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Serum thyrotropin level of 30 μIU/mL is inadequate for preablative thyroglobulin to serve as a prognostic marker for differentiated thyroid cancer

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Purpose: Preablative-stimulated thyroglobulin (ps-Tg) has manifested its potential for predicting prognosis in patients with differentiated thyroid carcinoma (DTC), but its level can be affected by thyrotropin (TSH). The objective of this study was to evaluate the utility of ps-Tg in predicting individual response after radioactive iodine (RAI) therapy, and further explore the appropriate TSH level for ps-Tg to serve as a prognostic marker in DTC without initial distant metastasis (DM). Methods: A total of 208 consecutive non-DM DTC patients with serial ps-Tg, TSH, and anti-Tg antibody (TgAb) measured simultaneously were enrolled. The initial and last measurements of ps-Tg were marked as Tg1 and Tg2, respectively, with a median interval of 8 days, so does TSH. Clinical response was retrospectively evaluated as excellent, indeterminate, biochemical incomplete, or structural incomplete response (ER, IDR, BIR, or SIR) after a mean follow-up of 21.5 months. Tg1 and Tg2 were tested and compared for their performances in predicting ER and incomplete response (IR, including BIR and SIR) by receiver operating characteristic (ROC) curve analysis. The 416 ps-Tg levels (Tg1 and Tg2) were then categorized by their corresponding TSH grouping of 30-<60 (n = 100), 60-<90 (n = 131), 90-<120 (n = 99), and ≥120 μIU/mL (n = 86), and the predictive performances were further compared among TSH groups. Results: Tg2, with a higher corresponding TSH level than Tg1 (median: 104.763 vs. 65.046 μIU/mL), presented higher area under the ROC curve (AUC) in predicting both ER and IR (ER: 0.889 vs. 0.836, P = 0.003; IR: 0.925 vs. 0.869, P = 0.046). The performances of ps-Tg in predicting ER and IR were both improved significantly as TSH rose from 30-<60 to 60-<90 μIU/mL, with an increase in AUC from 0.810 to 0.888 in predicting ER (P = 0.006) and from 0811 to 0.937 in predicting IR (P = 0.014), respectively. However, this kind of benefit was not further enlarged as TSH rose from 60-<90 to 90-<120 μIU/mL (both P > 0.05). Conclusion: In comparison with the TSH context of 30 μIU/mL, a higher preablative TSH level of 60-<90 μIU/mL might be more appropriate for ps-Tg to serve as a prognostic marker for DTC.
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ORIGINAL ARTICLE
Serum thyrotropin level of 30 lIU/mL is inadequate
for preablative thyroglobulin to serve as a prognostic marker
for differentiated thyroid cancer
Teng Zhao
1,4
Jun Liang
2
Zhenqing Guo
3
Jiao Li
4
Yansong Lin
1
Received: 4 November 2015 / Accepted: 19 December 2015 / Published online: 18 January 2016
ÓSpringer Science+Business Media New York 2016
Abstract
Purpose Preablative-stimulated thyroglobulin (ps-Tg)
has manifested its potential for predicting prognosis in
patients with differentiated thyroid carcinoma (DTC), but
its level can be affected by thyrotropin (TSH). The
objective of this study was to evaluate the utility of ps-Tg
in predicting individual response after radioactive iodine
(RAI) therapy, and further explore the appropriate TSH
level for ps-Tg to serve as a prognostic marker in DTC
without initial distant metastasis (DM).
Methods A total of 208 consecutive non-DM DTC
patients with serial ps-Tg, TSH, and anti-Tg antibody
(TgAb) measured simultaneously were enrolled. The initial
and last measurements of ps-Tg were marked as Tg1 and
Tg2, respectively, with a median interval of 8 days, so does
TSH. Clinical response was retrospectively evaluated as
excellent, indeterminate, biochemical incomplete, or
structural incomplete response (ER, IDR, BIR, or SIR)
after a mean follow-up of 21.5 months. Tg1 and Tg2 were
tested and compared for their performances in predicting
ER and incomplete response (IR, including BIR and SIR)
by receiver operating characteristic (ROC) curve analysis.
