rhTSH-aided radioiodine ablation and treatment of differentiated thyroid carcinoma: a comprehensive review

Traditionally, withdrawal of thyroid hormone has been used to attain the increase in serum TSH concentrations that are believed to optimize the trapping and retention of radioiodine for diagnostic procedures, thyroid remnant ablation and treatment of patients with differentiated thyroid cancer (DTC). However, withdrawal frequently causes clinical hypothyroidism, with resultant cognitive impairment, emotional dysfunction, physical discomfort, health risks in patients who are elderly, frail or have concomitant illness, and impaired quality of life and ability to work. Recombinant human TSH (rhTSH) was developed to provide TSH stimulation without withdrawal of thyroid hormone and the associated morbidity. rhTSH has been approved as an adjunct for diagnostic procedures in patients with DTC, but is currently an experimental aid in thyroid remnant ablation and the treatment of thyroid tumours. In the period 1997-2004, nearly 30 medical centres worldwide have reported on almost 400 patients with DTC who were given rhTSH in preparation for radioiodine ablation of thyroid remnants or treatment of local tumours of metastatic disease. We have analysed and summarized the findings reported in this literature. Ablation aided by the standard course of rhTSH, two consecutive daily injections of 0.9 mg, had success rates better than 84% in 90 patients given radioiodine activities in excess of 4000 MBq. However, when 1110 MBq was administered, success rates were 81.2% in 16 patients given the standard course of rhTSH and 4-day withdrawal of thyroid hormone around the time of radioiodine administration in one study, but 54% in 70 patients in another study. rhTSH-aided treatment of persistent or recurrent local or metastatic cancer, or both, with from one to six courses of radioiodine 1000-19055 MBq, achieved 2% complete remission, 36% partial response and 27% disease stabilization rates, for a 65% clinical benefit rate, in 115 primarily elderly, late-stage patients for whom responses were reported. Twelve of these patients died as a result of progressive disease or were discharged from hospital into hospice care. Generally, rhTSH was very well tolerated. However, in a minority of patients with central nervous system, spinal or bone metastases, or bulky thyroid remnant or neck lesions with or without poor pulmonary reserve, administration of rhTSH, like thyroid hormone withdrawal, was found to stimulate expansion of the tumour, with ensuing compression of key anatomical structures and neurological, respiratory or other clinical complications. The rapid onset, response to glucocorticoids and radiological findings of peritumoural oedema or, less commonly, haemorrhage in the published cases, strongly suggest that the tumour expansion was the result of swelling rather than growth. As in the case of thyroid hormone withdrawal, special attention and glucocorticoid premedication are thus warranted when rhTSH is given to patients known or suspected to have the above characteristics. Dosimetric data suggest that whole-body and whole-blood radioiodine clearance may be faster in euthyroid patients after administration of rhTSH. In theory, the faster clearance could allow, or demand, increased radioiodine activities when rhTSH is used, but clinical data to date suggest that this may be unnecessary. The faster clearance also might result in safety or convenience benefits with the use of rhTSH, such as decreased exposure of extrathyroid areas to radiation, and shorter hospital stays. In conclusion, in preliminary results from open-label studies, both rhTSH-aided tumour ablation and treatment have been well tolerated and have shown efficacy in substantial proportions of patients. rhTSH-aided ablation merits further study. rhTSH-aided treatment may be preferred in patients who are at greater risk of hypothyroid complications from withdrawal of thyroid hormone or are unable to produce sufficient endogenous TSH, and warrants additional investigation in younger patients at earlier stages of thyroid cancer.