The role of a new polyclonal competitive thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer with structural disease but low levels of serum thyroglobulin by immunometric and LC-MS/MS methods

Guastapaglia, Leila; Kasamatsu, Teresa S.; Nakabashi, Cláudia C. D.; Camacho, Cleber; Maciel, Rui M. B.; Vieira, José Gilberto H.; Biscolla, Rosa Paula M.

doi:10.1007/s12020-020-02526-8

Cited by 5 publications

(3 citation statements)

References 26 publications

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“…In the follow-up of DTC, the greatest challenge is patients with serum Tg–IMA concentrations suggesting tumour absence in whom it is not possible to ensure whether this finding indicates complete remission or underestimated Tg due to the interference of TgAb ( 6 ). Many studies have focused on improving Tg detection technologies, such as liquid chromatography/tandem mass spectrometry and radioimmunoassay, but the former may cause false-negative results in many patients with structural disease ( 7 – 9 ); the latter is unsuitable for large-scale clinical applications and may cause false-positive results positives.…”

Section: Introductionmentioning

confidence: 99%

Antithyroglobulin Antibody Variation During Follow-Up Has a Good Prognostic Value for Preoperative Antithyroglobulin Antibody-Positive Differentiated Thyroid Cancer Patients: A Retrospective Study in Southwest China

Liu

Yin

2021

Front. Endocrinol.

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ObjectiveAntithyroglobulin antibody (TgAb) is a potential tumour marker for detecting differentiated thyroid cancer (DTC) recurrence, but insufficient data have supported its clinical applications. Our study aimed to describe the changing trend of TgAb after surgery and identify the relationship between this trend and clinical outcomes.Patients and MethodsWe reviewed the electronic records of 1,686 DTC patients who had undergone total thyroidectomy (TT) and radioactive iodine (131I) therapy at West China Hospital of Sichuan University from January 2015 to December 2017. Finally, 289 preoperative TgAb-positive DTC patients were included and divided into four subgroups depending on the clinical outcome: Group A (tumour free), Group B (uncertain), Group C (incomplete biochemical response), and Group D (structural disease). The patient demographics, tumour characteristics, operations, pathology reports, and all serological biomarkers were reviewed and compared, and the prognostic efficacy of TgAb was evaluated.ResultsAmong all 1,686 patients, 393 (23.65%) were TgAb positive (>40 IU/ml) preoperatively. The TgAb level in Group A decreased significantly after surgery and 131I therapy and stabilised at a low level after 1–2 years of 131I therapy. However, in the other three groups, the decrease in TgAb was not significant after treatment. Conversely, TgAb declined slowly and remained stable or increased. The variations in TgAb relative to the preoperative level of Group A were significantly larger than those of Groups B, C, and D at most time points of follow-up (p < 0.001). By receiver operating characteristic (ROC) analyses, the variations of TgAb > −77.9% at 6 months after 131I therapy (area under the curve (AUC) = 0.862; p < 0.001) and TgAb > −88.6% at 2 years after 131I therapy (AUC = 0.901; p < 0.001) had good prognostic efficacy in tumour-free survival. When the variation in TgAb > −88.6% at 2 years after 131I therapy was incorporated as a variable in the American Thyroid Association (ATA) categories, both intermediate- and high-risk patients also had a significantly increased chance of being tumour free (from 75.68% to 93.88% and 42.0% to 82.61%, respectively).ConclusionsFor preoperative TgAb-positive DTC patients, variations in TgAb > −77.9% at 6 months after 131I therapy and TgAb > −88.6% at 2 years after 131I therapy had good prognostic efficacy. Their incorporation as variables in the ATA risk stratification system could more accurately predict disease-free survival.

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Section: Introductionmentioning

confidence: 99%

Antithyroglobulin Antibody Variation During Follow-Up Has a Good Prognostic Value for Preoperative Antithyroglobulin Antibody-Positive Differentiated Thyroid Cancer Patients: A Retrospective Study in Southwest China

Liu

Yin

2021

Front. Endocrinol.

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“…They had shown feasibility in detecting circulating TG via mass spectrometry technique. However, this needs to be further optimised to improve the current sensitivity of 40–60% as there were patients with structural disease and TG Ab with negative TG measured on LC-MS/MS ( Spencer et al, 2014 ; Netzel et al, 2015 ; Azmat et al, 2016 ; Guastapaglia et al, 2020 ). TG measurement by radioimmunoassay (RIA) is an alternative technique for TG assessment in the presence of TG Ab though it had been reported to be associated with false-positive TG measurement in patients with TG Ab ( Netzel et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

