Early Post-operative Stimulated Serum Thyroglobulin: Role in Preventing Unnecessary Radioactive Iodine Treatment in Low to Intermediate Risk Papillary Thyroid Cancer.

AIM: The aims of the study are to evaluate the predictive value of early post-operative stimulated thyroglobulin (sTg) analysis on the recurrence risk, and to define a cut-off value that is related to recurrence risk in low to intermediate risk papillary thyroid cancer (PTC). METHODS: This retrospective cohort study included individuals who were diagnosed with PTC aged 18 years or older and had been operated by experienced surgeons of a tertiary university hospital between the years 2011 and 2021. The American Thyroid Association thyroid cancer guidelines version 2015 was used as the risk stratification system. Early sTg measurement obtained at 3-4 weeks after surgery when TSH >30 µIU/mL. Data was collected from the hospital database. A total of 328 patients who had post-operative early sTg values with negative anti-Tg antibodies were included. RESULTS: The median age was 44 years. Of the 328 patients, 223 (68%) were women. The median tumor diameter was 11 mm. One hundred ninety-one patients (58.2%) had low risk and 137 (41.8%) had intermediate risk for recurrent disease. Of the 328 patients, 4.0% had recurrent disease. In multivariate Cox regression, post-operative early sTg value [OR: 1.070 (1.038-1.116), P = .000], and the pre-operative malign cytology [OR: 1.483 (1.080-2.245), P = .042] were independent risk factors for recurrence. On the ROC curve analysis, the cut-off value of early sTg was 4.1 ng/mL for those with recurrent disease. CONCLUSION: This study demonstrated that early sTg could predict recurrent disease in patients with low to intermediate risk PTC. A cut-off of 4.1 ng/mL was identified with a high negative predictive value.

Predictive value of highly sensitive basal versus stimulated thyroglobulin measurement in long-term follow-up of thyroid cancer.

Objective: Recurrence of differentiated thyroid cancer (DTC) is associated with reduced quality of life, and therefore, early identification of patients at risk is urgently needed.Here we investigated the predictive power of various cut-off values of single stimulated thyroglobulin (s-Tg) and single highly sensitive measured, unstimulated thyroglobulin (u-hsTg) measurements close to the end of primary therapy for recurrence-free survival (RFS) in long-term follow-up (>10 years) of patients with DTC. Methods: In DTC patients with adjuvant radioiodine therapy, we assessed retrospectively u-hsTg (6 ± 3 months before s-Tg measurement) and s-Tg measurements (≤24 months after last radioiodine therapy). Positive predictive (PPV)/negative predictive values (NPV) of various cut-off values (s-Tg: 0.5/1.0 ng/mL; u-hsTg: 0.09/0.2 ng/mL) for patient outcomes as well as additional factors associated with disease development were analyzed. Results: In total, 175 patients were retrospectively reviewed (tumor recurrence: n = 14/complete remission: n = 161). Examined cut-off values for s-Tg and u-hsTg showed significant predictive power for RFS (log-rank: all P < 0.001). NPV/PPV for s-Tg were 98.6%/36.4%, respectively (0.5 ng/mL cut-off) and 96.7%/42.9%, respectively (1.0 ng/mL cut-off); those for u-hsTg were 97.3%/35.7%, respectively (0.09 ng/mL cut-off) and 95.2%/85.7%, respectively (0.2 ng/mL cut-off). U-hsTg (P < 0.001) and patient age (P < 0.05) were significantly associated with tumor recurrence. One-third of patients with tumor recurrence in the course initially showed undetectable u-hsTg after completion of primary therapy. Conclusion: With >10 years of follow-up, both s-Tg and u-hsTg have a comparably high predictive power for RFS, while only u-hsTg was significantly associated with a recurrence event.Serial u-hsTg measurements seem warranted since patients with tumor recurrence during follow-up may have an undetectable tumor marker at baseline.

Changing Paradigm in Treatment of Differentiated Thyroid Cancer.

Differentiated thyroid cancer is an indolent cancer with an excellent prognosis when treated adequately. The treatment algorithm is well established and standardized. Surgery followed by radio-iodine treatment has stood the test of time. In the last decade, the paradigm has slightly shifted with newer diagnostic approaches like stimulated thyroglobulin and anti-thyroglobulin antibodies impacting the treatment decisions. The diagnostic whole body radio-iodine scan has also got innovated with the introduction of r-TSH injection protocol wherein the scan is performed while the patient is on thyroxine thereby minimizing patient discomfort. The new RISK-based classification system has resulted in altered treatment algorithms by sub dividing patients into low-, intermediate-, and high-risk groups. There has also been identification of TWO new class of thyroid cancer patients-radio-iodine-resistant thyroid cancer and TENIS syndrome (thyroglobulin elevated negative iodine scan) patients. Both these groups posed major challenge to treatment and this resulted in incorporation of TARGETED THERAPY based on the mutations that occur in these TWO groups of patients. The introduction of Sorafenib and Lenvatinib has made significant impact on progression-free and overall survival of these patients. The introduction of THYROPET (124-I PET scan) is gaining momentum as an alternative to 123/131-I scans due to high-resolution images on PET scan increasing the detection sensitivity. All the above factors have resulted in paradigm shift in the management of differentiated thyroid cancer patients.

