Radioactive iodine(RAI)therapy remains a cornerstone in the management of differentiated thyroid cancer(DTC).The therapeutic efficacy of RAI depends on thyroid-stimulating hormone(TSH)-driven uptake via the sodium-iod...Radioactive iodine(RAI)therapy remains a cornerstone in the management of differentiated thyroid cancer(DTC).The therapeutic efficacy of RAI depends on thyroid-stimulating hormone(TSH)-driven uptake via the sodium-iodide symporter(NIS).Although elevated TSH levels are routinely achieved before RAI administration,the circadian rhythm of TSH,which peaks overnight,is largely overlooked in treatment protocols.Aligning RAI administration with this physiological peak,particularly through evening dosing,may enhance iodine uptake,improve therapeutic efficacy,and reduce systemic exposure.Preclinical data and the known circadian regulation of TSH and NIS support this approach,although clinical validation is lacking.Evening dosing may also improve patient convenience and clinic workflow.However,logistical challenges and the absence of human trials present barriers to implementation.In this narrative review,we synthesize current evidence and tentatively propose the chronotherapeutic alignment of RAI timing as a novel,potentially impactful optimization strategy in DTC management.Prospective studies are needed to evaluate its clinical benefits and feasibility.展开更多
Objective Telomerase reverse transcriptase(TERT) promoter mutations have recently been described in thyroid carcinoma.The purpose of this study was to investigate the clinical significance of(v-raf murine sarcoma vira...Objective Telomerase reverse transcriptase(TERT) promoter mutations have recently been described in thyroid carcinoma.The purpose of this study was to investigate the clinical significance of(v-raf murine sarcoma viral oncogene homolog B1) BRAF V600 E and TERT promoter mutations in differentiated thyroid carcinoma(DTC).The relationship between the two mutations and NIS/TSHR expression was also analyzed.Methods We have detected BRAF V600 E and TERT promoter mutations by direct sequencing and NIS/TSHR expression by immunohistochemistry in 229 cases of DTC,52 cases of benign nodular goiter,and 31 cases of normal thyroid tissue.Results The BRAF V600 E mutation was detected in 142(62.0%) of 229 cases of DTC [141 cases of papillary thyroid carcinoma(PTC) and 1 case of follicular thyroid carcinoma(FTC)].TERT promoter mutations were detected in 18(7.9%) of 229 cases of DTC(14 cases of PTC and 4 cases of FTC),including the mutations C228T(0.9%) and C250T(7.0%),which were mutually exclusive.Moreover,11(61.1%) cases also harbored the BRAF V600 E mutation,which was not associated with gender,age,tumor size,lymph node metastasis,and recurrence risk stratification(P >0.05).The rate of TERT promoter mutation was higher in males,age ≥45,and in the middle/high-risk group(P <0.05),and the rate of simultaneous BRAF V600 E and TERT promoter mutations were higher in the middle/high-risk group(P <0.05).In addition,NIS positive rate in the concurrent BRAF V600 E and TERT promoter mutation group(45.5 %) was lower than in other groups(that is,the DTC group with BRAF V600 E or TERT promoter mutations(55.1%),the DTC group with no BRAF V600 E or TERT promoter mutation(57.5%),the nodules and normal group(75.9%);| r | = 0.171,P = 0.002).Conclusion TERT promoter mutations were lower in patients with DTC,with the C250 T mutation being the most common.The detection of BRAF V600 E mutation combined with TERT promoter mutations was instructive for the prognosis assessment and treatment of DTC.展开更多
文摘Radioactive iodine(RAI)therapy remains a cornerstone in the management of differentiated thyroid cancer(DTC).The therapeutic efficacy of RAI depends on thyroid-stimulating hormone(TSH)-driven uptake via the sodium-iodide symporter(NIS).Although elevated TSH levels are routinely achieved before RAI administration,the circadian rhythm of TSH,which peaks overnight,is largely overlooked in treatment protocols.Aligning RAI administration with this physiological peak,particularly through evening dosing,may enhance iodine uptake,improve therapeutic efficacy,and reduce systemic exposure.Preclinical data and the known circadian regulation of TSH and NIS support this approach,although clinical validation is lacking.Evening dosing may also improve patient convenience and clinic workflow.However,logistical challenges and the absence of human trials present barriers to implementation.In this narrative review,we synthesize current evidence and tentatively propose the chronotherapeutic alignment of RAI timing as a novel,potentially impactful optimization strategy in DTC management.Prospective studies are needed to evaluate its clinical benefits and feasibility.
基金Supported by a grant from the Beijing Medical Awards Foundation(No.YJHYXK YJJ-206)
文摘Objective Telomerase reverse transcriptase(TERT) promoter mutations have recently been described in thyroid carcinoma.The purpose of this study was to investigate the clinical significance of(v-raf murine sarcoma viral oncogene homolog B1) BRAF V600 E and TERT promoter mutations in differentiated thyroid carcinoma(DTC).The relationship between the two mutations and NIS/TSHR expression was also analyzed.Methods We have detected BRAF V600 E and TERT promoter mutations by direct sequencing and NIS/TSHR expression by immunohistochemistry in 229 cases of DTC,52 cases of benign nodular goiter,and 31 cases of normal thyroid tissue.Results The BRAF V600 E mutation was detected in 142(62.0%) of 229 cases of DTC [141 cases of papillary thyroid carcinoma(PTC) and 1 case of follicular thyroid carcinoma(FTC)].TERT promoter mutations were detected in 18(7.9%) of 229 cases of DTC(14 cases of PTC and 4 cases of FTC),including the mutations C228T(0.9%) and C250T(7.0%),which were mutually exclusive.Moreover,11(61.1%) cases also harbored the BRAF V600 E mutation,which was not associated with gender,age,tumor size,lymph node metastasis,and recurrence risk stratification(P >0.05).The rate of TERT promoter mutation was higher in males,age ≥45,and in the middle/high-risk group(P <0.05),and the rate of simultaneous BRAF V600 E and TERT promoter mutations were higher in the middle/high-risk group(P <0.05).In addition,NIS positive rate in the concurrent BRAF V600 E and TERT promoter mutation group(45.5 %) was lower than in other groups(that is,the DTC group with BRAF V600 E or TERT promoter mutations(55.1%),the DTC group with no BRAF V600 E or TERT promoter mutation(57.5%),the nodules and normal group(75.9%);| r | = 0.171,P = 0.002).Conclusion TERT promoter mutations were lower in patients with DTC,with the C250 T mutation being the most common.The detection of BRAF V600 E mutation combined with TERT promoter mutations was instructive for the prognosis assessment and treatment of DTC.
