Serum trace elements show association with thyroperoxidase autoantibodies in Thyroid Imaging Reporting and Data System (TI-RADS) 4 nodules.

Thyroid nodule (TN) has been becoming a great concern worldwide due to its high incidence. Although some studies have reported associations between trace elements exposure and the risk of TNs, the linkage was not inconclusive. The present study aimed to identify the association of selected serum trace elements (Ca, Mg, V, Fe, Co, Cu, Zn, Se, Mn and Mo) with TNs among general adults. A cross-sectional study was conducted in January 2021 in Chengdu, China. 1282 subjects completed the questionnaire and gave at least one human biological material after an overnight fast, venous blood, and urine, including 377 TN participants defined through ultrasound. Various trace elements in serum specimens were determined by inductively coupled plasma mass spectrometry. Thyroid functions were tested by chemiluminescent microparticle immunoassay (CMIA). The associations between trace elements levels and the risk of TNs were examined by restricted cubic splines (RCS) regression and bayesian kernel machine regression (BKMR) models. TNs were more common in females (P < 0.001) and in the elderly (P < 0.001) and that they were also frequently associated with fertility, marital status, annual household income, drinking, anxiety, vitamin supplement, tea consumption, hypertension and hyperlipidemia. After adjusting for confounders by a propensity score matching model, the association between trace elements concentrations and TNs risk was found to be statistically insignificant in the RCS (P for nonlinear > 0.05) and BKMR models. FT3 or T4 (total or free) increased significantly with increasing total trace elements mixture levels. In TI-RADS-4 TN subjects, TPO-Ab level increased significantly with increasing total trace elements mixture levels in the high-dose range. Ca, Zn, Mo at their 75th percentile showed positive individual effects on TPO-Ab, which was examined to be interactive. The detection of trace elements for TNs in general adults may be of no significance, but once individuals classified as TI-RADS-4 TNs are detected with abnormal TPO-Ab, Ca, Zn and Mo level are recommended to measure. The substantive association on it still needs to be continuously explored in the future.

Associations between thyroid function, thyroid diseases, and primary aldosteronism.

OBJECTIVE: Previous studies focusing on primary aldosteronism (PA) and thyroid diseases were controversial. Hence, this study aimed to examine associations between thyroid function, thyroid diseases, and PA and its subtypes. DESIGN AND METHODS: This was a cross-sectional study, which enrolled 1023 patients with PA and 6138 patients with essential hypertension (EH) admitted to Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region from August 2011 to June 2022. All patients with PA were accurately classified into aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) by adrenal vein sampling (AVS). Multivariate logistic regression analysis was used to assess the relationship of thyroid function, thyroid nodules, and PA and its subtypes. RESULTS: A total of 7161 patients (327 APA and 696 IHA, and 6138 EH) were included with a mean age of 48.20 ± 8.83 years. PA patients and PA subtypes showed lower FT4, FT3, TT4, TT3, and prevalence of positive TPOAb, meanwhile higher prevalence of thyroid nodules than EH patients (PA: 56.10%, IHA: 56.90%, APA: 54.80%, and EH: 48.90%, respectively). PA (adjusted OR: 1.290, 95% CI: 1.035-1.607, P = .02) and its subtype (IHA) (adjusted OR: 1.316, 95% CI: 1.005-1.724, P = .04) were significantly associated with thyroid nodules. Compared to patients with lower plasma aldosterone concentration (PAC) levels (<12 ng/dL), patients with PAC levels ≥ 12 ng/dL presented a higher prevalence of thyroid nodules. CONCLUSIONS: PA patients had lower thyroid function and higher prevalence of thyroid nodules compared to EH patients. Therefore, the screening of thyroid function and thyroid nodules may be indispensable for PA patients.

Clinical Significance of IgG4 Serum Concentration in Graves' Disease.

