The efficacy and assessment value of the level of thyroglobulin wash-out after fine-needle aspiration cytodiagnosis in the evaluation of lymph node metastasis in papillary thyroid carcinoma.

OBJECTIVE: The purpose of this study was to evaluate the efficacy and clinical value of US, FNAC,FNA-Tg and FNAC + FNA-Tg, as well as the cutoff values of FNA-Tg to evaluate LN metastasis. METHODS: We analyzed the diagnostic value of different US signs, the efficiency of US, FNAC, FNA-Tg and FNAC + FNA-Tg among the LN- and LN + groups, and the cutoff value of FNA-Tg to evaluate LN metastasis. We punctured LNs multiple times and measured the levels of FNA-Tg. Furthermore, the LNs were marked with immunohistochemical Tg and LCA to distinguish the presence of Tg in the para-cancerous tissue of the LNs. RESULTS: The s-Tg and FNA-Tg of the LN + group were higher than those of the LN- group (P = 0.018, ≤ 0.001). The LN + group had more abnormal US signs than the LN- group. The cutoff value of FNA-Tg was 3.2 ng/mL. US had a high sensitivity (92.42), but the specificity was not satisfactory (55.1). FNA-Tg had a higher sensitivity (92.42 vs. 89.39), specificity (100 vs. 93.88), and accuracy (92.42 vs. 83.27) than FNAC. However, the sensitivity of FNAC + FNA-Tg increased further, while the specificity and accuracy decreased slightly. The presence of Tg in the normal lymphocytes adjacent to the cancer was confirmed. CONCLUSION: Ultrasonography provides a noninvasive, dynamic, multidimensional assessment of LNs. With a cutoff value of 3.2 ng/mL, FNA-Tg has higher accuracy and a lower false-negative rate than various single diagnoses. However, FNAC combined with FNA-Tg does not cause additional pain to patients and offers a higher diagnostic efficacy and clinical value.

Improvement in neck ultrasound report quality following the implementation of European Thyroid Association guidelines for postoperative cervical ultrasound for thyroid cancer follow-up, a prospective population study.

Objective: The aim of this study was to prospectively evaluate the quality of postoperative neck ultrasound (POU) for thyroid cancer patients after implementing European Thyroid Association (ETA) guideline-based POU assessment. Methods: Our analysis involved 672 differentiated thyroid cancer patients. POU report quality was compared between the implementation radiology group (IRG), which implemented ETA guideline-based assessment in 2018, and all non-implementation radiology groups (NIRG). Differences in POU quality were evaluated before and after the implementation of guideline-based assessment. Additionally, we evaluated the ability of serum thyroglobulin (Tg) level <0.2 ng/mL or between 0.21 and 0.99 ng/mL and normal POU lesion status at 1-year follow-up to predict the absence of persistent disease or relapse at 3-year follow-up. Results: IRG had significantly higher mean utility scores for POU reports of abnormal thyroid bed nodules compared to NIRG (P < 0.001). IRG's POU reports for suspicious nodules and lymph nodes were considered sufficient in 94% and 85% of cases, respectively, compared to 45% and 68% for NIRG. For patients with normal US lesion status and Tg <0.2 ng/mL or Tg 0.21-0.99 ng/mL at 1-year follow-up, the negative predictive values were 96% for both. Conclusions: Implementation of 2013 ETA POU-reporting guidelines allowed for the provision of high-quality POU reports, which may lead to increased accuracy in assessing the response to treatment and in estimating the risk of recurrence of thyroid cancer and likely reduce unnecessary repeat POU or FNA.

Predictive Value of FNA-Tg and TgAb in Cervical Lymph Node Metastasis of Papillary Thyroid Carcinoma.

