, et al. Clinical aggressiveness and long-term outcome in patients with papillary thyroid cancer and circulating anti-thyroglobulin autoantibodies. Thyroid. 2014;24:1139-1145.
61. Adil A, Jafri RA, Waqar A, et al. Frequency and clinical importance of anti-Tg auto-antibodies (ATG). J Coll Physicians Surg Pak. 2003;13:504-506.
62. Soyluk O, Boztepe H, Aral F, Alagol F, Özbey NC. Papillary thyroid carcinoma patients assessed to be at low or intermediary risk after primary treatment are at greater risk of long term recurrence if they are thyroglobulin antibody positive or do not have distinctly low thyroglobulin at initial assessment. Thyroid. 2011;21:1301-1308.
63. Tumino S, Belfiore A. Appearance of antithyroglobulin antibodies as the sole sign of metastatic lymph nodes in a patient operated on for papillary thyroid cancer: a case report. Thyroid. 2000;10:431-433.
64. Chiovato L, Latrofa F, Braverman LE, et al. Disappearance of humoral thyroid autoimmunity after complete removal of thyroid antigens. Ann Intern Med. 2003;139:346-351.
65. Kim WG, Yoon JH, Kim WB, et al. Change of serum antithyroglobulin antibody levels is useful for prediction of clinical recurrence in thyroglobulin-negative patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2008;93:4683-4689.
66. Tsushima Y, Miyauchi A, Ito Y, et al. Prognostic significance of changes in serum thyroglobulin antibody levels of pre- and post-total thyroidectomy in thyroglobulin antibody-positive papillary thyroid carcinoma patients. Endocr J. 2013;60:871-876.
67. Dvorkin S, Robenshtok E, Hirsch D, Strenov Y, Shimon I, Benbassat CA. Differentiated thyroid cancer is associated with less aggressive disease and better outcome in patients with coexisting Hashimoto's thyroiditis. J Clin Endocrinol Metab. 2013;98:2409-2414.
68. Hsieh CJ, Wang PW. Sequential changes of serum antithyroglobulin antibody levels are a good predictor of disease activity in thyroglob-ulin- negative patients with papillary thyroid carcinoma. Thyroid. 2014;24:488-493.
69. Jensen E, Petersen PH, Blaabjerg O, Hegedüs L. Biological variation of thyroid autoantibodies and thyroglobulin. Clin Chem Lab Med. 2007;45:1058-1064.