Combination of Stimulated Thyroglobulin and Antithyroglobulin Antibody Predicts the Efficacy and Prognosis of 131I Therapy in Patients With Differentiated Thyroid Cancer Following Total Thyroidectomy: A Retrospective Study.

Background and Purpose: This study aimed to analyze the diagnostic ability of the combination of stimulated thyroglobulin (sTg) and antithyroglobulin antibody (TgAb) in predicting the efficacy and prognosis of radioactive iodine (131I) therapy (RAIT) in patients with differentiated thyroid carcinomas (DTCs) after total thyroidectomy (TT). Methods: This retrospective study comprised 409 DTC patients who underwent 131I treatment following TT in the First Affiliated Hospital of Zhengzhou University from January 2019 to August 2020, and they were followed up to November 2021. Patients were divided into the successful ablation and the unsuccessful ablation group based on the classification of the efficacy of RAIT in the 2015 American Thyroid Association guidelines. The clinical characteristics and the efficacy of the initial RAIT were evaluated. The cutoffs of preablation sTg, sTg/thyroid-stimulating hormone (TSH) ratio, and sTg×TgAb product were calculated to predict the efficacy of RAIT. Univariate and multivariate logistic regression analyses were used to identify the independent risk factors for unsuccessful ablation. Kaplan-Meier curves were used to estimate the prognostic value of sTg×TgAb product affecting progression-free survival (PFS). Results: The cohort consisted of 222 cases in the successful ablation group and 187 cases in the unsuccessful ablation group. Between the two groups, preablation sTg, sTg/TSH ratio, and sTg×TgAb product were significantly higher in the unsuccessful ablation group. The area under the curve (AUC) of the sTg×TgAb product was the highest among the above three factors. The cutoffs for the worse therapeutic effect of the initial RAIT in sTg, sTg/TSH ratio, and sTg×TgAb were >2.99 ng/ml, >0.029 mg/IU, and >34.18, respectively. STg >2.99 ng/ml and sTg×TgAb product >34.18 were independent risk factors for unsuccessful ablation. Patients with sTg×TgAb product >34.18 had shorter PFS than that of patients with sTg×TgAb product ≤34.18. In separate analyses of TgAb-negative and TgAb-positive subgroups, higher sTg×TgAb was both associated with a lower success rate of RAIT and a shorter PFS. Conclusion: STg×TgAb product predicted the efficacy and prognosis of 131I therapy for both TgAb-negative and TgAb-positive DTC patients before the initial 131I treatment following TT. Thus, it can be used as a clinical reference indicator for the surveillance of DTC patients.

Comparison Between Transoral Endoscopic Thyroidectomy Vestibular Approach (TOETVA) and Conventional Open Thyroidectomy for Patients Undergoing Total Thyroidectomy and Central Neck Dissection: A Propensity Score-Matching Analysis.

Background: Use of the novel transoral endoscopic thyroidectomy vestibular approach (TOETVA) is increasing worldwide. Although several studies have compared safety and efficacy of TOETVA and other approaches, most focused on comparisons in the context of unilateral thyroidectomy. Therefore, the present study aimed to compare the safety and surgical completeness of TOETVA with conventional open thyroidectomy (COT) in patients with papillary thyroid carcinoma (PTC) undergoing total thyroidectomy and central neck dissection. Methods: The medical records of patients who underwent TOETVA or COT by a single surgeon between June 2017 and October 2021 were retrospectively reviewed. All patients were diagnosed with PTC and underwent total thyroidectomy with central neck dissection. Propensity score-matching (PSM) was used to reduce potential selection bias and to adjust for differences in baseline clinicopathological characteristics. Results: After PSM, 84 (TOETVA: 28; COT: 56) patients remained in the study population. There were no significant differences in sex, mean age, combined thyroiditis, tumor size, capsule invasion, tumor multifocality in the same lobe, or tumor location between the groups. Operative time was longer (190.54 ± 28.26 vs. 123.93 ± 29.78 min, P<0.001), while postoperative drainage volume (161.07 ± 225.30 vs. 71.16 ± 28.56 ml, P=0.045) was greater, in the TOETVA group than in the COT group. The groups exhibited no significant differences in the mean number of central lymph nodes retrieved (9.39 ± 4.01 vs. 10.71 ± 5.17, P=0.202), mean number of metastatic central lymph nodes (1.36 ± 1.93 vs. 1.77 ± 2.31, P=0.421), postoperative mean thyroglobulin levels (0.08 ± 0.24 vs. 0.10 ± 0.27, P=0.686), rate of transient hypoparathyroidism (TOETVA: 67.9% vs. COT: 66.1%, P=0.870), rate of transient vocal cord palsy (TOETVA: 0% vs. COT: 1.8%, P=1.000), or other complications (TOETVA: 3.6% vs. COT: 0%, P=0.333). Conclusions: TOETVA is a safe approach in select patients with PTC and exhibits similar efficacy to COT in terms of surgical completeness.

