Ultrasound-guided fine needle aspiration thyroglobulin in the diagnosis of lymph node metastasis of differentiated papillary thyroid carcinoma and its influencing factors.

Background: Ultrasound-guided fine needle aspiration thyroglobulin (FNA-Tg) is recommended for the diagnosis of lymph node metastasis (LNM) in differentiated thyroid cancer (DTC), but its optimal cutoff value remains controversial, and the effect of potential influencing factors on FNA-Tg levels is unclear. Method: In this study, a retrospective analysis was conducted on 281 patients diagnosed with DTC, encompassing 333 lymph nodes. We analyze the optimal cutoff value and diagnostic efficacy of FNA-Tg, while also evaluating the potential influence of various factors on FNA-Tg. Results: For FNA-Tg, the optimal cutoff value was 16.1 ng/mL (area under the curve (AUC)= 0.942). The optimal cutoff value for FNA-Tg/sTg was 1.42 (AUC = 0.933). The AUC for FNA combined with FNA-Tg yielded the highest value compared to other combined diagnostic methods (AUC = 0.955). It has been found that serum thyroglobulin (sTg) is positively correlated with FNA-Tg (Rs = 0.318), while serum thyroglobulin antibodies (sTgAb) is negatively correlated with FNA-Tg (Rs = -0.147). In cases where the TNM stage indicated N1b, the presence of large or high volume lymph node metastasis(HVLNM), lymph node lateralization/suspicion (L/S) ratio ≤ 2, ultrasound findings indicating lymph node liquefaction, calcification, and increased blood flow, patients with coexisting Hashimoto's thyroiditis (HT), a tumor size ≥10 mm, and postoperative pathology confirming invasion of the thyroid capsule, higher levels of FNA-Tg were observed. However, the subgroup classification of DTC and the presence or absence of thyroid tissue did not demonstrate any significant impact on the levels of FNA-Tg. Conclusion: The findings of this study indicate that the utilization of FNA in conjunction with FNA-Tg is a crucial approach for detecting LNM in DTC. TNM stage indicated N1b, the presence of HVLNM, the presence of HT, lymph node L/S ratio, liquefaction, calcification, tumor diameter, sTg and sTgAb are factors that can impact FNA-Tg levels.In the context of clinical application, it is imperative to individualize the use of FNA-Tg.

Acupuncture treatment for Hashimoto's thyroiditis: An exploratory randomized controlled trial.

Background: Hashimoto's thyroiditis (HT) has a high incidence rate and unresolved clinical symptoms. Although Hand Yangming Meridian Penetrating Acupuncture has been used to treat thyroid diseases in China, there is no randomized controlled trial (RCT) on HT. Methods: This exploratory RCT aims to preliminarily evaluate the efficacy, safety, and feasibility of Hand Yangming Meridian Penetrating Acupuncture in the treatment of HT. Included subjects were randomly assigned to the acupuncture group and the waiting treatment group at a ratio of 1:1. Subjects in the acupuncture group received 16 weeks of acupuncture treatment, followed by a 16-week follow-up observation phase. Subjects in the waiting group received thyroxine supplementation for 16 weeks, followed by 16 weeks of compensation treatment. Serum thyroid peroxidase antibody (TPOab) and thyroglobulin antibody (TGab) levels were the main indicators, and Thyroid-Related Patient-Reported Outcome short form (ThyPRO-39), MOS Item Short Form Health Survey (SF-36), and Hospital Anxiety and Depression Scale (HADS) scores were also recorded. Results: In total, 58 subjects were included. After 16 weeks of treatment, there was no statistical difference in the changes in TPOab levels between the two groups, but the TGab level in the acupuncture group was significantly lower than in the waiting group (difference: -141.97 [95 % CI: -222.4 to -61.5], P = 0.011). Moreover, the total ThyPRO-39 and SF-36 scores were statistically different between the two groups (PThyPRO-39 < 0.001, PSF-36 = 0.005). There was no statistical difference in HADS between the two groups. Conclusions: Hand Yangming Meridian Penetrating Acupuncture may be safe and feasible for HT hypothyroidism to improve symptoms and reduce TGab levels. Trial registration number: This trial was registered at Acupuncture-Moxibustion Clinical Trial Registry: AMCTR-IOR-19000308 (ChiCTR1900026830, https://www.chictr.org.cn/searchprojEN.html).

