Purpose Thyroid hormone withdrawal (THW) inevitably induced hypothyroidism in patients with differentiated thyroid cancer (DTC), we aimed to evaluate the safety and efficacy of a novel recombinant human thyroid-stimulating hormone (rhTSH, ZGrhTSH) as an alternative of THW in China.
Methods Totally, 64 DTC patients were enrolled with 24 in the dose-escalation cohort equally grouped into 0.9 mg×1d, 0.9 mg×2d, 1.8 mg×1d and 1.8 mg×2d dosage, and 40 further enrolled into 0.9 mg×2d dose-expansion cohort. All patients underwent both ZGrhTSH phase and levothyroxine (L-T4) withdrawal phase for self-comparison in terms of TSH levels, the radioactive iodine (RAI) uptake, stimulated thyroglobulin level, and the quality of life (QoL).
Results In ZGrhTSH phase, no major serious adverse events was observed, mild symptom of headache was observed in 6.3%, lethargy in 4.7%, asthenia in 3.1% of the patients, and mostly resolved spontaneously within 2 days. Concordant RAI uptake was noticed in 89.1% (57/64) of the patients between ZGrhTSH and L-T4 withdrawal phases. The concordant thyroglobulin level with a cut-off of 1 mg/L was noticed in 84.7% (50/59) of the patients without the interference of anti-thyroglobulin antibody. The QoL was far better during ZGrhTSH phase than L-T4 withdrawal phase, with lower Billewicz (-51.30±4.70 vs. -39.10±16.61, P<0.001) and POMS (91.70±16.70 vs. 100.40±22.11, P=0.011) scores which indicate the lower the better. Serum TSH level rose from basal 0.11±0.12 mU/L to a peak of 122.11±42.44 mU/L 24h after the last dose of ZGrhTSH. In L-T4 withdrawal phase, a median of 23 days after L-T4 withdrawal was needed, with the mean TSH level of 82.20±31.37 mU/L. The half-life for ZGrhTSH clearance was about 20h.
Conclusion The ZGrhTSH held the promise to be a safe and effective modality in facilitating RAI uptake and serum thyroglobulin stimulation, with better QoL of patients with DTC compared with L-T4 withdrawal.