Objectives: To analyze whether thyroglobulin (Tg) and anti-Tg antibody (TgAb) detection in fine-needle aspiration (FNA) of cervical lymph node (LN; LN-FNA-Tg and LN-FNA-TgAb) can predict LN metastasis and obtain the best cutoff value. Methods: The patients admitted to our hospital from January 2020 to March 2021 were prospectively enrolled. The LNs were sampled by FNA. All patients underwent thyroid surgery and neck dissection. LN-FNA-Tg, LN-FNA-TgAb, and blood Tg and TgAb were measured. The receiver operating characteristic curve analysis was used to determine the best cutoff points for positive LN. Results: There were 29 participants in the LN metastasis group and 42 in the nonmetastasis group. Compared with the nonmetastasis group, the participants in the metastasis group had higher LN-FNA-Tg (median: 1897 vs 7.74 ng/mL, P < .001), higher LN-FNA-TgAb (median: 15.65 vs 8.21 IU/mL, P < .001), and higher serum Tg (median: 25.4 vs 18.81 ng/mL); there were no differences in serum TgAb (median: 26.6 vs 28.6 IU/mL, P = .477). The best accuracy (87.5%) was observed with LN-FNA-Tg of >227.1 ng/mL, resulting in an area under the curve of 0.927, 84.5% sensitivity, and 89.5% specificity. LN-FNA-TgAb >10.85 IS/mL had an accuracy of 79.6%, sensitivity 64.8%, and specificity 89.5%. Serum Tg and TgAb had the lowest accuracy, with 64.2% and 57.4%, respectively, sensitivity of 53.5% and 67.6%, and specificity of 71.4% and 50.5%. Similar results were observed in first-operation participants and postoperative participants. Conclusions: LN-FNA-Tg has high accuracy, sensitivity, and specificity for detecting cervical LN in patients with papillary thyroid cancer.

Impact of Thyroid Tissue Status on the Cut-Off Value of Lymph Node Fine-Needle Aspiration Thyroglobulin Measurements in Papillary Thyroid Cancer.

Objective: To study the optimal cut-off value of thyroglobulin measurement in a fine-needle aspiration (FNA-Tg) in diagnosing malignant lymph nodes and benign lymph nodes (LNs) according to the thyroid tissue status. Methods: A total of 517 LNs were aspirated: 401 preoperative LNs, 42 LNs after subtotal thyroidectomy and 74 suspected LNs after total thyroidectomy. The cut-off value of FNA-Tg was obtained from receiver operating characteristic (ROC) analysis. The cut-off value with the best diagnostic performance was then obtained by comparing different cut-off values from other studies. Results: LN FNA-Tg levels differed between preoperative and total thyroid disease (p < 0.001) and subtotal thyroidectomy and total thyroidectomy (p = 0.03), but not between preoperative and subtotal thyroidectomy (p = 1.00). Accordingly, those 443 LNs with preoperative and subtotal thyroidectomy were compared to those 74 without thyroid tissue. The optimal cut-off value in thyroid tissue group was 19.4 ng/ml and the area under the ROC curve (AUC) was 0.95 (95% CI 0.92-0.97). The optimal cut-off value in thyroid tissue absence group was 1.2 ng/ml and the AUC was 0.93 (0.85-0.98). After the analysis and comparison of multiple cut-off values, the optimal diagnostic performance was still found to be 19.4 ng/ml and 1.2 ng/ml. Conclusion: The influential factors of FNA-Tg are still controversial, and the optimal cut-off value of FNA-Tg can be determined based on the presence or absence of thyroid tissue. FNA-Tg can be used as an important auxiliary method for diagnosing cervical metastatic LNs of thyroid cancer.

Active Surveillance of Small Metastatic Lymph Nodes as an Alternative to Surgery in Selected Patients with Low-Risk Papillary Thyroid Cancer: A Retrospective Cohort Study.

