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.

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.

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.

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.

Exosomal miRNAs are potential diagnostic biomarkers between malignant and benign thyroid nodules based on next-generation sequencing.

An accurate biomarker or method for diagnosis of thyroid nodule with indeterminate fine-needle aspiration result is essential for clinical treatment. Micro RNAs (miRNAs) of exosomes are advantageous in the diagnosis of tumors because they are highly stable, and be protected by a bilayer membrane structure. Exosomes were isolated from 13 papillary thyroid carcinoma (PTC) and 7 nodular goiter (NG) patients' plasma. Small RNA sequencing was performed on exosomes' RNA in next-generation sequencing (NGS) platform. Then, we performed comprehensive analysis on miRNA expression profile in exosome of two groups. One hundred and twenty-nine differentially expressed miRNAs were identified in plasma exosomes between PTC and NG patients. Forty-nine miRNAs were up-regulated, and 80 miRNAs were down-regulated in PTC patients. Receiver operating characteristic (ROC) curves of 129 miRNAs were plotted. Area under curve (AUC) of 129 miRNAs was 0.571-0.951, with distribution peak of 0.82-0.86. AUC of 11 miRNAs was above 0.9, miR-5189-3p had the most optimal performance for diagnosis between PTC and NG, with 0.951 of AUC. Target genes of 129 miRNAs were enriched into 7 cancer-related signaling pathways, including mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF), NF-kappa B signaling pathway and so on. This study profiled the miRNA signature of exosomes from PTC patients and NG patients. We proposed a group of miRNAs in plasma exosomes as candidate biomarkers for thyroid nodule diagnosis.

Usefulness of Serum Calcitonin in Patients with Thyroid Nodules ≤ 1 cm Without an Indication for Fine-Needle Aspiration.

Fine-needle aspiration (FNA) is not necessary in adults with nodules ≤ 1 cm without apparent extrathyroidal extension (ETE) or lymph node (LN) involvement on ultrasonography (US). In the absence of FNA and serum calcitonin (Ctn) measurement, medullary thyroid microcarcinomas (microMTC) are not diagnosed. The aim of this prospective study was to evaluate Ctn levels in adults with a low clinical risk of MTC and nodules ≤ 1 cm without ETE or LN involvement on US. A total of 506 consecutively seen adults who had nodules with two or more suspicious features were included. Patients with elevated basal Ctn underwent a calcium stimulation test and FNA. Basal Ctn was normal in 490 patients (96.8%). In the 16 patients with elevated basal Ctn, FNA revealed MTC in only one patient and MTC was not suspected in the 15 patients with elevated basal Ctn. Three patients with stimulated Ctn<100 pg/ml and benign cytology were not submitted to surgery. MTC was excluded by histology in three patients with stimulated Ctn<100 pg/ml and indeterminate or suspicious cytology and in eight patients with stimulated Ctn>100 pg/ml. One patient with stimulated Ctn>100 pg/ml had MTC. Ctn was undetectable 6 months after surgery in two patients with MTC. Although uncommon, even subjects without a suspicious history and with nodules ≤ 1 cm without ETE or LN involvement on US, but with suspicious findings, can have microMTC. The measurement of Ctn permits the diagnosis of these cases.

Calcitonin testing for detection of medullary thyroid cancer in people with thyroid nodules.