Correlation analysis of serum thyroglobulin, thyroid-stimulating hormone levels, and thyroid-cancer risk in thyroid nodule surgery.

BACKGROUND: Thyroglobulin (Tg) is one of the markers of thyroid cancer, and its concentration may be elevated in patients with malignant thyroid tumors. Thyroid-stimulating hormone (TSH) is secreted by the pituitary gland, which has a significant impact on thyroid gland function. Excessively high or low TSH levels may be associated with an increased risk of thyroid cancer. Thus, in-depth studies on the association of serum Tg and TSH levels with thyroid cancer risk in patients with thyroid nodules are warranted. This can help determine whether Tg and TSH levels can predict the degree of malignancy of thyroid nodules, which can in turn guide doctors in making accurate diagnoses and treatment decisions. Furthermore, such studies can provide more accurate diagnostic methods for thyroid nodules and help patients become aware of the presence of thyroid cancer as early as possible, thereby improving the success rate of treatment and prognosis. AIM: To investigate the association of serum Tg and TSH levels with the risk of thyroid cancer in patients undergoing thyroid nodule surgery. METHODS: The clinical data and laboratory examination results of 130 patients who underwent thyroid nodule surgery were retrospectively analyzed. Furthermore, their preoperative serum Tg and TSH levels were recorded. Histopathological examination conducted during follow-up revealed the presence of thyroid cancer. Correlation analysis were used to analyze the association of Tg and TSH levels with the risk of thyroid cancer. RESULTS: Of the 130 patients, 60 were diagnosed with thyroid cancer. Statistical analysis revealed a significant positive correlation between serum Tg levels and the risk of thyroid cancer (P < 0.05). This suggests that high serum Tg levels are associated with an increased risk of thyroid cancer. However, no significant correlation was observed between serum TSH levels and the risk of thyroid cancer (P > 0.05). CONCLUSION: In patients who underwent thyroid nodule surgery, serum Tg levels exhibited a significant correlation with the risk of thyroid cancer but serum TSH levels did not. These findings suggest that serum Tg can serve as an important biomarker for assessing the risk of thyroid cancer in these patients.

Serum thyroglobulin testing after thyroid lobectomy in patients with 1-4 cm papillary thyroid carcinoma.

BACKGROUND: The role of measuring serum thyroglobulin (Tg) levels in patients who have undergone lobectomy has not been proven. The goal of this research is to see if serum Tg levels can predict the recurrence of papillary thyroid carcinoma (PTC) after lobectomy. METHODS: The 463 patients with 1-4 cm PTC who underwent lobectomy between January 2005 and December 2012, were included in this retrospective cohort study. Postoperative serum Tg levels and neck ultrasound were evaluated every 6-12 months after lobectomy during a median 7.8-year follow-up period. The receiver operating characteristic (ROC) curve and its area under the ROC curve (AUC) was used to assess the diagnostic performance of serum Tg levels. RESULTS: During the follow-up, the structural recurrent disease was confirmed in 30 patients (6.5%). The serum Tg levels measured by initial Tg, maximal Tg, and last Tg did not differ statistically between the recurrence and non-recurrence groups. According to our findings, serial patterns of serum maximal Tg variations in 30 patients with recurrence showed no obvious trend and no rising trend toward recurrence before detecting recurrence. The AUC was 54.5% (IQR 43.1%-65.9%) in the ROC curve analysis, indicating that it was not significantly different from the random classifier. CONCLUSION: Serum Tg levels did not differ significantly between the recurrence and non-recurrence groups, and there was no tendency for the recurrence group to increase Tg levels. In patients with PTC who underwent lobectomy, monitoring Tg levels regularly provides little benefit in predicting recurrence.

Nomogram model based on preoperative serum thyroglobulin and clinical characteristics of papillary thyroid carcinoma to predict cervical lymph node metastasis.