Background: It has been suggested that small metastatic lymph nodes (LNs) detected after initial surgery in patients with differentiated thyroid cancer (DTC) can be managed with active surveillance (AS). However, there is still concern regarding the clinical outcomes of these patients. The main aims of our study were as follows: (1) to assess the frequency of growth and the need of additional treatment in a group of patients with LN recurrences selected for AS, and (2) to determine predictive factors of LN progression. Methods: We retrospectively reviewed 856 clinical records from our DTC patient's database (May 2010 to January 2022). Eighty patients had suspicious cervical LNs on consecutive ultrasound (US) after initial surgery, but we included 50 patients with cytological confirmation of metastatic disease and at least 12 months follow-up. Exclusion criteria were as follows: any LN ≥2 cm or multiple LNs ≥1.5 cm in size, proximity to vital structures, PET-positive disease (standard uptake value ≥5), aggressive histology, and distant metastasis. Patients were followed with thyroglobulin (Tg) and thyroglobulin antibodies measurements on suppressive therapy and neck US every 6-12 months. LN growth was defined as an increase of ≥3 mm in any of its diameters. Results: A total of 50 patients had a median age of 41 years (range, 18-75). Most patients were women (80%) and had classical papillary thyroid cancer (86%). The mean size of the LNs was 10.1 ± 4.4 mm. After a median follow-up of 29 months (range, 12-144), 12 patients (24%) had an increase in size of the metastatic LN, 7 (58%) of whom were surgically removed. None of these seven patients had a structural incomplete response at the end of follow-up. The only variable that predicted an increase in LN size was a rise in Tg levels ≥0.5 ng/mL (p = 0.016). Based on a multivariate analysis, patients with increase in Tg levels ≥0.5 ng/mL had a significantly higher chance of developing LN growth (odds ratio [OR] 16.2 [confidence interval, CI 1.5-120.2], p = 0.020). The median progression-free survival rate was 6.6 years [CI 5.6-9.5]. Conclusion: AS of small LNs could be a feasible alternative to immediate surgery in properly selected patients.

Análisis de tiroglobulina preablativa y cáncer diferenciado de tiroides preoperatorio / Analysis of pre-ablative and preoperative thyroglobulin in differentiated thyroid cancer

BACKGROUND: The measurement of plasma thyroglobulin (Tg) is widely used in the monitoring of differentiated thyroid cancer (CDT). In recent years, its value as a prognostic marker prior to ablation with radioiodine has increased, demonstrating its high negative predictive value. Recent studies indicate that a wide variety of factors could potentially influence pre-ablative Tg values, including residual tumor burden and stimulation modality. Aim: To relate the value of pre-ablative Tg with the amount of preoperative disease burden, lymph node metastases, treatment, and presence of residual disease. MATERIAL AND METHODS: Retrospective observational study of 70 patients with CDT treated between 2012 and 2018. The amount of disease burden was defined as the sum of largest diameter of individual tumors in each patient, and as the individually largest tumor per patient and number of metastatic lymph nodes. RESULTS: A smaller tumor size and absence of remnant tissue was associated with lower Tg values, although the association was not always significant. Furthermore, no significant difference was found between Tg levels measured within or more than 14 days after the surgical procedure. Thus, an early measurement of pTg after surgery would allow an initial therapeutic decision making. Conclusions: A statistical association between pre-ablative Tg levels and the amount of preoperative tumor tissue burden was found in some subgroups of patients.

Retrospective Analysis of the Development of Human Thyroglobulin during Pregnancy in Patients with Treated Non-Recurrent Differentiated Thyroid Cancer.

Aim: Therapy success in patients with differentiated thyroid cancer (DTC) after thyroidectomy and radioiodine therapy (RIT) is proven by permanent decrease in human thyroglobulin (hTg) to <1 ng/mL. In this retrospective analysis hTg development before, during and after pregnancy were analyzed. Material and methods: A descriptive analysis of hTg courses in 47 women with 57 pregnancies under levothyroxine substitution was performed after treatment of DTC without evidence of residual or recurrent disease. We compared hTg levels before, during and after pregnancies. A median of four measurements were performed during pregnancy. Results: In five out of the 47 patients at least one hTg increase to ≥1.0 ng/mL occurred during pregnancy (P1: 1.1; P2: 1.75; P3: 1.0; P4: 1.1; P5: 1.07 ng/mL). In another three cases an increase to ≥0.5 ng/mL occurred. After delivery, all patients returned to undetectable hTg levels. Human Tg maxima during pregnancy were significantly elevated according to Friedman´s Chi2 and p Holm−Bonferroni. Conclusion: In women with ablative thyroid therapy after DTC, a temporary elevation in hTg levels during pregnancy may occur. The reason therefore remains unclear and requires further investigation.