The 416 ps-Tg levels (Tg1 and Tg2) were then categorized
by their corresponding TSH grouping of 30-\60
(n=100), 60-\90 (n=131), 90-\120 (n=99),
and C120 lIU/mL (n=86), and the predictive perfor-
mances were further compared among TSH groups.
Results Tg2, with a higher corresponding TSH level than
Tg1 (median: 104.763 vs. 65.046 lIU/mL), presented
higher area under the ROC curve (AUC) in predicting both
ER and IR (ER: 0.889 vs. 0.836, P=0.003; IR: 0.925 vs.
0.869, P=0.046). The performances of ps-Tg in predict-
ing ER and IR were both improved significantly as TSH
rose from 30-\60 to 60-\90 lIU/mL, with an increase in
AUC from 0.810 to 0.888 in predicting ER (P=0.006)
and from 0811 to 0.937 in predicting IR (P=0.014),
respectively. However, this kind of benefit was not further
enlarged as TSH rose from 60-\90 to 90-\120 lIU/mL
(both P[0.05).
Conclusion In comparison with the TSH context of
30 lIU/mL, a higher preablative TSH level of
60-\90 lIU/mL might be more appropriate for ps-Tg to
serve as a prognostic marker for DTC.
Keywords Differentiated thyroid cancer Thyrotropin
Thyroglobulin Radioactive iodine therapy
Introduction
Serum thyroglobulin (Tg) is a well-established tumor
marker in the follow-up of differentiated thyroid carcinoma
(DTC) after total or near-total thyroidectomy and
Teng Zhao and Jun Liang have contributed equally as first authors.
&Yansong Lin
linys@pumch.cn
1
Department of Nuclear Medicine, Peking Union Medical
College Hospital, No. 1 Shuaifuyuan, Wangfujing St.,
Dongcheng District, Beijing 100730, China
2
Department of Oncology, Peking University International
Hospital, No. 1 Life Park St., Zhongguancun Life Science
Park, Haidian District, Beijing 102206, China
3
Department of Medical Records, The Affiliated Hospital of
Qingdao University, No. 16 Jiangsu St., Shinan District,
Qingdao 266000, China
4
Department of Oncology, The Affiliated Hospital of Qingdao
University, No. 59 Haier St., Laoshan District,
Qingdao 266000, China
123
Endocrine (2016) 53:166–173
DOI 10.1007/s12020-015-0842-0
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... Our previous studies have revealed the potential of pre-RAI stimulated thyroglobulin (ps-Tg) levels in predicting DM-DTC, with a cut-off value of 52.75 ng/mL (6,7), which manifested its potential role in facilitating initial risk stratification and timely RAI dose adjustment to avoid inadequate therapy. Nevertheless, our recent study showed that the predictive value of ps-Tg might be affected by the corresponding thyrotropin (TSH) level (8), and that the presence of massive remnant thyroid in non-DM patients could also cause elevated ps-Tg levels, which might lead to the misdiagnosis of DM (9). ...
... However, it is still a great challenge for clinicians to identify DM-DTC timely enough to tailor appropriate management prior to RAI therapy, especially in cases with no pre-RAI imaging evidence. ps-Tg was indicated to be a predictive marker for DM-DTC in our previous studies, and a cut-off of 52.75 ng/mL was further obtained using ROC analysis (6,7). Results from other studies also documented the role of ps-Tg in identifying DM-DTC (19,20). ...
... Regarding thyroid remnants, no statistical difference was found between the M1 and M0 groups; hence we believe that the differences in the serological parameters between the two groups did not come from the residual thyroid tissue. However, the optimal cut-off value for Tg2 was 22.10 ng/mL, much lower than the 52.75 ng/mL that we reported previously (7). Possible explanations for this variability are: 1) less influence from residual thyroid tissue due to improvement in total thyroidectomy surgical techniques in recent years in China; 2) enrollment of some patients in this study who received a repeated RAI treatment with less or no remnant thyroid; and 3) different levels of TSH at the time of ps-Tg testing. ...
