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Carole A. Spencer, Challenges of Serum Thyroglobulin (Tg) Measurement in the Presence of Tg Autoantibodies, The Journal of Clinical Endocrinology & Metabolism, Volume 89, Issue 8, 1 August 2004, Pages 3702–3704, https://doi.org/10.1210/jc.2004-0986
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The study of Gupta and colleagues (1) reports that the presence of TSH receptor (TSHR) mRNA and/or thyroglobulin (Tg) mRNA, detected by RT-PCR in the peripheral blood of patients with differentiated thyroid carcinomas (DTCs), is a highly sensitive and specific marker for disease in both the pre- and postoperative periods. The authors assert that rigorous primer selection was the reason that their Tg mRNA analyses had a higher specificity for disease than reported by other studies.
Several limitations of the Gupta study (1) include a relatively small number of patients, the modality used to detect recurrent disease, and the Tg cut-off values used to assess the presence of disease. This study primarily used low-dose radioiodine (RAI) imaging to detect disease—a modality that is now considered less sensitive than serum Tg measurement, especially when Tg testing is made under the influence of TSH stimulation (2). In fact, false-negative low-dose RAI scans occur in approximately 20% of cases after thyroid hormone withdrawal and approximately 30% of cases after recombinant human TSH (rhTSH) (3). As the authors acknowledge, the qualitative detection of Tg mRNA is unlikely to replace quantitation of serum Tg protein as a DTC tumor marker test. The Gupta study (1) assessed the sensitivity and specificity of Tg protein measurements using serum Tg cut-off values of greater or equal to 1 μg/liter during thyroid hormone suppression of TSH (THST) and/or greater or equal to 2 μg/liter after rhTSH stimulation. There is growing recognition that the clinical sensitivity of Tg testing is compromised by the use of such high cut-off values. Specifically, serum Tg concentrations in the 1–2 μg/liter range are close to the lower reference limit for healthy euthyroid subjects with intact thyroid glands, thus making it increasingly difficult to discern between true disease and normal remnant tissue (2–4). Despite the use of these high Tg cut-off values, there was only a minor difference in clinical sensitivity between the detection of TSHR and/or Tg mRNAs vs. the detection of serum Tg protein. In the future, as more sensitive Tg assays become available, it is likely that measurement of serum Tg protein during THST will prove superior to mRNA detection and that rhTSH stimulation will become unnecessary (5). Indeed, the authors acknowledge that mRNA determinations are unlikely to replace serum Tg measurements as postoperative tumor marker tests in patients without Tg autoantibodies (TgAbs), but they suggest that Tg and/or TSHR mRNA testing may prove useful disease markers when the clinical utility of serum Tg testing is compromised by TgAb interference.
