A Sensitive Tg Assay or rhTSH Stimulated Tg: What's the Best in the Long-Term Follow-Up of Patients with Differentiated Thyroid Carcinoma?

Sensitivity of thyroglobulin (Tg) measurement in the follow-up of differentiated thyroid carcinoma (DTC) can be optimized by using a sensitive Tg assay and rhTSH stimulation. We evaluated the diagnostic yield of a sensitive Tg assay and rhTSH stimulated Tg in the detection of recurrences in the follow-up of DTC. Additionally the value of imaging techniques for the localization of recurrences was evaluated. We included 121 disease free patients in long-term follow-up for DTC (median 10 years, range 1–34). Tg during thyroid hormone suppression therapy (Tg-on) and rhTSH stimulated Tg were measured with a sensitive Tg assay. Patients with rhTSH stimulated Tg ≥1.0 ng/ml underwent imaging with neck ultrasound, FDG-PET and post therapy 131I WBS. Sensitive Tg measurement resulted in 3 patients with Tg-on ≥1.0 ng/ml, recurrence could be localized in 2 of them. RhTSH stimulation resulted in Tg ≥1.0 ng/ml in another 17 of 118 patients. Recurrence could be localized in only 1 additional patient (1 out of 118 patients). Recurrence was localized by neck ultrasound in 1 of 3, by FDG-PET in 2 of 3 and by post therapy 131I WBS in 2 of 3 patients. In the detection of recurrences in DTC, rhTSH stimulation had very limited additional value in comparison to Tg-on measurement with a sensitive Tg assay. We consider this too low to justify rhTSH stimulation in all patients during long-term follow up. Neck ultrasound, FDG-PET and post therapy 131I WBS showed complementary value in localization of disease, but were only positive in a small fracture of all procedures

Clinical utility of an automated immunochemiluminometric thyroglobulin assay in differentiated thyroid carcinoma

Background: Thyroglobulin (Tg) measurements are important in the follow-up of patients with differentiated thyroid carcinoma (DTC). We evaluated the analytical and clinical performance of a new automated immunochemiluminometric assay for Tg (Tg-ICMA; Nichols Advantage Tg; Nichols Institute Diagnostics). Methods: We used the Tg-ICMA to measure Tg concentrations in serum samples from 110 Tg antibody-negative DTC patients undergoing thyroid-hormone suppression therapy. Disease state at the time of measurement was assessed on the basis of routine follow-up data. We compared the clinical performance of this assay with the routinely used IRMA (ELSA-hTG; CIS Bio International). Results: The detection limit and functional sensitivity of the Tg-ICMA, based on direct calibration to CRM457, were 0.05 and 0.6 mu g/L, respectively. No Tg-IRMA-positive cases were missed by the Tg-ICMA. Tg was measurable by Tg-ICMA (0.6-8.6 mu g/L) but undetectable by Tg-IRMA (<1.5 mu g/L) in 12 patients (11%). Clinical data showed evidence of disease in 4 of 12 patients (33%). Conclusions: The Tg-ICMA is a sensitive and reproducible assay for identifying patients in follow-up for DTC with evidence of disease, but uncertainty remains with regard to interpreting findings of measurable serum Tg in patients with no evidence of disease. Follow-up data are required to determine the predictive value of these isolated Tg results. New concepts, i.e., serial Tg measurements and risk stratification of patients, need to be tested to confirm the applicability of this assay for clinical practice. (c) 2006 American Association for Clinical Chemistry

Thyroglobulin (Tg) recovery testing with quantitative Tg antibody measurement for determining interference in serum Tg assays in differentiated thyroid carcinoma

Background: Thyroglobulin (Tg) measurements are complicated by interference from Tg autoantibodies (TgAbs) or heterophilic antibodies (HAMAs). We used a new automated immunochemiluminometric assay (ICMA) with Tg recovery (TgR) on the Nichols Advantage (R) platform to reassess the clinical utility of recovery testing in detecting interference in serum Tg measurement in patients with differentiated thyroid carcinoma. Methods: We used 2 TgAb methods to detect Tg measurement interference with TgR and quantitative TgAb measurement in sera from 127 patients. In a limited number of samples, we used an RIA as comparison method because it appeared to be minimally affected by Tg. Results: Prevalence of TgAbs was 13% (17 of 127) in either 1 or both TgAb assays. A compromised TgR (= 70%) corresponded with TgAb negativity in both assays for 95 of 101 samples (94%). In 6 TgAb-positive sera with TgR within the reference interval, there were no discrepancies between RIA and ICMA results. We obtained discordant, RIA and ICMA results for 6 of 9 TgAb-positive sera with decreased TgR. In 1 TgAb-negative sample, the Tg result was falsely increased because of interference by HAMAs, as shown by an overrecovery of 126%. Conclusions: The Nichols Advantage TgR assay is a valuable complementary method to overcome the technical problem of interference by TgAbs or HAMAs in TgAb assays. Further studies are needed to confirm the potential added value of this TgR assay. (c) 2006 American Association for Clinical Chemistry