Background

A highly accurate Thyroglobulin (Tg) assay is essential for the effective management of patients with differentiated thyroid cancer (DTC) following thyroidectomy, when very little Tg-producing tissue is left. The technical limitations of Tg measurement include between-method variability, sub-optimal functional sensitivity (FS), hook effects, and Tg interference by antibodies. Highly sensitive Tg assays can give an increase in sensitivity but may be at the expense of specificity¹. Current guidelines recommend using FS as a means to determine Tg assay sensitivity, which is a clinically relevant parameter based on low-end precision with 20% CV.

Method

Six patients with positive thyroid bed uptake on post-radioiodine therapy scans after total thyroidectomy but had undetectable Tg with no Tg antibodies had their samples investigated on the Immulite2000 and Roche Cobas analysers in serial dilutions.

Results

Investigating the functional sensitivity of the two assays, the Immulite2000 was noted to give significant errors when values dropped below 0.5μg/L. On other hand, the Roche Cobas was generating 25% errors at a level of 1.5 μg/L (Fig 1). In 2011, the two assays showed strong concordance with little bias. However, since 2012, our quality control indicates that the Roche Cobas assay has progressively shown a proportional positive bias throughout the measurement range (Fig 2).

Conclusion

Current immunometric assays are still prone to limitations at the low-end of FS. A new assay with 100-fold increased FS is about to be released and may have the potential to change the sensitivity and specificity of the Tg assay. This is currently being evaluated in our laboratory. This should provide an adequate assay for monitoring recurrence of thyroid cancers.

 Figure 1

Figure 2

¹Schlumberger et al. J. Clin. Endocrinol. Metab. 92(7):2487–2495, 2007