Distinction Between Autoimmune and Non-Autoimmune Hyperthyroidism by Determination of TSH-Receptor Antibodies in Patients with the Initial Diagnosis of Toxic Multinodular Goiter

Abstract

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.

Performance of a third‐generation TSH‐receptor antibody in a UK clinic

“…In our cohort ten patients (4% of the total group tested for TRAb) were diagnosed with features of Graves’ disease within a multinodular goitre on thyroid scintigraphy and 50% had positive TRAb antibodies (median 2·33, range 0·53–6·49 U/l). Positive TRAb antibodies in patients with a multinodular goitre have been noted in previous studies from Denmark and Germany 15,28,29 . At least some of these cases may represent Graves’ disease with functioning nodules that are clinically characterised as Graves’ disease rather that autonomous nodular thyroid disease (Marine–Lenhart syndrome) 30 .…”

Epidemiology of subtypes of hyperthyroidism in Denmark: a population-based study

“…We previously reported that up to 15-20% of hyperthyroid patients with a multinodular scintigraphic pattern are TRAb positive (28). Even higher frequencies of TRAb positivity have been reported in clinic-based studies from Germany (51). The difference may be caused by differences in iodine intake and study design.…”

American Association Of Clinical Endocrinologists, Associazione Medici Endocrinologi, And European Thyroid Association Medical Guidelines For Clinical Practice For The Diagnosis And Management Of Thyroid Nodules

“…TRAb determination should be performed in patients with hyperthyroidism for more complete etiologic clarification (82), because 17% of patients in iodine-deficient areas with scintigraphic criteria for toxic MNG are positive for TRAb (83).…”