Improving the prediction of persistent and recurrent differentiated thyroid cancer using the American Thyroid Association 2015 risk stratification system.

PURPOSE: The 2015 American Thyroid Association risk stratification system (ATA RSS) is used in patients with differentiated thyroid carcinoma (DTC) to assess their risk of persistent/recurrent disease. Our aims were to validate the 2015 ATA RSS in a registry of DTC patients and to examine whether the addition of factors not included in it, such as pre-radioactive iodine therapy stimulated thyroglobulin (pre-RAI sTg), gender, and age could increase its predictive ability. METHODS: We studied 403 patients with DTC, treated at a tertiary center from 1990 to 2018 and subjected to total thyroidectomy. All patients had received RAI therapy, except those with low-risk papillary microcarcinoma. RESULTS: Of our patients, 81.9% were women and 91.1% had papillary thyroid carcinoma. After a median follow-up of 5.0 years, 53 cases of persistent and 21 cases of recurrent disease were recorded. The proportion of variance explained (PVE) regarding the outcome (presence or absence of recurrent/persistent disease) using the 2015 ATA RSS alone was 18.3% (persistence) and 16.9% (recurrence), increasing to 74.4% and 52.0%, respectively, when pre-RAI sTg was added to the logistic regression model. Gender and age were not associated with the disease outcome. In ROC analysis, pre-RAI sTg had a high predictive value for persistent (AUC 0.983, 95% CI 0.962-1.000) and recurrent disease (AUC 0.856, 95% CI 0.715-0.997). The optimal cut-offs and sensitivity, specificity, and positive and negative predictive value for pre-RAI sTg were the following: for persistence 12.75 ng/ml, 100%, 90.5%, 64%, and 100%, and for recurrence 8.05 ng/ml, 77.8%, 85.5%, 36.8%, and 97%. CONCLUSIONS: The 2015 ATA RSS displayed moderate performance in predicting recurrent/persistent disease in patients with DTC, which improved with the inclusion of pre-RAI sTg values; pre-RAI sTg was an independent predictor of the disease outcome, with high negative prognostic value.

Preablative Stimulated Thyroglobulin and Thyroglobulin Reduction Index as Decision-Making Markers for Second Radioactive Iodine Therapy in Patients with Structural Incomplete Response.

PURPOSE: The aim of this study was to evaluate the value of preablative stimulated thyroglobulin (presTg) and thyroglobulin reduction index (TRI) to predict the different responses to second radioactive iodine (RAI) therapy in differentiated thyroid cancer (DTC) patients with structural incomplete response (SIR). PATIENTS AND METHODS: A single-center retrospective study analyzed the different clinical outcomes after second RAI therapy in 206 patients with SIR. PresTg1 and presTg2 were measured before first and second RAI management and TRI was the reduction index of presTg1 and presTg2. Cut-off values of presTg and TRI were obtained using receiver operating characteristic analysis. The univariate logistic regression analysis was performed to confirm these parameters as prognostic factors to predict different responses to second RAI therapy. RESULTS: Only ATA risk stratification, the post-therapy whole-body scanning (Rx-WBS) findings, presTg1, presTg2, TRI, were different in patients with SIR. After second RAI therapy, 28.2% (58/206) of patients with SIR initially were reclassified as excellent response (ER). PresTg1 <6.6 ng/mL, presTg2 <1.2ng/mL, and TRI >74.2% were excellent indications to predict ER from non-ER after second RAI treatment. PresTg1 >14.9 ng/mL, presTg2 >1.8ng/mL and TRI <66.5% were well markers to predict poor outcome (SIR). High risk and distant metastases could still be considered as risk factors. CONCLUSION: DTC patients with SIR could benefit through second RAI treatment. PresTg before each RAI therapy and TRI could be considered as effective decision-making markers for second RAI therapy and as predictive indications for clinical outcomes.

Urinary iodine concentration and radioactive iodine therapeutic response in patients with differentiated thyroid cancer.