BACKGROUND: Thyroid nodules are very common in general medical practice, but rarely turn out to be a medullary thyroid carcinoma (MTC). Calcitonin is a sensitive tumour marker for the detection of MTC (basal calcitonin). Sometimes a stimulation test is used to improve specificity (stimulated calcitonin). Although the European Thyroid Association's guideline advocates calcitonin determination in people with thyroid nodules, the role of routine calcitonin testing in individuals with thyroid nodules is still questionable. OBJECTIVES: The objective of this review was to determine the diagnostic accuracy of basal and/or stimulated calcitonin as a triage or add-on test for detection of MTC in people with thyroid nodules. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and Web of Science from inception to June 2018. SELECTION CRITERIA: We included all retrospective and prospective cohort studies in which all participants with thyroid nodules had undergone determination of basal calcitonin levels (and stimulated calcitonin, if performed). DATA COLLECTION AND ANALYSIS: Two review authors independently scanned all retrieved records. We extracted data using a standard data extraction form. We assessed risk of bias and applicability using the QUADAS-2 tool. Using the hierarchical summary receiver operating characteristic (HSROC) model, we estimated summary curves across different thresholds and also obtained summary estimates of sensitivity and specificity at a common threshold when possible. MAIN RESULTS: In 16 studies, we identified 72,368 participants with nodular thyroid disease in whom routinely calcitonin testing was performed. All included studies performed the calcitonin test as a triage test. Median prevalence of MTC was 0.32%. Sensitivity in these studies ranged between 83% and 100% and specificity ranged between 94% and 100%. An important limitation in 15 of the 16 studies (94%) was the absence of adequate reference standards and follow-up in calcitonin-negative participants. This resulted in a high risk of bias with regard to flow and timing in the methodological quality assessment. At the median specificity of 96.6% from the included studies, the estimated sensitivity (95% confidence interval (CI)) from the summary curve was 99.7% ( 68.8% to 100%). For the median prevalence of MTC of 0.23%, the positive predictive value (PPV) for basal calcitonin testing at a threshold of 10 pg/mL was 7.7% (4.9% to 12.1%). Summary estimates of sensitivity and specificity for the threshold of 10 pg/mL of basal calcitonin testing was 100% (95% CI 99.7 to 100) and 97.2% (95% CI 95.9 to 98.6), respectively. For combined basal and stimulated calcitonin testing, sensitivity ranged between 82% and 100% with specificity between 99% and 100%. The median specificity was 99.8% with an estimated sensitivity of 98.8% (95% CI 65.8 to 100) . AUTHORS' CONCLUSIONS: Both basal and combined basal and stimulated calcitonin testing have a high sensitivity and specificity. However, this may be an overestimation due to high risk of bias in the use and choice of reference standard The value of routine testing in patients with thyroid nodules remains questionable, due to the low prevalence, which results in a low PPV of basal calcitonin testing. Whether routine calcitonin testing improves prognosis in MTC patients remains unclear.

Thyroglobulin can be a functional biomarker of iodine deficiency, thyroid nodules, and goiter in Chinese pregnant women.

BACKGROUND AND OBJECTIVES: Thyroglobulin (Tg) is considered a sensitive indicator of iodine status for children and adults, but its usefulness for pregnant women is unknown. The aim of this study was attempting to explore the relationship between Tg and iodine status and the association between elevated Tg and thyroid diseases. METHODS AND STUDY DESIGN: A total of 2163 pregnant women were recruited in this study. The ratio of urine iodine concentration and urine creatinine concentration (UI/Cr) was measured in spot urine samples. Serum thyroid hormones and thyroglobulin were measured. Thyroid nodules and thyroid volume were diagnosed by ultrasound. RESULTS: The geometric mean of serum Tg was significantly higher in the UI/Cr <100 µg/g group (10.94 [2.47] µg/L) and the UI/Cr >500 µg/g group (11.48 [2.35] µg/L) than in the 150-249 µg/g group (9.64 [2.32] µg/L). The generalized linear model analysis showed that Serum log(10) Tg concentration was much higher in the UI/Cr <100 µg/g group (ß=0.052, p=0.026) than in the 150-249 µg/g group. Multivariate logistic regression models demonstrated that elevated Tg may be a risk factor for both goiter (OR=8.30) and thyroid nodules (OR=2.73). CONCLUSIONS: Pregnant women with UI/Cr <100 µg/g have a higher Tg, and those with elevated Tg concentrations have a higher risk of thyroid nodules and goiter. Tg can be a functional biomarker of iodine deficient, thyroid nodules and goiter.

Serum-plasma matched metabolomics for comprehensive characterization of benign thyroid nodule and papillary thyroid carcinoma.