Elevated immunoglobulin G4 (IgG4) serum antibodies are an important feature of IgG4-related disease. However, IgG4 antibodies can play a role in autoimmune thyroid disorders. In this study, we aimed to evaluate the impact of serum IgG4 levels on clinical features of Graves' disease (GD). We recruited 60 patients with GD (48 patients without thyroid eye disease, 12 patients with moderate-to-severe Graves' orbitopathy [GO], and 25 healthy control subjects). The prevalence of high IgG4 serum concentration was 4.2% among GD patients without GO and 33.33% in patients with moderate-to-severe GO. The group with GO had significantly higher median IgG4 levels (87.9 mg/dL) than the control group (41.2 mg/dL, P = 0.034) and the GD without GO group (30.75 mg/dL, P < 0.001). Patients with thyroid nodules had lower IgG4 levels than patients without thyroid nodules, but the difference was not statistically significant (35.7 [24.8; 41.53] mg/dL vs. 43 [30.1; 92.7] mg/dL, P = 0.064). IgG4 as a diagnostic tool for moderate-to-severe GO had the following parameters: area under the curve (AUC): 0.851 (P < 0.001), at the cut-off value of 49 mg/dL, negative predictive value: 100%, positive predictive value: 48%, sensitivity: 100%, specificity: 73%. There were no significant differences between the high and normal IgG4 groups in thyroid hormones, antithyroid antibodies, and ultrasound features. Serum IgG4 levels are associated with some of the clinical features of GD and can help in the diagnostic process of the disease. More research is needed to better understand the pathophysiology of IgG4 involvement in GD.

Combining TSH measurement with TIRADS assessment to further improve the detection of thyroid cancers.

BACKGROUND: Thyroid Imaging Reporting and Data Systems (TIRADSs) have demonstrated high performance in risk stratification of thyroid nodules (TNs). However, further improvements are needed in view of the ongoing project of an international TIRADS. Even if thyroid-stimulating hormone (TSH) measurement is traditionally used to assess the thyroid function, several papers have reported that higher TSH levels are associated with the presence of differentiated thyroid carcinoma (DTC). The present study aimed to investigate the role of TSH levels as improvement factor of American College of Radiology (ACR-), European Thyroid Association (EU-), and Korean Society (K-)TIRADS. METHODS: Patients undergoing thyroidectomy were reviewed and TNs were re-assessed according to TIRADSs. Different TSH subgroups were attained. Histology was the reference standard. DTC risk of relapse was assessed according to American Thyroid Association guidelines. RESULTS: The study series included 97 patients with 39.2% cancer prevalence. ACR-, EU-, and K-TIRADS indicated fine-needle aspiration cytology (FNAC) in 78.9%, 81.6%, and 92.1% of cases, respectively. All high-risk DTC had FNAC indication according to the three TIRADSs. The cancer rate was significantly lower in patients with TSH<0.4 mIU/L (P=0.04). The receiver operating characteristic (ROC) curve analysis showed that the best TSH cut-off to detect DTC patient was >1.3 mIU/L with Area Under the Curve (AUC)=0.70. Combining TSH data with TIRADS, the sensitivity of ACR-, EU-, and K-TIRADS increased to 92.1% 89.5%, and 94.7%, respectively. Conversely, the rate of unnecessary FNAC raised. At multivariate analysis, gender, TSH, and TIRADS were independent predictors of cancer. CONCLUSIONS: Even if TIRADSs are strongly reliable to stratify the risk of malignancy of TNs, measuring TSH can further improve our sensitivity in detecting DTC.

Serum cholesterol levels are inversely associated with the risk of malignancy in subjects with Bethesda category IV thyroid nodules.