Screening of 23 candidate genes by next-generation sequencing of patients with permanent congenital hypothyroidism: novel variants in TG, TSHR, DUOX2, FOXE1, and SLC26A7.

PURPOSE: To date, many genes have been associated with congenital hypothyroidism (CH). Our aim was to identify the mutational spectrum of 23 causative genes in Turkish patients with permanent CH, including thyroid dysgenesis (TD) and dyshormonogenesis (TDH) cases. METHODS: A total of 134 patients with permanent CH (130 primary, 4 central) were included. To identify the genetic etiology, we screened 23 candidate genes associated with CH by next-generation sequencing. For confirmation and to detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. RESULTS: Possible pathogenic variants were found in 5.2% of patients with TD and in 64.0% of the patients with normal-sized thyroid or goiter. In all patients, variants were most frequently found in TSHR, followed by TPO and TG. The same homozygous TSHB variant (c.162 + 5G > A) was identified in four patients with central CH. In addition, we detected novel variants in the TSHR, TG, SLC26A7, FOXE1, and DUOX2. CONCLUSION: Genetic causes were determined in the majority of CH patients with TDH, however, despite advances in genetics, we were unable to identify the genetic etiology of most CH patients with TD, suggesting the effect of unknown genes or environmental factors. The previous studies and our findings suggest that TSHR and TPO mutations is the main genetic defect of CH in the Turkish population.

[Analysis of pre-ablative and preoperative thyroglobulin in differentiated thyroid cancer]. / Análisis de tiroglobulina preablativa y cáncer diferenciado de tiroides preoperatorio.

BACKGROUND: The measurement of plasma thyroglobulin (Tg) is widely used in the monitoring of differentiated thyroid cancer (CDT). In recent years, its value as a prognostic marker prior to ablation with radioiodine has increased, demonstrating its high negative predictive value. Recent studies indicate that a wide variety of factors could potentially influence pre-ablative Tg values, including residual tumor burden and stimulation modality. AIM: To relate the value of pre-ablative Tg with the amount of preoperative disease burden, lymph node metastases, treatment, and presence of residual disease. MATERIAL AND METHODS: Retrospective observational study of 70 patients with CDT treated between 2012 and 2018. The amount of disease burden was defined as the sum of largest diameter of individual tumors in each patient, and as the individually largest tumor per patient and number of metastatic lymph nodes. RESULTS: A smaller tumor size and absence of remnant tissue was associated with lower Tg values, although the association was not always significant. Furthermore, no significant difference was found between Tg levels measured within or more than 14 days after the surgical procedure. Thus, an early measurement of pTg after surgery would allow an initial therapeutic decision making. CONCLUSIONS: A statistical association between pre-ablative Tg levels and the amount of preoperative tumor tissue burden was found in some subgroups of patients.

Diagnostic performance of Midkine ratios in fine-needle aspirates for evaluation of Cytologically indeterminate thyroid nodules.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is a basic diagnostic tool for thyroid nodules. However, 15-30% of nodules are cytologically indeterminate. Midkine (MK), a pleiotropic growth factor, is often upregulated in patients with cancers. This study aimed to evaluate the role of MK and its ratios in fine-needle aspirates (FNA) for predicting thyroid malignancy. METHODS: This retrospective study included patients with thyroid nodules who underwent preoperative FNA and/or thyroidectomy between April 2017 and September 2017. MK levels in FNA washout were measured by enzyme-linked immunosorbent assay, and thyroglobulin (TG) and free thyroxine (FT4) levels in FNA washout were measured by chemiluminescent immunometric assays. RESULTS: A total of 217 patients with 242 nodules were included in this study. The concentrations of TG, FT4, MK/TG, MK/FT4, and FT4/MK were significantly different between papillary thyroid carcinomas and benign thyroid nodules. Both MK/TG and MK/FT4 ratios were positively correlated with maximum tumor diameter, extrathyroidal extension, and T and N stages. The area under the curve for MK/TG was 0.719 with a cutoff value of 55.57 ng/mg, while the area under the curve for MK/FT4 was 0.677 with a cutoff value of 0.11 µg/pmol. FNAC in combination with MK/FT4 had a higher sensitivity (95% vs. 91%) and accuracy (96% vs. 92%) than FNAC alone for cytologically indeterminate specimens, those of unknown significance, or those suspected of malignancy. CONCLUSIONS: MK/FT4 and MK/TG may have diagnostic utility for evaluation of papillary thyroid carcinomas, particularly for cytologically indeterminate thyroid nodules.

