BACKGROUND AND OBJECTIVES: Selenium is an important trace element for thyroid hormone metabolism, and its deficiency can cause hypothyroidism. Serum selenium concentration is the best biomarker to reflect selenium intake and reserve, although other markers can reflect. Therefore, we preliminarily assessed serum and urine selenium concentrations in patients with thyroid disease compared to those of a healthy population. We also investigated the correlation between serum and urine selenium concentration, thyroid hormone and urinary iodine concentration (UIC). MATERIALS AND METHODS: A total of 97 patients (32 men, 65 women, 52.4±14.7 years) with benign thyroid nodules or thyroid dysfunction who visited the Samsung Medical Center between 2008 and 2013 were included. Data for 175 healthy subjects provided by Lee et al. were used as the control. Serum T3, free T4, and thyroid stimulating hormone (TSH) were measured using commercialized RIA or IRMA kits. Serum/urine selenium and UIC were measured by inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: Median serum selenium concentration was 110 µg/L (95% CI, 73-156). Median urine selenium concentration was 66.3 µg/gCr (95% CI, 28.7-283.5). Compared to 175 healthy subjects (serum 84 µg/L [95% CI, 30-144], urine 34.5 µg/gCr [95% CI, 0.8-107.2]), serum and urine selenium concentrations of patients with thyroid disease were significantly higher than those of healthy subjects (p<0.001). Serum selenium concentration was significantly correlated with urine selenium concentration after log transformation (r=0.88, p=0.022), but was not significantly correlated with UIC, T3, free T4 and TSH. CONCLUSION: Selenium concentrations of patients with thyroid disease were significantly higher than those of healthy subjects. Serum selenium concentration was significantly correlated with urine selenium concentration.
Female ; Healthy Volunteers ; Humans ; Hypothyroidism ; Iodine ; Male ; Metabolism ; Selenium* ; Spectrum Analysis ; Thyroid Diseases* ; Thyroid Gland* ; Thyroid Nodule ; Thyrotropin

BACKGROUND AND OBJECTIVES: Selenium is an important trace element for thyroid hormone metabolism, and its deficiency can cause hypothyroidism. Serum selenium concentration is the best biomarker to reflect selenium intake and reserve, although other markers can reflect. Therefore, we preliminarily assessed serum and urine selenium concentrations in patients with thyroid disease compared to those of a healthy population. We also investigated the correlation between serum and urine selenium concentration, thyroid hormone and urinary iodine concentration (UIC). MATERIALS AND METHODS: A total of 97 patients (32 men, 65 women, 52.4±14.7 years) with benign thyroid nodules or thyroid dysfunction who visited the Samsung Medical Center between 2008 and 2013 were included. Data for 175 healthy subjects provided by Lee et al. were used as the control. Serum T3, free T4, and thyroid stimulating hormone (TSH) were measured using commercialized RIA or IRMA kits. Serum/urine selenium and UIC were measured by inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: Median serum selenium concentration was 110 µg/L (95% CI, 73-156). Median urine selenium concentration was 66.3 µg/gCr (95% CI, 28.7-283.5). Compared to 175 healthy subjects (serum 84 µg/L [95% CI, 30-144], urine 34.5 µg/gCr [95% CI, 0.8-107.2]), serum and urine selenium concentrations of patients with thyroid disease were significantly higher than those of healthy subjects (p<0.001). Serum selenium concentration was significantly correlated with urine selenium concentration after log transformation (r=0.88, p=0.022), but was not significantly correlated with UIC, T3, free T4 and TSH. CONCLUSION: Selenium concentrations of patients with thyroid disease were significantly higher than those of healthy subjects. Serum selenium concentration was significantly correlated with urine selenium concentration.
Female ; Healthy Volunteers ; Humans ; Hypothyroidism ; Iodine ; Male ; Metabolism ; Selenium* ; Spectrum Analysis ; Thyroid Diseases* ; Thyroid Gland* ; Thyroid Nodule ; Thyrotropin

