Modified-Release Recombinant Human TSH (MRrhTSH) Augments the Effect of 131I Therapy in Benign Multinodular Goiter: Results from a Multicenter International, Randomized, Placebo-Controlled Study

Background: Recombinant human TSH (rhTSH) can be used to enhance I-131 therapy for shrinkage of multinodular goiter (MG). Objective, Design, and Setting: The objective of the study was to compare the efficacy and safety of 0.01 and 0.03 mg modified-release (MR) rhTSH as an adjuvant to I-131 therapy, vs. I-131 alone, in a randomized, placebo-controlled, international, multicenter study. Patients and Intervention: Ninety-five patients (57.2 +/- 9.6 yr old, 85% females, 83% Caucasians) with MG (median size 96.0, range 31.9-242.2 ml) were randomized to receive placebo (group A, n = 32), MRrhTSH 0.01 mg (group B, n = 30), or MRrhTSH 0.03 mg (group C, n = 33) 24 h before a calculated activity of I-131. Main Outcome Measures: The primary end point was a change in thyroid volume (by computerized tomography scan, at 6 months). Secondary end points were the smallest cross-sectional area of the trachea; thyroid function tests; Thyroid Quality of Life Questionnaire; electrocardiogram; and hyperthyroid symptom scale. Results: Thyroid volume decreased significantly in all groups. The reduction was comparable in groups A and B (23.1 +/- 8.8 and 23.3 +/- 16.5%, respectively; P = 0.95). In group C, the reduction (32.9 +/- 20.7%) was more pronounced than in groups A(P = 0.03) and B. The smallest cross-sectional area of the trachea increased in all groups: 3.8 +/- 2.9% in A, 4.8 +/- 3.3% in B, and 10.2 +/- 33.2% in C, with no significant difference among the groups. Goiter-related symptoms were effectively reduced and there were no major safety concerns. Conclusion: In this dose-selection study, 0.03 mg MRrhTSH was the most efficacious dose as an adjuvant to I-131 therapy of MG. It was well tolerated and significantly augmented the effect of I-131 therapy in the short term. Larger studies with long-term follow-up are warranted. (J Clin Endocrinol Metab 96: 1368-1376, 2011)