Thyroglobulin measurements in washouts of fine-needle aspiration biopsy in the monitoring of patients with differentiated thyroid carcinoma.

INTRODUCTION: Approximately 35% patients with papillary thyroid carcinoma (PTC) and 13% with follicular thyroid carcinoma (FTC) present with metastases of cervical lymph nodes (LNs) at the time of diagnosis. In addition, 15-20% of patients treated with total thyroidectomy develop, after an interval of five years, metastases to the neck LNs on ultrasound examination. Fine-needle aspiration biopsy (FNAB) represents the gold standard technique for the detection of cervical LNs metastases. The aim of the study was to evaluate the diagnostic performance of the technique of thyroglobulin (Tg) measurement of washout FNAB (FNAB-Tg) in diagnostics of LNs metastases in different groups of patients with differentiated thyroid carcinoma (DTC). MATERIAL AND METHODS: Two hundred FNAB-Tg samples from 200 patients [158 women; 42 men; mean age 51.37 ± 16.77 (53)] diagnosed with DTC were examined for the assessment of the diagnostic utility of FNAB-Tg from suspicious LNs. FNAB-Tg ranged from 1.96 to 5000 ng/mL in metastatic LNs [mean; 1510 ± 1486 ng/mL (958.5)] and from 0.04 to 635.9 ng/mL in nonmetastatic LNs [mean; 57.86 ± 319.19 ng/mL (1.96)], p < 0.001. RESULTS: The most accurate diagnostic performance was displayed for the concentration of 33.28 ng/mL in FNAB-Tg with AUC of 0.91 and high sensitivity and specificity (0.92 and 0.93). FNAB-Tg in conjunction with the cytopathological examination of suspicious LNs in differentiated thyroid carcinoma (DTC) patients increases the diagnostic accuracy of FNAB (sensitivity 0.99; specificity 0.99; AUC 1.00). CONCLUSIONS: FNAB-Tg may be particularly useful in detecting LN metastases in DTC patients, and in differential diagnosis of various LN metastasizing malignancies. The combination of FNAB and FNAB-Tg measurement has high specificity and sensitivity in the detection of LN metastases of DTC.

Ectopic thyroid in left parotid gland with an orthotopic thyroid gland: A rare case scenario.

Benign ectopic thyroid tissue within the parotid gland is very rare with only one case reported till date in the world literature. We report a case of ectopic thyroid in the left parotid gland with an orthotopic thyroid in an elderly female, who was presented to us with the simultaneous onset of right-sided thyroid swelling and left parotid swelling for 6 months. Fine-needle aspiration cytology (FNAC) was done from both the swellings and a diagnosis of Hurthle cell neoplasm metastasizing to the left parotid gland was initially made. However, histopathological examination along with the immunohistochemistry (IHC) panel proved it to be an ectopic thyroid in the parotid. The case is being documented here for its rarity as well as an unusual presentation so that the readers are aware of this entity and the complete workup required to prevent diagnostic pitfalls.

Immunohistochemically detectable thyroglobulin expression in extrathyroidal cancer is 100% specific for thyroidal tumor origin.

