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Endocrine Care: C. A. Spencer, L. M. Bergoglio, M. Kazarosyan, S. Fatemi, and J. S. LoPresti Clinical Impact of Thyroglobulin (Tg) and Tg Autoantibody Method Differences on the Management of Patients with Differentiated Thyroid Carcinomas J Clin Endocrinol Metab 2005; 90: 5566-5575 [Abstract] [Full text] [PDF]

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Thyroglobulin measurements in differentiated thyroid cancer – time for action

Bernard Rees Smith   (7 December 2005)

Thyroglobulin measurements in differentiated thyroid cancer – time for action 7 December 2005
Bernard Rees Smith, Managing Director FIRS Laboratories, RSR Ltd, Parc Ty Glas, Llanishen, Cardiff, CF14 5DU, UK Send letter to journal: Re: Thyroglobulin measurements in differentiated thyroid cancer – time for action firs{at}rsrltd.eclipse.co.uk Bernard Rees Smith	The October 2005 issue of JCEM contains a report of thyroglobulin (Tg) and Tg autoantibody (TgAb) measurements with several different assays (14 for Tg and 11 for TgAb) in patients with differentiated thyroid cancer (1). It is a pity that additional controls were not included, in particular, the international standard for Tg (CRM-457) and for TgAb (NIBSC 65/093). If these two reference preparations, diluted in the appropriate diluent had been incorporated into the study in a rigorous way, comparison of the ng/mL of Tg and units/mL of TgAb quoted by different laboratories would have been greatly facilitated. The report (1) and an accompanying editorial (2) emphasize the problem of the same serum sample giving different Tg results in different assays even in the absence of potentially interfering factors. The most important interfering factors in serum Tg measurements are serum TgAb but just as TgAb can interfere in Tg measurements, Tg can interfere in TgAb measurements (3). In some assays Tg can cause a lowering of the TgAb concentrations and assays affected in this way include immunoprecipitation assays and sandwich type assays (4). In the case of competitive assays where TgAb inhibit the binding of Tg to monoclonal or polyclonal antibodies, higher concentrations of Tg inhibit this reaction causing false positive results. Furthermore, many TgAb assays are designed to detect the higher levels of TgAb associated with autoimmune thyroid disease and for maximum laboratory conveniency. Consequently, they may not always be appropriate for measuring TgAb when there is likely interference by Tg. The Immunology of Diabetes Society (IDS), dealing with a similar problem which occurred in measurements of diabetes associated autoantibodies, has run a proficiency program (Diabetes Autoantibody Standardization Program; DASP) (5) in in conjunction with the Centers for Disease Control and Prevention (CDC; Atlanta, USA). The program involves the CDC dispatching samples blind to participating laboratories which are also required to include dilutions of an international reference preparation (NIBSC 97/550). The impact on the measurement of autoantibodies to GAD and to IA-2 has been striking, and now there is mostly good agreement between different laboratories worldwide. Representatives of the ATA, AOTA, LATS and the ETA should discuss the current problem of standardization of Tg measurements with the CDC. References 1. Spencer CA, Bergoglio LM, Kazarosyan M, Fatemi S, LoPresti JS 2005 Clinical impact of thyroglobulin (Tg) and Tg autoantibody method differences on the management of patients with differentiated thyroid carcinomas. J Clin Endocrinol Metab 90:5566-5575 2. Stockigt JR 2005 Ambiguous thyroglobulin assay results in the follow-up of differentiated thyroid carcinoma. J Clin Endocrinol Metab 90:5904-5905 3. Guillen C, Sartorio G 2005 Influence of thyroglobulin (Tg) on thyroglobulin autoantibodies (TgAb). Thyroid 15 (Suppl 1): S143-144 4. Burne P, Mitchell S, Rees Smith B 2005 Point-of-care assays for autoantibodies to thyroid peroxidase and to thyroglobulin. Thyroid 15:1005-1010 5. Bingley PJ, Bonifacio E, Mueller PW, participating laboratories 2003 Diabetes autoantibody standardization program: first assay proficiency evaluation. Diabetes 52:1128-1136