TSH-receptor antibody measurement for differentiation of hyperthyroidism into Graves' disease and multinodular toxic goitre: a comparison of two competitive binding assays.

Abstract

OBJECTIVES:

Graves' disease is characterized by stimulating autoantibodies to the TSH-receptor (TRAb). The aim of this study was to compare the performance of a new TRAb assay based on competitive binding to recombinant human TSH-receptors (H-TRAb) with an assay employing purified porcine TSH-receptors (P-TRAb). Furthermore, to evaluate the applicability of the H-TRAb assay to discriminate between patients with hyperthyroidism due to Graves' disease (GD) and multinodular toxic goitre (MNTG).

DESIGN AND MEASUREMENTS:

H-TRAb and P-TRAb were measured in patients with newly diagnosed hyperthyroidism due to GD (n = 106) and MNTG (n = 94). For comparison, TRAb was measured in patients with primary autoimmune hypothyroidism, euthyroid subjects with an enlarged thyroid gland by ultrasound, and healthy controls (n = 100 for each group). Patients were consecutively included from a population survey.

RESULTS:

If the cut-off values recommended by the manufacturer for TSH-receptor antibody positivity were used for evaluation, the sensitivity of the H-TRAb assay vs. the P-TRAb assay in diagnosing GD was: 95.3/67.9% (P < 0.001). Specificity was (H/P-TRAb): 99/99%. The sensitivity of P-TRAb was increased if the upper 97.5% limit of measurements in controls was used as cut-off (H-TRAb vs. P-TRAb: 95.3/80.2%, P < 0.001). Specificity (H/P-TRAb): 98/98%. The difference between assay performance may partly be due to a better technical performance of the H-TRAb assay with more reliable results in the low range of measurements. However, even in GD patients with clearly measurable TRAb, 25% had a P-TRAb < 50% of the value expected from the H-TRAb measurement. This suggests that a subgroup of patients produce TRAb with a higher affinity for the human than the porcine TSH receptor. A relatively high proportion of patients with MNTG were TRAb positive (H-TRAb/P-TRAb: 17/9%). Characteristics of H-TRAb positive and negative MNTG patients were compared. There was no difference between size of thyroid gland and number of nodules by ultrasonography. H-TRAb positive patients had significantly higher serum T4 and T3 and a greater number were TPO-Ab positive.

CONCLUSIONS:

H-TRAb diagnosed Graves' disease with a high sensitivity and specificity than P-TRAb. The high occurrence of TRAb in multinodular toxic goitre might in part reflect an overlap between Graves' disease and multinodular toxic goitre in some patients.

• Authors: I B Pedersen, N Knudsen, H Perrild, L Ovesen, P Laurberg
• Journal: Clinical endocrinology (Clin Endocrinol (Oxf)) Vol. 55 Issue 3 Pg. 381-90 (Sep 2001) ISSN: 0300-0664 [Print] England
• PMID: 11589682 (Publication Type: Comparative Study, Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Receptors, Thyrotropin
• Recombinant Proteins

Topics

• Adult
• Aged
• Animals
• Autoantibodies (blood)
• Binding, Competitive
• Cross-Sectional Studies
• Diagnosis, Differential
• Female
• Goiter, Nodular (diagnosis, immunology)
• Graves Disease (diagnosis, immunology)
• Humans
• Male
• Middle Aged
• Radioimmunoassay (methods)
• Receptors, Thyrotropin (immunology)
• Recombinant Proteins (immunology)
• Registries
• Sensitivity and Specificity
• Swine