Metabolomics offers a noninvasive methodology to identify metabolic markers for pathogenesis and diagnosis of diseases. This work aimed to characterize circulating metabolic signatures of benign thyroid nodule (BTN) and papillary thyroid carcinoma (PTC) via serum-plasma matched metabolomics. A cohort of 1,540 serum-plasma matched samples and 114 tissues were obtained from healthy volunteers, BTN and PTC patients enrolled from 6 independent centers. Untargeted metabolomics was determined by liquid chromatography-quadrupole time-of-flight mass spectrometric and multivariate statistical analyses. The use of serum-plasma matched samples afforded a broad-scope detection of 1,570 metabolic features. Metabolic phenotypes revealed significant pattern differences for healthy versus BTN and healthy versus PTC. Perturbed metabolic pathways related mainly to amino acid and lipid metabolism. It is worth noting that, BTN and PTC showed no significant differences but rather overlap in circulating metabolic signatures, and this observation was replicated in all study centers. For differential diagnosis of healthy versus thyroid nodules (BTN + PTC), a panel of 6 metabolic markers, namely myo-inositol, α-N-phenylacetyl-L-glutamine, proline betaine, L-glutamic acid, LysoPC(18:0) and LysoPC(18:1) provided area under the curve of 97.68% in the discovery phase and predictive accuracies of 84.78-98.18% in the 4 validation centers. Taken together, serum-plasma matched metabolomics showed significant differences in circulating metabolites for healthy versus nodules but not for BTN versus PTC. Our results highlight the true metabolic nature of thyroid nodules, and potentially decrease overtreatment that exposes patients to unnecessary risks.

Evaluating pre- and post-operation plasma miRNAs of papillary thyroid carcinoma (PTC) patients in comparison to benign nodules.

BACKGROUND: Thyroid cancer is the most common endocrinology cancer that its incidence has increased in recent decades. miRNAs are new biomarkers in recent studies in the diagnosis and follow-up of these patients. METHODS: Blood and thyroid tissue samples were obtained from two groups of included patients (PTC and benign nodules), pre- and post-operation. miRNAs were extracted from these plasma samples and were measured quantitatively. After cDNA synthesis, qPCR was carried out. Then tissue samples were investigated, and their relation to miR expression was studied. These results were analyzed by paired- and independent samples t-test, and non-parametric tests. RESULTS: miR-222 and miR-181a declined in PTC patients before and after surgery, significantly (P < 0.001 for both groups), with no significant difference in control group before and after surgery (P = 0.61 for miR-222 and P = 0.06 for miR-181a). The difference between the two groups, pre-and post-operation, was statistically significant (P = 0.01 for miR-222 and P < 0.001 for miR-181a). Comparing case and control groups, pre- and post-operatively, yielded no significant difference, in miR-155-5p levels (P = 0.61 and P = 0.53, respectively). Comparing PTC and control groups before surgery showed a significant difference (P = 0.01), while no significant difference was observed comparing them after surgery, in miR146-a (P = 0.27). Our results depicted a higher miR-155-5p and miR-146a expression before surgery than after it (P < 0.001 in both groups, for both miRs). We found a significant relationship between miR-222 and BRAFV600E mutation and significantly higher levels of miR-181a with increasing tumor size in PTC patients. CONCLUSION: miR-222 showed overexpression in all PTC cases, which is indicative of a relation between miRNA and PTC. Also, comparing miR-181 and miR-146a showed a significant difference between cancerous and benign cases. miR-155-5p as an inflammatory factor, showed no significant changes, comparing two groups.

Variation in the Quality of Thyroid Nodule Evaluations Before Surgical Referral.

