Clinical Endocrinology (2007) doi: 10.1111/j.1365-2265.2007.02907.x © 2007 The Authors Journal compilation © 2007 Blackwell Publishing Ltd 1 ORIGINAL ARTICLE Blackwell Publishing Ltd Clinical relevance of highly sensitive Tg assay in monitoring patients treated for differentiated thyroid cancer A. Iervasi*, G. Iervasi*, M. Ferdeghini†, C. Solimeo*, A. Bottoni*, L. Rossi†, C. Colato‡ and G. C. Zucchelli* *Institute of Clinical Physiology, National Council of Research, Pisa, †Division of Morphological and Biomedical Sciences and ‡Department of Pathology, Verona University, Verona, Italy Summary Objective Serum thyroglobulin (Tg) represents a highly specific biomarker for detecting residual thyroid tissue/recurrence/ metastases after treatment for differentiated thyroid cancer (DTC). We evaluated the clinical impact of a highly sensitive Tg assay during routine follow-up of DTC patients. Design Tg values were measured by a highly sensitive Tg assay during L-T4 suppressive therapy and after recombinant human thyrotropin (rh-TSH) stimulation and were compared with those obtained by using a routinely employed Tg assay. Patients One hundred and sixty consecutive DTC-treated patients (papillary carcinoma n = 124, follicular carcinoma n = 36) were studied. Measurements Measured variables included neck ultrasonography, 131 I whole body scanning, and Tg assayed by Immulite (Diagnostic Products Corporation, Los Angeles, CA) and by the highly sensitive Access assay (Beckman Coulter, Brea, CA). Results During L-T4 therapy, measurable Tg was found in only two patients (1% of total) by Immulite and in 23 patients (14% of total) by Access assay. Using the institutional cut-off of 2 μg/l after rh-TSH, a negative response was associated with undetectable Immulite Tg during L-T4 therapy in all patients (negative predictive value, NPV, 100%) and in 137 out of 152 patients with Access assay (NPV 90%). Measurable Tg during L-T4 therapy was found in 17% of positive patients with Immulite and in 100% of patients with Access, respectively. Conclusions The use of a highly sensitive Tg assay may represent a useful diagnostic tool for improving the interpretation of Tg results during monitoring of DTC-treated patients for the early detection of recurrence and for optimizing the use of the more expensive rh-TSH test. (Received 29 November 2006; returned for revision 22 December 2006; finally revised 5 February 2007; accepted 12 April 2007) Introduction Measurement of thyroglobulin (Tg) in serum represents a highly specific biomarker for the detection of residual functioning thyroid tissue and/or recurrence/metastases in the follow-up of patients previously treated for differentiated thyroid cancer (DTC) by total, or near-total thyroidectomy and 131 I remnant ablation. 1–3 In recent years, the population of DTC patients has changed and more indi- viduals have been identified at an earlier stage of the disease. To reduce the number of unnecessary investigations and to identify the few individuals with a previously unrecognized risk of recurrence, the follow-up of such patients should be guided by a protocol with a high negative predictive value. 4,5 In this context, the assay perform- ance represents a critical step for a correct interpretation of clinical significance of minimal changes in serum Tg. 6–9 Recently, several highly sensitive Tg assays have been developed, yet their real clinical benefit still remains undetermined. 10–15 The aim of the present study was to evaluate the clinical impact of Tg measured by a highly sensitive (functional sensitivity 0·1 μg/l) automated Tg assay in a group of 160 DTC-treated patients, sub- mitted to routine follow-up that included neck ultrasonography (US), 131 I whole body scanning, Tg measurement during L-thyroxine (L-T4) suppressive therapy, and after rh-TSH stimulation. The results were compared to those obtained with a routinely employed Tg assay, with a functional sensitivity that satisfies all the criteria required by the NACB guidelines. 16 Materials and methods Patients We evaluated 160 consecutive DTC-treated patients (105 women and 55 men, mean 51·2 years, median 47·7 years, stage I to III according to the AJCC/TNM Cancer Staging Manual classification); 17,18 n = 124 with papillary carcinoma and n = 36 with follicular carcinoma, all previously subjected to total or near total thyroidectomy followed by radioiodine ablation of residual tissue. In all cases suppression of TSH was defined as TSH values < 0·1 mIU/l during L-T4 therapy. DTC patients came from the Division of Morphological and Biomedical Sciences, Verona University, and from the Institute of Clinical Physiology, Council of National Research, Pisa, Italy. All patients had undetectable anti-Tg antibodies (TgAb). Whole body scanning was Correspondence: Giorgio Iervasi, Institute of Clinical Physiology, C.N.R, Loc. S. Cataldo, Via G. Moruzzi, 1, 56124 Pisa, Italy. Tel.: +39 050 3152017; Fax: +39 050 3152166; E-mail: iervasi@ifc.cnr.it