title: Modified-release recombinant human TSH (MRrhTSH) augments the effect of (131)I therapy in benign multinodular goiter: results from a multicenter international, randomized, placebo-controlled study.
abstract: BACKGROUND
  Recombinant human TSH (rhTSH) can be used to enhance (131)I therapy for shrinkage of multinodular goiter (MG).
  
  
  OBJECTIVE
  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 (131)I therapy, vs. (131)I alone, in a randomized, placebo-controlled, international, multicenter study.
  
  
  METHODS
  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 (131)I.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  In this dose-selection study, 0.03 mg MRrhTSH was the most efficacious dose as an adjuvant to (131)I therapy of MG. It was well tolerated and significantly augmented the effect of (131)I therapy in the short term. Larger studies with long-term follow-up are warranted.
authors.affiliation: Serviço de Endocrinologia e Metabologia do Hospital de Clínicas da Universidade Federal do Paraná, 80810-070 Curitiba, Brazil. hansgraf@bighost.com.br
authors.forename: H
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authors.lastname: Fast
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authors.lastname: Pacini
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authors.lastname: Pinchera
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authors.lastname: Leung
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authors.lastname: Vaisman
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authors.lastname: Reiners
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authors.initials: JL
authors.lastname: Wemeau
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authors.initials: D
authors.lastname: Huysmans
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authors.lastname: Harper
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authors.lastname: Driedger
authors.forename: H Noemberg
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authors.lastname: de Souza
authors.forename: M G
authors.initials: MG
authors.lastname: Castagna
authors.forename: L
authors.initials: L
authors.lastname: Antonangeli
authors.forename: L
authors.initials: L
authors.lastname: Braverman
authors.forename: R
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authors.lastname: Corbo
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authors.initials: C
authors.lastname: Düren
authors.forename: E
authors.initials: E
authors.lastname: Proust-Lemoine
authors.forename: M A
authors.initials: MA
authors.lastname: Edelbroek
authors.forename: C
authors.initials: C
authors.lastname: Marriott
authors.forename: I
authors.initials: I
authors.lastname: Rachinsky
authors.forename: P
authors.initials: P
authors.lastname: Grupe
authors.forename: T
authors.initials: T
authors.lastname: Watt
authors.forename: J
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authors.lastname: Hegedus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019412:Anatomy, Cross-Sectional; D003131:Combined Modality Therapy; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006044:Goiter, Nodular / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D011994:Recombinant Proteins / Q000627:therapeutic use; D013960:Thyroid Function Tests; D013963:Thyroid Hormones / Q000097:blood; D013965:Thyroidectomy; D013972:Thyrotropin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014132:Trachea / Q000033:anatomy & histology
chemical_list: D003692:Delayed-Action Preparations; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D013963:Thyroid Hormones; D013972:Thyrotropin