BACKGROUND: Several molecular assays have been developed to detect the BRAF V600E mutation in fine needle aspirates (FNAs) for the diagnosis of papillary thyroid cancer. Using a multiplex PCR technique, we evaluated the Anyplex BRAF V600E Real-time Detection (Anyplex) assay and compared its efficacy with that of the Seeplex BRAF V600E ACE Detection (Seeplex) method. METHODS: We tested 258 consecutive FNA specimens using the Seeplex and Anyplex assays. Any conflicting results between the two assays were confirmed by using mutant enrichment with 3'-modified oligonucleotide (MEMO) sequencing. The limits of detection (LODs) and reproducibility for each assay were evaluated with serially diluted DNA from a BRAF V600E-positive cell line. RESULTS: The BRAF V600E mutation was detected in 36.4% (94/258) FNA specimens by either the Seeplex or Anyplex assay. Results for the two assays showed 93.4% (241/258) agreement, with a kappa value of 0.861 (95% confidence interval, 0.798-0.923). Of the eight specimens that were BRAF V600E-positive by the Anyplex assay but not by the Seeplex assay, five were found to be BRAF V600E-positive by MEMO sequencing. The mutation detection rate of the Seeplex and Anyplex assays was 79.0% and 84.0%, respectively, in the FNA specimens diagnosed as malignant (n=81). The LOD as determined by probit analysis was 0.046% (95% confidence interval, 0.019-0.532%). CONCLUSIONS: The Anyplex assay performed better than the Seeplex assay with respect to the detection of the BRAF V600E mutation.
Adult ; Aged ; Asian Continental Ancestry Group/genetics ; Biopsy, Fine-Needle ; DNA/chemistry/metabolism ; DNA Mutational Analysis/*methods ; DNA Primers/*metabolism ; Female ; Humans ; Male ; Middle Aged ; Multiplex Polymerase Chain Reaction ; Oligonucleotides/metabolism ; Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins B-raf/*genetics ; Republic of Korea ; Thyroid Nodule/*metabolism/pathology

PURPOSE: We investigated the merit of ultrasound (US) features and BRAF(V600E) mutation as an additional study of cytology and compared the diagnostic performances of cytology alone, cytology with US correlation, cytology with BRAF(V600E) mutation, and a combination of cytology, US, and BRAF(V600E) mutation all together. MATERIALS AND METHODS: This study included 185 patients (mean age, 48.4 years; range 20-77 years) with 191 thyroid nodules who underwent US-guided fine-needle aspiration (FNA) with an additional BRAF(V600E) mutation test. Three radiologists highly experienced in thyroid imaging retrospectively reviewed US images and classified each nodule into two categories (positive for malignancy or negative for malignancy). Interobserver variability (IOV) of US assessment between the three readers was estimated using the generalized kappa statistic of Landis and Koch. We also calculated the diagnostic performances of these studies. RESULTS: There were 131 cases of malignancy (131/191, 68.6%) and 60 cases of benign nodules (60/191, 31.4%). In terms of IOV of US assessment, the generalized kappa value was 0.242, indicating fair agreement was reached. The combination of cytology with BRAF(V600E) showed higher specificity (100%) and positive predictive value (PPV) (100%) compared to the combination of cytology, BRAF(V600E), and US (specificity 28.3%, 66.7%, 68.3%; PPV 74.6%, 86.6%, 86.8%, respectively; p<0.001). However, cytology with BRAF(V600E) showed lower sensitivity (84.7%) than cytology with BRAF(V600E) and US (96.2%, 98.5%, 95.4%, respectively; p<0.001). CONCLUSION: Considering the diagnostic performance and low reproducibility of US, the combination of FNA with BRAF(V600E) is the most reliable and objective method for diagnosing thyroid malignancy.
Adult ; Aged ; Biological Markers ; Biopsy, Fine-Needle ; Carcinoma/*diagnosis/genetics/*ultrasonography ; Cytodiagnosis ; Female ; Humans ; Male ; Middle Aged ; Proto-Oncogene Proteins B-raf/*genetics ; Retrospective Studies ; Thyroid Gland/metabolism/pathology ; Thyroid Neoplasms/*diagnosis/genetics/*ultrasonography ; Thyroid Nodule/metabolism/pathology ; Young Adult