Objective: Preoperative evaluation of cervical lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) has been one of the serious clinical challenges. The present study aims at understanding the relationship between preoperative serum thyroglobulin (PS-Tg) and LNM and intends to establish nomogram models to predict cervical LNM. Methods: The data of 1,324 PTC patients were retrospectively collected and randomly divided into training cohort (n = 993) and validation cohort (n = 331). Univariate and multivariate logistic regression analyses were performed to determine the risk factors of central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM). The nomogram models were constructed and further evaluated by 1,000 resampling bootstrap analyses. The receiver operating characteristic curve (ROC curve), calibration curve, and decision curve analysis (DCA) of the nomogram models were carried out for the training, validation, and external validation cohorts. Results: Analyses revealed that age, male, maximum tumor size >1 cm, PS-Tg ≥31.650 ng/ml, extrathyroidal extension (ETE), and multifocality were the significant risk factors for CLNM in PTC patients. Similarly, such factors as maximum tumor size >1 cm, PS-Tg ≥30.175 ng/ml, CLNM positive, ETE, and multifocality were significantly related to LLNM. Two nomogram models predicting the risk of CLNM and LLNM were established with a favorable C-index of 0.801 and 0.911, respectively. Both nomogram models demonstrated good calibration and clinical benefits in the training and validation cohorts. Conclusion: PS-Tg level is an independent risk factor for both CLNM and LLNM. The nomogram based on PS-Tg and other clinical characteristics are effective for predicting cervical LNM in PTC patients.

Thyroglobulin Levels in Patients who have Undergone Hemithyroidectomy for Differentiated Thyroid Cancer. An Assessment of Levels and Trends at a Tertiary Referral Centre.

Subramanian Kannan Serum thyroglobulin (Tg) and thyroglobulin antibody (TgAb) levels are used to monitor patients with differentiated thyroid cancer (DTC) after total thyroidectomy with or without radioiodine (RAI) ablation. However, they are also measured in patients who are treated with thyroid lobectomy (TL)/hemithyroidectomy (HT). Data on the levels of Tg and its trend in those undergoing TL/HT is sparse in India. We reviewed retrospective data of DTC patients who underwent TL/HT and were followed-up with postoperative Tg levels between 2015 and 2020. Out of 247 patients, 17 had undergone either TL or HT, which included papillary thyroid cancer ( n = 12), follicular thyroid cancer ( n = 4), and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in 1 patient. All patients with DTC had tumor size < 4 cm (T1/2, clinical N0, Mx). The median follow-up was 15 months (range, 1-125) and the median Tg level was 7.5 ng/mL (interquartile range [IQR]; 3.6, 7.5) and ranged from 0.9 to 36.7 ng/mL. The median thyroid-stimulating hormone (TSH) level was 2.03 IU/L (IQR; 1.21, 3.59) and it ranged from 0.05 to 8.54 IU/L. As of last follow-up, none of them underwent completion thyroidectomy; however, eight patients had a decline in Tg ranging from 8 to 64%, four patients had increase in Tg ranging from 14 to 145%, three patients had stable Tg, and one of them had an increase in TgAb titers. As per American Thyroid Association (ATA) response-to-treatment category, six patients had indeterminate response, five patients had biochemical incomplete response, four patients had excellent response, and two did not have follow-up Tg and TgAb levels. While absolute values of Tg were well below 30 ng/mL in almost all patients with HT/TL, the Tg trends were difficult to predict, and only 23% of patients were able to satisfy the criteria for "excellent response" on follow-up. We suggest keeping this factor in mind in follow-up and while counselling for HT in patients with low-risk DTC.

Low correlation between serum thyroglobulin and 131I radioiodine whole body scintigraphy: implication for postoperative disease surveillance in differentiated thyroid cancer.

PURPOSE: To evaluate postoperative serum thyroglobulin (Tg) as a reliable tumor marker in low-risk differentiated thyroid cancer (DTC). METHODS: Two hundred and three patients met the selection criteria of >18 years old; who had undergone total or near total thyroidectomy; had a postoperative Tg, and had undergone 131I pre ablation whole body scan (PA-WBS). The primary endpoint was the correlation between Tg level and functional remnant thyroid tissues. Outcomes were categorized as concordant and discordant. Concordant results were positive Tg (>1 ng/ml) with positive PA-WBS or negative Tg (<1 ng/ml) with negative PA-WBS. Discordant results were negative Tg with a positive PA-WBS or positive Tg with a negative PA-WBS. To increase the sensitivity of Tg detection, we evaluated Tg in patients with high thyroid stimulating hormone (TSH) with serum level >30 mU/l on thyroxine withdrawal protocol. RESULTS: One hundred ten patients (54.1%) had discordant results (p < 0.05) with positive PA-WBS and Tg <1 ng/ml, while 93 patients (45.9%) had concordant results. For concordant results, 88 patients had positive PA-WBS and Tg >1 ng/ml, and 5 patients had negative PA-WBS and Tg <1 ng/ml. There was no patient with Tg >1 ng/ml and negative PA-WBS. There were 74 patients with high TSH (>30 mU/l) on abstention (thyroxine withdrawal protocol). Twenty-four (32.5%) had discordant results (p < 0.001) and 50 (67.5%) had concordant results. CONCLUSION: There is low correlation between postoperative Tg and PA-WBS. The sole use of Tg as a serum biomarker for postoperative disease status may not be reliable.