Thyroglobulin is a secreted 660 kDa glycoprotein produced by thyroid follicular cells used in diagnostic pathology to secure or exclude a thyroidal origin of metastases of unknown primary tumors. This study was performed to estimate specificity of thyroglobulin immunohistochemistry. 9974 tumor samples from 109 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry in a tissue microarray format. Thyroglobulin was strongly expressed in all normal thyroid samples but not in any other normal tissues. Thyroglobulin immunostaining was detected in 99.1% of 106 thyroid adenomas, 98.1% of 364 papillary, 95.2% of 147 follicular, and 7.5% of 40 anaplastic thyroid cancers. Twelve of 15 thyroid samples that were thyroglobulin negative on TMAs showed at least a weak focal thyroglobulin positivity in corresponding large sections, suggesting higher sensitivity of large section analysis. Thyroglobulin positivity in one diffuse large B-cell lymphoma of the thyroid, one chondrosarcoma metastasis to the thyroid, and 42.4% of 92 medullary thyroid cancers was considered to be caused by diffusion of thyroidal colloid from destroyed or even intact adjacent follicles. Thyroglobulin positivity was, however, not seen in 6403 extrathyroidal tumors from 104 different tumor types and subtypes. Our data demonstrate a complete specificity of positive thyroglobulin immunostaining for thyroid origin in tumor tissues obtained from extrathyroidal locations. However, for all tumors located within the thyroid, false positivity can occur as a result of tissue contamination by thyroglobulin rich thyroid colloid from adjacent normal tissue.

Highly sensitive electrochemical immunosensor using a protein-polyvinylidene fluoride nanocomposite for human thyroglobulin.

The highly sensitive detection of serum thyroglobulin (Tg) is essential in the post-treatment follow-up of patients with differentiated thyroid cancer undergoing total or partial thyroidectomy and radioactive iodine ablation and requires sensitive, accurate and stable methods. This work proposes an electrochemical immunosensor for the detection of serum Tg antigen, making use of innovative nanocomposites including polyvinylidene fluoride (PVDF) microparticles coated with streptavidin (MP) and gold nanoparticles (AuNPs). The functionalized polymer matrices were characterized by UV-Vis, FTIR, XPS, SEM, dynamic light scattering, and free surface energy. Immobilization of biotin-labeled anti-thyroglobulin monoclonal antibodies was achieved by binding these to the polymer nanocomposite via streptavidin proteins. The analytical response was measured in quintuplicate and had a linear profile from 2.0 to 10.0 ng/mL Tg, with r2 of 0.985. The limits of detection and quantification were excellent, equal to 0.015 and 0.047 ng/mL, respectively. In addition, the recovery factor was equal to 95.4% (1.0 ng/mL Tg). Overall, the innovative polymer-based nanocomposite used herein enabled the production of an electrochemical-based immunosensor with excellent sensitivity, selectivity, and reproducibility. It evidenced the remarkable potential of determining low levels of Tg in in vitro assays, thereby suggesting that it may be considered for the analyzes of serum patients.

[Cystic cervical lymph node swelling - Thyroglobin-FNA allows to diagnose metastasizing papillary thyroid carcinoma]. / Zystische zervikale Lymphknotenschwellung ­ TG-Bestimmung im Punktat sichert das lymphatisch metastasierte papilläre Schilddrüsenkarzinom.

HISTORY: A patient presented with a cystic mass in the lateral triangle of the neck. FINDINGS AND DIAGNOSIS: After ultrasound and MRI, a fine needle aspiration cytology (FNAC) was performed. It did not reveal malignant disease. By virtue of repeated FNAC and detection of thyroglobin in the cyst fluid, the diagnosis of thyroid carcinoma was firmly established. THERAPY AND COURSE: The necessary surgery could be performed in a single step intervention. Three weeks after surgery, radioiodine therapy with 3.7 GBq I131 was performed. CONCLUSION: Swelling of the cervical lymph nodes may have many causes, and rarely may be the metastasis of a thyroid carcinoma. We present a simple way to detect lymphatic metastatic thyroid carcinoma with the help of a case report.

Biotin Interference in Assays for Thyroid Hormones, Thyrotropin and Thyroglobulin.