BACKGROUND: Thyroid nodules are highly prevalent, and owing to their malignant potential, proper evaluation is imperative. The objective of this study was to characterize variation in thyroid nodule evaluations. MATERIALS AND METHODS: This retrospective review included all consecutive surgical referrals for thyroid nodules from October to December 2017 at a single institution. We determined the proportion of evaluations that contained a thyroid-stimulating hormone (TSH) level and a high-quality ultrasound because these components of thyroid nodule evaluations are common to several evidence-based guidelines. RESULTS: The study cohort included 64 patients, with a median age of 51.5 y. Primary care providers referred most patients (51.6%), followed by endocrinologists (40.6%), and other specialists (7.8%). In total, 35.9% of evaluations did not include a TSH value, which is vital to any thyroid nodule evaluation. Most evaluations (95.3%) included a dedicated ultrasound, but only 12.3% of ultrasound reports commented on nodule size in three dimensions, structure, echogenicity, and lymph nodes, which we considered the minimum commentary indicative of a high-quality ultrasound. Only 51.5% of evaluations included both a TSH and a thyroid ultrasound. If patients receiving low-quality ultrasound reports were excluded, 9.4% of the entire cohort received a guideline-concordant, high-quality evaluation. CONCLUSIONS: Great variation exists in the quality of thyroid nodule evaluations before surgical referral. Two necessary components of thyroid nodule evaluations that contribute most to the observed deviation from guidelines are obtaining a TSH value and obtaining an ultrasound with enough information to risk stratify the nodule.

Changes of serum 25(OH) D3 and IGF-1 levels in patients with thyroid nodules.

BACKGROUND: The present study aimed to study the relationship between serum 25 hydroxyvitamin D3(25(OH)D3) and insulin-like growth factor-1 (IGF-1) and thyroid nodules. METHODS: Two hundred eighty-nine cases with thyroid nodules and 109 health subjects (control group) who admitted to the Hebei General Hospital during June 2016 to December 2016 were included in the study. Basic clinical information (age, sex, thyroid function, liver and kidney function, hypertension history, etc.) of patients were collected. Serum 25(OH) D3 and Serum IGF-1 were detected by electrochemiluminescence and radioimmunoassay methods, respectively. The relationship between the above-mentioned factors and thyroid nodules was statistically analyzed. RESULTS: Serum 25(OH)D3, IGF-1, fasting blood glucose (FBG), total cholesterol (TC), waist circumference (WC), total triiodothyronine (TT3), total thyroxine (TT4), hypertension history, and drinking history were significantly different between the nodules group and the control group (P < 0.05). Logistic regression analysis showed that there was a negative correlation between thyroid nodules and levels of 25(OH)D3, IGF-1, TT3, as well as a positive correlation with FBG, TC, TT4, and hypertension. There was a positive correlation between IGF-1 and serum 25(OH)D3 in thyroid nodules (P < 0.05). After correcting the aforementioned factors, high-level of serum 25(OH)D3 was significantly correlated with the decreased incidence of thyroid nodules. CONCLUSIONS: The incidence of thyroid nodules is relatively lower in a high-level of serum 25(OH)D3, and serum 25(OH)D3 may be a direct protective factor for thyroid nodules. Serum IGF-1 can be one of the indirect protective factors for thyroid nodules as well.

Calcitonin negative Medullary Thyroid Carcinoma: a challenging diagnosis or a medical dilemma?

BACKGROUND: Medullary thyroid carcinoma is a neuroendocrine tumor belonging form a malignant growth of the thyroid parafollicular C-cells, representing from 1 to 10% of all thyroid cancer. The biochemical activity of medullary thyroid carcinoma includes the production of calcitonin and carcinoembryogenic antigen, which are sensitive tumor markers, facilitating the diagnosis, follow-up and prognostication. The diagnosis is reached through the identification of high basal calcitonin serum level or after pentagastrin stimulation test. Medullary thyroid carcinoma is able to produce other relevant biomarkers as procalcitonin, carcinoembryionic antigen and chromogranin A. In Literature are described few cases of medullary thyroid carcinoma without elevation of serum calcitonin, an extremely rare event. The aim of this study was to analyse the presentation, the main features and therapeutic management of medullary thyroid carcinoma associated with negative serum calcitonin levels. METHODS: Using the PubMed database, a systematic review of the current Literature was carried out, up to February 2018. Finally, nineteen articles met our inclusion criteria and were selected according to the modified Newcastle-Ottawa scale. RESULTS: Fourty-nine patients with definitive pathology confirming medullary thyroid carcinoma and with calcitonin serum level in the normal range were identified (24 female, 24 male and not reported gender in 1 case). Mean age was 51.7 years. Serum calcitonin levels were reported for 20 patients with a mean value of 8.66 pg/mL and a range of 0.8-38 pg/mL. Despite the low or undetectable calcitonin serum level, at immunochemistry in almost the half of the cases reported by the Authors, the tumors presented diffuse or focal positivity for calcitonin and carcinoembryionic antigen, while was reported a chromogranin A positivity in 41 of the 43 tested patients. CONCLUSIONS: Calcitonin negative medullary thyroid carcinoma is an extremely rare pathology. The diagnosis and the surveillance is often challenging and delayed, due to the lack of elevation of serum markers as calcitonin and carcinoembryionic antigen. Further studies are needed, to better define options for management of non secretory medullary thyroid carcinoma and to identify new and reliable biomarkers associated to diagnosis and relapse of this medical dilemma.