INTRODUCTION: Some epidemiological data suggest that there may be an inverse relationship between cholesterol levels and the risk of thyroid cancer in the overall population. The present study was aimed to evaluate the lipid profile specifically in subjects with Bethesda category IV thyroid nodules, and compare whether there were any differences between those with benign and malignant nodules. METHODS: Single-centre, retrospective study on 204 subjects treated by partial or total thyroidectomy for excision of a Bethesda category IV thyroid nodule, who had undergone a blood lipid profile test in the 12 months prior to surgery. In addition to lipid measures, other demographic, clinical, biochemical and ultrasound data were collected. RESULTS: Seventy-five subjects (36.8%) were diagnosed with thyroid carcinoma in the definitive histopathological examination. Patients with thyroid cancer had lower levels of total cholesterol, LDL-cholesterol and non-HDL-cholesterol than subjects with benign thyroid diseases. There were no differences in HDL-cholesterol, triglycerides or total cholesterol/HDL-cholesterol ratio. There were no differences either between groups in other clinical, biochemical and ultrasound variables, including the use of lipid-lowering drugs. In multivariate analysis, only LDL-cholesterol was independently associated with malignancy. Subjects with follicular carcinoma showed the lowest cholesterol levels, while those with papillary carcinoma had intermediate values between the group with follicular carcinoma and the group with benign thyroid diseases. CONCLUSIONS: In subjects with cytologically indeterminate Bethesda category IV thyroid nodules, levels of total cholesterol, non-HDL-cholesterol and, particularly, LDL-cholesterol are lower among those with malignant nodules.

Assessment of inflammatory parameters as predictive markers for malignancy in thyroid nodules: a study on the correlation with Bethesda classification.

OBJECTIVE: The study aimed to assess the predictive significance of inflammatory parameters as potential markers for malignancy in individuals with thyroid nodules. METHOD: Nine hundred and ninety-one patients with thyroid nodules who had undergone thyroid fine-needle aspiration biopsy were included and classified according to the Bethesda system. Neutrophil lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) values obtained from hemogram parameters were determined for each patient. The study examined the correlation between the Bethesda classification and NLR/SII levels. In addition, a comparison was made between the inflammatory parameters of the benign and malignant Bethesda groups. RESULTS: Five hundred and seventy-three patients were classified as Bethesda 2 (benign), 34 as Bethesda 6 (malignant). A correlation was observed between the Bethesda classification and NLR and SII levels (r: 0.230, p < 0.001; r: 0.207 p < 0.001, respectively). NLR and SII values were significantly higher in the malignant group (p < 0.001). The cutoff value for SII in predicting benign and malignant thyroid nodules was 489.86 × 103/mm3 with a sensitivity of 88.2% and a specificity of 63.7%. The cutoff value for NLR for the same prediction was 2.06 with a sensitivity of 82.4% and a specificity of 83.4%. CONCLUSIONS: The findings of this study indicate that SII and NLR may be valuable prognostic markers for predicting the malignancy of thyroid nodules.

OBJETIVO: Evaluar parámetros inflamatorios como posibles marcadores de malignidad en individuos con nódulos tiroideos. MÉTODO: Se incluyeron 991 pacientes con nódulos tiroideos que se sometieron a biopsia por aspiración con aguja fina y se clasificaron según el sistema de Bethesda. Se determinaron los valores de la relación neutrófilo-linfocito (NLR) y el índice de inflamación inmunitaria sistémica (SII). El estudio exploró la correlación entre la clasificación de Bethesda y los valores de NLR/SII, y comparó los parámetros inflamatorios de los grupos benignos y malignos de Bethesda. RESULTADOS: Se clasificaron 573 pacientes como Bethesda 2 (benigno) y 34 como Bethesda 6 (maligno). Se observó una correlación entre la clasificación de Bethesda y los valores de NLR y SII (r: 0.230; r: 0.207). Los valores de NLR y SII fueron mayores en el grupo maligno (p < 0.001). El valor de corte para SII en la predicción de nódulos tiroideos benignos y malignos fue de 489.86 × 103/mm3, con una sensibilidad del 88.2% y una especificidad del 63.7%; para NLR fue de 2.06, con una sensibilidad del 82.4% y una especificidad del 83.4%. CONCLUSIONES: El SII y el NLR pueden ser valiosos marcadores pronósticos para predecir la malignidad de los nódulos tiroideos.

Sex-specific associations between the developmental alterations in the pituitary-thyroid hormone axis and thyroid nodules in Chinese euthyroid adults: a community-based cross-sectional study.

