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Highly Sensitive Serum Thyroglobulin and Circulating Thyroglobulin mRNA Evaluations in the Management of Patients with Differentiated Thyroid Cancer in Apparent Remission

Institute of Endocrine Sciences (L.F., N.C., M.B., D.M., G.V., P.B.-P.), University of Milan, Ospedale Maggiore Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS); Istituto Auxologico Italiano IRCCS (L.P., E.G.); and Laboratory of Molecular Biology (A.M., M.R., E.P., A.M.D.B.), Istituto Auxologico Italiano IRCCS, 20122 Milan, Italy

Address all correspondence and requests for reprints to: Paolo Beck-Peccoz, M.D., Institute of Endocrine Sciences, Ospedale Maggiore IRCCS (Padiglione Granelli), Via Franceses Sforza 35, Milan 20122, Italy. E-mail: . paolo.beckpeccoz{at}unimi.it

Abstract

We studied the potential role of innovative diagnostic tools for the management of patients with differentiated thyroid cancer (DTC). Several methods for the detection of the tumor marker thyroglobulin (Tg) have been employed in 36 patients in apparent remission at the moment of the study. All patients had negative anti-Tg antibodies and were evaluated during L-T₄ suppressive therapy before and after stimulation with recombinant human TSH (rhTSH). Serum Tg was measured by means of conventional [nonhighly sensitive (nhs)] or highly sensitive (hs) immunoassays with positive cut-off values set at 1.0 and 0.18 µg/liter, respectively. The RT-PCR conditions for the qualitative determination of Tg mRNA from peripheral blood were optimized to prevent interference by illegitimate transcription. The patients have been classified on the basis of a hs-basal Tg testing by taking into account the results of their baseline samples in hs immunoassay and RT-PCR method; hs-basal Tg testing was considered positive when the marker was detectable in at least one of the two tests. The predictive value of hs-basal Tg testing was estimated on the basis of a global clinical evaluation, including serum Tg response after rhTSH stimulation and reports of contemporary ¹³¹I scan and neck ultrasound. The clinical evaluation was considered positive when at least one of these criteria yielded positive results. Although nhs-Tg measurement was poorly predictive of the clinical status, basal hs-Tg evaluation was found to be concordant with the clinical evaluation in 71% of cases. Results of basal Tg mRNA detection did not vary after rhTSH stimulation and were concordant with the clinical evaluation in 66% of cases. Tg mRNA evaluation alone showed 10 apparently false-positive results, and serum basal hs-Tg was falsely negative in 11 additional cases, suggesting that a suitable predictability could be obtained by the association of these 2 parameters. Indeed, the combination of hs-Tg assay and mRNA detection in the hs-basal Tg testing allowed the identification of 22 patients with a positive persistent/recurrent disease or normal thyroid residue, as well as identification of all 6 patients with a negative clinical evaluation. In conclusion, the combined evaluation of circulating Tg mRNA and serum Tg by means of hs noncompetitive immunoassay (hs-basal Tg testing) can give useful information on the clinical status of patients with DTC who are apparently disease-free, even on L-T₄ TSH-suppressive therapy. Therefore, these combined evaluations retain a potential role in the clinical monitoring of DTC patients. In particular, a negative hs-basal Tg testing would indicate disease remission and the opportunity to lengthen the intervals between rhTSH stimulations and/or to shift patients to a less profound TSH suppression with L-T₄.

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