The effect of disease activity on thyroid nodules in patients with acromegaly.

Nodular thyroid disease is a very common disorder in patients with acromegaly. Insulin-like growth factor-1 (IGF-1) is a thyroid growth factor, and there is a correlation between IGF-1 levels and thyroid volume (TV) in patients with acromegaly. There is no study investigating the impact of somatostatin analog (SSA) treatment on thyroid nodule volume in patients with acromegaly. We aimed to assess thyroid nodule volume change with SSA treatment in patients with persistent acromegaly. We retrospectively analyzed data from 108 consecutive patients with acromegaly who were followed up by our clinic after undergoing surgery between 2002 and 2014. Patients who were cured after surgery were excluded. We only selected 43 patients (21 males, 22 females, mean age 52.8 ± 11.9 years) who did not meet the criteria of remission postoperatively, who were treated with SSA for at least six months and had normal thyroid function. Patients were divided into three groups (well-controlled, controlled, and active) according to their IGF-1 and growth hormone (GH) levels. All patients underwent an evaluation of TV and total thyroid nodule volume (TTNV) by ultrasound. TTNV decreased significantly in patients with well-controlled acromegaly (0.44 [0.75] to 0.23 [0.73], p < 0.001). TTNV did not change in controlled patients (0.18 [1.28] to 0.13 [1.54], p = 0.959); however TTNV increased in patients with active acromegaly (0.77 [1.46] to 1.03 [1.88], p = 0.028). Successful medical treatment of patients with active acromegaly decreases thyroid nodule volume. Sustained exposure to IGF-1 may cause an increase in thyroid nodule volume in patients with acromegaly.

MEAN PLATELET VOLUME: AN OVERLOOKED HERALD OF MALIGNANT THYROID NODULES.

Physicians and surgeons pay much attention to evaluating thyroid nodules due to the malignant potential of these growths. Inflammation has a crucial role in the development of cancer. Increase in the mean platelet volume (MPV) has been described in various inflammatory conditions. Since some of thyroid nodules are malignant, we aimed to compare MPV values between patients with malignant and benign thyroid nodules after precise pathologic diagnosis. We retrospectively analyzed hemograms of patients having undergone thyroid surgery for thyroid nodule between January 2013 and January 2015, and compared them to those recorded in healthy subjects. MPV was higher in the malignant thyroid nodule group than in the benign nodule group (9.1±1 fL vs. 7.8±0.8 fL). The difference was statistically significant (p<0.001). Increased MPV should be considered as an assistive diagnostic tool in differentiating malignant and benign thyroid nodules. However, further prospective studies are required to confirm its usefulness in this population.

Procalcitonin measurement to screen medullary thyroid carcinoma: A prospective evaluation in a series of 2705 patients with thyroid nodules.

