Objective:To evaluate the efficacy by using domestic recombinant human thyroid-stimulating hormone (rhTSH) in patients with differentiated thyroid cancer (DTC) before or after 131I therapy. Methods:From May 2019 to November 2020, a total of 24 patients with DTC (5 males, 19 females, median age 41 years) in Peking Union Medical College Hospital and Affiliated Tumor Hospital of Zhengzhou University were enrolled into the open-label, dose escalation phase Ⅰ study. All patients were divided into 4 domestic rhTSH dose groups: 0.9 mg×1 d (group A), 0.9 mg×2 d (group B), 1.8 mg×1 d (group C), 1.8 mg×2 d (group D) in succession, with 6 patients in each group. Each patient underwent rhTSH phase and thyroid hormone withdrawal (THW) phase. The end point included safety, tolerability, the quality of life (hypothyroidism symptom and sign score (Billewicz score), profile of mood states (POMS)), effectiveness (thyroid-stimulating hormone (TSH) and thyroglobulin (Tg) levels, diagnostic whole-body scan (Dx-WBS)) and pharmacokinetic characteristics (peak time, peak concentration) of rhTSH. Paired t test and Wilcoxon signed rank test were used for statistical analysis. Results:There were no dose-limiting toxicities, serious adverse events, or no grade ≥3 adverse events reported. The quality of life in rhTSH phase was significantly better than those in THW phase, including the lower Billewicz score (-53.00(-53.00, -53.00) vs -39.50(-47.00, -23.00); S=119.50, P<0.001) and the lower POMS score (91.92±12.06 vs 99.67±19.13; t=0.95, P=0.025). Serum TSH level was increased from 0.04(0.02, 0.11) mU/L (baseline) to 150.00(105.20, 173.31) mU/L 24 h after the last rhTSH administration, which was increased along with the elevation of rhTSH doses. In the THW phase, patients′ TSH levels were≥30 mU/L after 23 d (median) of THW, with the median of 73.51(57.22, 106.22) mU/L. Median Tg level of baseline was 0.10(0.10, 0.41) μg/L, which reached a peak of 0.85(0.12, 3.01) μg/L at 48 h after rhTSH administration. The peak Tg level in the THW phase was 0.88(0.15, 8.04) μg/L. The Dx-WBS consistency rate between rhTSH and THW phase was 95.8%(23/24). Conclusion:rhTSH is a safe and effective method to stimulate the serum Tg level and radioiodine uptake in patients undergoing post-operation or post- 131I assessment for DTC, as well as maintain a higher quality of life in comparison to THW phase.

Objective:To explore the value of preablative stimulated thyroglobulin (ps-Tg) in predicting distant metastasis (DM) at the time of 131I therapy in children and adolescents with differentiated thyroid cancer (DTC). Methods:From January 2016 to March 2020, 54 children and adolescents who underwent total thyroidectomy due to DTC in Peking Union Medical College Hospital were retrospectively reviewed and divided into 2 groups according to the presence of DM or not: M0 group( n=29, 10 males, 19 females, age (16.3±3.8) years) and M1 group( n=25, 13 males, 12 females, age (12.4±4.3) years). Independent-sample t test, χ2 test (or Fisher′s exact test) and Mann-Whitney U test were used to analyze the general characteristics between the two groups. According to status of regional lymph node (RLN) at the time of 131I therapy, the two groups were further divided into M1RLN+ ( n=8) and M1RLN-( n=17), M0RLN+ ( n=5) and M0RLN-( n=24) subgroups. Mann-Whitney U test was used to analyze the different ps-Tg levels between M0 and M1, M1RLN+ and M1RLN-, as well as M0RLN+ and M0RLN-groups. The receiver operating characteristic (ROC) curve analysis was employed to obtain a cut-off value of ps-Tg as a predictor of DM. Results:Patients with DM tended to have higher ps-Tg level (medians: 406.80 μg/L vs 7.90 μg/L, U=690.000, P<0.001), younger age ( t=-3.559, P=0.001), larger tumor size ( t=3.523, P=0.001), more advanced T stage ( U=506.500, P=0.010) and more multifocality( P=0.013) in comparison with those without DM. Though ps-Tg did not significantly differ between M1RLN+ group and M1RLN-group ( U=98.500, P>0.05) or between M0RLN+ group and M0RLN-group ( U=63.000, P>0.05), the two RLN+ groups tended to hold higher medians than the two RLN-groups (18.05 vs 5.71 μg/L; 1 698.50 vs 216.40 μg/L). In order to avoid the possible influence on the ps-Tg cut-off value, 13 RLN+ samples were removed, and the area under the ROC curve was 0.946 (95% CI: 0.883-1.000). The ps-Tg level of 55.87 μg/L was established as the optimal cut-off value to distinguish M0RLN- from M1RLN-, with the sensitivity and specificity of 14/17 and 95.8%(23/24), respectively. Conclusion:Ps-Tg holds a high predictive value in identifying DM, which may be of great help in avoiding inadequate 131I treatment in children and adolescents with metastatic DTC ignored by radiological examinations.