Serum thyroglobulin evaluation on LC-MS/MS and immunoassay in TgAb-positive patients with papillary thyroid carcinoma.

Objective: This study aimed to elucidate disproportionately low serum thyroglobulin (Tg) values in Tg antibody (TgAb)-positive patients with structural recurrence of papillary thyroid carcinoma (PTC) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Design: A retrospective study was performed on 176 patients in whom Tg and TgAb levels were measured between 2016 and 2021. Several comprehensive analyses of Tg-LC-MS/MS with an electrochemiluminescence immunoassay for Tg (Tg-ECLIA) were conducted using serum samples. Methods: TgAb-positive patients who underwent total thyroidectomy with multiple lung metastases due to PTC were evaluated using Tg-LC-MS/MS and Tg-ECLIA. Tg expression in lymph node metastases and metastatic lesions was evaluated by immunohistochemistry and Tg levels of aspiration washouts were also evaluated. Two in vitro assays were performed to elucidate TgAb interference. Results: Tg concentrations of negative TgAb in both assays were similar (R2 = 0.99; n = 52). Patients with structural recurrence showed higher Tg values with Tg-LC-MS/MS than with Tg-ECLIA. The undetectable proportion was significantly lower with Tg-LC-MS/MS (31.6%, 6/19) than with Tg-ECLIA (68.4%, 13/19; P = 0.023). The spike-recovery rate and Tg concentrations determined by the serum mixture text (n = 29) were significantly reduced to 75.0% (118.3-88.7%) and 81.3% (107.0-87.0%), respectively, with TgAb using Tg-ECLIA (both P > 0.001) confirming assay interference but not using Tg-LC-MS/MS (91.8-92.3%, P = 0.77 and 98.4-100.8%, P = 0.18, respectively). Conclusions: TgAb had no effect on the Tg-LC-MS/MS assay but yielded 19-25% lower values in Tg-ECLIA. Tg-LC-MS/MS is preferable for monitoring serum Tg levels in TgAb-positive patients, although those with structural recurrence often had disproportionally low Tg values.

The Utility of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Differentiated Thyroid Cancer Patients with Biochemical Recurrence and Negative Whole-Body Radioiodine Scintigraphy and Evaluation of the Possible Role of a Limited Regional Scan.

PURPOSE OF THE STUDY: 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is used in the management of recurrent differentiated thyroid cancer (DTC) patients presented with rising thyroglobulin (Tg) or anti-Tg antibody (Atg) levels and negative whole-body I-131 scan (WBS). We aimed to evaluate the utility of regional or limited PET/CT in a large population preset with variable Tg/(ATg) levels. MATERIALS AND METHODS: In a retrospective study, we analyzed 137 PET/CT done on DTC patients presented with raised Tg/Atg and negative WBS. Retrospective evaluation of other available clinical information was done. RESULTS: One hundred and thirty-seven patients aged 8-72 years (41 ± 17.7 years) were included in the study. Eighty-nine (64.9%) patients had positive findings on 18F-FDG PET-CT. It included thyroid bed recurrence, cervical, mediastinal lymphadenopathy, lung, and bone lesions. In addition, 36 patients had metabolically inactive lung nodules detected on CT. Serum Tg and female sex were the only predictors for a positive PET scan. In most (97.1%) of the patients, the disease was limited to the neck and thoracic region. CONCLUSIONS: PET/CT is an excellent imaging modality for evaluating DTC patients presented with biochemical recurrence. It not only finds the disease in more than 80% of the patients but also detects distant metastatic disease, which precludes regional therapies. Lesions were noted mostly in the neck and thoracic region with very few distant skeletal metastases (4/137 patients). In most of the patients, routine vertex to mid-thigh imaging could be avoided.

Thyroglobulin Measurement in Needle Aspiration for Detection of Recurrences and Neck Metastases in Patients with Differentiated Thyroid Carcinoma: Significance of Anti-Tg Antibodies.