Aim: Urinary iodine concentration (UIC) may assess radioactive iodine ablation. Materials & methods: According the 2015 American Thyroid Association guidelines, patients were categorized into low- to intermediate-risk or high-risk groups. The iodine concentration in the morning urine specimens was measured by the ceric ion-arsenious acid method. Results: In the low- to intermediate-risk group (113 cases), nonexcellent response (non-ER) was associated with higher UIC, higher UIC subgroups (p < 0.05), higher pre-ablative stimulated thyroglobulin levels (p < 0.01). In the high-risk group (68 cases), the non-ER rate was higher in the higher pre-ablative stimulated thyroglobulin group (p < 0.01), but not significantly different between the UIC and UIC subgroups (p > 0.05). Conclusion: The non-ER rate was related to UIC in the low- to intermediate-risk group; however, UIC did not affect the non-ER rate in the high-risk group.

Residual Pyramidal Lobe Increases Stimulated Thyroglobulin and Decreases Endogenous Thyroid Stimulating Hormone Stimulation in Differentiated Thyroid Cancer Patients.

OBJECTIVE: To determine the frequency of pyramidal lobe remnants after total thyroidectomy (TT) and the effect on stimulated thyroglobulin (Tg). METHODS: The study included 1740 differentiated thyroid cancer (DTC) patients who were followed up by our center. The department database was searched to identify DTC patients with residual pyramidal lobe after TT. All postoperative technetium-99m pertechnetate thyroid scintigraphy images were re-evaluated for pyramidal lobe residue. Serum stimulated Tg and thyroid stimulating hormone (TSH) levels measured within the first 6 months after TT were retrieved from the database. RESULTS: Pyramidal lobe residue was detected in 10.4% of the patients who underwent TT. Evidence of the pyramidal lobe was present on preoperative ultrasonography in 1.6% of the patients with residual pyramidal lobe. Stimulated Tg in patients with pyramidal lobe residue was significantly higher than that in patients without residue (P = .01). Endogenous stimulated TSH in patients with residual pyramidal lobe was significantly lower than that in patients without residue (P = .036). In 5.7% of patients with pyramidal lobe residue, a TSH level of >30 mIU/L was not achieved, which was a significantly higher rate than that in patients without pyramidal lobe residue (P = .034) and is the level required for maximum radioiodine uptake. CONCLUSION: Pyramidal lobe residue was found in almost 10% of DTC patients. The pyramidal lobe is often missed on preoperative ultrasonography. Residual pyramidal lobe increased stimulated Tg and decreased endogenous stimulated TSH. Residual pyramidal lobe may complicate the follow-up of DTC patients.

Early preablation rhTSH-stimulated thyroglobulin predicts outcome of differentiated thyroid cancer (DTC) patients.

AIM: Total thyroidectomy and risk-adapted 131-radioiodine therapy (RaIT) are the treatments of choice in differentiated thyroid cancer (DTC) patients. The response to treatments is assessed 6-12 months after RaIT. However, thyroglobulin (Tg) values obtained just before RaIT also provide reliable informations on patients'outcome. As available data were mostly obtained in hypothyroid status, we evaluated the predictive role of preablation-Tg in patients underwent RaIT after rhTSH stimulation. MATERIAL AND METHODS: We enrolled 299 low-to-intermediate risk DTC patients underwent rhTSH-stimulated RaIT (standard protocol). Serum Tg levels were measured before rhTSH administration (basal Tg), before RaIT (early-stimulated Tg), and 2 days after RaIT (late-stimulated Tg). The early response assessment was done 12 months after RaIT according to 2015 American Thyroid Association (2015 ATA) criteria. RESULTS: Most patients (277/299, 92.6%) had an excellent response (ER) to RaIT, while 15/299 (5.1%) and 7/299 (2.3%) patients showed biochemical incomplete/indeterminate response or persistent structural disease, respectively. At receiver operating characteristic analysis, the optimal cutoff to predict ER was set at 1.55 (AUC = 0.792), 2.6 (AUC = 0.931), and 4.9 (AUC = 0.874) ng/mL, for basal, early-, and late-stimulated Tg, respectively. The overall sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for basal, early-, and late-stimulated Tg were 50%, 96.7%, 93.3%, 55%, and 96.1%; 90.9%, 84.5%, 84.9%, 31.7%, and 99.1%; and 90.9%, 71.8%, 73.2%, 20.4%, and 99%, respectively. In univariate and multivariate logistic regression analysis, early-stimulated Tg cutoff resulted as an independent prognostic marker for predicting ER regardless of gender, age, histotype, histological variant, tumor size, risk classification, and stage of disease. CONCLUSION: Early-stimulated Tg is a reliable diagnostic tool for predicting the response to primary treatment of DTC.

Recombinant human thyrotropin versus thyroid hormone withdrawal in differentiated thyroid carcinoma follow-up: a single center experience.