Background: Previous studies have revealed the sex-specific features of pituitary-thyroid hormone (TH) actions and the prevalence of thyroid nodules (TNs) in children and adolescents. However, it was unclear in adults. We aimed to investigate the features of pituitary-TH actions in women and men at different ages, and the associations of thyrotropin (TSH), THs, and central sensitivity to THs indices including the thyroid feedback quantile-based index by FT4 (TFQIFT4) and the thyroid feedback quantile-based index by FT3(TFQIFT3) with of TNs in Chinese euthyroid adults. Methods: 8771 euthyroid adults from the communities in China were involved. Demographic, behavioral, and anthropometric data were gathered through the questionnaires. Ultrasound was performed to evaluate the TNs. TSH and THs levels were measured. The multivariable logistic regression and multivariable ordinal logistic regression were conducted. Results: TFQIFT3 among both genders, except women aged 43 to 59 years, where it increased slightly. Additionally, there was an age-related decline in TFQIFT4 levels in both women and men at ages < 50 and < 53, respectively, but a marked increase after that. Lower TSH levels were significantly associated with a higher prevalence and lower odds of having fewer TNs using multiple nodules as the base category in both men and women (both P for trend < 0.05). Additionally, lower TFQIFT3 and TFQIFT4 levels were significantly associated with a higher prevalence of TNs in women (both P for trend < 0.05), and lower TFQIFT3 levels were significantly associated with a higher prevalence of TNs in men. Both higher TFQIFT3 and TFQIFT4 levels were significantly associated with higher odds of having fewer TNs using multiple nodules as the base category in women. However, the relationships between TFQIFT4 and the prevalence or number of TNs in men were not found. Conclusions: The trends of THs, TSH, TFQIFT4, and TFQIFT3 at different ages were sex-dependent. Both TFQIFT4 and TFQIFT3 levels were negatively associated with the prevalence and number of TNs in women. The present results may lead to a better understanding of the sex-specific relationships between the development of the pituitary-TH axis and the formation of TNs.

Relationship Between Urinary Iodine Concentration and the Prevalence of Thyroid Nodules and Subclinical Hypothyroidism.

The aim of the study was to investigate the iodine intake in the resident population in Xi'an and analyze the relationship between iodine nutritional status and the prevalence of subclinical hypothyroidism and thyroid nodules (TNs). A total of 2507 people were enrolled in Xi'an. Venous serum thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb), urinary iodine concentration (UIC), and thyroid ultrasonography were collected. Patients with abnormal TSH were checked for free thyroxine (FT4) and triiodothyronine (FT3). Adults in Xi'an had median UICs of 220.80 µg/L and 178.56 µg/l, respectively. A sum of 16.78% of people had subclinical hypothyroidism. Both iodine excess and iodine deficit increased the frequency of subclinical hypothyroidism. The lowest was around 15.09% in females with urine iodine levels between 200 and 299 µg/l. With a rate of 10.69%, the lowest prevalence range for males was 100-199 µg/l. In Xi'an, 11.37% of people have TNs. In comparison to other UIC categories, TN occurrences were higher in females (18.5%) and males (12%) when UIC were below 100 µg/l. In conclusion, iodine intake was sufficient in the Xi'an area, while the adults' UIC remains slightly higher than the criteria. Iodine excess or deficiency can lead to an increase in the prevalence of subclinical hypothyroidism. Patients with iodine deficiency are more likely to develop TNs.

Sex-Specific Associations of Five Serum Essential Metal Elements with Thyroid Nodules in Euthyroid Adults: a Cross­sectional Study.