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Objective Preablative stimulated thyroglobulin (ps-Tg) has the potential to be used in identifying distant metastatic differentiated thyroid carcinoma (DM-DTC), but its single level can be affected by remnant thyroid tissue and thyrotropin (TSH). The objective of this retrospective study was to evaluate the value of serial ps-Tg measurements in identifying DM-DTC specifically. Methods A total of 317 DTC patients with serial measurements of ps-Tg, TSH and anti-Tg antibody were divided into M1 (n=72) and M0 (n=245) according to the presence of distant metastasis (DM) or not. The initial ps-Tg measurement, with a corresponding TSH exceeding 30 μIU/mL, was marked as Tg1, and ps-Tg measured right before radioactive iodine (RAI) therapy was defined as Tg2, with a median interval of 8 days. ΔTg denotes Tg2–Tg1, and ΔTSH denotes TSH2–TSH1. Tg1, Tg2, ΔTg, and ΔTg/ΔTSH were tested for efficacy in identifying DM-DTC using receiver operating characteristic (ROC) curve analysis, and further compared with chest computed tomography (CT) and posttreatment whole-body RAI scan (RxWBS). Results Compared with single ps-Tg measurement (Tg1 or Tg2), both ΔTg and ΔTg/ΔTSH were more narrowly distributed around zero in the M0 group, which made their distribution in the M1 group more distinguished in a relatively dispersed way. ΔTg/ΔTSH manifested a higher accuracy (88.64%) and specificity (90.20%) in identifying DM-DTC than Tg1 or Tg2 measurements, with a much higher specificity than chest CT (90.20% vs. 66.00%) and a much higher sensitivity than RxWBS (83.33% vs. 61.11%). Conclusions Serial ps-Tg measurements even over as short an interval as 8 days hold incremental value in identifying DM-DTC. ΔTg/ΔTSH is a specific early biochemical marker for DM-DTC.
... Unfortunately, the ideal TSH level to stimulate Tg production by the remaining thyroid/neoplastic cells has not yet been fully established. Concentrations above 30 mU/L seem to be necessary, however, levels between 60 and 90 mU/L would be more reliable for evaluating the marker (18). It is also difficult to compare different STg measurements and the marker level evolution considering the possibility that TSH concentration may be different in each sample. ...
... As already cited, despite its excellent performance, STg can be influenced by TSH level. In fact, although patients with excellent or incomplete response do not seem to significantly differ in terms of STg levels, when these are obtained with TSH values between 30-60 mU/L, higher concentrations of the pituitary hormone can cause more significant elevations in the marker, providing differentiation between these groups (18). It is true that, with the advent of recombinant TSH, this discussion could seem to be without reason. ...
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Objective: Thyrotropin-stimulated thyroglobulin (STg) after total thyroidectomy is a prognosis marker for differentiated thyroid carcinoma (DTC). As Tg level is influenced by thyrotropin (TSH), perhaps the STg/TSH ratio is also a prognosis marker for these tumours. We aimed to compare STg/TSH ratio and first STg level in differentiated thyroid carcinoma patients for their ability to predict the long-term response to initial treatment. Methods: This retrospective study evaluated data from 181 DTC patients for first (1st) STg and STg/TSH ratio, at 1-3 months post-total thyroidectomy and before iodine-131 therapy, according to response to initial therapy [Excellent/Indeterminate or Incomplete (Biochemical/Structural)] observed at final evaluation, and with the survival time with excellent/indeterminate response. Results: Cases with incomplete response presented higher STg level [225.13 ± 585.26 ng/mL versus (vs) 20.4 ± 192.9 ng/mL; p < 0.001] and STg/TSH ratio (3.01 ± 7.8 vs 0.27 ± 2.58; p < 0.001). Cutoffs of 5 ng/mL for STg and 0.085 for STg/TSH displayed sensitivities of 76.7% and 76.9%, and specificities of 79.2% and 82.6%, respectively, in predicting response to therapy. Values below these cutoffs were associated with longer survival time in excellent/indeterminate response (140.4 vs 15.9 and 144.6 vs 15.9 months, respectively). Conclusion: STg/TSH ratio has a similar performance to the 1st STg in predicting long-term response to initial therapy.