Introduction: Our goal was to evaluate and compare the diagnostic utility of thyroid hormone withdrawal (THW) and recombinant thyroid-stimulating hormone (rhTSH) methods in detecting recurrence/persistence (R/PD) of differentiated thyroid carcinoma (DTC). Methods: The study included 413 patients with DTC who underwent total thyroidectomy and had remnant ablation. DxWBS, s-Tg levels, R/PD were evaluated retrospectively. A s-Tg level≥2 ng/mL was considered as "positive s-Tg". Results: DxWBS and s-Tg levels were evaluated with rhTSH in 116 and THW in 297 subjects, respectively. The sensitivity and specificity of "positive s-Tg" for R/PD in THW group were 77.3% and 92.7%, with 90.3% accuracy, respectively. The sensitivity and specificity of "positive s-Tg" for R/PD in rhTSH group were 58.8% and 100% with 93.9 % accuracy, respectively. An uptake outside thyroid bed at WBS showed a sensitivity of 17.1%, specificity of 100% for R/PD with 89.4% accuracy in THW group. An uptake outside thyroid bed at WBS showed a sensitivity of 7.7%, specificity of 100% for R/PD with 88.8% accuracy in rhTSH group. Conclusion: Method of TSH stimulation did not influence the reliability of DxWBS. The "positive s-Tg level" had a higher sensitivity with THW when compared to rhTSH in detecting R/PD.

Utility of Stimulated Thyroglobulin in Reclassifying Low Risk Thyroid Cancer Patients' Following Thyroidectomy and Radioactive Iodine Ablation: A 7-Year Prospective Trial.

Context: Following total thyroidectomy and radioactive iodine (RAI) ablation, serum thyroglobulin levels should be undetectable to assure that patients are excellent responders and at very low risk of recurrence. Objective: To assess the utility of stimulated (sTg) and non-stimulated (nsTg) thyroglobulin levels in prediction of patients outcomes with differentiated thyroid cancer (DTC) following total thyroidectomy and RAI ablation. Method: A prospective observational study conducted at a University Hospital in Saudi Arabia. Patients diagnosed with differentiated thyroid cancer and were post total thyroidectomy and RAI ablation. Thyroglobulin levels (nsTg and sTg) were estimated 3-6 months post-RAI. Patients with nsTg <2 ng/ml were stratified based on their levels and were followed-up for 5 years and clinical responses were measured. Results: Of 196 patients, nsTg levels were <0.1 ng/ml in 122 (62%) patients and 0.1-2.0 ng/ml in 74 (38%). Of 122 patients with nsTg <0.1 ng/ml, 120 (98%) had sTg levels <1 ng/ml, with no structural or functional disease. sTg levels >1 occurred in 26 (35%) of patients with nsTg 0.1-2.0 ng/ml, 11 (15%) had structural incomplete response. None of the patients with sTg levels <1 ng/ml developed structural or functional disease over the follow-up period. Conclusion: Suppressed thyroglobulin (nsTg < 0.1 ng/ml) indicates a very low risk of recurrence that does not require stimulation. Stimulated thyroglobulin is beneficial with nsTg 0.1-2 ng/ml for re-classifying patients and estimating their risk for incomplete responses over a 7 years follow-up period.

Transoral endoscopic thyroidectomy for thyroid carcinoma: outcomes and surgical completeness in 150 single-surgeon cases.

BACKGROUND: Transoral endoscopic thyroid surgery vestibular approach (TOETVA) is a promising technique involving no skin incision. Since its first use in 60 patients in 2015, TOETVA has been adopted by several hospitals worldwide. However, reports of TOETVA for thyroid cancer are scarce. METHODS: Between August 2016 and March 2019, 150 and 125 thyroid cancer patients underwent TOETVA and open thyroidectomy (OT), respectively, by a single endocrine surgeon. Comparative analyses were performed on clinical and pathological findings, complications, and surgical completeness in total thyroidectomy cases, as indicated by the serum thyroglobulin (Tg) level. Data were collected prospectively and analyzed retrospectively. RESULTS: Mean age was younger in the TOETVA than in the OT group (43.06 ± 10.90 vs. 51.02 ± 12.42). The percentage of females was 96.7% in the TOETVA group. Total thyroidectomy was higher in the OT group (26.7% vs. 65.0%). Operation time (min) was longer in the TOETVA group for lobectomy (102.12 ± 32.59 vs. 76.38 ± 21.24) and total thyroidectomy (132.65 ± 34.79 vs. 90.71 ± 25.09). The largest tumor diameter was 0.91 (± 1.00) in the TOETVA group and 1.19 (± 1.07) in the OT group. The harvested lymph node number was not significantly different between the two groups for lobectomy (3.19 ± 2.89 vs. 3.49 ± 2.41, p = 0.319) and total thyroidectomy (4.98 ± 3.12 vs. 5.70 ± 4.35, p = 0.714). The thyroid-stimulating hormone stimulated Tg level before administration of the first dose of radioactive iodine was also not different (3.38 ± 10.87 vs. 3.44 ± 11.51, p = 0.595). Percentage of stimulated Tg below 1.0 ng/ml was 80.0% in the TOETVA group. CONCLUSIONS: TOETVA is feasible in selected thyroid cancer patients, not only because it is cosmetically advantageous but also because it is oncologically safe. A large prospective cohort study including recurrence surveillance is needed to consolidate the feasibility of TOETVA.

