Horm Metab Res 2006; 38(1): 53-56
DOI: 10.1055/s-2006-924979
Original Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Does Autoantibody-negative Graves’ Disease Exist? A Second Evaluation of the Clinical Diagnosis

J.  Paunkovic1 , N.  Paunkovic1
  • 1 Medical Center, Department of Nuclear Medicine, Zajecar, Serbia
Further Information

Publication History

Received 3 May 2005

Accepted after revision 11 August 2005

Publication Date:
13 February 2006 (online)

Abstract

Advanced technical methods are essential for accurate diagnosis of Graves’ or Basedow’s disease (GD). Inadequate methods may lead to a false diagnostic conclusion. We have analyzed the clinical features and methodology aspects of cases diagnosed as GD with negative findings for TSH receptor autoantibodies. The initial diagnosis was based on clinical findings (patient record, hypermetabolic state, goiter palpation) and laboratory testing (fT4 and TSH). From a total of 255 newly registered patients with GD, fifty-one (20 %) were negative in a conventional porcine TBII assay. All fifty-one patients were retested with 131I or 99 mTc uptake tests, thyroid scintigraphy, and a second-generation TBII assay. Results disclosed twenty-one cases (8.3 %) with diagnosis other than GD: ten cases of autonomous hyperthyroidism (Plummer’s disease), seven cases of painless thyroiditis and four cases of euthyroid endocrine ophthalmopathy. All twenty-one patients remained negative in the second-generation TBII assay. Measurement by second-generation TBII assay was performed on the remaining thirty patients initially found negative for TBII. As a result of this reevaluation, only 234 of the original 255 patients had GD. Of those, 231 (204 according to porcine plus 27 according to human TRAb assay) had detectable TBII (98.7 %). This investigation stresses the problem of correct diagnosis and the methodological limitations in the assessment of laboratory parameter validity in GD. Based on this work, TSH receptor autoantibody-negative GD is extremely rare.

References

  • 1 Rapoport B, Chazenbalk G D, Jaume J C, McLachlan S M. The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies.  Endocr Rev. 1998;  19 673-716
  • 2 Weetman A P. Graves' disease.  N Engl J Med. 2000;  343 1236-1248
  • 3 Smith B R, Hall R. Thyroid-stimulating immunoglobulins in Graves' disease.  Lancet. 1974;  2 427-431
  • 4 Morgenthaler N G. New assay systems for thyrotropin receptor antibodies.  Curr Opin Endocrinol Diabetes. 1999;  6 251-260
  • 5 Costagliola S, Morgenthaler N G, Hoermann R, Badenhoop K, Struck J, Freitag D, Poertl S, Weglohner W, Hollidt J M, Quadbeck B, Dumont J E, Schumm-Draeger P M, Bergmann A, Mann K, Vassart G, Usadel K H. Second-generation assay for thyrotropin receptor antibodies has superior diagnostic sensitivity for Graves' disease.  J Clin Endocrinol Metab. 1999;  84 90-97
  • 6 Schott M, Feldkamp J, Bathan C, Fritzen R, Scherbaum W A, Seissler J. Detecting TSH-receptor antibodies with the recombinant TBII assay: technical and clinical evaluation.  Horm Metab Res. 2000;  32 429-435
  • 7 Pedersen I B, Knudsen N, Perrild H, Ovesen L, Laurberg P. TSH-receptor antibody measurement for differentiation of hyperthyroidism into Graves' disease and multinodular toxic goitre: a comparison of two competitive binding assays.  Clin Endocrinol (Oxf). 2001;  55 381-390
  • 8 Kasagi K, Konishi J, Iida Y, Ikekubo K, Mori T, Kuma K, Torizuka K. A new in vitro assay for human thyroid stimulator using cultured thyroid cells: effect of sodium chloride on adenosine 3',5'-monophosphate increase.  J Clin Endocrinol Metab. 1982;  54 108-114
  • 9 Kasagi K, Konishi J, Iida Y, Tokuda Y, Arai K, Endo K, Torizuka K. A sensitive and practical assay for thyroid-stimulating antibodies using FRTL-5 thyroid cells.  Acta Endocrinol (Copenh). 1987;  115 30-36
  • 10 Wallaschofski H, Orda C, Georgi P, Miehle K, Paschke R. Distinction between autoimmune and non-autoimmune hyperthyroidism by determination of TSH-receptor antibodies in patients with the initial diagnosis of toxic multinodular goiter.  Horm Metab Res. 2001;  33 504-507
  • 11 Wallaschofski H, Orda C, Fuhrer D, Holzapfel H P, Krohn K, Miehle K, Neumann S, Georgi P, Paschke R. Distinction between autoimmune and nonautoimmune hyperthyroidism by determination of thyrotropin-receptor antibodies in patients with the scintigraphic diagnosis of disseminated autonomy.  Thyroid. 2001;  11 710-711
  • 12 Meller J, Jauho A, Hufner M, Gratz S, Becker W. Disseminated thyroid autonomy of Graves' disease: reevaluation by a secind generation TSH receptor antibody assay.  Thyroid. 2000;  10 1073-1079
  • 13 Weetman A P. Graves' disease by any other name? Guest Editorial.  Thyroid. 2000;  10 1071-1072
  • 14 Paunkovic N, Paunkovic J. Diagnostic sensitivity of two radioreceptor assays (TRAK Assay and TRAK Dyno human) for the detection of TSH receptor antibodies.  Nuclear Medicine Review. 2003;  6 119-122

Jane Paunkovic

Department of Nuclear Medicine · Medical Center · Zajecar

Rasadnicka b.b. · 19000 Zajecar · Serbia and Montenegro

Phone: +381 (19) 443 521

Fax: +381 (19) 420 672

Email: janep@sezampro.yu

    >