Factors influencing the therapeutic outcome of I-131 therapy of differentiated thyroid cancer (DTC): Do we really need stimulated TSH levels?

Almost 20 years ago, Maxon et al. published (N Engl J Med 1983; 309: 937) and updated (J Nucl Med 1992; 33: 1132) a detailed analysis of factors influencing the dosimetry and efficacy of the 131I therapy of DTC. The aim of this study was to re-investigate whether these factors hold true for a different patient population (Europe vs. the US) with lower alimentary iodine supply, and to identify additional variables affecting the outcome of DTC therapy. Sixty-seven patients (39 papillary, 23 follicular, 3 Huerthle cell, 2 partially anaplastic cancers) were given 30-350 mCi Na131I for remnant ablation (n=37) or treatment of metastatic disease (n=30). 14 additional patients underwent a prior 'diagnostic' dose (2-100 mCi) within 1 week before the actual therapy. All had stopped thyroid hormone intake in order to obtain stimulated TSH levels. For dosimetry, quantitative conjugate view whole-body scans were performed daily for ≥ 96 h. The mean 131I uptake values were ∼3-fold higher in remnants (18.2 μCi/mCixg) than in metastases (5.6 μCi/mCixg), whereas effective t1/2s were not significantly different. The biological t1-/2s in remnants and metastases were strongly dependent upon TSH values (the higher the TSH, the shorter the biological t1/2), whereas, surprisingly, no correlation was found between TSH and uptakes: as a result, at TSH ≥ 30 μU/ml, mean radiation doses to remnants or metastases were >10-fold lower than at physiological TSH. Mean doses to remnants were 8.6 Gy/mCi, to metastases 2.8 Gy/mCi. In patients having received a prior 'diagnostic' dose, stunning began at activities > 2 mCi (corresponding to radiation doses > 6 Gy). Actual doses, and not administered activities were best predictors of therapeutic success (reliable remnant ablation at ≥ 300 Gy, metastasis ablation at ≥ 80-200 Gy). Threshold doses for successful tissue ablation were similar in this study as compared to those published earlier. The finding that increasing TSH levels do not seem to enhance the uptake, but dramatically decrease the biological t1/2s, thus radiation doses, stands in clear contrast to the traditional paradigm of the necessity of stimulated TSH levels and warrants further investigation