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Uptake of ²⁰¹Tl into Primary Cell Cultures from Human Thyroid Tissue Is Multiplied by TSH

¹ Nuklearmedizinische Klinik mit Poliklinik, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
² Institut für Medizininformatik, Biometrie und Epidemiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
³ Pathologisches Institut, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
⁴ Chirurgische Klinik mit Poliklinik, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

According to current guidelines, ²⁰¹Tl scintigraphy aiming at the detection of iodine-negative metastases of differentiated thyroid carcinoma is usually performed during hormone replacement in thyroid-stimulating hormone (TSH)–suppressive doses. The aim of this study was to determine the effect of TSH on thyroid ²⁰¹Tl uptake in vitro. Methods: Adherent monolayers of human thyroid tissue (1.965–3.000 million cells) were cultured after mechanical disintegration and enzymatic digestion by neutral protease. The samples were derived from patients undergoing surgical treatment of nodular goiter. Studies were performed on paranodular tissue components, exclusively. Cells originating from identical tissue samples were dispensed into matched-pair cultures and incubated in parallel by a TSH-free medium and by a medium containing 10 IU/L bovine TSH. Thyroglobulin (Tg) accumulation was calculated after repetitive measurements of Tg concentrations by radioimmunoassay. Uptake studies were initiated by adding fresh medium containing ²⁰¹Tl (8.2–91.0 kBq). After 1 h of incubation, the media were removed and the cells were detached by trypsin and collected by centrifugation. Uptake was measured by a -counter, and cellular uptake values were calculated as percentages of total activity normalized to 1 million cells. The statistical significance of differences in Tg release and ²⁰¹Tl uptake was corroborated in a generalized estimating equations analysis taking the variability of unbalanced replicate measurements into account. Results: Cells cultured in the presence of TSH displayed a 2-fold release of Tg (12.949 ng/h/million cells vs. 6.049 ng/h/million cells, P = 0.001) and triplicate ²⁰¹Tl uptake (0.718%/million cells vs. 0.249%/million cells, P = 0.0002). Conclusion: ²⁰¹Tl uptake in human thyroid cells is significantly increased by TSH. These data suggest that withdrawal of thyroid hormone substitution has the potential to improve the sensitivity of ²⁰¹Tl scintigraphy for detecting thyroid remnants or cancer recurrences. This suggestion should be further investigated in patients and in cell cultures from thyroid carcinomas.

Key Words: ²⁰¹Tl • differentiated thyroid carcinoma • thyroid • thyroid-stimulating hormone • thyrotropin