What role for recombinant human TSH in the treatment of metastatic thyroid cancer?

Abstract

The introduction into clinical practice of recombinant human thyroid-stimulating hormone (rhTSH) has marked a turning point in the management of patients with differentiated thyroid cancer. RhTSH offers a safe and reliable alternative to thyroid hormone withdrawal by avoiding both the clinical consequences of hypothyroidism, with a positive impact on quality of life and work productivity, and the potential risk of cancer growth due to a long-lasting endogenous TSH stimulation.In the follow-up of thyroid cancer patients, rhTSH stimulated thyroglobulin is now routinely proposed as it has been shown to be as sensitive as endogenously stimulated thyroglobulin for the detection of residual and metastatic cancer [1].More recently, the use of rhTSH has been approved for the preparation of adult low-risk patients for postsurgical radioiodine ablation of thyroid remnants with 3.7 GBq 131 I [2]. Although the activity necessary to achieve a comparable rate of ablation is probably higher than that required under hypothyroidism [3,4], the use of rhTSH is associated with a lower whole-body radiation exposure [5] and allows a shorter hospitalization length, which partially compensates for its cost [6].The use of rhTSH in the treatment of metastatic thyroid cancer is much more controversial. Although rhTSH has not been formally approved so far for this indication, it has been used off-label since the 1990s to treat patients in which thyroid hormones could not be stopped [7]. This includes patients unable to raise an adequate endogenous TSH response, either because of hypopituitarism or continued production of thyroxine by a thyroid remnant or metastatic tumour, and patients in poor condition due to advanced disease. The results obtained in some patients are encouraging.One may raise the question whether a wider use of rhTSH can be advovated in the therapeutic setting. In our opinion, both clinical and biological data from the literature argue against a more liberal use of rhTSH for the therapy of metastatic thyroid cancer. First, tumour cells of thyroid cancer have a reduced expression of most thyroid-specific genes, including the TSH receptor and the Na + /I − symporter (NIS) gene [8]. Although the standard two injections protocol of rhTSH provides a high plasma TSH peak, roughly in the range 100-150 mIU/L 24 h after the second injection [9], the concentration increase is short-lived [10]. In order to improve the number of NIS and TSH receptors, and thus enhance the iodine-trapping ability of the cells, a high and prolonged period of TSH stimulation elevation is desirable [11]. Indeed, a 131 I whole-body scan under hypothyroidism is more sensitive than the same scan after rhTSH administration [12]. It should be remembered that a posttherapeutic scan of good quality is an invaluable tool to discover unsuspected metastases and to assess the efficacy of repeated 131 I treatment in metastatic patients [13].Second, published experience shows that rhTSH stimulates the uptake of radioiodine in metastatic lesions [7]. However, prospec...

Influence of the first radioactive iodine ablation on peripheral complete blood count in patients with differentiated thyroid cancer

“…[7] The use of rhTSH for the therapy of metastatic DTC is still controversial. [24] Some studies show that rhTSH preparation is just suitable for young patients with a limited extent of disease, who have an overall good prognosis and a long disease-free survival. [25–27] What is more, the cost of rhTSH preparation is much more expensive than THW preparation.…”