A cutoff thyroglobulin value suggestive of distant metastases in differentiated thyroid cancer patients

Serum thyroglobulin is used as part of the early postoperative assessment of differentiated thyroid cancer (DTC) since there is a clear relationship between an increased risk of recurrence and persistent disease after initial treatment and high postoperative stimulated thyroglobulin (ps-Tg) values. Thus, although ps-Tg above 10-30 ng/mL is considered an independent predictor of worse prognosis, the value that is associated with distant metastases is not defined. Thus, this was our objective. We selected 655 DTC patients from a nuclear medicine department database (Irmandade Santa Casa de Misericórdia de São Paulo, Brazil). All patients had received total thyroidectomy and radioactive iodine (RAI) therapy and had ps-Tg values higher than 10 ng/mL with negative anti-thyroglobulin antibodies. Then, we selected patients who presented post-therapy whole-body scan with pulmonary and/or bone uptake but with no mediastinum or cervical uptake. Patients with negative findings on functional imaging or any doubt on lung/bone uptake were submitted to additional exams to exclude another non-thyroid tumor. Of the 655 patients, 14.3% had pulmonary and 4.4% bone metastases. There was a significant difference in ps-Tg levels between patients with and without metastases (P<0.001). The cutoff value of ps-Tg was 117.5 ng/mL (sensitivity: 70.2%; specificity: 71.7%) for those with lung metastasis, and 150.5 ng/mL (sensitivity: 79.3%; specificity: 85%) for those with bone metastasis. The cutoff value for patients with eitherpulmonary or bone metastasis was 117.5 ng/mL (sensitivity: 70.2%; specificity: 83.7%). Our findings demonstrated that ps-Tg could predict distant metastasis in DTC patients. We identified a cutoff of 117.5 ng/mL with a high negative predictive value of 93.7%.

Value of the Postablative Thyroglobulin Measurements for Assessment of Disease-Free Status in Patients with Differentiated Thyroid Cancer.

AIM: The aim of the study is to evaluate the value of thyroid-stimulating hormone (TSH)-stimulated thyroglobulin (sTg) measurements by the end of the 1st-year postablation in differentiated thyroid cancer (DTC) patients with biochemical non complete response (indeterminate and incomplete response). PATIENTS AND METHODS: One hundred patients with DTC underwent near-total thyroidectomy and radioactive remnant ablation by iodine-131 (I131) with regular follow-up every 6 months during the first 2 years and at 6-12-month intervals thereafter by I131 whole-body scan (WBS), neck ultrasound, and sTg measurement in the hypothyroid state (TSH >30 mU/L). Patients were divided according to the imaging findings and sTg level into three groups: excellent response (ER) - no evidence of disease by imaging and sTg <1 ng/mL, indeterminate or acceptable response (AR) - nonspecific findings on imaging studies and sTg < 10 ng/mL, and incomplete response (IR) - patients with incomplete structural and/or incomplete biochemical response (sTg > 10 ng/mL). RESULTS: The follow-up at 6-month postablation showed ER in 3 (3%) patients, AR in 29 (29%) patients, and IR in 68 (68%) patients. The second follow-up at 9-12-month postablation showed dramatic biochemical response with ER, indeterminate, and IR in 50 (50%), 34 (34%), and 16 (16%) patients, respectively, and 14 (14%) patient had structural recurrence. This change is highly statistically significant (P = 0.00). In the last follow-up (ranges from 3 to 10 years), 53 (55.8%) patients achieved ER, 42 (44.2%) AR and no patient with non complete response. The change in patients with IR between the second and the last follow-up is also statistically significant (P = 0.001). CONCLUSION: sTg measurement by the end of the 1st year is more reliable in the follow-up of patients with DTC and biochemical non complete response and considered significant predictor of disease-free status. Patients with biochemical IR still have the chance to achieve ER or AR by the passage of time without additional therapies.

Is hemi-thyroidectomy adequate in low risk differentiated thyroid cancer?