PURPOSE: We investigated the merit of ultrasound (US) features and BRAF(V600E) mutation as an additional study of cytology and compared the diagnostic performances of cytology alone, cytology with US correlation, cytology with BRAF(V600E) mutation, and a combination of cytology, US, and BRAF(V600E) mutation all together. MATERIALS AND METHODS: This study included 185 patients (mean age, 48.4 years; range 20-77 years) with 191 thyroid nodules who underwent US-guided fine-needle aspiration (FNA) with an additional BRAF(V600E) mutation test. Three radiologists highly experienced in thyroid imaging retrospectively reviewed US images and classified each nodule into two categories (positive for malignancy or negative for malignancy). Interobserver variability (IOV) of US assessment between the three readers was estimated using the generalized kappa statistic of Landis and Koch. We also calculated the diagnostic performances of these studies. RESULTS: There were 131 cases of malignancy (131/191, 68.6%) and 60 cases of benign nodules (60/191, 31.4%). In terms of IOV of US assessment, the generalized kappa value was 0.242, indicating fair agreement was reached. The combination of cytology with BRAF(V600E) showed higher specificity (100%) and positive predictive value (PPV) (100%) compared to the combination of cytology, BRAF(V600E), and US (specificity 28.3%, 66.7%, 68.3%; PPV 74.6%, 86.6%, 86.8%, respectively; p<0.001). However, cytology with BRAF(V600E) showed lower sensitivity (84.7%) than cytology with BRAF(V600E) and US (96.2%, 98.5%, 95.4%, respectively; p<0.001). CONCLUSION: Considering the diagnostic performance and low reproducibility of US, the combination of FNA with BRAF(V600E) is the most reliable and objective method for diagnosing thyroid malignancy.
Adult ; Aged ; Biological Markers ; Biopsy, Fine-Needle ; Carcinoma/*diagnosis/genetics/*ultrasonography ; Cytodiagnosis ; Female ; Humans ; Male ; Middle Aged ; Proto-Oncogene Proteins B-raf/*genetics ; Retrospective Studies ; Thyroid Gland/metabolism/pathology ; Thyroid Neoplasms/*diagnosis/genetics/*ultrasonography ; Thyroid Nodule/metabolism/pathology ; Young Adult

Carcinoma, Mucoepidermoid ; complications ; metabolism ; pathology ; DNA-Binding Proteins ; metabolism ; Diagnosis, Differential ; Eosinophilia ; complications ; metabolism ; pathology ; Epithelial Cells ; pathology ; Female ; Hashimoto Disease ; metabolism ; pathology ; surgery ; Humans ; Keratin-19 ; metabolism ; Membrane Proteins ; metabolism ; Middle Aged ; Thyroid Gland ; metabolism ; pathology ; surgery ; Thyroid Nodule ; metabolism ; pathology ; surgery ; Transcription Factors ; beta Catenin ; metabolism

Papillary thyroid carcinoma (PTC) is the most common malignant thyroid tumor, and 36-69% of PTC cases are caused by mutations in the BRAF gene. The substitution of a valine for a glutamic acid (V600E) comprises up to 95-100% of BRAF mutations; therefore, most diagnostic methods, including allele-specific PCR and real-time PCR, are designed to detect this mutation. Nevertheless, other mutations can also comprise the genetic background of PTC. Recently, a novel and sensitive technique called mutant enrichment with 3'-modified oligonucleotides (MEMO) PCR has been introduced. When we applied allelespecific PCR and MEMO-PCR for the detection of the BRAF V600E mutation, we found an unusual 3' bp deletion mutation (c.1799_1801delTGA) only when using MEMO-PCR. This deletion results in the introduction of a glutamic acid into the B-Raf activation segment (p.V600_K601delinsE), leading to an elevated basal kinase activity of BRAF. This is the first report of a rare 3 bp BRAF deletion in a PTC patient that could not be detected by allele-specific PCR.
Alleles ; Base Sequence ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Oligonucleotides/genetics ; Polymerase Chain Reaction/*methods ; Proto-Oncogene Proteins B-raf/*genetics/metabolism ; Sequence Deletion ; Thyroid Neoplasms/genetics/pathology ; Thyroid Nodule/metabolism