Background: Biotin has been reported to interfere with several commonly used laboratory assays resulting in misleading values and possible erroneous diagnosis and treatment. This report describes a prospective study of possible biotin interference in thyroid-related laboratory assays, with a comparison of different commonly used assay platforms. Materials and Methods: Thirteen adult subjects (mean age 45 ± 13 years old) were administered biotin 10 mg/day for eight days. Blood specimens were collected at three time points on day 1 and on day 8 (baseline, two, and five hours after biotin ingestion). Thyrotropin (TSH), free triiodothyronine (fT3), free thyroxine (fT4), total triiodothyronine (TT3), total thyroxine (TT4), thyroxine binding globulin (TBG), and thyroglobulin (Tg) levels were analyzed with four different platforms: Abbott Architect, Roche Cobas 6000, Siemens IMMULITE 2000, and liquid chromatography with tandem mass spectrometry (LC-MS/MS). TSH, fT3, fT4, TT3, and TT4 were measured with Abbott Architect and Roche Cobas 6000. fT3, fT4, TT3, and TT4 were also measured by LC-MS/MS. Tg was measured by Siemens IMMULITE 2000. TBG was assessed with Siemens IMMULITE 2000. Results: Significant changes in TSH, fT4, and TT3 measurements were observed after biotin exposure when the Roche Cobas 6000 platform was used. Biotin intake resulted in a falsely lower Tg level when measurements were performed with Siemens IMMULITE 2000. At the time points examined, maximal biotin interference was observed two hours after biotin exposure both on day 1 and day 8. Conclusions: A daily dose of 10 mg was shown to interfere with specific assays for TSH, fT4, TT3, and Tg. Physicians must be aware of the potential risk of erroneous test results in subjects taking biotin supplements. Altered test results for TSH and Tg can be particularly problematic in patients requiring careful titration of levothyroxine therapy such as those with thyroid cancer.

Production, characterization and in-vitro applications of single-domain antibody against thyroglobulin selected from novel T7 phage display library.

Single- domain antibodies (SdAbs) have been deployed in various biomedical applications in the recent past. However, there are no reports of their use in the immunoradiometric assays (IRMA) for thyroglobulin (Tg). Tg is the precursor molecule for the biosynthesis of thyroid hormones: thyroxine and triiodothyronine, which are essential for the regulation of normal metabolism in all vertebrates. Patients with differentiated thyroid cancer (DTC) require periodic monitoring of their serum thyroglobulin levels, as it serves as a prognostic marker for DTC. Here, we report a methodology to produce SdAbs against human-Tg, by a hybrid immunization/directed-evolution approach by displaying the SdAb gene-repertoire derived from a hyperimmune camel in the T7 phage display system. We have demonstrated the immunoreactivity of anti-Tg-SdAb (KT75) in immunoassays for thyroglobulin and measured its affinity by surface plasmon resonance (KD ~ 18 picomolar). Additionally, we have shown the quantitative-binding property of SdAb for the first time in IRMA for thyroglobulin. The serum Tg values obtained from SdAb-Tg-IRMA and in-house assay using murine anti-Tg-monoclonal antibody as tracer significantly correlated, r = 0.81, p < 0.05. Our results highlight the scope of using the T7 phage display system as an alternative for the conventional M13-phage to construct single-domain antibody display libraries.

Advanced papillary thyroid carcinoma responding to nivolumab.

INTRODUCTION: Clinical indications of immune checkpoint inhibitors have expanded to a variety of malignancies. Approximately one in six patients with hepatocellular carcinoma respond to programmed death 1 inhibitors nivolumab and pembrolizumab. CASE REPORT: We report herein a patient with synchronous metastatic hepatocellular carcinoma and advanced papillary thyroid carcinoma treated with nivolumab in the second-line therapy.Management and outcome: The hepatocellular carcinoma showed a durable response to the second-line agent nivolumab. Remarkably, the patient's papillary thyroid carcinoma also responded to this programmed death 1 inhibitor. DISCUSSION: To our knowledge, this is the first case report showing the efficacy of nivolumab in the treatment of metastatic papillary thyroid carcinoma. Further studies with immune checkpoint inhibitors in papillary thyroid carcinoma seem warranted.