The association between the serum essential metal elements (magnesium, iron, copper, zinc, and calcium) and thyroid nodules is still inconsistent. The current study aims to investigate the relationship of metal elements with thyroid nodules and their malignant tendency. A total of 6480 Chinese euthyroid adults were included in our study. We collect basic information through questionnaires and medical checkups. We diagnose thyroid nodules by ultrasound and detect serum trace metal concentrations by using an automatic biochemical analyzer. Binary and multinomial logistic regressions were used to investigate the associations. As a result, we found that serum copper concentrations were positively associated with thyroid nodules in the second, third, and fourth quartiles, compared to the first quartile (P = 0.024, P = 0.016, P = 0.032) in women and P for trend is 0.038. There is a significant sex-specific association between copper concentrations and thyroid nodules (P for interaction = 0.009). The results of the multinomial logistic regression analyses indicate high serum calcium and magnesium concentrations emerged as consistent risk factors for thyroid nodules in both genders, whereas low zinc was a sex-specific factor. We also observed significant sex interactions in the relationships of magnesium (P for interaction = 0.043) with thyroid nodules with malignant tendency among participants with thyroid nodules. In conclusion, our study suggests that gender is an important factor when studying the association between serum metals and thyroid nodules. The imbalance of selected metal elements (calcium, copper, zinc, and magnesium) may relate to thyroid nodules and their malignant tendency, and future prospective studies are needed to further confirm the associations.

Adjusted association between type 2 immunity and low risk thyroid nodules: a retrospective cohort study.

BACKGROUND: Immune responses, especially type 2 immunity, might be related to the prevalence of thyroid nodules, while the key regulators and potential pathways are remaining largely unknown. In addition, the immune status of individuals could be affected by mixed metabolic background. Herein our aim was to investigate the adjusted association between ultrasound-diagnosed low risk thyroid nodules and immune responses, excluding the interference of metabolic effects on immunity. METHODS: We retrospectively enrolled 1764 subjects who underwent a thorough thyroid ultrasound examination. To eliminate the interference of confounders, we used propensity score matching (PSM) to match age, gender, cigarette smoking and alcohol drinking, parameters that are related with metabolic syndrome (MetS). Then the potential effectors of immune responses involved in the laboratorial assays were evaluated. Binary logistic regression analysis was used to assess the independent predictors of thyroid nodules in a multivariate manner. RESULTS: The 1172 subjects were remained after PSM, and differences of demographic background between subjects with and without thyroid nodules were eliminated. Metabolic parameters comprising blood pressure, fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein and serum uric acid were shown no significant difference between post-PSM subjects with and without thyroid nodules. Among the biochemistry and hematological parameters, white blood cell count and the positive rate of eosinophil percentage were increased in subjects with thyroid nodules than in those without thyroid nodules. In contrast, the positive rate of basophil percentage was lower in subjects with thyroid nodules than in those without thyroid nodules. In addition, the thyroid function test results showed that subjects with thyroid nodules had higher positive rates of antithyroglobulin antibody (TgAb) and antithyroid peroxidase antibody (TPOAb) than subjects without thyroid nodules. The logistic regression analysis indicated that the positive value of TgAb as well as high level of white blood cell count and BMI could serve as independent risk factors of thyroid nodules. CONCLUSIONS: The type 2 immune responses mediated by increased level of eosinophils, along with positive value of TgAb and TPOAb were associated with the presence of thyroid nodules. In addition, the potential role of basophils in protecting against thyroid nodules and the pathogenesis of immune-metabolic status remains to be elucidated.

Clinical challenges with calcitonin-negative medullary thyroid carcinoma: three case reports and a review of the literature.

Medullary thyroid carcinoma (MTC) is relatively rare, and has the main feature of calcitonin (Ct) secretion. However, a few cases of MTC with negative serum calcitonin have been reported in the literature, so the diagnosis and follow up of Ct-negative MTCs are still a challenge. Here we present three cases of Ct-negative MTCs, illustrating the rarity of the disease and challenges in managing it, together with a review of the literature of 39 MTCs with negative serum Ct.

Preoperative thyroid-stimulating hormone associated risk of differentiated thyroid cancer in patients with thyroid nodules.