The worldwide incidence of differentiated thyroid cancer (DTC) has increased in recent decades, likely due to frequent use of cervical ultrasonography (US) and US-guided fine needle aspiration biopsy (FNA)., US is performed during follow-up after thyroidectomy, and US-guided FNA with cytology is used if suspicious cervical lymph nodes (LN) or thyroid bed masses are detected. Knowing that serum anti-Tg antibodies (sTgAb) affect the use of serum Tg (sTg) as a tumor marker, the aim of our study was to assess the usefulness of Tg determination in needle aspirates (FNA-Tg) in presence of sTgAb. This retrospective study included 149 patients with DTC and 159 aspirations of suspicious LN and thyroid bed masses. As expected, there was a negative correlation between sTg and sTgAb levels (p<0.05), while FNA-Tg levels had a positive correlation with FNA-TgAb levels (p<0.05). Furthermore, we found a positive correlation between sTg and FNA-Tg levels (p<0.05), but not between sTgAb and FNA-TgAb or sTgAb and FNA-Tg. In conclusion, these results show that FNA-Tg values were not affected by sTgAb and that FNA-Tg measurement were highly effective in detecting cervical DTC metastases. However, combined use with cytology is suggested for neck evaluation because cytology could reveal metastases from other tumor sites.

Surveillance for Differentiated Thyroid Cancer Recurrence.

Serum thyroglobulin monitoring along with anatomic and functional imaging play key roles in the surveillance of patients with differentiated thyroid cancer after initial treatment. Among patients with a disease stage justifying thyroid remnant ablation or with suspected metastatic disease, radioiodine whole-body scans are essential in the months after surgery. For patients with low to moderate-risk cancers, ultrasonography of the neck (with measurement of serum thyroglobulin on thyroid hormone replacement) are the best initial diagnostic modalities, and are often the only tests required. In individuals suspected of having distant metastases, CT, MRI, and 18F-FDG PET can make important contributions in localizing residual disease and monitoring its progression and responses to therapy, provided they are used in the appropriate setting.

An enhanced treatment effect can be expected from a higher serum thyroglobulin level after radioactive iodine therapy.

OBJECTIVE: The aim of this study was to investigate if increased serum thyroglobulin (Tg) levels after radioactive iodine (RAI) showed more therapeutic effects in patients with differentiated thyroid cancer (DTC). METHODS: Data of 65 patients with DTC who underwent RAI from June 2014 to September 2016 were reviewed. Serum thyroglobulin was measured immediately before (Tg1) and 48 h (Tg2) after RAI under TSH stimulation. Differences and ratios between serum Tg measurements (DeltaTg = Tg2 - Tg1 and RatioTg = Tg2/Tg1) were calculated. The treatment response of distant metastasis was assessed using the RECIST criteria. RESULTS: There was no difference in the median values of Tg1 and Tg2 (2.6 [range, 0.7-1957.5] ng/mL vs. 7.4 [range, 0.7-5276.0] ng/mL, p = 0.240) in all patients (73 scans, 65 patients). In subgroup analysis, Tg levels increased slightly in patients with distant metastasis (8 scans, 7 patients) (Tg1 vs. Tg2; 48.9 [range, 2.4-1957.5] ng/mL vs. 63.2 [range, 4.4-5276.0] ng/mL, p = 0.408). Among patients with distant metastasis, one patient with a partial response to treatment had a more than 4000fold increase in Tg levels and one patient with stable disease showed a 20fold increase in Tg levels. In contrast, five patients with disease progression showed only two to eightfold increase or more than 100fold decrease in Tg levels at 48 h after RAI. However, there was a significant increase in serum Tg levels in patients without distant metastasis (65 scans, 58 patients) after RAI (Tg1 vs. Tg2; 2.0 [range, 0.7-141.9] ng/mL vs. 6.8 [range, 0.7-577.7] ng/mL, p = 0.026). CONCLUSIONS: A higher elevation of Tg levels after RAI may be associated with a better treatment outcome in DTC patients with distant metastasis. An increase in Tg levels after RAI may reflect the destruction of cancer and thyroid cells.

Papillary Thyroid Carcinoma Recurrence: Low Yield of Neck Ultrasound With an Undetectable Serum Thyroglobulin Level.