A Multiplex Thyroid-Specific Assay for Quantification of Circulating Thyroid Cell-Free RNA in Plasma of Thyroid Cancer Patients

et al. 2021

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BackgroundThe standard of care for thyroid cancer management is thyroidectomy and adjuvant radioactive iodine (RAI). There is a paucity of clinical tool that quantifies residual thyroid volume reliably for precise adjuvant RAI dosing. Serum thyroglobulin (TG), tumour marker for thyroid cancer, takes 4 weeks for complete clearance due to its long half-life, and might be undetectable in 12% of structural disease patients. It detects recurrence with a sensitivity of 19–40%, mainly attributed to issue of TG antibody interference with TG immunometric assay. We hypothesise that the quantity of thyroid-specific cell-free RNA (cfRNA) is indicative of amount of thyroid tissues, and that during thyroid surgery, cfRNA levels decrease accordingly.MethodsWe identified 11 biologically significant and highly expressed thyroid-specific targets from Human Protein Atlas and literature. To assess for a fall in thyroid-specific cfRNA level, we recruited 16 patients undergoing thyroid surgery or RAI for malignant or benign thyroid disease, and tracked longitudinal trend of cfRNA. To assess the utility of cfRNA in detecting metastatic thyroid cancer, cfRNA of 11 patients at intermediate to high risk of recurrence was measured during surveillance and at time of clinical recurrence.ResultsThe multiplex assay was capable of amplifying and quantifying multiple thyroid-specific genes in a single reaction. The selected targets were amplified successfully from RNA extracted directly from the thyroid (positive control), indicating that they were highly expressed within thyroid tissue. These cfRNAs were present in plasma, in amounts quantifiable using qRT-PCR. Four cfRNA transcripts (TPO, GFRA2, IVD, TG) fell post-treatment in more than 50% of cohort. The thyroid peroxidase (TPO) cfRNA fell post-therapy in 63% of cohort by 80%, as early as 1 day post-treatment, supporting the potential role as early indicator of remnant thyroid tissue volume. We demonstrated the clinical relevance of circulating TPO cfRNA by tracking temporal changes in setting of peri-treatment, recurrence, and TG Ab positive state.ConclusionUsing a multiplex pre-amplification approach, the TPO cfRNA was a potential biomarker that can track residual thyroid mass. It can be further optimised for quantification of thyroid volume to guide RAI doses and for detection of thyroid cancer recurrence.

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“…A great response to treatment is indicated by undetectable TG measured, while patients under TSH suppression following complete thyroidectomy and radio-iodine ablation. TG elevation, on the other hand, might signify disease recurrence (Guastapaglia, et al 2021).…”

Section: Introductionmentioning

confidence: 99%

Effect of thyroglobulin level before ablative Radioactive Iodine on response and survival among patients with Differentiated Thyroid Carcinoma

Abdelrahman

2023

International Journal of Cancer and Biomedical Research

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Background: Thyroid carcinoma is the most common endocrine malignancy, accounting for 3-4% of all cancers. Aim: This retrospective study was designed to correlate stimulated thyroglobulin (sTG) levels before treatment with radioactive iodine (RAI) and the response in patients with differentiated thyroid cancer after thyroidectomy, as well as to evaluate sTG before RAI impact on disease free survival (DFS). Patients and Methods: This study included fifty-seven patients (43 females and 32 males). who had recruited in the period between January 2015 and April 2020 with the following criteria: first operated with total thyroidectomy with confirmed pathology of differentiated thyroid carcinoma (DTC) and then treated with RAI ablation. 91.2% of the patients had papillary thyroid carcinoma (PTC) and 44 (77.2%) were early-stage T1 and T2, while 13 (22.9%) were late stage T3 and T4. Results: The post ablation TG was <1 ng/ml in 52.6%, from 1-10 ng/ml in 36.8% and >10 ng/ml in 10.5% of patients. The univariate and multivariate analyses showed disease stage and RAI dose as two independent prognostic factors of DFS. However, factors as age, gender, histopathological type, T-stage, nodal status, and sTG level were of no statistical significance to DFS. In pairwise Fisher's exact tests statistical significance difference was irrelevant between all pairs (P=0.303) comparing intermediate vs. both excellent and incomplete. Also, there was a significant difference in the baseline level of sTG between the three levels of response (P=0.05). The low levels sTG was correlated with the most excellent response, while, most incomplete response showed high level (P=0.025). Comparing the level in excellent vs. intermediate and between intermediate vs. incomplete showed no statistical significance (P=0.145 and P=0.422), respectively. Conclusion: The sTG level is associated with risk stratification in patients with DTC. sTG is considered as response-to-initial therapy predictor, recurrence, and metastasis.

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The role of a new polyclonal competitive thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer with structural disease but low levels of serum thyroglobulin by immunometric and LC-MS/MS methods

Cited by 5 publications

References 26 publications

Antithyroglobulin Antibody Variation During Follow-Up Has a Good Prognostic Value for Preoperative Antithyroglobulin Antibody-Positive Differentiated Thyroid Cancer Patients: A Retrospective Study in Southwest China

Antithyroglobulin Antibody Variation During Follow-Up Has a Good Prognostic Value for Preoperative Antithyroglobulin Antibody-Positive Differentiated Thyroid Cancer Patients: A Retrospective Study in Southwest China

A Multiplex Thyroid-Specific Assay for Quantification of Circulating Thyroid Cell-Free RNA in Plasma of Thyroid Cancer Patients

Effect of thyroglobulin level before ablative Radioactive Iodine on response and survival among patients with Differentiated Thyroid Carcinoma

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