In an assessment of risk for differentiated thyroid cancer (DTC) in individuals with human papillary thyroid cancer (PTC) and thyroid nodules a cohort prospective study was undertaken to establish the significance of preoperative thyroid-stimulating hormone (TSH) levels. Confirmed histologically PTC cases in one tertiary care center, and matched healthy individuals were tested for TSH, T3, T4 and T4 free total. The ORs and 95% confidence intervals have been calculated using conditional logistic regression models (CI). The blood TSH levels were related to the higher risk of PTC for men (OR,0,09; 95% Ci, 04-0,21, 95% CI and women) compared with the middle tertile of the TSH levels in the normal range (OR,0,07; 95 percent CI, 0,04-0,1). Over the normal range of TSH levels, an elevated PTC risks were connected amongst women (OR 0,09; 95% CI, 0,04-0,21) but not amongst men (OR,0,07; 95% CI, 0,04-0,1). With an increase in TSH level in the normal range between men and women, the risk for PTC reduced (Ptrend=0.041 and 0.0001). The risk of PTC related to TSH levels has been dramatically elevated above  the normal range for men  and TSH values below the normal range for women.

Distinguishing Benign and Malignant Thyroid Nodules and Identifying Lymph Node Metastasis in Papillary Thyroid Cancer by Plasma N-Glycomics.

Background: Biomarkers are needed for patient stratification between benign thyroid nodules (BTN) and thyroid cancer (TC) and identifying metastasis in TC. Though plasma N-glycome profiling has shown potential in the discovery of biomarkers and can provide new insight into the mechanisms involved, little is known about it in TC and BTN. Besides, several studies have indicated associations between abnormal glycosylation and TC. Here, we aimed to explore plasma protein N-glycome of a TC cohort with regard to their applicability to serve as biomarkers. Methods: Plasma protein N-glycomes of TC, BTN, and matched healthy controls (HC) were obtained using a robust quantitative strategy based on MALDI-TOF MS and included linkage-specific sialylation information. Results: Plasma N-glycans were found to differ between BTN, TC, and HC in main glycosylation features, namely complexity, galactosylation, fucosylation, and sialylation. Four altered glycan traits, which were consecutively decreased in BTN and TC, and classification models based on them showed high potential as biomarkers for discrimination between BTN and TC ("moderately accurate" to "accurate"). Additionally, strong associations were found between plasma N-glycans and lymph node metastasis in TC, which added the accuracy of predicting metastasis before surgery to the existing method. Conclusions: We comprehensively evaluated the plasma N-glycomic changes in patients with TC or BTN for the first time. We determined several N-glycan biomarkers, some of them have potential in the differential diagnosis of TC, and the others can help to stratify TC patients to low or high risk of lymph node metastasis. The findings enhanced the understanding of TC.

Changes in thyroid antibody and T lymphocyte subsets after radiofrequency ablation of thyroid nodules in patients with autoimmune thyroiditis.

SETTINGS AND DESIGN: The aim was to study the changes in thyroid antibody and T lymphocyte subsets after radiofrequency ablation (RFA) of thyroid nodules in patients with autoimmune thyroiditis. SUBJECTS AND METHODS: Patients (n = 135) with autoimmune thyroiditis and thyroid nodules were treated by RFA. The indices of thyroid function and thyroid antibody and T lymphocyte subsets were examined preoperation and on the 1st day and the 1st month after ablation. Any complications were recorded. STATISTICAL ANALYSIS: The software SPSS 17.0.0 (version: 2008-8-23) running under Windows 8 was used for statistical analysis. The measurement data were expressed as x ± s, with P < 0.01 indicating a significant difference in the statistical data. RESULTS: Levels of free triiodothyronine, free thyroxine, and thyroid-stimulating hormone were in the normal range before ablation, and no significant changes occurred on the 1st day or in the 1st month after ablation. The change in the percentage of CD8+T cells and the absolute value of B cells were not statistically significant (P > 0.01), and the values were in the normal range. Compared with values recorded preoperation, the value of TG-Ab, TPO-Ab, CD4+/CD8+, the percentage of CD4+T cells, the absolute values of lymphocytes, T cells, CD4+T cells, and CD8+T cells decreased significantly at the 1st day after ablation (P < 0.01) and then recovered to preoperative levels during the first 30 days after ablation (P > 0.01). Within 1 month after ablation, none of the patients had complications such as active bleeding, infection, recurrent laryngeal nerve injury, parathyroid gland injury, skin scald, and so on. CONCLUSIONS: After RFA of thyroid nodules in patients with autoimmune thyroiditis, thyroid function is not affected and no serious complications occurred. TG-Ab and TPO-Ab levels can be significantly decreased, and the distribution of T lymphocyte subsets can be changed in the short term after ablation.

