title: Clinical experience with recombinant human thyrotrophin (rhTSH) in the management of patients with differentiated thyroid cancer.
abstract: The purpose of this work was to gain clinical experience with and to identify the optimal conditions for the use of recombinant human TSH (rhTSH, commercially available as Thyrogen) in the management of patients with differentiated thyroid cancer (DTC). The study involved 22 patients for a total of 27 administration cycles of rhTSH, for either diagnostic (in 19 instances) and/or therapeutic purposes (in 8 instances). There were 19 patients with papillary cancer (follicular variant in 4, columnar variant in 1) and 3 patients with follicular cancer (1 Hurtle cell variant). All patients had previously undergone total thyroidectomy and 1-5 cycles of 131I-therapy. Thyrogen was administered i.m. according to the suggested protocol: 0.9 mg i.m. on days 1 and 2, radioiodine on day 3. Peak serum TSH levels between 68-237 microIU/mL were observed after rhTSH administration; these were on average 65% higher, on a patient-by-patient basis, than peak serum TSH observed after conventional withdrawal of thyroxine treatment in 19 patients, while in 3 patients they were 28% lower, but still in the potent stimulation range (86-94 microIU/mL). There was general agreement between imaging results obtained under rhTSH stimulation and those obtained on prior occasions during thyroxine withdrawal, although radioiodine uptake was interpreted as less intense following Thyrogen administration. Of 18 patients undergoing rhTSH administration for diagnostic purposes, 11 patients had a negative radioiodine whole-body scan (WBS) and 7 had a positive WBS. Three of the WBS-negative patients were shown to be actually affected by tumor recurrence, respectively by PET with [18F]FDG (in 2 cases) and by post-131I therapy scan. Serum thyroglobulin (hTg) increased to abnormal levels following rhTSH stimulation in 3/7 of the WBS-positive patients as well as in 1/11 WBS-negative patients. In 3/7 WBS-positive as well as in 3/11 WBS-negative patients, serum hTg progressively rose under rhTSH stimulation, yet still remaining below 3 ng/mL. Post-131I therapy scans following Thyrogen administration showed good radioiodine uptake in 7/8 patients, the single unsuccessful case being most likely due to expansion of the iodine pool because of recent use of an iodinated contrast medium. The overall results show the feasibility and practical advantages of employing rhTSH stimulation in the general clinical setting rather than thyroxine withdrawal in the management of DTC patients. Caution should be raised on the interpretation of the serum hTg response to such potent but short-lived TSH stimulation.
authors.affiliation: Nuclear Medicine Service, DIMI, Univ of Genoa, Italy. mariani@unige.it
authors.forename: G
authors.initials: G
authors.lastname: Mariani
authors.forename: M
authors.initials: M
authors.lastname: Ferdeghini
authors.forename: C
authors.initials: C
authors.lastname: Augeri
authors.forename: G
authors.initials: G
authors.lastname: Villa
authors.forename: G Z
authors.initials: GZ
authors.lastname: Taddei
authors.forename: G
authors.initials: G
authors.lastname: Scopinaro
authors.forename: G
authors.initials: G
authors.lastname: Boni
authors.forename: L
authors.initials: L
authors.lastname: Bodei
authors.forename: C
authors.initials: C
authors.lastname: Rabitti
authors.forename: E
authors.initials: E
authors.lastname: Molinari
authors.forename: R
authors.initials: R
authors.lastname: Bianchi
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D002291:Carcinoma, Papillary / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D019090:Case Management; D002454:Cell Differentiation; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging / Q000532:radiotherapy; D011877:Radionuclide Imaging; D011994:Recombinant Proteins / Q000627:therapeutic use; D013954:Thyroglobulin / Q000097:blood; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood / Q000627:therapeutic use; D013974:Thyroxine / Q000008:administration & dosage / Q000627:therapeutic use; D014915:Whole-Body Counting
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D007457:Iodine Radioisotopes; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D013972:Thyrotropin; D013954:Thyroglobulin; D013974:Thyroxine