In low-risk differentiated thyroid carcinoma (LRDTC), appropriate surgical procedure in terms of hemi/total thyroidectomy (TT) has been an area of debate. The aim was to determine whether in LRDTC patients, hemithyroidectomy would be an adequate treatment, determine incidence of disease in contralateral lobe and evaluate the effect of radioactive iodine ablation (RAIA). Retrospective study was done from 2008 to 2014 at a single institution. Preoperative ultrasound (USG) and histopathology reports of all LRDTC patients following total/completion thyroidectomy were recorded. Details of postthyroidectomy, thyroid whole body scan, and stimulated serum thyroglobulin (sTg) levels were also documented and results analyzed. A total of 114/562 patients met inclusion criteria. Of these, 25/114 (22%) underwent hemithyroidectomy followed by a completion thyroidectomy while remaining 89/114 (78%) underwent TT initially. Preoperative USG detected single-lobe involvement in 44 patients; however, among them, histopathology revealed bilateral lobe disease in 17 (38.6%). There was a significant fall of sTg level following RAIA as compared to that before RAIA in T1b-T2 (P = 0.009 and 0.012, respectively). Median follow-up was 2 years (range: 1-7 years) with no distant metastasis or deaths recorded till 2017, except for one local recurrence 4 years after RAIA. In conclusion, the role of TT in LRDTC patients is important as 46% of patients were found to have tumor in contralateral lobe as well. Significant fall in sTg levels following RAIA justifies RAIA of remnant lobe even in LRDTC (T > 1a). It facilitates early detection of recurrence when sTg alone is used for follow-up.

Is TSH suppression still necessary in intermediate- and high-risk papillary thyroid cancer patients with pre-ablation stimulated thyroglobulin <1 ng/mL before the first disease assessment?

OBJECTIVE: Since papillary thyroid cancer (PTC) patients with pre-ablation stimulated thyroglobulin (s-Tg) < 1 ng/mL generally have a favorable prognosis, is TSH suppression still necessary in intermediate- and high-risk PTC patients with pre-ablation s-Tg < 1 ng/mL after initial therapy? The aim of this study was to assess the rate of disease recurrence in intermediate- and high-risk PTC patients with pre-ablation s-Tg < 1 ng/mL according to TSH levels measured 1 year after initial therapy. METHODS: A retrospective series of intermediate- and high-risk PTC patients with pre-ablation s-Tg < 1 ng/mL was analyzed. Disease status was defined as the presence or absence of structural disease during late follow-up. Patients were grouped according to TSH level at 1 year: group 1, TSH < 0.1 mIU/L; group 2, TSH 0.1‒0.5 mIU/L; group 3, 0.5‒2 mIU/L; group 4, >2 mIU/L. RESULTS: This study included 166 patients (78.3% females, median age 44 years) of whom the risk of recurrence was intermediate in 97 (58.4%) and high in 69 (41.6%). The response to initial therapy at 1 year was excellent in 163 patients (98.2%) and indeterminate in 3 (1.8%). Group 1 consisted of 63 patients (38%), group 2 of 47 (28%), group 3 of 28 (17%), and group 4 of 28 (17%). During a median follow-up duration of 5.8 years, disease recurrence was observed in only 4 patients (2.4%). The rate of disease recurrence was not significantly different between the TSH groups. CONCLUSION: TSH suppression before the first response to treatment assessment does not seem to influence the rate of disease recurrence after initial therapy in intermediate- and high-risk PTC patients with pre-ablation s-Tg < 1 ng/mL.

Clinical utility of an ultrasensitive thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer: can the stimulation test be avoided in patients with an intermediate recurrence risk?

SUMMARY: Serum thyroglobulin (Tg) measurement during suppression with levothyroxine (LT4) using an ultrasensitive assay (OnT4-Tg) has been proposed as a replacement of TSH-stimulated Tg measurement (OffT4-Tg) in management of patients with differentiated thyroid cancer (DTC). The aim of this study is to evaluate the capacity of an ultrasensitive Tg assay in predicting an OffT4-Tg > 2.0 ng/mL based on the OnT4-Tg in patients with DTC and an intermediate recurrence risk. We analysed 101 patients with DTC and an intermediate (n = 92) or high risk of recurrence (n = 9) who were treated with total thyroidectomy and ablation with 131I, and followed for an average of 6 years. OnT4-Tg was undetectable in 64 of 101 patients; OffT4-Tg was #x003C; 2.0 ng/mL in 61 of these 64 patients, all with negative imaging results. Furthermore, 37 of 101 patients had detectable OnT4-Tg; 32 of these 37 patients also presented OffT4-Tg > 2.0 ng/mL, and only 3 of these 32 patients had metastases detected by neck ultrasound. Considering a cutoff point of 0.1 ng/mL for OnT4-Tg, the assay had a sensitivity of 91%, specificity of 92%, positive predictive value (PPV) of 86% and the negative predictive value (NPV) of 95% when predicting an OffT4-Tg > 2.0 ng/mL (biochemical disease). The use of an ultrasensitive Tg assay allows prediction of which patients will remain disease-free even if they are at an intermediate risk of recurrence, and to decrease the need for stimulated Tg assays in two-thirds of these patients.

