Current status and performance goals for serum thyroglobulin assays

Abstract

Serum thyroglobulin (Tg) measurements are used as a tumor marker for monitoring patients with differentiated thyroid carcinoma. The clinical utility of six different Tg methods [RIA or immunometric assay (IMA)] currently used in Europe and the US was evaluated, with focus on methodologic standardization, sensitivity, interassay precision across the typical clinical monitoring interval (6 to 12 months), "hook" effects (IMA methods), and Tg autoantibody interference. The methods evaluated were: DYNOtest Tg (Henning), OptiQuant Tg (Kronus), SELco Tg (Medipan), Thyroglobulin IRMA (Pasteur), Nichols Chemiluminescent ICMA (Corning Nichols), and an RIA developed by us (USC Endocrine Services Laboratory). The clinical impact of the current methodologic problems on the use of serum Tg measurements is reviewed. Optimal performance goals are recommended for manufacturers developing and laboratories and physicians selecting a serum Tg method to use for serial long-term monitoring of thyroid cancer patients.

Serum thyroglobulin concentrations predict disease‐free remission and death in differentiated thyroid carcinoma

“…Tg cut-off levels are influenced not only by clinical considerations but also by analytical aspects. Analytical problems include the lack of universal standardization of the Tg assays, 21 intra-assay variability, 'Hook' effects and the presence of Tg autoantibodies. 22,23 Another important point, not addressed in this study, is the observation that Tg increases may be more informative than absolute Tg levels.…”

Clinical relevance of highly sensitive Tg assay in monitoring patients treated for differentiated thyroid cancer

“…Serum Tg determinations were obtained during thyroid hormone suppression of TSH by L-T4 therapy and after rh-TSH stimulation according to the commonly accepted international protocols. 4,16,[18][19][20] The study was approved by the institutional ethics committee; informed consent was obtained from all subjects.…”

Unusual results from immunoassays and the role of the clinical endocrinologist

“…88 The exact mechanism of interference varies between different assay formats but no method is free from it. 89 Autoantibody prevalence is between 4% and 27% in the normal population. Between 15% and 30% in patients with differentiated thyroid carcinoma have these antibodies, which lead to under-or overestimation of the total thyroglobulin regardless of the type of method used.…”

“…Between 15% and 30% in patients with differentiated thyroid carcinoma have these antibodies, which lead to under-or overestimation of the total thyroglobulin regardless of the type of method used. 89,90 Although some of the more recent immunometric assays have been designed with the goal of minimizing interferences by anti-thyroglobulin antibodies using blocking reagents, even these newer-generation assays are not completely free from interference by either anti-thyroglobulin antibodies 88,91 (as patients produce autoantibodies to thyroglobulin that are quite variable in the sites that they recognize) 92 or indeed other heterophilic antibodies. 74,75 It has been suggested that one in 2500 people without thyroid disease have autoantibodies to T3 or T4.…”