... According to the relevant literature [5,9], we combined the changes in serology and diagnostic imaging (ultrasound, CT, MRI, Dx-WBS and/or WBI) 6-12 months after the Intermediate and high recurrence risk Current or recent treatment with drugs affecting the immune system Followed up for more than six months after the initial RT course Immunodeficiency disorders caused by nonneoplastic diseases TgAb < 115 IU/mL Incomplete follow-up data initial RT course to categorize the therapeutic response of RT as an excellent response (ER), biochemical incomplete response (BIR), uncertain response (IDR), and structural incomplete response (SIR). Then, patients with a BIR and those with a SIR were included in the incomplete response (IR) group, while patients with an ER and those with an IDR were included in the nonincomplete response (Non-IR) group [14][15][16]. ...
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The aim of the present study was to investigate the factors influencing the short-term response to the initial radioiodine therapy (RT) course in patients with intermediate- and high-risk papillary thyroid carcinoma (PTC). A total of 182 patients with intermediate- and high-risk PTC who underwent RT in our hospital from March 2018 to October 2020 were retrospectively enrolled. The patients were divided into incomplete response (IR) and nonincomplete response (Non-IR) groups according to the response observed in clinical follow-up within 6–12 months after RT. Univariate and multivariate logistic regression analyses were used to investigate the effects of 15 observed factors on the response to RT. Receiver operating characteristic (ROC) curve analysis was used to determine the value of factors found to be significant in multivariate analyses for predicting an IR. A total of 182 patients with intermediate- and high-risk PTC were analyzed; the percentage of patients with a Non-IR was 61.54% (112/182), and the percentage of patients with an IR was 38.46% (70/182). The CD4⁺ T-cell percentage (t = 4.757, P = 0.000), CD4/CD8 (z = − 2.632, P = 0.008), stimulated thyroglobulin (sTg) level (z = − 8.273, P = 0.000) and M stage (χ² = 17.823, P = 0.000) of the two groups were significantly different. Multivariate analysis showed that only the sTg level (OR: 1.116, 95% CI 1.068–1.165, P < 0.001) and CD4⁺ T-cell percentage (OR: 0.909, 95% CI 0.854–0.968, P = 0.003) were independent factors associated with the therapeutic response to RT. The cutoff sTg level and CD4⁺ T-cell percentage for predicting an IR were 7.62 μg/L and 40.95%, respectively. The sTg level and CD4⁺ T-cell percentage were verified to be independent predictive factors of RT response. Higher sTg levels and lower CD4⁺ T-cell percentages were related to an IR in patients with intermediate- and high-risk PTC.
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Objectives Follicular variant papillary thyroid carcinoma (FVPTC) is treated similarly to classical variant papillary thyroid carcinoma (cPTC). However, FVPTC has unique tumour features and behaviours. We investigated whether a low dose of radioiodine was as effective as a high dose for remnant ablation in patients with FVPTC and evaluated the recurrence of low-intermediate risk FVPTC. Methods Data from cPTC and FVPTC patients treated with I-131 from 2004 to 2014 were reviewed. Demographics, tumour behaviour, lymph node metastasis, and local recurrence data were compared between FVPTC and cPTC patients. Then, low-intermediate risk FVPTC patients were divided into low, intermediate, and high I-131 dose groups, and postoperative I-131 activities were analysed to evaluate the effectiveness of I-131 therapy for thyroid remnant ablation. Results In total, 799 cases of FVPTC (n = 168) and cPTC (n = 631) treated with I-131 were identified. Patients with FVPTC had a larger primary nodule size than cPTC, but lymph node metastases and local recurrence were more prevalent in cPTC than in FVPTC. For the low-, intermediate-, and high-dose groups, success rates of ablation did not differ (82.0%, 80%, and 81.3%, respectively). Conclusion FVPTC differs from cPTC in behaviour. Low-dose ablation may be sufficient in FVPTC patients with low-intermediate disease risk.
... The 131 I uptake by metastatic DTC might continue to increase as TSH rose to a higher level. Recently, one study has also confirmed that ssTg measured under a higher preablative TSH level might be more convincing as a prognostic marker for DTC 38 . In our study, 18 F-FDG PET/CT was carried out just one day before 131 I administration to maximize TSH stimulation without additional preparation and minimize inconvenience to patients. ...
