title: Recombinant human TSH and ablation of post-surgical thyroid remnants in differentiated thyroid cancer: the effect of pre-treatment with furosemide and furosemide plus lithium.
abstract: OBJECTIVE
  Recombinant human TSH (rhTSH) can be used for post-surgical radioiodine (I-131) thyroid remnants ablation in differentiated thyroid cancer (DTC) patients after surgery. Debate exists in literature about the optimal amount of I-131 that should be given for obtaining an effective ablation and about the role of iodine pool during treatment. Therefore, the aim of the present study was to assess whether I-131 ablation during rhTSH stimulus can be improved by reducing the circulating iodine pool and by increasing thyroid cell uptake and retention of I-131 obtained by administering furosemide and lithium.
  
  
  METHODS
  A total of 201 consecutive DTC patients were entered in the study: they were treated by total thyroidectomy and I-131 therapy during rhTSH stimulus to ablate thyroid remnants. Patients were divided into two groups according to the TNM stage: group 1 included patients in stage I-II who were treated with a low 30-mCi I-131 dose, while group 2 included patients in stage III-IV who were treated by a high 100-mCi I-131 dose. Moreover, both groups were further subdivided into three subgroups. Subgroup (a) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day withdrawal of L-thyroxine (LT4). Subgroup (b) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day withdrawal of L-T4, and after furosemide administration (25 mg/day orally) during the 3 days before I-131. Subgroup (c) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day L-T4 withdrawal, and after administration of furosemide (25 mg/day orally) during the 3 days prior I-131 and lithium (450 mg/day orally) during the 3 days following I-131. Another group (group 3) of 20 patients characterized by a very low-risk cancer (unifocal tumor <1.0 cm in diameter, without extra-capsular extension, N0) was treated with a 30-mCi I-131 dose under rhTSH stimulus without performing the short 4-day L-4 withdrawal: this group was taken as the control. Follow-up was performed by neck ultrasonography (US), and Tg measurement and I-131 WBS under rhTSH stimulus.
  
  
  RESULTS
  Among the patients from group 1, those pre-treated with furosemide or with furosemide plus lithium showed a better outcome of ablation both in terms of undetectable Tg values (97.7% and 95.5 % vs. 79.5%, p < 0.05) and of WBS negativity (97.7% vs. 81.8%, p < 0.05) during the rhTSH stimulus. No similar findings were observed in group 2 patients. Moreover, in patients from group 3 (I-131 30 mCi, without L-T4 withdrawal), the outcome of ablation was significantly lower in comparison to patients from group 1 (I-131 30 mCi, with L-T4 withdrawal) in terms of undetectable Tg during the rhTSH stimulus (55.0%, p < 0.001).
  
  
  CONCLUSIONS
  rhTSH is highly effective for post-surgical thyroid remnant ablation in low-risk cancer patients using the low 30-mCi dose protocol combined with the short 4-day withdrawal of L-T4. Moreover, in these patients the pre-treatment with furosemide seems to play an important role to further improve the outcome of ablation by reducing the iodine pool.
authors.affiliation: General Hospital of Livorno, Livorno, Italy. danielebarbaro@katamail.com
authors.forename: Daniele
authors.initials: D
authors.lastname: Barbaro
authors.forename: Mariano
authors.initials: M
authors.lastname: Grosso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Boni
authors.forename: Paola
authors.initials: P
authors.lastname: Lapi
authors.forename: Cristina
authors.initials: C
authors.lastname: Pasquini
authors.forename: Paola
authors.initials: P
authors.lastname: Orsini
authors.forename: Anna
authors.initials: A
authors.lastname: Turco
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Meucci
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Marzola
authors.forename: Piero
authors.initials: P
authors.lastname: Berti
authors.forename: Paolo
authors.initials: P
authors.lastname: Miccoli
authors.forename: Giuliano
authors.initials: G
authors.lastname: Mariani
authors.forename: Domenico
authors.initials: D
authors.lastname: Rubello
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005260:Female; D005665:Furosemide / Q000008:administration & dosage*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D018020:Lithium Compounds / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D011292:Premedication / Q000379:methods*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000628:therapy*; D013965:Thyroidectomy; D013972:Thyrotropin / Q000008:administration & dosage* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D018020:Lithium Compounds; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; D005665:Furosemide; D013972:Thyrotropin