title: 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.
abstract: BACKGROUND
  Enhanced reduction of multinodular goiter (MNG) can be achieved by stimulation with recombinant human thyrotropin (rhTSH) before radioiodine ((131)I) therapy. The objective was to compare the long-term efficacy and safety of two low doses of modified release rhTSH (MRrhTSH) in combination with (131)I 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 96.0 mL; range 31.9-242.2 mL) were randomized to receive placebo (n=32), 0.01 mg MRrhTSH (n=30), or 0.03 mg MRrhTSH (n=33) 24 hours before a calculated (131)I 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 0.03 mg MRrhTSH group (32.9% vs. 23.1% in the placebo group; p=0.03) but not in the 0.01 mg 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 0.01 mg MRrhTSH group, and 53 ± 18.6% in the 0.03 mg MRrhTSH group, with no statistically significant differences among the groups, p=0.105. In the 0.03 mg MRrhTSH group, the subset of patients with basal (131)I 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 0.03 mg MRrhTSH group (13.4 ± 23.2%), but this was not statistically different from the increases observed in the placebo or the 0.01 mg 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, 0.01 mg, and 0.03 mg MRrhTSH groups respectively. The overall safety profile of the study was favorable.
  
  
  CONCLUSIONS
  When used as adjuvant to (131)I, enhanced MNG reduction could not be demonstrated with MRrhTSH doses ≤ 0.03 mg, indicating that the lower threshold for efficacy is around this level.
authors.affiliation: 1 Department of Endocrinology and Metabolism, Odense University Hospital , Odense, Denmark .
authors.forename: Søren
authors.initials: S
authors.lastname: Fast
authors.forename: Laszlo
authors.initials: L
authors.lastname: Hegedüs
authors.forename: Furio
authors.initials: F
authors.lastname: Pacini
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
authors.forename: Angela M
authors.initials: AM
authors.lastname: Leung
authors.forename: Mario
authors.initials: M
authors.lastname: Vaisman
authors.forename: Christoph
authors.initials: C
authors.lastname: Reiners
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Wemeau
authors.forename: Dyde A
authors.initials: DA
authors.lastname: Huysmans
authors.forename: William
authors.initials: W
authors.lastname: Harper
authors.forename: Irina
authors.initials: I
authors.lastname: Rachinsky
authors.forename: Hevelyn Noemberg
authors.initials: HN
authors.lastname: de Souza
authors.forename: Maria G
authors.initials: MG
authors.lastname: Castagna
authors.forename: Lucia
authors.initials: L
authors.lastname: Antonangeli
authors.forename: Lewis E
authors.initials: LE
authors.lastname: Braverman
authors.forename: Rossana
authors.initials: R
authors.lastname: Corbo
authors.forename: Christian
authors.initials: C
authors.lastname: Düren
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Proust-Lemoine
authors.forename: Christopher
authors.initials: C
authors.lastname: Marriott
authors.forename: Albert
authors.initials: A
authors.lastname: Driedger
authors.forename: Peter
authors.initials: P
authors.lastname: Grupe
authors.forename: Torquil
authors.initials: T
authors.lastname: Watt
authors.forename: James
authors.initials: J
authors.lastname: Magner
authors.forename: Annie
authors.initials: A
authors.lastname: Purvis
authors.forename: Hans
authors.initials: H
authors.lastname: Graf
mesh_terms: D000368:Aged; D017024:Chemotherapy, Adjuvant; D003692:Delayed-Action Preparations; D005260:Female; D006044:Goiter, Nodular / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000187:drug effects / Q000528:radiation effects; D011994:Recombinant Proteins / Q000008:administration & dosage; D016037:Single-Blind Method; D013960:Thyroid Function Tests; D057073:Thyrotropin Alfa / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D057073:Thyrotropin Alfa