OBJECTIVES: To assess the yield of neck ultrasound (US) when serum thyroglobulin (Tg) is undetectable (<0.1 ng/mL) compared to elevated serum Tg in patients with differentiated papillary thyroid carcinoma (PTC) treated with thyroidectomy and radioactive iodine 131 (RAI) ablation. METHODS: A retrospective chart review was conducted from 2010 through 2015 at an academic institution evaluating US results in patients with serum Tg levels obtained within 6 months of a neck US examination after thyroidectomy and RAI. The reference standard for recurrence was pathologic results from US-guided fine-needle aspiration (FNA) or follow-up for at least 1 year. RESULTS: Among 76 patients with undetectable serum Tg levels, there were 19 examinations in 18 patients in which US raised the possibility of recurrence. None of these 18 patients had recurrence by FNA (n = 8) or clinical follow-up of at least 1 year (n = 10). Among 65 patients with elevated serum Tg levels, there were 24 examinations in 22 patients in which US raised the possibility of recurrence. Twelve patients underwent FNA, with 9 patients (34.6%) showing PTC; 7 patients had follow-up neck US examinations showing stability of findings; and 3 patients were lost to follow up. The yield of neck US was significantly lower when serum Tg was undetectable compared to when levels were elevated (P = .001). CONCLUSIONS: Neck US did not identify recurrent PTC when the serum Tg level was undetectable in patients who underwent total thyroidectomy and RAI therapy. Eliminating neck US when serum TG levels are undetectable could decrease unnecessary imaging examinations without negatively affecting the ability to detect recurrent disease.

Stimulated Serum Thyroglobulin Levels versus Unstimulated Serum Thyroglobulin in the Follow-up of Patients with Papillary Thyroid Carcinoma.

Serum thyroglobulin (Tg) and thyroid whole-body radioiodine scintigraphy (TWBS) are used in the follow-up of patients with papillary thyroid carcinoma (PTC) after total thyroidectomy. Symptoms of hypothyroidism are frequent as patients discontinue levothyroxine 1 month before visit, favoring the use of unstimulated serum Tg (uSTg) only. This study was done to determine the reliability of stimulated serum Tg levels (sSTg) over uSTg. A total of 650 patients with PTC came for follow-up between June 2011 and 2016. In those who had levels of uSTg and sSTg months measured within an interval of median of 3 months (range from 1 to 8 months), risk stratification was done as per the American Thyroid Association guidelines 2015. Intervention was based on a cutoff value of sSTg >10 ng/ml in our institution and the same was used for data analysis. Out of 650 patients, 106 had paired Tg values. Low-, intermediate-, and high-risk groups comprised 40, 31, and 35 patients, respectively. The sSTg >10 ng/ml with uSTg <10 ng/ml in the same patient was noted in 22.5% (9/40) of the low-risk, 41.9% (13/31) of the intermediate-risk, and 14.2% (5/35) of the high-risk groups. The levels were corroborated with tumor burden as determined by additional clinical, ultrasonography neck, and TWBS findings. Our study highlights the superiority of sSTg over uSTg in the follow-up of PTC patients. Follow-up with uSTg alone may result in underestimating the tumor burden.

Prognostic implication of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography in patients with recurrent papillary thyroid cancer.

BACKGROUND: Fluorine-18 fluorodeoxyglucose positron emission tomography/CT (18 F-FDG PET/CT) has been widely accepted as an effective method for detecting recurrent papillary thyroid cancer (PTC) in patients with increased serum thyroglobulin (Tg) or Tg antibody (TgAb) levels and negative whole-body scintigraphy (WBS) results. The role of WBS as a diagnostic tool in detecting recurrence has relatively decreased recently. However, only a few studies have examined the usefulness of 18 F-FDG PET/CT for evaluating patients with recurrent PTC, regardless of the WBS results. The purpose of this analysis was to evaluate the diagnostic value and prognostic role of 18 F-FDG PET/CT for patients with recurrent PTC, irrespective of their WBS results. METHODS: Sixty-six patients with locoregional recurrent PTC who underwent 18 F-FDG PET/CT and neck CT within 6 months before surgical treatment were included in this retrospective analysis. Imaging findings were compared with postoperative histopathologic results. The diagnostic values of 18 F-FDG PET/CT and neck CT were compared according to the serum Tg and TgAb levels and cervical levels. Each patient's status at the last follow-up was also reviewed, and survival probabilities were estimated using the Kaplan-Meier plot. RESULTS: The sensitivity, specificity, and diagnostic accuracy of 18 F-FDG PET/CT for the entire patient group were 38.5%, 90.2%, and 58.3%, respectively. The corresponding neck CT values were 55.0%, 85.7%, and 66.7%, respectively. According to the serum Tg and TgAb levels, except for the specificity, most diagnostic values of 18 F-FDG PET/CT were worse than those of the neck CTs, with or without statistical significance. For the high maximum standardized uptake value (SUVmax) group (SUVmax >10) and the low SUVmax group, the median locoregional disease-free survival times were 33.3 months and 81.8 months, respectively (P < .001). CONCLUSION: The diagnostic value of 18 F-FDG PET/CT for localizing recurrent lesions was worse than that of the neck CT, irrespective of the WBS results. However, patients with a higher SUVmax showed a significantly worse prognosis than did those with a lower SUVmax. Therefore, we suggest that, in patients with recurrent PTC, 18 F-FDG PET/CT should be considered for prognostication rather than diagnosis.