BACKGROUND: To prospectively evaluate the role of procalcitonin (PCT) in screening of patients with thyroid nodules for medullary thyroid carcinoma (MTC). MATERIALS AND METHODS: We measured PCT in 2705 patients with thyroid nodules referred to our centre between January 2011 and December 2017. Those with a positive PCT were operated after positive confirmatory tests such as fine-needle aspiration, measurement of calcitonin (CT) in serum and fine-needle aspiration washouts or CT stimulation testing. Patients with a negative PCT were operated based on the results of further diagnostics. The diagnostic performance of PCT was evaluated, and the best cut-off level was selected by ROC curve analysis. RESULTS: Among 2705 patients, 9 with positive serum PCT (ie, above 0.1 µg/L) and 370 with negative PCT underwent thyroid surgery. MTC was histologically confirmed in all patients with positive PCT but not found in patients with negative PCT. Serum PCT levels were significantly higher in patients with MTC (median 0.64 µg/L, range 0.16-12.9 µg/L) than in those without (median 0.075 µg/L, range 0.075-0.16 µg/L; P < .0001). ROC curves were plotted to calculate the optimal PCT value separating patients with MTC from those without. The best cut-off was 0.155 µg/L with sensitivity, specificity, positive and negative predictive values as well as accuracy of 100%, 99.7%, 91.7%, 100% and 99.7%, respectively. Positive and negative likelihood ratios were 329 and zero, respectively. CONCLUSIONS: Measurement of PCT is a sensitive and accurate method for detecting MTC in patients with thyroid nodules and can thus be a reliable alternative to CT measurement.

A predictive model of thyroid malignancy using clinical, biochemical and sonographic parameters for patients in a multi-center setting.

BACKGROUND: Thyroid nodules are highly prevalent, but a robust, feasible method for malignancy differentiation has not yet been well documented. This study aimed to establish a practical model for thyroid nodule discrimination. METHODS: Records for 2984 patients who underwent thyroidectomy were analyzed. Clinical, laboratory, and US variables were assessed retrospectively. Multivariate logistic regression analysis was performed and a mathematical model was established for malignancy prediction. RESULTS: The results showed that the malignant group was younger and had smaller nodules than the benign group (43.5 ± 11.6 vs. 48.5 ± 11.5 y, p < 0.001; 1.96 ± 1.16 vs. 2.75 ± 1.70 cm, p < 0.001, respectively). The serum thyrotropin (TSH) level (median = 1.63 mIU/L, IQR (0.89-2.66) vs. 1.19 (0.59-2.10), p < 0.001) was higher in the malignant group than in the benign group. Patients with malignancies tested positive for anti-thyroglobulin antibody (TGAb) and anti-thyroid peroxidase antibody (TPOAb) more frequently than those with benign nodules (TGAb, 30.3% vs. 15.0%, p < 0.001; TPOAb, 25.6% vs. 18.0%, p = 0.028). The prevalence of ultrasound (US) features (irregular shape, ill-defined margin, solid structure, hypoechogenicity, microcalcifications, macrocalcifications and central intranodular flow) was significantly higher in the malignant group. Multivariate logistic regression analysis confirmed that age (OR = 0.963, 95% CI = 0.934-0.993, p = 0.017), TGAb (OR = 4.435, 95% CI = 1.902-10.345, p = 0.001), hypoechogenicity (OR = 2.830, 95% CI = 1.113-7.195, p = 0.029), microcalcifications (OR = 4.624, 95% CI = 2.008-10.646, p < 0.001), and central intranodular flow (OR = 2.155, 95% CI = 1.011-4.594, p < 0.05) were independent predictors of thyroid malignancy. A predictive model including four variables (age, TGAb, hypoechogenicity and microcalcification) showed an optimal discriminatory accuracy (area under the curve, AUC) of 0.808 (95% CI = 0.761-0.855). The best cut-off value for prediction was 0.52, achieving sensitivity and specificity of 84.6% and 76.3%, respectively. CONCLUSION: A predictive model of malignancy that combines clinical, laboratory and sonographic characteristics would aid clinicians in avoiding unnecessary procedures and making better clinical decisions.

Retrospective Analysis of Thyroid Nodules: Thyroid Cancer Risk Factors in Suzhou, China.

