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Low Specificity of Blood Thyroglobulin Messenger Ribonucleic Acid Assay Prevents Its Use in the Follow-Up of Differentiated Thyroid Cancer Patients

Department of Endocrinology and Metabolism (R.E., A.V., L.A., E.M., C.N., L.G., A.P.), University of Pisa, 56124 Pisa, Italy; and Section of Endocrinology (F.P.), Department of Internal Medicine, Endocrinology and Metabolism, and Biochemistry, University of Siena, 53100 Siena, Italy

Address all correspondence and requests for reprints to: R. Elisei, M.D., Department of Endocrinology, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy. E-mail: relisei{at}endoc.med.unipi.it.

Thyroglobulin (Tg) is a glycoprotein specifically synthesized by follicular thyroid epithelium. After thyroidectomy and remnant ¹³¹I ablation, serum Tg is a specific and sensitive marker for the presence of thyroid cancer tissue, and its measurement is fundamental in the follow-up of patients affected by differentiated thyroid carcinomas (DTCs), being even more sensitive than diagnostic whole-body scan. Unfortunately, serum Tg measurement becomes useless in approximately 15–25% of DTC cases who are positive for anti-Tg antibodies that interfere with the Tg measurement. In these cases, Tg mRNA measurement has been proposed as an alternative to serum Tg determination. The aim of this study was to verify the sensitivity and specificity of Tg mRNA measurement, performed by quantitative real-time RT-PCR, in a series of 100 subjects (80 DTC patients and 20 controls). From our data, the sensitivity and the specificity of the blood Tg mRNA measurement are 82.3 and 24.2%, respectively, with a positive predictive value and a negative predictive value of 65.6 and 43.7%, respectively. The comparison of the Tg mRNA with the serum Tg, measured by both chemiluminescent and ultrasensitive ELISA methods, confirmed the low specificity of the Tg mRNA assay. The hypothesis that Tg mRNA detectable levels could be predictive of future recurrences is not supported by the long follow-up (median, 7 yr; range, 3–29 yr) of our disease-free patients, who did not develop any recurrences in their clinical history. Moreover, nine disease-free patients, who showed positive levels of Tg mRNA (11.8–336 pg equivalents/µg RNA), were confirmed to be serum Tg free, both in basal conditions and after recombinant human TSH stimulation, 4 yr after the Tg mRNA detection. In conclusion, we demonstrated that the Tg mRNA assay is of poor utility in the follow-up of DTC patients. On the contrary, serum Tg measurement is a very sensitive and specific thyroid tumor marker, and we recommend that the follow-up of patients affected by DTC must be performed using serum Tg rather than blood Tg mRNA measurement.

This study has been supported in part by a grant from Ministero dell’Università e della Ricerca Scientifica e Tecnologica (40%) 2001 and Associazione Italiana per la Ricerca sul Cancro (AIRC). L.A. was a recipient of an AIRC fellowship during this study.

Abbreviations: DTC, Differentiated thyroid carcinoma; rh, recombinant human; Tg, thyroglobulin; WBS, whole-body scan.

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