Optimal threshold of stimulated serum thyroglobulin level for 18F-FDG PET/CT imaging in patients with thyroid cancer.

This study was to explore the optimal threshold of thyroid-stimulating hormone (TSH)-stimulated serum thyroglobulin (s-Tg) for patients who were to receive 18F-fluorodeoxyglucose (18F-FDG) PET/CT scan owing to clinical suspicion of differentiated thyroid cancer (DTC) recurrence but negative post-therapeutic 131I whole-body scan (131I-WBS). A total of 60 qualified patients underwent PET/CT scanning from October 2010 to July 2014. The receiver operating characteristic (ROC) curve analyses showed that s-Tg levels over 49 µg/L led to the highest diagnostic accuracy of PET/CT to detect recurrence, with a sensitivity of 89.5% and a specificity of 90.9%. Besides, bivariate correlation analysis showed positive correlation between s-Tg levels and the maximum standardized uptake values (SUVmax) of 18F-FDG in patients with positive PET/CT scanning, suggesting a significant influence of TSH both on Tg release and uptake of 18F-FDG. So, positive PET/CT imaging is expected when patients have negative 131I-WBS but s-Tg levels over 49 µg/L.

Reliability of thyroglobulin in serum compared with urinary iodine when assessing individual and population iodine nutrition status.

The occurrence of thyroid disorders relies on I nutrition and monitoring of all populations is recommended. Measuring I in urine is standard but thyroglobulin in serum is an alternative. This led us to assess the reliability of studies using serum thyroglobulin compared with urinary I to assess the I nutrition level and calculate the number of participants needed in a study with repeated data sampling in the same individuals for 1 year. Diet, supplement use and life style factors were assessed by questionnaires. We measured thyroglobulin and thyroglobulin antibodies in serum and I in urine. Participants were thirty-three Caucasians and sixty-four Inuit living in Greenland aged 30-49 years. Serum thyroglobulin decreased with rising I excretion (Kendall's τ -0·29, P=0·005) and did not differ with ethnicity. Variation in individuals was lower for serum-thyroglobulin than for urinary I (mean individual CV: 15·1 v. 46·1 %; P<0·01). It required 245 urine samples to be 95 % certain of having a urinary I excretion within 10 % of the true mean of the population. For serum-thyroglobulin the same precision required 206 samples. In an individual ten times more samples were needed to depict I deficiency when using urinary I excretion compared with serum-thyroglobulin. In conclusion, more participants are need to portray I deficiency in a population when using urinary I compared with serum-thyroglobulin, and about ten times more samples are needed in an individual. Adding serum-thyroglobulin to urinary I may inform surveys of I nutrition by allowing subgroup analysis with similar reliability.

Variability of Serum Thyroglobulin Levels in Post- Thyroidectomy Patients with Well-Differentiated Thyroid Cancer: the ATA Guidelines.