PURPOSE: Whole body Positron Emission Tomography (PET) was used to evaluate the existence of cancer cells. However, PET had limitations in identifying thyroid cancer cells because of their slow progression, and evidence regarding its accuracy in finding thyroid cancer cells is insufficient. Therefore, we investigated the usefulness of PET for evaluation of patients with thyroid nodules by studying the relationships between PET and thyroid ultrasonography. METHODS: We evaluated 4,627 patients who had undergone PET from January 2007 to October 2011 and selected 370 patients who had undergone thyroid ultrasonography. We compared and analyzed the amount of thyroid SUVmax of PET, the pattern of glucose uptake, and findings of thyroid ultrasonography based on their size, shape, location, and FNAC. RESULTS: Of 370 patients, 197 (53.2%) subjects were found to have thyroid nodules, and 211 (57.0%) subjects had higher sugar metabolism, regardless of having thyroid nodules. No statistical correlations were observed among nodule size, nodule location,and higher sugar metabolism, however, noticeable relationships were observed between the shape of the cells on thyroid ultrasonography and FDG uptake of PET. In cases of papillary thyroid cancer, there was higher FDG uptake, compared to benign lesions in particular, SUVmax of the papillary thyroid cancer showed a significantly elevated level of FDG uptake. CONCLUSION: Despite its limited usefulness in identifying the characteristics of thyroid nodules being benign or malignant, PET is appropriate for evaluation of the malignancy of thyroid cells
Diagnosis* ; Electrons* ; Glucose ; Humans ; Metabolism ; Positron-Emission Tomography* ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroid Nodule* ; Ultrasonography

Indeterminate cytology results increase the number of repetitive procedure and unnecessary surgery. This study was designed to find useful and simple predictive tools to differentiate malignant thyroid nodules from indeterminate nodules. We retrospectively enrolled 164 patients who had undergone thyroid surgery as a result of indeterminate cytology in the National Cancer Center. We reviewed patients' age at diagnosis, sex, preoperative biochemical markers such as thyroglobulin (Tg), anti-Tg antibody, free T4 and TSH level, and sonographical and pathological findings, which were subjected to statistical analysis. We found several clinical and sonographical predictive factors that showed significant differences. Young age, male, preoperative high Tg level, and hypoechoic nodule on sonography all increased cancer probability significantly in multivariate analysis. With a cut-off value of 187.5 ng/mL Tg, sensitivity and specificity were 54.8% and 90.1%, respectively (AUC 0.748, P < 0.001). In the case of nodule size > 1.7 cm, elevated serum Tg predicts the risk of malignancy; especially Tg > 70 ng/mL (odds ratio 3.245, 95% confidence interval 1.115-9.450, P = 0.038). Preoperative Tg levels had very high specificity in predicting thyroid cancer in case of suspicious follicular neoplasm. Therefore, Tg levels may be a useful marker for differentiating thyroid cancer from benign thyroid nodules in the cytological diagnosis of indeterminate nodules.
Adenocarcinoma, Follicular/*diagnosis/metabolism/pathology ; Adult ; Age Factors ; Aged ; Autoantibodies/blood ; Biological Markers/blood ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; ROC Curve ; Retrospective Studies ; Sensitivity and Specificity ; Sex Factors ; Thyroglobulin/*blood ; Thyroid Nodule/ultrasonography

The purpose of this review is to investigate the value of the calcification in differentiating malignant thyroid neoplasm and the molecular mechanisms for the formation of the calcification. Many published reports have proved the presence of calcifications in thyroid neoplasm and calcified nodules in these studies are more frequently malignant than noncalcified nodules. Through viewing the related references, we found that psammoma bodies (PBs), Runx2, osteocalcin, osteopontin, CD44v6 play an important role in the molecular mechanisms in the formation of the calcification in PTC. But further study is required for elucidating the mode of action.
Calcinosis ; diagnosis ; pathology ; Core Binding Factor Alpha 1 Subunit ; metabolism ; Humans ; Hyaluronan Receptors ; metabolism ; Osteocalcin ; metabolism ; Osteopontin ; metabolism ; Thyroid Neoplasms ; diagnosis ; pathology ; Thyroid Nodule ; pathology