Horm Metab Res 2013; 45(10): 728-735
DOI: 10.1055/s-0033-1349890
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Relationship Between Antithyroglobulin Autoantibodies and Thyroglobulin Recovery Rates Using Different Thyroglobulin Concentrations in the Recovery Buffer

F. A. Verburg
1   Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany
2   Department of Nuclear Medicine, University Hospital Aachen, Aachen, Germany
,
D. Hartmann
1   Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany
,
I. Grelle
1   Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany
,
L. Giovanella
3   Oncology Institute of Southern Switzerland, Department of Nuclear Medicine, Bellinzona, Switzerland
,
A. K. Buck
1   Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany
,
C. Reiners
1   Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany
› Author Affiliations
Further Information

Publication History

received 16 December 2012

accepted 19 June 2013

Publication Date:
19 August 2013 (online)

Abstract

The aim of the work was to examine the relationship between thyroglobulin autoantibody (TgAb) levels and the Tg recovery rate (TgRR) using different concentrations of Tg (50, 10, 5, and 1 μg/l) in the recovery buffer. A total number of 225 serum samples from individual patients were analyzed. Samples were selected for their TgAb in 6 groups: TgAb<limit of detection (LoD; n=50), LoD<TgAb≤60 IU/ml (n=62), 60 IU/ml<TgAb≤100 IU/ml (n=30), 100 IU/ml<TgAb≤500 IU/ml (n=41), 500 IU/ml< TgAb≤1 000 IU/ml (n=13) and TgAb>1 000 IU/ml (n=28). TgAb were measured with 2 different assays (VARELISA and BRAHMS Anti-Tgn RIA). TgAb levels and the TgRR determined using the 50, 10, 5, and 1 µg/l buffers showed strong significant correlations with a Spearmans’ rho of − 0.720, − 0.688, − 0.686, and − 0.356, respectively, for the VARELISA assay and − 0.670, −0.617, − 0.570, and − 0.274, respectively, for the Anti-Tgn assay (all p<0.001). TgRRs were a median of 94.8% (30.5–113.0%), 90.8% (40.6127.6%), 90.0% (8.2–119.3%), and 89.4% (range − 43.6–121.6%) for the TgRR determined using recovery buffers with concentrations of 50, 10, 5, and 1 μg/l respectively. With decreasing Tg concentration in the recovery buffer the percentage of abnormal results increased, although the extreme increase we found in the 1 μg/l group is largely caused by a lack of analytical precision in the 73 sera with Tg levels exceeding 5 μg/l. Our results give cause for further investigation into reviving the concept of Tg-recovery measurement using 5 μg/l Tg in the recovery buffer instead of the traditional 50 μg/l.

