Yan-Song Lin1,2,3, Hui Yang4, Xiao-Yi Li5, Li-Qing Wu6, Jin-Guo Xu7, Ai-Min Yang8, Zai-Rong Gao9,10,11, Yong Ding12, Ying-Qiang Zhang13,14,15, Kai Chen4, Zhuan-Zhuan Mu13,14,15, Jian-Min Jia4, Na Niu13,14,15, Di Sun13,14,15, Xin Zhang13,14,15, Shao-Qiang Zhang16, Qian-Qian Geng8, Ya-Jing Zhang9,10,11, Fang-Ni Chen12, Bao-Xia He17. 1. Department of Nuclear Medicine, Dongcheng District, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences & PUMC, No.1 Shuaifuyuan, Wangfujing St, Beijing, 100730, China. linyansong1968@163.com. 2. State Key Laboratory of Complex Severe and Rare Diseases, Beijing, China. linyansong1968@163.com. 3. Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China. linyansong1968@163.com. 4. Department of Nuclear Medicine, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China. 5. Department of General Surgery, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences & PUMC, Beijing, China. 6. Clinical Research Department, Suzhou Zelgen Biopharmaceuticals Co., Ltd, Suzhou, China. 7. Biological R&D Department, Suzhou Zelgen Biopharmaceuticals Co., Ltd, Suzhou, China. 8. Department of Nuclear Medicine, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China. 9. Department of Nuclear Medicine, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China. 10. Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China. 11. Key Laboratory of Biological Targeted Therapy, the Ministry of Education, Wuhan, China. 12. Department of Nuclear Medicine, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China. 13. Department of Nuclear Medicine, Dongcheng District, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences & PUMC, No.1 Shuaifuyuan, Wangfujing St, Beijing, 100730, China. 14. State Key Laboratory of Complex Severe and Rare Diseases, Beijing, China. 15. Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China. 16. Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China. 17. Phase I Clinical Research Center, Zhengzhou University Affiliated Cancer Hospital, Zhengzhou, China.
Abstract
PURPOSE: Thyroid hormone withdrawal (THW) inevitably induced hypothyroidism in patients with differentiated thyroid cancer (DTC), and 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 × 1 day, 0.9 mg × 2 day, 1.8 mg × 1 day, and 1.8 mg × 2 day dosage, and 40 further enrolled into 0.9 mg × 2 day 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 were observed, and mild symptoms of headache were observed in 6.3%, lethargy in 4.7%, and 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 μg/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 24 h 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 20 h. 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.
PURPOSE: Thyroid hormone withdrawal (THW) inevitably induced hypothyroidism in patients with differentiated thyroid cancer (DTC), and 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 × 1 day, 0.9 mg × 2 day, 1.8 mg × 1 day, and 1.8 mg × 2 day dosage, and 40 further enrolled into 0.9 mg × 2 day 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 were observed, and mild symptoms of headache were observed in 6.3%, lethargy in 4.7%, and 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 μg/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 24 h 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 20 h. 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.
Authors: P W Ladenson; L E Braverman; E L Mazzaferri; F Brucker-Davis; D S Cooper; J R Garber; F E Wondisford; T F Davies; L J DeGroot; G H Daniels; D S Ross; B D Weintraub Journal: N Engl J Med Date: 1997-09-25 Impact factor: 91.245
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Authors: Ujjal Mallick; Clive Harmer; Beng Yap; Jonathan Wadsley; Susan Clarke; Laura Moss; Alice Nicol; Penelope M Clark; Kate Farnell; Ralph McCready; James Smellie; Jayne A Franklyn; Rhys John; Christopher M Nutting; Kate Newbold; Catherine Lemon; Georgina Gerrard; Abdel Abdel-Hamid; John Hardman; Elena Macias; Tom Roques; Stephen Whitaker; Rengarajan Vijayan; Pablo Alvarez; Sandy Beare; Sharon Forsyth; Latha Kadalayil; Allan Hackshaw Journal: N Engl J Med Date: 2012-05-03 Impact factor: 91.245
Authors: B R Haugen; F Pacini; C Reiners; M Schlumberger; P W Ladenson; S I Sherman; D S Cooper; K E Graham; L E Braverman; M C Skarulis; T F Davies; L J DeGroot; E L Mazzaferri; G H Daniels; D S Ross; M Luster; M H Samuels; D V Becker; H R Maxon; R R Cavalieri; C A Spencer; K McEllin; B D Weintraub; E C Ridgway Journal: J Clin Endocrinol Metab Date: 1999-11 Impact factor: 5.958
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