Is thyroid stunning a real phenomenon or just fiction?

Thyroid stunning is usually defined as decreased uptake or trapping of radioiodine 131I by normal thyroid tissue or differentiated thyroid cancer after diagnostic administration of 131I. As simple as this definition might be, it is as important to understand the mechanisms by which this phenomenon, if real, is caused. There are 2 possible explanations: Stunning may result either from a reduction of the number of functional thyroid cells simply caused by cell death due to the -radiation of 131I (this would be, rather, a partial ablation) or from a decreased ability of viable thyroid cells to trap or retain radioiodine for a more-or-less specific time interval. The first explanation for stunning—that is, a partial ablation caused by activities administered diagnostically in cancer patients that are comparable with activities used therapeutically for thyrotoxicosis—would indicate therapeutic effects comparable with a fractionated therapy. Another possible ablation mechanism could be intratherapeutic necrosis due to high radiation doses of 131I within the first 24–48 h, as observed by Guiraud-Vitaux et al. (1), resulting in a reduced number of cells and, thus, reduced uptake when intratherapeutic imaging or uptake measurements are usually performed after 48 h or later. However, the second explanation for stunning—a radiation-induced reduction of iodine uptake or metabolism in viable cells— would imply a potential reduction of the therapeutic efficacy of radioiodine treatment after diagnostic 131I imaging, raising the question of whether the management of patients has to be changed. Since the first report on intratherapeutically reduced uptake of 131I after diagnostic studies with this radioisotope by Rawson et al. (2) in 1951, the phenomenon of thyroid stunning has been investigated by several authors, who have reported contradictory findings. Interestingly, most of the articles using a quantitative approach did show evidence for stunning, whereas the reports dealing with qualitative methods (i.e., visual assessment of scans or assessment of the therapeutic outcome of patients) yielded conflicting results. For example, Leger et al. (3) and Kao and Yen (4) described a visually reduced or suppressed uptake of radioiodine in thyroid remnants after scanning with 185 and 111 MBq 131I, respectively, whereas other authors, such as McDougall (5) or Cholewinski et al. (6), found no changes of the 131I uptake pattern when diagnostic and subsequent therapeutic scans were compared. Contradictory results were also obtained in studies on ablation rates of thyroid remnants. For example, Muratet et al. (7) detected a significantly higher ablation rate of postsurgical remnants in patients after a diagnostic scan with 37 MBq than after a scanning dose of 111 MBq 131I (76% vs. 50%; P 0.001). On the other hand, Morris et al. (8) reported on the nonimpact of thyroid stunning for the remnant ablation rates in nonscanned and scanned patients using 111–185 MBq 131I. However, quantitative studies by Leger et al., Huic et al. (9), and Sabri et al. (10) always proved a reduced therapeutic versus diagnostic 131I uptake. Furthermore, data indicate that stunning, as expected from a radiobiologic point of view, is related to dose: Sabri et al. clearly showed that stunning exists in benign thyroid disease and that there was a significant correlation between thyroid stunning and the first absorbed energy dose. Jeevanram et al. (11) observed a reduction in uptake that was proportional to the calculated radiation dose, ranging from 31 to 73 Gy in postthyroidectomy patients, and Medvedec (12) reported on significant stunning effects above doses as low as 10 Gy. On the basis of clinical papers providing quantitative data, Coakley (13) recently concluded in his editorial: “Evidence that stunning is a real phenomenon is now strong, albeit not yet conclusive.” Besides the aforementioned clinical studies, few experimental studies dealing with radiation-induced changes and thyroid stunning have been published (1,14). Guiraud-Vitaux et al. (1) observed morphologic and ultrastructural changes in rat thyroid cells after administration of diagnostic and therapeutic amounts of 131I typical for necrosis of the cells with no signs of apoptosis. Thereby, the effects of 131I varied only in quantity, with a much higher number of damaged cells in the therapeutic group. Furthermore, in the diagnostic group the damage was observed only at 24 h but not at 48 h, whereas in the therapeutic group changes were found at any time. In 2 animals that received 9 MBq 131I 8 d after injection of 0.45 MBq 131I (1.85 MBq/g of thyroid tissue), radioiodine uptake per gram of thyroid was similar to that obtained in the therapeutic group. A completely new and functional approach dealing with thyroid stunning at the cellular level is presented by Postgård et al. (15) in this issue of The Journal of Nuclear Medicine. Porcine thyroid cells were cultured in a bicameral system in which the cell monoReceived Feb. 5, 2002; accepted Feb. 22, 2002. For correspondence or reprints contact: Winfried Brenner, MD, Universitätsklinikum Kiel, Arnold-Heller-Strasse 9, D-24105 Kiel, Germany. E-mail: [email protected]