Abstract
The aim of this study was to evaluate the ability of the more sensitive second-generation
TSH receptor (TRAb) assay to predict recurrent Graves’ disease (GD) vs. remission depending on TRAb levels. 93 patients with active GD were included in the
study. By using a cut-off limit of 1.0 IU/l, all 93 patients were positive for TRAb
(median: 4.6 IU/l) at the time of their first visit (single point measurement in median
5.1 months after initial diagnosis). Subsequently, 33 patients went into remission
and were euthyroid during follow-up (median follow-up: 21.7 months), whereas 60 patients
did not go into remission or developed relapse over the following 24 months. Median
TRAb levels in the group of remission were significantly (p < 0.0001) lower than TRAb
values in the relapse group (2.1 compared to 8.6 IU/l). Applying ROC plot analysis
to compare different TRAb thresholds, a cut-off of 10 IU/l was established. Here,
the specificity for relapse was 97 % as only 1 of 29 patients with TRAb values above
10 IU/l went into remission during follow-up, whereas all other 28 patients developed
a relapse (positive predictive value for relapse: 96.4 %). In contrast, TRAb values
lower than 10 IU/l had no impact on the prediction of remission. In conclusion, our
data clearly indicate that TRAb measurement is useful for identifying patients that
will not benefit from long-term antithyroid drug treatment.
Key words
Human TRAK assay - Graves’ disease - Remission - Relapse - TSH-receptor antibodies
References
- 1
Weetman A P.
Graves’ disease.
New England Journal of Medicine.
2000;
343
1236-1248
- 2
Rapoport B, Chazenbalk G D, Jaume J C, McLachlan S M.
The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies.
Endocrine Reviews.
1998;
19
673-716
- 3
Morgenthaler N G.
New assay systems for thyrotropin receptor antibodies.
Current Opinion of Endocrinology and Diabetes.
1999;
6
251-260
- 4
Smith B R, Hall R.
Thyroid-stimulating immunoglobulins in Graves’ disease.
Lancet.
1974;
2
427-431
- 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.
Journal of Clinical Endocrinology and Metabolism.
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.
Hormone and Metabolic Research.
2000;
32
429-435
- 7
Massart C, Orgiazzi J, Maugendre D.
Clinical validity of a new commercial method for detection of TSH- receptor binding
antibodies in sera from patients with Graves’ disease treated with antithyroid drugs.
Clinica Chimica Acta.
2001;
304
39-47
- 8
Maugendre D, Massart C.
Clinical value of a new TSH binding inihibitory activity assay using human TSH receptors
in the follow-up of antithyroid drug treated Graves’ disease. Comparison with thyroid
stimulating antibody bioassay.
Clinical Endocrinology.
2001;
54
89-96
- 9
Giovanella L, Ceriani L, Garancini S.
Clinical applications of the 2nd generation assay for anti-TSH receptor antibodies
in Graves’ disease. Evaluation in patients with negative 1st generation test.
Clinical Chemistry and Laboratory Medicine.
2001;
39
25-28
- 10
Zimmermann-Belsing T, Nygaard B, Rasmussen A K, Feldt-Rasmussen U.
Use of the 2nd generation TRAK human assay did not improve prediction of relapse after
antithyroid medical therapy of Graves’ disease.
European Journal of Endocrinology.
2002;
146
173-177
- 11
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.
Clinical Endocrinology.
2001;
55
381-390
- 12
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.
Hormone and Metabolic Research.
2001;
33
504-507
- 13
Morgenthaler N G, Nagata A, Katayama S, Bergmann A, Iitaka M.
Detection of low titre TBII in patients with Graves’ disease using recombinant human
TSH receptor.
Clinical Endocrinology.
2002;
57
193-198
- 14
Schleusener H, Schwander J, Fischer C, Holle R, Holl G, Badenhoop K.
Prospective multicentre study on the prediction of relapse after antithyroid drug
treatment in patients with Graves’ disease.
Acta Endocrinol.
1989;
120
689-701
- 15
Feldt-Rasmussen U, Schleusener H, Carayon P.
Meta-analysis evaluation of the impact of thyrotropin receptor antibodies on long
term remission after medical therapy of Graves’ disease.
Journal of Clinical Endocrinology and Metabolism.
1994;
78
98-102
- 16
Wartofsky L, Glinoer D, Solomon B, Nagataki S, Lagasse R, Nagayama Y, Izumi M.
Differences and similarities in the diagnosis and treatment of Graves’ disease in
Europe, Japan, and the United States.
Thyroid.
1991;
1
129-135
- 17
McIver B, Rae P, Beckett G, Wilkinson E, Gold A, Toft A.
Lack of effect of thyroxine in patients with Graves’ hyperthyroidism who are treated
with an antithyroid drug.
The New England Journal of Medicine.
1991;
334
220-224
- 18
Vitti P, Rago T, Chiovato L, Pallini S, Santini F, Fiore E, Rocchi R, Martino E, Pinchera A.
Clinical features of patients with Graves’ disease undergoing remission after antithyroid
drug treatment.
Thyroid.
1997;
7
369-375
- 19
Michelangeli V, Poon C, Taft J, Newnham H, Topliss D, Colman P.
The prognostic value of thyrotropin receptor antibody measurement in the early stages
of treatment of Graves’ disease with antithyroid drugs.
Thyroid.
1998;
8
119-124
M. Schott,M. D.
Department of Endocrinology · Heinrich-Heine-University Duesseldorf ·
Moorenstraße 5 · 40225 Duesseldorf · Germany
Phone: + 49 (211) 811 78 10
Fax: + 49 (211) 811 78 60 ·
Email: schottmt@uni-duesseldorf.de