Detection of distant metastasis at the time of ablation in children with differentiated thyroid cancer: the value of pre-ablation stimulated thyroglobulin.

Background The present study was designed to determine the value of pre-ablation stimulated thyroglobulin (s-Tg) in predicting distant metastasis (DM) at the time of ablation in children with differentiated thyroid cancer. Methods From August 2009 to December 2016, consecutive children with differentiated thyroid cancer undergoing remnant ablation were retrospectively analyzed. Serum s-Tg was measured with the high-sensitive electrochemiluminescence immunoassay during hypothyroidism at ablation just before the ablative radioactive iodine (131I) administration. Post-ablation, whole body planar scintigraphy was obtained 5 days after administration of ablation activity of 131I. Single photon emission computed tomography/low-dose computed tomography (SPECT/CT) was added for children whose planar findings were inconclusive. Receiver-operating characteristics (ROC) curve analysis was employed to find a cut-off level of pre-ablation s-Tg as a predictor of DM at the time of ablation. Results Fifty-seven children were included for the analysis. Metastases were noticed on post-ablation scintigraphy in 20 (35%) children: five post-operative residual neck lymph node metastases, four post-operative residual neck lymph node and lung metastases, three mediastinal lymph node and lung metastases and eight lung metastases. A significant difference in pre-ablation s-Tg levels was found in children with DM compared with those without DM, 603.5 vs. 5.7 ng/mL, respectively. A pre-ablation s-Tg level of 156 ng/mL was established as the optimal cut-off point to predict DM. Conclusions This study demonstrated that pre-ablation s-Tg could potentially act as a predictor of DM at the time of ablation in children with differentiated thyroid cancer. We also propose a specific pre-ablation s-Tg cut-off value of 156 ng/mL as an optimal threshold for practical use.

Serial post-surgical stimulated and unstimulated highly sensitive thyroglobulin measurements in low- and intermediate-risk papillary thyroid carcinoma patients not receiving radioactive iodine.

The purpose of this study was to determine the natural temporal trends of serial thyroglobulin (Tg) among low/intermediate-risk PTC patients not receiving radioactive iodine (RAI) using TSH-stimulated Tg (Stim-Tg) and unstimulated highly sensitive Tg (u-hsTg). We prospectively analyzed serial Stim-Tg measurements after total thyroidectomy ± therapeutic central neck dissection among 121 consecutive low/intermediate-risk PTC patients who did not receive RAI, of whom 104 also had serial u-hsTg measurements available. Median follow-up was 6.5 years with Stim-Tg measurements commencing 3 months after surgery and u-hsTg commencing 1.8 years after surgery (when the assay became available). TSH stimulation was performed with 9-day T3 withdrawal, 22-day T4 withdrawal, or using recombinant human TSH (rhTSH). To account for within-patient correlations of repeated Tg measurements, temporal trends in Stim-Tg and u-hsTg were assessed using Generalized Estimating Equations. Stim-Tg models were adjusted for the method of TSH stimulation, whereas the u-hsTg models were adjusted for concurrent TSH level. Linear regression modeling was used to assess the trend in serial Stim-Tg and u-hsTg measurements as a function time from time of surgery throughout the duration of follow-up. The main outcome measured was the change in u-hsTg and Stim-Tg measurements over time. A total of 337 Stim-Tg (2.8/patient) and 602 u-hsTg (5.8/patient) measurements were analyzed. Among the 337 Stim-Tg measurements, Stim-Tg was assessed using rhTSH in 202 (60 %), T4 withdrawal in 41 (12 %), and T3 withdrawal in 94 (28 %) measurements. The overall mean ± 1SD for Stim-Tg and u-hsTg measured was 1.0 ± 1.2 and 0.2 ± 0.1 µg/L, respectively. When adjusted for method of TSH stimulation, serial Stim-Tg measurements did not significantly change over time (all p = NS). The estimated changes in Stim-Tg per year for rhTSH, T4 withdrawal, and T3 withdrawal were 0.01, -0.08, and 0.04 µg/L, respectively. Upon exclusion of 73 patients with an initial undetectable Stim-Tg (n = 48), serial Stim-Tg measurements did not change significantly over time (all p = NS). For these patients, the estimated changes in Stim-Tg per year for rhTSH, T4 withdrawal, and T3 withdrawal were -0.09, -0.10, and 0.01 µg/L, respectively. Serial u-hsTg measurements did not significantly change over time after adjusting for TSH level (p = NS). The estimated change in u-hsTg per year was -0.003 µg/L. No patients had any clinical or imaging evidence of a recurrence during the duration of their follow-up. Among low/intermediate-risk PTC patients not treated with RAI, serial post-surgical Stim-Tg and u-hsTg measurements do not change significantly over a median follow-up of 6.5 years.