CYFRA21-1/TG ratio as an accurate risk factor to predict eye metastasis in nasopharyngeal carcinoma: A STROBE-compliant article.

Nasopharyngeal carcinoma (NPC) has a distinctive geographical distribution in China, especially southern China. There are several risk factors for NPC, such as Epstein-Barr virus, genetics, and environmental exposures. Although the incidence of eye metastasis (EM) is lower than metastasis in other body parts, it often indicates poor prognosis.We assessed several serum biomarkers for their ability to predict EM in NPC. Patients with NPC were selected (n = 963), and were separated into two groups, EM and no eye metastasis. Ten factors were analyzed in both groups including triglyceride (TG), high-density lipoprotein, low-density lipoprotein, alkaline phosphatase, alpha fetoprotein, carbohydrate antigen-199, cancer antigen-153, apolipoproteins AI, apolipoprotein B, and cytokeratin fragment 19 (CYFRA21-1). Independent t tests, binary logistic regression, and receiver operating characteristic curves were used to assess the data.The EM group had significantly higher CYFRA21-1 and lower TG compared with the no eye metastasis group. Areas under the curve for CYFRA21-1, TG and CYFRA21-1/TG were 0.966, 0.771, and 0.976, respectively. The corresponding cut-off values were 12.12 ng/ml, 0.41 mmol/L, and 13.5. The sensitivity and specificity of CYFRA21-1/TG were 100% and 92.2%, respectively.The increased ratio of CYFRA21-1 to TG can be an accurate method to detect EM in patients with NPC.

Low intake of iodized salt and iodine containing supplements among pregnant women with apparently insufficient iodine status - time to change policy?

BACKGROUND: Iodine is an essential nutrient for human health throughout the life cycle, especially during early stages of intrauterine life and infancy, to ensure adequate neurocognitive development. The growing global reliance on desalinated iodine-diluted water raises the specter of increased iodine deficiency in several regions. The case of Israel may be instructive for exploring the link between iodine status and habitual iodine intake in the setting of extensive national reliance on desalinated water. The aim of this study was to explore the relationship between iodine intake, including iodized salt and iodine-containing supplements intake, and iodine status among pregnant women residing in a sub-district of Israel that is highly reliant on desalinated iodine-diluted water. METHODS: A total of 134 consecutive pregnant women were recruited on a voluntary basis from the obstetrics department of the Barzilai University Medical Center during 2018. Blood was drawn from participants to determine levels of serum thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb) and thyroglobulin (Tg). An iodine food frequency questionnaire (sIFFQ) was used to assess iodine intake from food, IS and ICS. A questionnaire was used to collect data on demographic and health characteristics. RESULTS: A total of 105 pregnant women without known or reported thyroid disease were included in the study. Elevated Tg values (≥ 13 µg/L), were found among 67% of participants, indicating insufficient iodine status. The estimated iodine intake (median, mean ± SD 189, 187 ± 106 µg/d by sIFFQ) was lower than the levels recommended by the World Health Organization and the Institute of Medicine (250 vs. 220 µg/day respectively). The prevalence of iodized salt intake and iodine containing supplement intake were 4 and 52% (respectively). Values of Tg > 13 µg/L were inversely associated with compliance with World Health Organization and Institute of Medicine recommendations. CONCLUSIONS: While the Israeli Ministry of Health has recommended the intake of iodized salt and iodine containing supplements, this is apparently insufficient for achieving optimal iodine status among Israeli pregnant women. The evidence of highly prevalent probable iodine deficiency in a sample of pregnant women suggests an urgent need for a national policy of iodized salt regulation, as well as guidelines to promote iodine containing supplements and adherence to them by caregivers. In addition, studies similar to this one should be undertaken in additional countries reliant on desalinated iodine-diluted water to further assess the impact of desalinization on maternal iodine status.