 
  • References

  • 1 Verburg FA, de Keizer B, van Isselt JW. Use of radiopharmaceuticals for diagnosis, treatment, and follow-up of differentiated thyroid carcinoma. Anticancer Agents Med Chem 2007; 7: 399-409
  • 2 Schlumberger MJ. Papillary and follicular thyroid carcinoma. N Engl J Med 1998; 338: 297-306
  • 3 Spencer CA, Takeuchi M, Kazarosyan M, Wang CC, Guttler RB, Singer PA, Fatemi S, LoPresti JS, Nicoloff JT. 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
  • 4 Mariotti S, Barbesino G, Caturegli P, Marino M, Manetti L, Pacini F, Centoni R, Pinchera A. Assay of thyroglobulin in serum with thyroglobulin autoantibodies: an unobtainable goal?. J Clin Endocrinol Metab 1995; 80: 468-472
  • 5 Spencer CA. Challenges of serum thyroglobulin (Tg) measurement in the presence of Tg autoantibodies. J Clin Endocrinol Metab 2004; 89: 3702-3704
  • 6 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
  • 7 Schaadt B, Feldt-Rasmussen U, Rasmusson B, Torring H, Foder B, Jorgensen K, Hansen HS. Assessment of the influence of thyroglobulin (Tg) autoantibodies and other interfering factors on the use of serum Tg as tumor marker in differentiated thyroid carcinoma. Thyroid 1995; 5: 165-170
  • 8 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
  • 9 Giovanella L, Keller F, Ceriani L, Tozzoli R. Heterophile antibodies may falsely increase or decrease thyroglobulin measurement in patients with differentiated thyroid carcinoma. Clin Chem Lab Med 2009; 47: 952-954
  • 10 Verburg FA, Waschle K, Reiners C, Giovanella L, Lentjes EG. Heterophile antibodies rarely influence the measurement of thyroglobulin and thyroglobulin antibodies in differentiated thyroid cancer patients. Horm Metab Res 2010; 42: 736-739
  • 11 Spencer CA, Wang CC. Thyroglobulin measurement. Techniques, clinical benefits, and pitfalls. Endocrinol Metab Clin North Am 1995; 24: 841-863
  • 12 Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009; 19: 1167-1214
  • 13 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
  • 14 Cubero JM, Rodriguez-Espinosa J, Gelpi C, Estorch M, Corcoy R. Thyroglobulin autoantibody levels below the cut-off for positivity can interfere with thyroglobulin measurement. Thyroid 2003; 13: 659-661
  • 15 Verburg FA, Grelle I, Giovanella L, Reiners C. Evaluation of the BRAHMS KRYPTOR Thyroglobulin “Mini-recovery” Test in Thyroid Healthy Subjects. Horm Metab Res 2012; 44: 555-557
  • 16 Giovanella L, Imperiali M, Verburg FA, Ceriani L. Evaluation of the BRAHMS Kryptor® Thyroglobulin Minirecovery Test in Patients with Differentiated Thyroid Carcinoma. Clin Chem Lab Med 2013; 51: 449-453
  • 17 Morgenthaler NG, Froehlich J, Rendl J, Willnich M, Alonso C, Bergmann A, Reiners C. Technical evaluation of a new immunoradiometric and a new immunoluminometric assay for thyroglobulin. Clin Chem 2002; 48: 1077-1083
  • 18 Feldt-Rasmussen U, Profilis C, Colinet E, Black E, Bornet H, Bourdoux P, Carayon P, Ericsson UB, Koutras DA, Lamas de Leon L, DeNayer P, Pacini F, Palumbo G, Santos A, Schlumberger M, Seidel C, Vanherle AJ, de Vijlder JJ. Human thyroglobulin reference material (CRM 457). 1st Part: Assessment of homogeneity, stability and immunoreactivity. Ann Biol Clin (Paris) 1996; 54: 337-342
  • 19 Feldt-Rasmussen U, Profilis C, Colinet E, Black E, Bornet H, Bourdoux P, Carayon P, Ericsson UB, Koutras DA, Lamas DL, DeNayer P, Pacini F, Palumbo G, Santos A, Schlumberger M, Seidel C, Van Herle AJ, DeVijlder JJ. Human thyroglobulin reference material (CRM 457). 2nd Part: Physicochemical characterization and certification. Ann Biol Clin (Paris) 1996; 54: 343-348
  • 20 Erali M, Bigelow RB, Meikle AW. ELISA for thyroglobulin in serum: recovery studies to evaluate autoantibody interference and reliability of thyroglobulin values. Clin Chem 1996; 42: 766-770
  • 21 Giovanella L, Suriano S, Ceriani L, Verburg FA. Undetectable thyroglobulin in patients with differentiated thyroid carcinoma and residual radioiodine uptake on a postablation whole-body scan. Clin Nucl Med 2011; 36: 109-112