Evaluation of serum insulin-like growth factor 1 and its significance in thyroid cancer: An observational study.

ABSTRACT: Serum insulin-like growth factor 1 (IGF-1) is elevated in different cancers. However, relationships between serum IGF-1 and thyroid cancer (TC) are scarce. The present study aimed to investigate the clinical significance of serum IGF-1 in TC.Serum was collected from 124 TC patients, 50 patients with benign nodules, and 50 healthy controls. Serum IGF-1 levels were measured and compared. Relationships were investigated between IGF-1 and clinical characteristics. A receiver operating characteristic (ROC) curve was plotted to explore the diagnostic value of IGF-1 in TC.Serum IGF-1 levels were significantly higher in TC than that of healthy controls and benign nodules (P = .003; P < .001). Serum IGF-1 levels were higher in TC patients with advanced stage than early stage (P = .029). Higher serum IGF-1 levels were found in patients with lymph node metastasis present and (tumor size >1 cm) than that of patients without lymph node metastasis (P = .018) and (tumor size ≤1 cm) (P = .031). Serum IGF-1 levels were higher in patients with a solitary nodule than multinodular nodules (P = .043). The serum IGF-1 cutoff value for a TC diagnosis was 216 ng/mL with a sensitivity of 53.2%, a specificity of 74.0%, a positive predictive value (PPV) of 83.5%, and an area under the curve was of 0.71.Serum IGF-1 was significantly correlated with tumor stage, size, and lymph node metastasis. Serum IGF-1 shows great potential as a laboratory marker for TC.

Plasma Cell-Free DNA to Differentiate Malignant from Benign Thyroid Nodules.

BACKGROUND: Molecular testing is increasingly used to identify malignancy in thyroid nodules (especially indeterminate category). Measurement of cell-free DNA (cfDNA) levels from plasma has been useful in diagnosis of cancers of other organs/tissues; herein we analyze cfDNA levels in patients with thyroid nodules to explore the possibility of establishing a cutoff for identification of malignancy. METHODS: Patients underwent ultrasonography (USG) and USG-guided fine needle aspiration as well as surgery, where indicated. Cell-free DNA was extracted from plasma and quantified. In initial analysis (determination of cutoff), cfDNA levels were compared between Bethesda 2 and Bethesda 5 &6 to establish a cutoff value that could differentiate malignant from benign nodules. In the subsequent analysis, the aforementioned cutoff was applied (validation of cutoff) to those with indeterminate nodules to check ability to predict malignancy. RESULTS: Fine needle aspiration (n = 119) yielded patients with Bethesda 2 (n = 69) Bethesda 5 & 6 (n = 13) who underwent histopathological confirmation. Cell-free DNA levels in these 2 groups were 22.85 ±â€…1.27 and 96.20 ±â€…8.31 (ng/mL) respectively. A cfDNA cutoff of 67.9 ng/mL, with area under the curve of 0.992 (95% CI, 0.97-1.0) with 100% sensitivity and 93% specificity was established to identify malignant lesions. Indeterminate group (Bethesda 3 & 4) underwent surgery (malignant n = 24), (benign n = 13), and using the previously identified cutoff for cfDNA, we were able to identify malignant lesions with a sensitivity of 100% and specificity of 92.3%. There was a very strong agreement between cfDNA-based classification with histopathology-based classification of benign and malignant nodules (Cohen's kappa 0.94; P < 0.001). CONCLUSION: Plasma cfDNA estimation could help differentiate malignant from benign thyroid nodules.

Identifying benign and malignant thyroid nodules based on blood serum surface-enhanced Raman spectroscopy.