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The quantitative relationship between iodine and glucose metabolism in metastases from differentiated thyroid cancer (DTC) remains unknown. Aim of the prospective study was to establish the value of18F-FDG PET/CT in predicting131I-avidity of metastases from DTC before the first radioiodine therapy. A total of 121 postoperative DTC patients with elevated stimulated serum thyroglobulin (ssTg) who underwent131I adjuvant therapy or therapy after18F-FDG PET/CT scan were enrolled. The Receiver operating characteristic curve was established to create an optimal cut-off point and evaluate the value of SUVmax for predicting131I-avidity. In our study, the median SUVmax in131I-nonavid metastatic target lesions was also significantly higher than that in131I-avid metastatic target lesions (5.37 vs. 3.30; P = 0.000). At a cut-off value of 4.0 in SUVmax, the area under curve was 0.62 with the sensitivity, specificity, positive predictive value and negative predictive value of 75.3%, 56.7%, 76.1%, and 54.8%, respectively. These results suggest that18F-FDG PET/CT may be of great value in identifying metastases in postoperative DTC patients with elevated ssTg before131I administration, leading to an improved management of disease.18F-FDG positive metastatic DTC with SUVmax of greater than 4.0 possesses higher probability of non-avidity to radioiodine.
... As a sensitive biomarker, Tg tests are indispensable for DTC patients, due to the usefulness during the followup as well as in predicting distant metastasis [2,6,7]. Our previous studies have demonstrated the impressing value of Tg in decision-making and prognosis estimation [8,9,10]. Decreasing of Tg after RAI implies the potential benefit from the therapy, while the increasing or stabilizing of Tg reflects the unsatisfied efficacy, which may be latent to be RAIR-DTC [11]. ...
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... The highest complete ablation rate of 72.2% was found in patients with a preablation TSH level of 30-89 μIU/ml. This is the same TSH range where a recent study found that preablation stimulated thyroglobulin level to best predict the outcome of ablation [14]. Zhao et al. [15], who also evaluated the relationship between preablation serum TSH level and outcome of radioiodine ablation of low-risk to intermediate-risk DTC, found a progressively increasing ER rate with higher serum TSH levels up to 120 μIU/ml. ...
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Aim: To investigate the association of CTLA-4 polymorphisms with efficacy of postoperative radioiodine-131 (I-131) treatment for differentiated thyroid carcinoma (DTC). Methods: A total of 324 DTC patients and 350 healthy individuals were enrolled in our study. Patients received I-131 remnant ablation following surgical resection. Based on the treatment efficacy, patients were divided into the effective (n = 183) and ineffective groups (n = 141). CTLA-4 polymorphisms (+49A>G, CT60A>G and -318C>T) were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Results: AG + AA genotype distribution and A allele frequency of +49A>G and CT60A>G polymorphisms were higher in the effective group than the ineffective group. Conclusion: +49A>G and CT60A>G polymorphisms were associated with the efficacy of postoperative I-131 treatment for DTC; and they might be bioindicators related to the prognosis of I-131 treatment.
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To validate the American Thyroid Association (ATA) initial risk of recurrence scheme and the Memorial Sloan Kettering Cancer Center (MSKCC) response to therapy re-stratification approach in a large cohort of patients with differentiated thyroid cancer (DTC) treated outside of the United States. Retrospective chart review. Five hundred and six patients with DTC followed for a median of 10 years after total thyroidectomy and RAI remnant ablation at a major cancer centre in Brazil. Final clinical outcomes were assessed based on American Joint Cancer Committee (AJCC)/Union Internationale Contre le Cancer (UICC) staging, ATA risk stratification and response to therapy assessment (excellent, acceptable, biochemical incomplete and structural incomplete). The AJCC/UICC staging system did not adequately stratify patients with regard to the risk of recurrence/persistent disease. However, the ATA system demonstrated a 13% risk of recurrent/persistent disease in low-risk patients, 36% in intermediate risk patients, and 68% in high-risk patients. Furthermore, an excellent response to therapy decreased the risk of recurrent/persistent disease to 1·4%. At the time of final follow-up, 34% of the biochemical incomplete response patients had been re-classified as having no evidence of disease (NED) without having received any additional therapy beyond continue levothyroxine suppression. Conversely, even after additional therapies, only 9% of the patients with an incomplete structural response were eventually re-classified as NED. These data validate the ATA risk classification as an excellent initial predictor of recurrent/persistent disease and confirm the clinical utility of the MSKCC dynamic risk assessment system in a cohort of patients evaluated and treated outside the United States.
