Clinical Experience with Recombinant Human Thyrotrophin (rhTSH) in the Management of Patients with Differentiated Thyroid Cancer

Abstract

The purpose of this work was to gain clinical experience with and to identify the optimal conditions for the use of recombinant human TSH (rhTSH, commercially available as Thyrogen) in the management of patients with differentiated thyroid cancer (DTC). The study involved 22 patients for a total of 27 administration cycles of rhTSH, for either diagnostic (in 19 instances) and/or therapeutic purposes (in 8 instances). There were 19 patients with papillary cancer (follicular variant in 4, columnar variant in 1) and 3 patients with follicular cancer (1 Hurtle cell variant). All patients had previously undergone total thyroidectomy and 1-5 cycles of 131I-therapy. Thyrogen was administered i.m. according to the suggested protocol: 0.9 mg i.m. on days 1 and 2, radioiodine on day 3. Peak serum TSH levels between 68-237 microIU/mL were observed after rhTSH administration; these were on average 65% higher, on a patient-by-patient basis, than peak serum TSH observed after conventional withdrawal of thyroxine treatment in 19 patients, while in 3 patients they were 28% lower, but still in the potent stimulation range (86-94 microIU/mL). There was general agreement between imaging results obtained under rhTSH stimulation and those obtained on prior occasions during thyroxine withdrawal, although radioiodine uptake was interpreted as less intense following Thyrogen administration. Of 18 patients undergoing rhTSH administration for diagnostic purposes, 11 patients had a negative radioiodine whole-body scan (WBS) and 7 had a positive WBS. Three of the WBS-negative patients were shown to be actually affected by tumor recurrence, respectively by PET with [18F]FDG (in 2 cases) and by post-131I therapy scan. Serum thyroglobulin (hTg) increased to abnormal levels following rhTSH stimulation in 3/7 of the WBS-positive patients as well as in 1/11 WBS-negative patients. In 3/7 WBS-positive as well as in 3/11 WBS-negative patients, serum hTg progressively rose under rhTSH stimulation, yet still remaining below 3 ng/mL. Post-131I therapy scans following Thyrogen administration showed good radioiodine uptake in 7/8 patients, the single unsuccessful case being most likely due to expansion of the iodine pool because of recent use of an iodinated contrast medium. The overall results show the feasibility and practical advantages of employing rhTSH stimulation in the general clinical setting rather than thyroxine withdrawal in the management of DTC patients. Caution should be raised on the interpretation of the serum hTg response to such potent but short-lived TSH stimulation.

Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Taskforce

“…In the treatment of locoregional or metastatic disease, no recommendation can be made about the superiority of one method of radioiodine administration over another (empiric high dose versus blood or body dosimetry)-Recommendation I rhTSH in the management of recurrent or metastatic disease. No randomized trial comparing thyroid hormone withdrawal therapy to rhTSH-mediated therapy has been reported, despite a growing body of nonrandomized studies regarding this use (229)(230)(231)(232)(233)(234)(235)(236)(237). The use of rhTSH does not eliminate and may even increase the possibility of rapid swelling of metastatic lesions (234,(238)(239)(240).…”

A Patient with Widely Fluctuating Thyroid-Stimulating Hormone Measurements

“…Two doses of 0.9 mg rhTSH, 24 hours apart, are optimal to achieve peak TSH concentrations of 60 -240 IU/mL 24 h after the second dose, and to maintain a 25-30 IU/mL therapeutic concentration on the day of 131 I administration (4,5 ). The increased TSH concentration was due in our patient to 2 injections of rhTSH on the days prior to the laboratory testing.…”

Recombinant human thyroid stimulating hormone in 2008: focus on thyroid cancer management

“…Thyrogen ® is FDA approved as an adjunct to RAI treatment of metastatic thyroid cancer only in patients who are either unable to mount an adequate endogenous TSH response to THW or in whom THW is medically contraindicated, as options are otherwise limited in that patient population. Although there are no randomized trials comparing rhTSH stimulated RAI treatment to THW prepration, data from this "compassionate use" population and other case series (Luster et al 2000;Mariani et al 2000;Lippi et al 2001;Pellegriti et al 2001;Berg et al 2002;de Keizer et al 2003;Jarzab et al 2003;Robbins et al 2006a), summarized in Table 3, provide some information about the effectiveness of this approach. Unfortunately, the literature is heterogeneous and limited in particular by the lack of outcome data.…”