After initial therapy of differentiated thyroid carcinomas, in most cases thyroidectomy and iodine-131 ablation of residual thyroid tissue, long term follow-up is currently based on periodic whole-body scintigraphy and serum thyroglobulin (Tg) determination. Both best performed after an adequate period without replacement therapy.
This protocol presumes that withdrawal of thyroxine therapy will result in an increase of endogenous thyroid stimulating hormone (TSH) and increased functional activity of any residual as well as metastatic thyroid tissue (thyroglobulin synthesis, I-131 uptake). However, withdrawing thyroxine induces hypothyroidism, which may not be well tolerated by the patient, and prolonged elevation of serum TSH levels may theoretically stimulate the growth of metastases.
As an alternative to hormonal withdrawal, exogenous TSH can be used to elevate serum TSH levels. Bovine thyrotropin was used for many years but has been associated with allergic reactions and the development of neutralizing antibodies to both bovine and human TSH, thereby hindering the accurate measurement in TSH assays and limiting the effectiveness of its repeated diagnostic use. Human pituitary derived TSH (h-TSH), obtained as a side product from the purification of human growth hormone, was also briefly used as a source of exogenous TSH. However, use of h-TSH has been discontinued due to potential transmission of Creutzfeldt-jacob disease.
Recently, a highly purified, recombinant form of the naturally occurring human protein TSH (Thyrogen) has been developed for use in elevating TSH levels in patients prior to both radioiodine scanning and thyroglobulin testing, while remaining on their hormone replacement therapy.
Thyrogen is produced by mammalian cell culture technology using a CHO ( Chinese hamster ovary) cell line co-transfected with recombinant plasmids containing DNA sequences encoding the alpha and beta subunits of TSH. Based on the fact that it has an amino acid sequence identical to that encoded by the human genome, it is unlikely that human subjects will mount an immune response to the drug as was observed with b-TSH. Animal studies have shown comparable biopotency and pharmacokinetics to those of natural pituitary TSH. Preliminary studies on safety of the drug suggest that it can be safely administered to patients with thyroid cancer with no incidence of serious or unanticipated side effects. A TSH serum concentration of greater than 100µ U/ml was achieved in thyroid cancer patients with a 10 IU two day dosing regimen, with TSH levels > 50 IU sustained for an average of 72 hr. Preliminary efficacy results suggest that it may be as effective as hormone withdrawal (endogenous TSH stimulation) in detection of remnants and metastases in patients with thyroid cancer undergoing I-131 whole body scanning. Both, however, were shown to be inferior to whole body scans obtained after a therapeutic dose of I-131. This is a not unexpected finding for it has been known from the results of several studies that one can find more and more remnants of thyroid tissues using higher and higher administered activity. Unfortunately, the larger the administered dose, the more likely is a sub lethal radiation effect on the metastasis which may lead to a decrease in its iodine concentrating ability and shorten the effective half life of iodine in the tumor, both will adversely affect the effectiveness of subsequent therapy.
Based on these considerations, it is preferred to perform the diagnostic whole body scintigraphy with a 2-5 mCi dose. Alternatively a Thallium scan, which has been reported to have a high sensitivity in detection of thyroid cancer metastases, can be performed. Thallium imaging, however, is unlikely to provide information on the iodine concentrating capability of the tissues, important consideration in planning radioactive iodine therapy. If a therapeutic dose is given, a whole body study 7-10 days later may provide the best evaluation for metastatic disease.
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