  • 22 Giovanella L, Ceriani L, Ghelfo A, Maffioli M, Keller F. Preoperative undetectable serum thyroglobulin in differentiated thyroid carcinoma: incidence, causes and management strategy. Clin Endocrinol (Oxf) 2007; 67: 547-551
  • 23 Giovanella L, Keller F, Ceriani L, Tozzoli R. Heterophile antibodies may falsely increase or decrease thyroglobulin measurement in patients with differentiated thyroid carcinoma. Clin Chem Lab Med 2009; 47: 952-954
  • 24 Preissner CM, O’Kane DJ, Singh RJ, Morris JC, Grebe SK. Phantoms in the assay tube: heterophile antibody interferences in serum thyroglobulin assays. J Clin Endocrinol Metab 2003; 88: 3069-3074
  • 25 Benvenga S, Burek CL, Talor M, Rose NR, Trimarchi F. Heterogeneity of the thyroglobulin epitopes associated with circulating thyroid hormone autoantibodies in hashimoto’s thyroiditis and non-autoimmune thyroid diseases. J Endocrinol Invest 2002; 25: 977-982
  • 26 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
  • 27 Rosario PW, Maia FF, Fagundes TA, Vasconcelos FP, Cardoso LD, Purisch S. Antithyroglobulin antibodies in patients with differentiated thyroid carcinoma: methods of detection, interference with serum thyroglobulin measurement and clinical significance. Arq Bras Endocrinol Metabol 2004; 48: 487-492
  • 28 Okosieme OE, Evans C, Moss L, Parkes AB, Premawardhana LD, Lazarus JH. Thyroglobulin antibodies in serum of patients with differentiated thyroid cancer: relationship between epitope specificities and thyroglobulin recovery. Clin Chem 2005; 51: 729-734
  • 29 Tozzoli R, Bizzaro N, Tonutti E, Pradella M, Manoni F, Vilalta D, Bassetti D, Piazza A, Rizzotti P. Immunoassay of anti-thyroid autoantibodies: high analytical variability in second generation methods. Clin Chem Lab Med 2002; 40: 568-573
  • 30 Krahn J, Dembinski T. Thyroglobulin and anti-thyroglobulin assays in thyroid cancer monitoring. Clin Biochem 2009; 42: 416-419
  • 31 Latrofa F, Ricci D, Grasso L, Vitti P, Masserini L, Basolo F, Ugolini C, Mascia G, Lucacchini A, Pinchera A. 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
  • 32 Sapin R, D’Herbomez M, Gasser F, Meyer L, Schlienger JL. Increased sensitivity of a new assay for anti-thyroglobulin antibody detection in patients with autoimmune thyroid disease. Clin Biochem 2003; 36: 611-616
  • 33 Haapala AM, Soppi E, Morsky P, Salmi J, Laine S, Mattila J. Thyroid antibodies in association with thyroid malignancy II: Qualitative properties of thyroglobulin antibodies. Scand J Clin Lab Invest 1995; 55: 317-322
  • 34 Giovanella L, Ceriani L. Comparison of thyroglobulin antibody interference in first- and second-generation thyroglobulin immunoassays. Clin Chem Lab Med 2011; 49: 1025-1027
  • 35 McLachlan SM, Feldt-Rasmussen U, Young ET, Middleton SL, Dlichert-Toft M, Siersboek-Nielsen K, Date J, Carr D, Clark F, Rees SB. IgG subclass distribution of thyroid autoantibodies: a ‛fingerprint’ of an individual’s response to thyroglobulin and thyroid microsomal antigen. Clin Endocrinol (Oxf) 1987; 26: 335-346
  • 36 Verburg FA, Luster M, Cupini C, Chiovato L, Duntas LH, Elisei R, Feldt-Rasmussen U, Smit JW, Rimmele H, Seregni E, Theimer C, Giovanella L. Implications of thyroglobulin antibody positivity in patients with differentiated thyroid cancer: a clinical position paper. Thyroid 2013; May 21 [Epub ahead of print]
  • 37 Feldt-Rasmussen U, Rasmussen AK. Autoimmunity in differentiated thyroid cancer: significance and related clinical problems. Hormones (Athens) 2010; 9: 109-117
  • 38 Chung JK, Park YJ, Kim TY, So Y, Kim SK, Park DJ, Lee DS, Lee MC, Cho BY. 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
  • 39 Heemstra KA, Liu YY, Stokkel M, Kievit J, Corssmit E, Pereira AM, Romijn JA, Smit JW. Serum thyroglobulin concentrations predict disease-free remission and death in differentiated thyroid carcinoma. Clin Endocrinol (Oxf) 2007; 66: 58-64
  • 40 Pacini F, Schlumberger M, Dralle H, Elisei R, Smit JW, Wiersinga W. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol 2006; 154: 787-803