title: Lithium as adjuvant to radioiodine therapy in differentiated thyroid carcinoma: clinical and in vitro studies.
abstract: OBJECTIVE
  Lithium has been reported to increase radioactive iodine (RaI) doses in benign thyroid disease and in differentiated thyroid carcinoma (DTC). It is not known whether lithium influences the outcome of RaI therapy in DTC. We therefore studied the clinical effects of RaI without and with lithium carbonate in patients with proven metastatic DTC. Controversy also exists on the mechanism by which lithium increases RaI dose in DTC. We performed an in vitro study specifically aimed at examining the effects of lithium on the sodium iodide symporter (NIS).
  
  
  METHODS
  In a clinical study, 12 patients were selected with metastases of DTC who had received previous RaI therapy without lithium (control) that had not influenced tumour progression, despite RaI accumulation in metastases. The patients received 1200 mg lithium carbonate/day followed by 6000 MBq RaI. Outcome parameters were RaI uptake, serum thyroglobulin (Tg) levels and radiological dimensions of metastases compared between RaI with lithium and control. In an in vitro study, iodide uptake was studied in the benign rat thyroid cell line FRTL-5, in the polarized non-thyroid MDCK cell line, stably transfected with human sodium iodide symporter (hNIS) to study the effects of lithium on NIS in a non-thyroid background, and the human follicular thyroid carcinoma cell line FTC133-hNIS to study lithium effects in a background of DTC. Lithium chloride (LiCl) was added in concentrations up to 2 mM for 0-48 h. Both steady-state iodide uptake (30 min) and initial rate (2 min) were studied using a specific activity of 100 mCi/mmol I, the latter experiment to determine lithium effects on substrate dependency. Iodide efflux studies were performed as well.
  
  
  RESULTS
  Despite an increased uptake of RaI in seven patients, no beneficial effect of RaI with lithium was observed on the clinical course as assessed by serum Tg measurements and radiographically. In the in vitro studies, no effects of LiCl on iodide uptake or efflux were observed.
  
  
  CONCLUSIONS
  The addition of lithium to RaI did not have any beneficial effects on the clinical course in 12 patients with metastatic DTC. No beneficial effects of lithium on iodide uptake were observed in vitro. Therefore, the clinical value of lithium in DTC remains subject to debate.
authors.affiliation: Department of Endocrinology, Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Liu
authors.forename: G
authors.initials: G
authors.lastname: van der Pluijm
authors.forename: M
authors.initials: M
authors.lastname: Karperien
authors.forename: M P M
authors.initials: MP
authors.lastname: Stokkel
authors.forename: A M
authors.initials: AM
authors.lastname: Pereira
authors.forename: J
authors.initials: J
authors.lastname: Morreau
authors.forename: J
authors.initials: J
authors.lastname: Kievit
authors.forename: J A
authors.initials: JA
authors.lastname: Romijn
authors.forename: J W A
authors.initials: JW
authors.lastname: Smit
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000627:therapeutic use; D000368:Aged; D000818:Animals; D013956:Antithyroid Agents / Q000627:therapeutic use*; D002291:Carcinoma, Papillary / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D018265:Carcinoma, Papillary, Follicular / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism / Q000627:therapeutic use*; D016651:Lithium Carbonate / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D051381:Rats; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D014162:Transfection / Q000379:methods; D017211:Treatment Failure; D000099209:Sodium-Iodide Symporters
chemical_list: D000277:Adjuvants, Pharmaceutic; D013956:Antithyroid Agents; D007457:Iodine Radioisotopes; D016651:Lithium Carbonate; D027981:Symporters; D000099209:Sodium-Iodide Symporters