Performance of a third-generation TSH-receptor antibody in a UK clinic.

Abstract

BACKGROUND:

UK national guidelines recommend the measurement of TSH receptor antibodies (TRAb) in certain clinical scenarios. A commercial third-generation TRAb autoantibody M22-biotin ELISA assay was introduced in May 2008 in our centre.

OBJECTIVE:

To evaluate the diagnostic performance of a TRAb assay in a retrospective and subsequently a prospective cohort in a UK centre.

DESIGN:

A retrospective review of patients with thyroid disease followed by a prospective observational study in consecutive patients with newly found suppressed serum thyrotrophin (TSH).

PATIENTS AND MEASUREMENTS:

Medical records of 200 consecutive patients with thyroid disorders who had TRAb measured since the introduction of the assay. In a prospective study 44 patients with newly identified hyperthyroidism (TSH < 0·02 mIU/l) had sera assayed for TRAb prior to their clinic appointment at which a final diagnosis was sought.

RESULTS:

In the retrospective cohort, the manufacturer's cut-off point of TRAb ≥0·4 U/l resulted in a positive predictive value (PPV) of 95%, sensitivity 85%, specificity 94% and negative predictive value (NVP) 79% to diagnose Graves' disease using defined criteria. Receiver operating characteristic (ROC) analysis determined an optimal cut-off point of TRAb ≥3·5 U/l with a 100% specificity to exclude patients without Graves' disease at the cost though of a lower sensitivity (43%). In the prospective study, the sensitivity, PPV, specificity and NPV were all 96% using the ≥0·4 U/l cut-off. When combining hyperthyroid patients from both cohorts the assay sensitivity and specificity at ≥0·4 U/l cut-off were 95% and 92% respectively. A positive TRAb result increased the probability of Graves' disease for a particular patient by 25-35% and only six (2·5%) patients had a diagnosis of hyperthyroidism of uncertain aetiology after TRAb testing.

CONCLUSIONS:

The assay studied specifically identifies patients with Graves' disease. It is a reliable tool in the initial clinical assessment to determine the aetiology of hyperthyroidism and has the potential for cost-savings.

• Authors: A Theodoraki, G Jones, J Parker, E Woolman, N Martin, S Perera, M Thomas, C Bunn, B Khoo, P M Bouloux, M P J Vanderpump
• Journal: Clinical endocrinology (Clin Endocrinol (Oxf)) Vol. 75 Issue 1 Pg. 127-33 (Jul 2011) ISSN: 1365-2265 [Electronic] England
• PMID: 21521291 (Publication Type: Evaluation Study, Journal Article)
• Copyright: © 2011 Blackwell Publishing Ltd.

Chemical References

• Antibodies, Monoclonal
• Immunoglobulins, Thyroid-Stimulating
• Receptors, Thyrotropin

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal
• Child
• Enzyme-Linked Immunosorbent Assay (standards)
• Female
• Graves Disease (diagnosis)
• Humans
• Immunoglobulins, Thyroid-Stimulating
• Male
• Middle Aged
• Receptors, Thyrotropin (immunology)
• Sensitivity and Specificity
• Thyroid Diseases (diagnosis)
• United Kingdom
• Young Adult