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Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations for therapeutic interventions. We developed a similarly formatted system to appraise the quality of such studies and resultant recommendations. The guideline panel had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, use of molecular markers, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to screening for thyroid cancer, staging and risk assessment, surgical management, radioiodine remnant ablation and therapy, and thyrotropin suppression therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using imaging and serum thyroglobulin, thyroid hormone therapy, management of recurrent and metastatic disease, consideration for clinical trials and targeted therapy, as well as directions for future research. Conclusions: We have developed evidence-based recommendations to inform clinical decision-making in the management of thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders.
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Thyroglobulin(Tg), the most commonly marker to determine remission of differentiated thyroid carcinoma(DTC), can take 18 months or longer to be undetectable. We hypothesized that Tg, stimulated after surgery and immediately before radioiodine treatment(baseline stimulated Tg) could be a good predictor of remission at 18-24 months. The aim of this study was to evaluate the role of baseline stimulated Tg as early prognostic marker of DTC. Retrospective study of 133 patients with DTC from 1998 to 2010(age at diagnosis 47.4+/-16.8, follow up 5.09+/-3.2 years). Initial subset analysis was performed after excluding patients with positive TgAb, that were later included in the second. Baseline stimulated Tg was divided into tertiles. Multivariate logistic regression analysis included baseline Tg and other known prognostic markers and receiver operating characteristic(ROC) curve to identify the best cut-off level of baseline Tg were performed. Baseline stimulated Tg in the highest tertile was the only predictive variable of persistence of disease at 18-24 months in the initial analysis(OR 45.3, p<0.01). In the second analysis, the predictive variables were baseline stimulated Tg(OR 39.6, p<0.001), presence of TgAb(OR 23.4,p<0.005) and uptake outside of the thyroid bed post-treatment-WBS(OR 5.3,p<0.05) were predictive of persistence of disease. The ROC curve showed that baseline stimulated Tg below 8.55 μg/L identified 95% of disease-free patients at 18-24 months after initial treatment. Baseline stimulated Tg is a good predictor of remission of disease at 18-24 months after initial treatment and could be a useful marker to stratify risk immediately after surgery. This article is protected by copyright. All rights reserved.
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Background: This study was conducted to identify the relevant cutoff value and to evaluate the usefulness of postoperative-stimulated serum thyroglobulin (Tg) at the time of (131)I ablation for the prediction of disease status in patients with differentiated thyroid carcinoma (DTC) who received high-dose (131)I ablation therapy after total thyroidectomy. Methods: We analyzed 218 consecutively enrolled patients who were diagnosed with DTC and underwent total thyroidectomy. All patients underwent (131)I ablation at doses of 100-200 mCi, and stimulated serum Tg was measured at the time of (131)I ablation therapy. To assess disease-free status after (131)I ablation therapy, stimulated serum Tg levels, diagnostic whole-body scan (DxWBS) and neck ultrasonography (US) were performed 6-12 months after (131)I ablation. Results: The relevant cutoff value of postoperative stimulated Tg for the prediction of disease-free status was 2 ng/mL. A total of 138 patients (63.3%) showed values of <2 ng/mL. Postoperative-stimulated Tg < 2 ng/mL had a negative predictive value of 94.9%, which increased to 97.7% when low Tg was combined with negative neck US findings. Conclusion: Postoperative-stimulated Tg at the time of (131)I remnant ablation is a useful biochemical marker for the prediction of disease status in patients with DTC. When high-dose (131)I remnant ablation is performed after total thyroidectomy, the stimulated Tg measurement and DxWBS that are usually performed 6-12 months after (131)I ablation therapy may be skipped, at least in low- and intermediate-risk patients with postoperative stimulated Tg of < 2 ng/mL and negative neck US findings.
