ABSTRACT
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.
ABSTRACT
Objective:To analyze the association between thyroglobulin antibody (TgAb) and differentiated thyroid cancer (DTC) metastases detected by post-radioactive iodine (RAI) therapy scan, when stimulated thyroglobulin (sTg) <1 μg/L.Methods:A total of 314 (68 males, 246 females, age (44.5±12.5) years) post-thyroidectomy DTC patients whose sTg <1 μg/L between March 2013 and May 2017 in Henan Cancer Hospital were enrolled retrospectively. Patients underwent 131I whole-body planar imaging ( 131I-WBS) and SPECT/CT imaging 5 d after 131I administration. Iodine avid metastases were compared between TgAb-positive group and TgAb-negative (TgAb<4 kU/L) group. Logistic regression analysis was conducted to assess odds ratio ( OR) for iodine avid metastases in each subgroup (Q1: 4 kU/L≤TgAb≤9.27 kU/L; Q2: 9.27 kU/L<TgAb≤26.75 kU/L; Q3: 26.75 kU/L<TgAb≤101.43 kU/L; Q4: TgAb>101.43 kU/L) of TgAb-positive patients, with the TgAb-negative patients as the reference. χ2 test was used to analyze the data. Results:Iodine avid metastases were found in 16.9% (53/314) of DTC patients and were more frequently in TgAb-positive group with TgAb>26.75 kU/L than TgAb-negative group (26.0%(19/73) vs 13.7%(23/168); χ2=5.382, P=0.02). Most metastases (92.5%, 49/53) occurred in cervical and mediastinal lymph nodes. The OR for iodine avid metastases was obviously high in TgAb-positive patients with 26.75 kU/L<TgAb≤101.43 kU/L ( OR(95% CI): 3.687(1.397-9.733), P=0.008) and with intermediate-high risk of recurrence ( OR(95% CI): 2.489(1.169-5.301), P=0.018), with the TgAb-negative group as the reference. Conclusion:The possibility of functional metastasis should be fully considered during 131I therapy in TgAb-positive DTC patients after surgery who have higher TgAb level and risk stratification, even if sTg<1 μg/L.
ABSTRACT
Objective To compare cerebralspinal fluid acetylcholine (ACh) and choline (Ch) in patients with Alzheimer's disease (AD) and vascular dementia (VD), and their correlation with cognitive impairment.Methods First, dementia scales of 22 ADs, 22 VDs and 20 controls were scored using MMSE. Then the concentrations of CSF ACh and Ch in AD and VD were examined using the high-performance liquid chromatography with electrochemical detector (HPLC-ECD). Finally, the scores of MMSE and concentrations of ACh and Ch were compared. Results The ACh concentrations in AD[(10.7?5.1)nmol/L] and VD [(16.8?7.4)nmol/L] were found to be significantly lower than in controls [(34.5?9.0)nmol/L]( P =0.001), and showed a significant positive correlation with MMSE scores. The Ch concentration in AD CSF [(627.6?145.1)nmol/L] was approximately the same as in controls [(716.0?159.4)nmol/L], and showed no correlation with MMSE scores. The Ch concentration in VD CSF [(887.4?187.4)nmol/L] was significantly higher than in AD ( P =0.001) and controls ( P =0.002).Conclusion (1)The depression of ACh is correlated with cognitive impairment, suggesting ACh is an important neurotransmitters for memory. (2) VD may have a similar pathogenesis as AD. (3) The depression of AD ACh concentration and elevation of VD Ch concentration in CSF may be a role in their differentiation. (4) The application of acetylcholinesterase inhibitors is suitable for AD and VD.