The aim of this study is to evaluate the feasibility of using blood serum surface-enhanced Raman spectroscopy (SERS) to identify benign and malignant thyroid nodules. Blood serum samples collected from three different groups including healthy volunteers (n = 22), patients with benign nodules (n = 19) and malignant nodules (n = 22) were measured by SERS. The spectral analysis results demonstrate that biomolecules in serum, such as amino acids, adenine and nucleic acid bases, change differently due to the different progression of nodules. By further combining with partial least square analysis and linear discriminant analysis (PLS-LDA) method, diagnostic accuracies of 93.65% and 82.93%, sensitivities of 92.68% and 81.82% and specificities of 95.45% and 84.21% can be achieved for differentiating healthy versus thyroid nodular groups and benign versus malignant groups, respectively. The above results have suggested that the blood serum SERS technique is helpful for precise diagnosis and timely treatment for patients with thyroid nodules.

MiRNA let-7 from TPO(+) Extracellular Vesicles is a Potential Marker for a Differential Diagnosis of Follicular Thyroid Nodules.

BACKGROUND: The current approaches to distinguish follicular adenomas (FA) and follicular thyroid cancer (FTC) at the pre-operative stage have low predictive value. Liquid biopsy-based analysis of circulating extracellular vesicles (EVs) presents a promising diagnostic method. However, the extreme heterogeneity of plasma EV population hampers the development of new diagnostic tests. We hypothesize that the isolation of EVs with thyroid-specific surface molecules followed by miRNA analysis, may have improved diagnostic potency. METHODS: The total population of EVs was isolated from the plasma of patients with FA (n = 30) and FTC (n = 30). Thyroid peroxidase (TPO)-positive EVs were isolated from the total populations using immune-beads. The miRNA from the TPO(+)EVs obtained from the plasma of FA and FTC patients was assayed by RT-PCR. The diagnostic potency of the selected miRNAs was estimated by the receiver operating characteristic (ROC) analysis. RESULTS: TPO(+)EVs can be efficiently isolated by immunobeads. The analysis of Let-7 family members in TPO(+)EVs allows one to distinguish FA and FTC with high accuracy (area under curve defined by ROC = 0.77-0.84). CONCLUSION: The isolation of TPO(+)EVs, followed by RT-qPCR analysis of Let-7 family members, may present a helpful approach to manage follicular nodules in the thyroid gland.

Serum Adiponectin and Progranulin Level in Patients with Benign Thyroid Nodule or Papillary Thyroid Cancer.

BACKGROUND: Obesity is associated with thyroid cancer risk. Adiponectin has insulin-sensitizing and anti-inflammatory effects, while progranulin is associated with inflammation and tumorigenesis. We investigated serum adiponectin and progranulin levels in patients with benign thyroid nodule (benign group) and papillary thyroid cancer (PTC; PTC group). The associations between these levels and the clinicopathological features of PTC were evaluated. METHODS: We included 157 patients who underwent thyroid surgery (17% of benign and 83% of PTC group). Clinicopathological features including size, lymph node metastasis, extrathyroidal extension (ETE), multifocality, American Thyroid Association risk stratification were evaluated. RESULTS: The age was 42.0 years, and 69% were female. Serum adiponectin and progranulin levels were 6.3 µg/mL and 101.5 ng/mL in the benign group and 5.4 µg/mL and 106.1 ng/mL in the PTC group, respectively (P=0.6 and P=0.4, respectively). Serum adiponectin levels showed no significant differences according to clinicopathological features of PTC. The proportions of patients with primary tumor size >1 cm were 3%, 5%, 8%, and 8% according to serum progranulin level quartiles, respectively (P=0.03). The proportions of patients with microscopic/gross ETE were 8%/0%, 9%/1%, 11%/1%, and 11%/2% according to serum progranulin level quartiles, respectively. Median serum progranulin level was significantly higher in patients with PTC >1 cm than in patients with papillary thyroid microcarcinoma (P=0.04, 115.3 ng/mL and 104.7 ng/mL, respectively). CONCLUSION: Serum adiponectin and progranulin levels showed no significant difference between benign and PTC groups. Increased serum progranulin levels were significantly associated with PTC >1 cm and microscopic and gross ETE.