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The aim of this study was to evaluate prognostic role of thyroglobulin (Tg) levels at the time of ablation (A-Tg) and stimulation Tg levels at 6-12 months after remnant ablation (S-Tg) combined with revised American Thyroid Association (ATA) guidelines risk stratification. Data of 359 patients (median follow-up duration: 66.3 months) with papillary thyroid carcinoma who had high-dose remnant ablation were analyzed. The cutoff value of A-Tg to predict the persistent/recurrent disease was calculated by receiver operating characteristic curve analysis. In each risk group by ATA guidelines, the association of A-Tg with persistent/recurrent disease was evaluated. The role of A-Tg and ATA risk stratification in each S-Tg group (group with S-Tg <2 ng/mL, 2-10 ng/mL, or >10 ng/mL) was also evaluated. Tg response was determined by the difference between A-Tg and S-Tg with consideration of the dose of radioactive iodine ablation. A-Tg above 5.22 ng/mL was associated with persistent/recurrent disease in all risk groups by ATA guidelines. A-Tg above the cutoff value and ATA risk assessment was related to persistent/recurrent disease in patients with S-Tg 2 to 10 ng/mL (P = 0.003) and S-Tg above 10 ng/mL (P = 0.019). However, no difference in the incidence of persistent/recurrent disease was found according to Tg response. The scoring system made up of A-Tg, S-Tg, and ATA staging showed elaborate discrimination of prognosis. Risk stratification using combined scoring with initial stimulated Tg levels, including A-Tg and S-Tg, and staging system by revised ATA guidelines can effectively predict persistent/recurrent disease in patients with papillary thyroid carcinoma.
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Background: The thyrotropin (TSH) level or duration of thyroid hormone withdrawal (THW) required to detect stimulated thyroglobulin (Tg) in differentiated thyroid cancer (DTC) monitoring is unknown. The objective of this study was to evaluate the TSH cutoff of >30 μU/mL as a means to detect stimulated Tg ≥2 ng/mL after THW (THW-Tg≥2), and sensitivity of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire for detecting hypothyroid symptoms. Methods: This was a prospective longitudinal cohort study done at a tertiary academic medical center. Forty-seven patients with DTC undergoing their first Tg stimulation or after previously abnormal Tg stimulation had weekly measurements of TSH and Tg during the 4 weeks THW, and repeated questionnaire assessments. Results: TSH did not reach a plateau in any patient, and in those whose Tg did not remain undetectable, Tg continued to rise. Seventy-five percent of patients had an undetectable Tg <0.2 ng/mL at baseline (95% were <0.5 mg/mL) with 16% remaining undetectable throughout THW. The majority of patients (72.7% and 97.8%) achieved TSH >30 μU/mL by 3 and 4 weeks THW, respectively. Of the 15 patients with maximum stimulated THW-Tg≥2, 38% were detected before the minimal TSH >30 μU/mL cutoff. At 2 weeks THW, 3 had a TSH>30 μU/mL, and none of them had Tg ≥2 ng/mL. At 3 weeks THW, 11 had a TSH >30 μU/mL, and 64% of them had Tg ≥2 ng/mL. Only 60% were detected at 3-week THW regardless of their TSH level. Eighty-six percent were detected by TSH 60-<80 μU/mL. Conversely, all patients whose serum Tg was <0.2 ng/mL when their serum TSH was >20 μU/mL did not achieve a THW-Tg≥2. Conclusion: The minimal TSH cutoff of >30 μU/mL was inadequate to detect many patients with final stimulated THW-Tg≥2 during complete THW. TSH >80-100 μU/mL was a better cutoff, achieved in only 53% after 4-week THW. Conversely, we propose a preliminary THW-stopping rule for ending THW early in selected patients. In patients with a Tg <0.2 ng/mL when TSH >20 μU/mL, all had a final stimulated Tg ≤2 ng/mL, potentially saving qualifying patients 40% of THW duration compared to 4-week THW. FACIT-F correlated with TSH, but was not sensitive to detect mild hypothyroidism.