Long-term efficacy of modified-release recombinant human thyrotropin augmented radioiodine therapy for benign multinodular goiter: Results from a multicenter, international, randomized, placebo-controlled, dose-selection study

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

  • Søren Fast
  • Laszlo Hegedüs
  • Furio Pacini
  • Aldo Pinchera
  • Angela M. Leung
  • Mario Vaisman
  • Christoph Reiners
  • Jean Louis Wemeau
  • Dyde A. Huysmans
  • William Harper
  • Irina Rachinsky
  • Hevelyn Noemberg De Souza
  • Maria G. Castagna
  • Lucia Antonangeli
  • Lewis E. Braverman
  • Rossana Corbo
  • Christian Düren
  • Emmanuelle Proust-Lemoine
  • Christopher Marriott
  • Albert Driedger
  • Peter Grupe
  • James Magner
  • Annie Purvis
  • Hans Graf

Background: Enhanced reduction of multinodular goiter (MNG) can be achieved by stimulation with recombinant human thyrotropin (rhTSH) before radioiodine (131I) therapy. The objective was to compare the long-term efficacy and safety of two low doses of modified release rhTSH (MRrhTSH) in combination with 131I therapy. Methods: In this phase II, single-blinded, placebo-controlled study, 95 patients (57.2±9.6 years old, 85% women, 83% Caucasians) with MNG (median size 96.0mL; range 31.9-242.2mL) were randomized to receive placebo (n=32), 0.01mg MRrhTSH (n=30), or 0.03mg MRrhTSH (n=33) 24 hours before a calculated 131I activity. Thyroid volume (TV) and smallest cross-sectional area of trachea (SCAT) were measured (by computed tomography scan) at baseline, six months, and 36 months. Thyroid function and quality of life (QoL) was evaluated at three-month and yearly intervals respectively. Results: At six months, TV reduction was enhanced in the 0.03mg MRrhTSH group (32.9% vs. 23.1% in the placebo group; p=0.03) but not in the 0.01mg MRrhTSH group. At 36 months, the mean percent TV reduction from baseline was 44±12.7% (SD) in the placebo group, 41±21.0% in the 0.01mg MRrhTSH group, and 53±18.6% in the 0.03mg MRrhTSH group, with no statistically significant differences among the groups, p=0.105. In the 0.03mg MRrhTSH group, the subset of patients with basal 131I uptake <20% had a 24% greater TV reduction at 36 months than the corresponding subset of patients in the placebo group (p=0.01). At 36 months, the largest relative increase in SCAT was observed in the 0.03mg MRrhTSH group (13.4±23.2%), but this was not statistically different from the increases observed in the placebo or the 0.01mg MRrhTSH group (p=0.15). Goiter-related symptoms were reduced and QoL improved, without any enhanced benefit from using MRrhTSH. At three years, the prevalence of permanent hypothyroidism was 13%, 33%, and 45% in the placebo, 0.01mg, and 0.03mg MRrhTSH groups respectively. The overall safety profile of the study was favorable. Conclusions: When used as adjuvant to 131I, enhanced MNG reduction could not be demonstrated with MRrhTSH doses ≤0.03mg, indicating that the lower threshold for efficacy is around this level.

Udgave nummer4
Sider (fra-til)727-735
Antal sider9
StatusUdgivet - 1 apr. 2014

ID: 303679421