OBJECTIVE: Evaluate the variability of stimulated serum thyroglobulin (Tg) levels in post-thyroidectomy patients with well-differentiated thyroid cancer (WDTC) and determine the frequency of undetectable Tg in patients with evidence of functional thyroid tissue after a 131-I whole-body scan (WBS). METHODS: A retrospective record review of patients with WDTC referred to our clinic from 1990 to 2010. Demographic data, histology, staging, imaging studies, stimulated Tg values, and the presence if applicable of Tg antibodies (TgAb) were documented. The images of whole-body radioiodine scans were reviewed to assess the extent of functional thyroid tissue. RESULTS: A total of 142 cases were evaluated with 417 studies. There were 112 women and 30 men; the median age was 47 years. The tumor histologies included 97 papillary (4 had the Hurthle cell variant), 33 papillary-follicular tumor, and 12 follicular tumors; 7 were multifocal. ATA classification was used; groups were divided into low (55%) and intermediate-high risk (45%). The final analysis comprised 84 patients, having among them 170 studies that included Tg values in their records. The cut-off value for Tg was 2.0 ng/ml, and for TgAb, it was 20 IU/ml or more. Residual functional tissue was present in 105 (62%) cases. Discordant Tg results were found in 55% of the low-risk patients; of those, only 3 had TgAb. In the intermediate- and high-risk group, 47% had discordant results; 2 cases had TgAb. CONCLUSION: The variability of the Tg levels and the high frequency of discordant results (positive WBSs with undectable Tg levels) bring into question the standard recommendation of conservative management for low-risk patients. Follow-ups should include a Tg assay and imaging studies.

Influence of thyroid gland status on the thyroglobulin cutoff level in washout fluid from cervical lymph nodes of patients with recurrent/metastatic papillary thyroid cancer.

BACKGROUND: The influence of serum thyroglobulin (Tg) and thyroidectomy status on Tg in fine-needle aspiration cytology (FNAC) washout fluid is unclear. METHODS: A total of 282 lymph nodes were prospectively subjected to FNAC, fine-needle aspiration (FNA)-Tg measurement, and frozen and permanent biopsies. We evaluated the diagnostic performance of several predetermined FNA-Tg cutoff values for recurrence/metastasis in lymph nodes according to thyroidectomy status. RESULTS: The diagnostic performance of FNA-Tg varied according to thyroidectomy status. The optimized cutoff value of FNA-Tg was 2.2 ng/mL. However, among FNAC-negative lymph nodes, the FNA-Tg cutoff value of 0.9 ng/mL showed better diagnostic performance in patients with a thyroid gland. An FNA-Tg/serum-Tg cutoff ratio of 1 showed the best diagnostic performance in patients without a thyroid gland. CONCLUSION: Applying the optimal cutoff values of FNA-Tg according to thyroid gland status and serum Tg level facilitates the diagnostic evaluation of neck lymph node recurrences/metastases in patients with papillary thyroid carcinoma (PTC). © 2015 Wiley Periodicals, Inc. Head Neck 38: E1705-E1712, 2016.

Value of post-therapeutic ¹³¹I scintigraphy in stimulated serum thyroglobulin-negative patients with metastatic differentiated thyroid carcinoma.

Metastatic differentiated thyroid carcinoma (DTC) with positive (131)I scintigraphy, but negative stimulated Tg (sTg) is relatively rare in clinical practice. The clinical characteristics of these patients were analyzed in the current study. A total of 3367 consecutive histologically proven DTC patients were analyzed retrospectively from January 2007 to June 2013. Tg negativity was defined as a sTg level of <2 ng/mL without positive anti-Tg antibody (TgAb level of <100 IU/mL) under thyroid-stimulating hormone stimulation (TSH level of ≥30 mIU/L). Analyses were performed using the Statistical Package for the Social Sciences, version 20.0 (SPSS, Chicago, IL, USA). Seventy-one patients (median age 45 years, range 17-68 years) were post-therapeutic (131)I-SPECT/CT positive and sTg negative (PTP-TN) constituting 2.1 % of all patients. Of these 71 patients, 2 (2.8 %) had bone metastasis, 11 (15.5 %) had lung metastasis, and 59 (83.1 %) had lymph node metastasis. Fifty-six patients had cervical lymph node metastasis (cLNM), and US was positive in 15 patients (26.8 %), while negative in 41 patients (73.2 %). When compared to patients with concordant positive results for sTg and (131)I scintigraphy, US showed a relatively lower positive rate in the detection of cLNM in PTP-TN patients (28.8 vs. 53.8 %; χ (2) = 6.70; P = 0.01). In conclusion, even with sTg <2 ng/mL, there is a low risk of metastatic DTC. US had limitations in PTP-TN patients, while post-therapy (131)I-SPECT/CT demonstrated an advantage in the detection of functioning metastasis despite low sTg levels in patients with metastatic DTC.