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: 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, Torquil Watt, James Magner, Annie Purvis, Hans Graf
• Journal: Thyroid : official journal of the American Thyroid Association (Thyroid) Vol. 24 Issue 4 Pg. 727-35 (Apr 2014) ISSN: 1557-9077 [Electronic] United States
• PMID: 24341527 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Delayed-Action Preparations
• Iodine Radioisotopes
• Recombinant Proteins
• Thyrotropin Alfa

Topics

• Aged
• Chemotherapy, Adjuvant
• Delayed-Action Preparations
• Female
• Goiter, Nodular (drug therapy, pathology, radiotherapy)
• Humans
• Iodine Radioisotopes (administration & dosage)
• Male
• Middle Aged
• Organ Size (drug effects, radiation effects)
• Recombinant Proteins (administration & dosage)
• Single-Blind Method
• Thyroid Function Tests
• Thyrotropin Alfa (administration & dosage)
• Treatment Outcome