Distinguishing Graves’ disease (GD) from a toxic multinodular goiter (TMG) subgroup
with a diffuse but uneven Tc-distribution depends on the diagnostic power of the TSH-receptor
antibody (TRAb) determination. Bioassays using CHO cell lines expressing the hTSH-receptor
or a new TBII assay, which uses the hTSH-receptor as an antigen (DYNOTEST TRAK human,
Brahms, Germany), showed a higher sensitivity for the detection of TRAbs in patients
with GD than assays using solubilized porcine epithelial cell membranes. The aim of
this study was to investigate whether the new Dynotest TRAK human assay has an increased
sensitivity to distinguish GD from non-autoimmune hyperthyroidism. Therefore, we examined
21 consecutive patients with the initial diagnosis of TMG for thyroid-stimulating
antibodies (TSAbs, JP26 cell assay) and TBII with the new highly sensitive Dynotest
TRAK human (Brahms, Germany). The initial diagnosis of TMG was based on suppressed
TSH and a patchy Tc-uptake of more than 1 % and less than 7 % or TSH of more than
0.3 mIE/l with a patchy Tc-uptake of more than 1.5 % and less than 7 % and negative
TBII values in a displacement assay using solubilized porcine epithelial cell membranes
(TRAK, Brahms, Germany). 11 sera from these 21 patients showed TSAb activity. Furthermore,
10 of these 11 TSAb-positive sera were also positive in the Dynotest TRAK human assay,
whereas one serum sample was borderline positive. TSAb activity and inhibition of
125 I-bTSH binding in the Dynotest TRAK human assay correlated well (r = 0.7). Therefore,
11 of the 21 investigated patients initially classified as TMG actually had GD, which
was undetectable using the porcine TBII assay. In conclusion, TSAbs or TRAbs detected
with the Dynotest TRAK human have the highest diagnostic power to differentiate GD
from TMG. Because of the less cumbersome assay technique, the Dynotest TRAK human
measurements should be obtained for all patients with non-typical TMG to differentiate
GD from non-autoimmune hyperthyroidism in order to select the appropriate therapy
for these patients.
Key words:
Hyperthyroidism - TSH Receptor Antibodies - Toxic Multinodular Goiter - Grave's Disease
References
1
Laurberg P, Pedersen K M, Vestergaard H, Sigurdsson G.
High incidence of multinodular toxic goitre in the elderly population in a low iodine
intake area vs. high incidence of Graves' disease in the young in a high iodine intake
area: comparative surveys of thyrotoxicosis epidemiology in East-Jutland Denmark and
Iceland.
J Intern Med.
1991;
229
415-420
2
Pedersen O M, Aardal N P, Larssen T B, Varhaug J E, Myking O, Vik-Mo H.
The value of ultrasonography in predicting autoimmune thyroid disease (In Process
Citation).
Thyroid.
2000;
10
251-259
3
Vitti P.
Grey scale thyroid ultrasonography in the evaluation of patients with Graves' disease.
Eur J Endocrinol.
2000;
142
22-24
4
Carnell N E, Valente W A.
Thyroid nodules in Graves' disease: classification, characterization, and response
to treatment (published erratum appears in Thyroid 1998; 8: 1079).
Thyroid.
1998;
8
647-652
5
Kraiem Z, Glaser B, Yigla M, Pauker J, Sadeh O, Sheinfeld M.
Toxic multinodular goiter: a variant of autoimmune hyperthyroidism.
J Clin Endocrinol Metab.
1987;
65
659-664
6
Rees S B, McLachlan S M, Furmaniak J.
Autoantibodies to the thyrotropin receptor.
Endocr Rev.
1988;
9
106-121
7
Vitti P, Elisei R, Tonacchera M, et al.
Detection of thyroid-stimulating antibody using Chinese hamster ovary cells transfected
with cloned human thyrotropin receptor.
J Clin Endocrinol Metab.
1993;
76
499-503
8
Costagliola S, Morgenthaler N G, Hoermann R, et al.
Second generation assay for thyrotropin receptor antibodies has superior diagnostic
sensitivity for Graves' disease.
J Clin Endocrinol Metab.
1999;
84
90-97
9
Wallaschofski H, Paschke R.
Detection of thyroid stimulating (TSAb)-and thyrotropin stimulation blocking (TSBAB)
antibodies with CHO cell lines expressing different TSH-receptor numbers.
Clin Endocrinol (Oxf.).
1999;
50
365-372
10
Huysmans A K, Hermus R M, Edelbroek M A, et al.
Autoimmune hyperthyroidism occurring late after radioiodine treatment for volume reduction
of large multinodular goiters.
Thyroid.
1977;
7
535-539
11
Huysmans D, Hermus A, Edelbroek M, Barentsz J, Corstens F, Kloppenborg P.
Radioiodine for nontoxic multinodular goiter.
Thyroid.
1977;
7
235-239
12
Nygaard B, Faber J, Veje A, Hegedus L, Hansen J M.
Transition of nodular toxic goiter to autoimmune hyperthyroidism triggered by 131I
therapy.
Thyroid.
1999;
9
477-481
13
Nygaard B, Metcalfe R A, Phipps J, Weetman A P, Hegedus L.
Graves' disease and thyroid associated ophthalmopathy triggered by 131I treatment
of non-toxic goiter.
J Endocrinol Invest.
1999;
22
481-485
14
Vitti P, Rago T, Mancusi F, et al..
Thyroid hypoechogenic pattern at ultrasonography as a tool for predicting recurrence
of hyperthyroidism after medical treatment in patients with Graves' disease.
Acta Endocrinol (Copenh.).
1992;
126
128-131
15
Sostre S, Reyes M M.
Sonographic diagnosis and grading of Hashimoto's thyroiditis.
J Endocrinol Invest.
1991;
14
115-121
16
Yoshida A, Adachi T, Noguchi T, et al.
Echographic findings and histological feature of the thyroid: a reverse relationship
between the level of echo-amplitude and lymphocytic infiltration.
Endocrinol Jpn.
1985;
32
681-690
Prof. Dr. med. R. Paschke
Universität Leipzig Zentrum für Innere Medizin Medizinische Klinik und Poliklinik III
Philipp-Rosenthal-Strasse 27 04103 Leipzig Germany
Telefon: + 49 (341) 97-13200
Fax: + 49 (341) 97-13209
eMail: pasr@medizin.uni-leipzig.de