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

Stimulation with recombinant human thyrotropin prior to (131)I therapy improves thyroid size reduction by 35%, with a 5-fold higher rate of hypothyroidism. These effects are, at least partially, mediated through mechanisms other than an increase in retained (131)I thyroid dose. Further recombinant human thyrotropin dose-finding studies are warranted before routine use.

On average, neither compression of the trachea nor deterioration of the pulmonary function was observed in the acute phase after rhTSH-augmented (131)I therapy. In the long term, tracheal compression is diminished, and the inspiratory capacity improved, compared with (131)I therapy alone.

The present study compares, in a randomized double-blinded design, the expected and the actual absorbed thyroid radioactive dose in response to 0.3 mg recombinant human (rh)TSH (n = 35) or placebo (n = 28) given 24 h before (131)I therapy in patients with nodular goiter (median volume, 69 ml; range, 20-440 ml). The (131)I activity calculation was based on thyroid (131)I uptake (RAIU) at 24 and 96 h after a tracer dose of 0.5 MBq (131)I. After (131)I therapy, 24- and 96-h RAIU were repeated allowing a more exact assessment of the actual absorbed thyroid dose. The median (131)I activity was 617 and 632 MBq, respectively, in the rhTSH and the placebo group. At baseline, the 24- and 96-h RAIU and the expected thyroid dose were 32.8 +/- 9.1%, 32.1 +/- 8.2%, and 96.3 +/- 16.3 Gy, respectively, in the rhTSH group and 35.7 +/- 11.8%, 35.2 +/- 11.3%, and 94.1 +/- 18.5 Gy, respectively, in the placebo group (P value not significant between groups). After (131)I therapy, the 24- and 96-h RAIU and the actual absorbed thyroid dose were 46.9 +/- 11.7%, 45.0 +/- 12.1%, and 136.7 +/- 47.9 Gy, respectively, in the rhTSH group and 33.0 +/- 11.4%, 31.0 +/- 11.3%, and 76.9 +/- 27.5 Gy, respectively, in the placebo group (P < 0.001 between groups). Comparing the expected with the actual absorbed thyroid dose, this corresponds to a mean increase of 36.4% (95% confidence interval, 21.3-53.4) in the rhTSH group and a decrease of 21.5% (95% confidence interval, -33.9 to -6.6) in the placebo group (P < 0.001), equivalent to an increase of 73.8% in the absorbed thyroid dose in the rhTSH-treated group. We have thus for the first time shown that stimulation with rhTSH before (131)I therapy not only hinders the decrease in the thyroid RAIU observed with conventional (131)I therapy but in fact also significantly enhances the absorbed thyroid dose. Whether this also leads to a significant increase in goiter size reduction needs additional study.

Enhanced goiter volume reduction with rhTSH-augmented (131)I therapy improves the long-term reduction in goiter-related symptoms and reduces the need for additional therapy compared with plain (131)I therapy. Overall patient satisfaction is benefited, despite a higher rate of permanent hypothyroidism.