Introduction: The effect of ¹³¹I therapy amplification by rhTSH pre-stimulation in very large goiters has not been evaluated in a double-blinded, placebo-controlled study.

Methods: 29 patients (22 females; age range: 37-87 yrs.) with a large multinodular goiter (median 160 ml, range: 99-440 ml) were randomized to receive placebo (n=15) or 0.3 mg rhTSH (n=14) 24h before ¹³¹I administration. Goiter volume was monitored by magnetic resonance imaging.

Results: On average, the goiter volume was unchanged one week after therapy in both groups, but the largest deviations from baseline were observed in the rhTSH group. After twelve months the median goiter volume was reduced from 170 ml to 121 ml in the placebo group, and from 151 ml to 72 ml in the rhTSH group, respectively (within-group: p=0.001; between-group: p=0.019). This corresponds to reductions of 34.1±3.2% and 53.3±3.3%, respectively (between-group: p<0.001). In the placebo group, the goiter reduction correlated positively with the retained thyroid ¹³¹I dose, while such a relationship was absent in the rhTSH group. Adverse effects, mainly related to thyroid pain and cervical compression, were more frequent in the rhTSH group. At 12 months, goiter related complaints were significantly reduced in both groups, without any between-group difference. One and three patients in the placebo and the rhTSH group, respectively, developed hypothyroidism.

Conclusion: rhTSH stimulated ¹³¹I therapy improves the reduction of very large goiters by more than 50%, compared with ¹³¹I therapy alone, but at the expense of more adverse effects following therapy. Our data suggest that rhTSH stimulation may work through mechanisms that go beyond the increase in thyroid ¹³¹I uptake.