title: Recombinant human thyroid-stimulating hormone (rhTSH): clinical development.
abstract: Recombinant human thyroid-stimulating hormone (rhTSH) was developed to safely provide exogenous TSH stimulation in patients on thyroid hormone suppression therapy (THST), which is integral to long-term management of well-differentiated thyroid cancer. Such stimulation allows detection of thyroid remnant and neoplastic tissue by serum thyroglobulin (Tg) testing and/or diagnostic iodine-131 (I-131) imaging, sparing patients THST withdrawal and resultant metabolic impairment, discomfort and morbidity needed to obtain endogenous TSH stimulation. An extensive clinical development process including nearly a decade of multinational, multicentre study or other follow-up of over 500 patients has demonstrated that: 1) rhTSH is safe and well-tolerated, with the main side effects transient, mild to moderate nausea in approximately 11% or headache in approximately 7% of patients. Of note, no antibodies to TSH were detected in any patient, even in 27 patients who have received multiple treatments; 2) in patients on THST, rhTSH effectively provides TSH stimulation that allows I-131 diagnostic imaging to detect persistent or recurrent disease with a generally equivalent sensitivity and image quality to those observed after THST withdrawal; 3) rhTSH increases the sensitivity of Tg testing in patients on THST; 4) rhTSH administration allows patients to remain euthyroid and obviates THST withdrawal; therefore, rhTSH administration avoids the significantly lower quality of life and greater discomfort and morbidity due to hypothyroidism during withdrawal, according to patients' and caregivers' ratings on validated instruments. These safety and efficacy findings have led to regulatory approval of rhTSH for diagnostic use in the United States in December 1998; regulatory approval is pending in the European Union.
authors.affiliation: Medical, Clinical and Regulatory Affairs, Genzyme Europe, Naarden, The Netherlands. Carlo.Incerti@genzyme.com
authors.forename: C
authors.initials: C
authors.lastname: Incerti
mesh_terms: D013956:Antithyroid Agents / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D007457:Iodine Radioisotopes; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D013954:Thyroglobulin / Q000097:blood; D013964:Thyroid Neoplasms / Q000175:diagnosis*; D013972:Thyrotropin / Q000493:pharmacokinetics
chemical_list: D013956:Antithyroid Agents; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D013972:Thyrotropin; D013954:Thyroglobulin