BACKGROUND: Thyroid nodules are common, frequently discovered in clinical practice and the incidence has increased in recent decades. They are clinically important primarily due to their malignant potential, because 2 to 5% are malignant. Correct identification of the malignancy in thyroid nodules is a diagnostic challenge, leading to potentially unnecessary surgery in patients for whom final histology is benign. Because there is no accurate preoperative detection, it is very important to predict the risk of malignancy in patients with nodular thyroid disease. METHODS: The medical records of 405 patients who underwent surgery for nodular thyroid disease were retrospectively reviewed. Then clinical parameters and preoperative serum markers were compared between benign thyroid nodular disease and thyroid cancer groups. RESULTS: Younger than 40 years (OR 2.14, 95% CI 1.02 - 4.47, p = 0.044), preoperative TSH levels equal to or higher than 1.79 mIU/L (OR 1.76, 95% CI 1.05 - 2.95, p = 0.033), TgAb positivity (OR 2.59 95% CI 1.25 - 5.37, p = 0.01) and nodules less than or equal to 1 cm (OR 5.51, 95% CI 2.61 - 11.66, p < 0.001) were associated with increased risk of thyroid cancer in patients with thyroid nodules. CONCLUSIONS: The retrospective analysis suggests that younger patients with nodular thyroid disease cannot ignore the small size nodules, especially those with higher TSH levels and TgAb positivity.

IS MEASUREMENT OF CIRCULATING TUMOR DNA OF DIAGNOSTIC USE IN PATIENTS WITH THYROID NODULES?

OBJECTIVE: Circulating tumor DNA (ctDNA), a subset of cell-free DNA (cfDNA), is a potential biomarker for thyroid cancer. We determined the performance of a ctDNA panel for detecting thyroid malignancy in patients with thyroid nodules. METHODS: Sixty-six patients with thyroid nodules without a prior history of cancer enrolled in a prospective, 1-year study in which blood was drawn for ctDNA analysis prior to undergoing fine-needle aspiration biopsy (FNAB) of thyroid nodules. The ctDNA panel consisted of 96-mutations in 9 cancer driver genes. The primary outcome measures were the sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of our ctDNA panel for the diagnosis of thyroid malignancy as determined by pathologic and/or molecular tissue examination. RESULTS: Results from 10 subjects could not be determined due to inadequate volume or technical issues. The final classifications of the thyroid nodules were 13 malignant and 43 benign lesions. A KRAS G12V mutation was detected in the plasma of 1 patient with stage IVA papillary carcinoma whose tissue contained the same mutation. Two of the 43 patients with benign lesions also had ctDNA detected, giving a sensitivity of 7.7%, specificity of 95.35%, PPV of 33.33%, and NPV of 77.35%. There were no significant differences between benign or malignant lesions in cfDNA levels. CONCLUSION: Neither cfDNA measurements nor our panel of ctDNA mutations are sensitive or specific enough to provide valuable information over FNAB. An expanded panel and the inclusion of proteomics may improve sensitivity and specificity for thyroid cancer detection. ABBREVIATIONS: cfDNA = cell-free DNA; ctDNA = circulating tumor DNA; FNAB = fine-needle aspiration biopsy; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features.

High Serum Thyrotropin Concentrations within the Reference Range: A Predictor of Malignancy in Nodular Thyroid Disease.

OBJECTIVE: This study assessed whether or not a simple biochemical parameter, serum thyrotropin (TSH), within the reference range can predict the likelihood of thyroid malignancy in subjects undergoing fine-needle aspiration biopsy (FNAB) for thyroid nodules. SUBJECTS AND METHODS: This cross-sectional study evaluated 236 patients without overt thyroid dysfunction who were not on levothyroxine therapy. They underwent FNAB of the thyroid nodules at the Clementino Fraga Filho University Hospital between 2011 and 2012. The reference range and serum TSH quartiles were determined according to age-specific values for serum TSH and then compared between the cases with benign thyroid nodular disease and differentiated thyroid carcinoma (DTC) based on surgical pathology reports. RESULTS: Of the 236 patients, 201 (85.1%) underwent a surgical procedure (thyroidectomy) and 89/236 (44.3%) had DTC. The mean TSH concentrations were 2.09 ± 1.15 mU/L in benign patients versus 2.73 ± 1.33 mU/L in cases of DTC (p < 0.01). As TSH increased from quartiles 1 to 4, the frequency of a malignant diagnosis also increased progressively from 22% in quartile 1 to 65% in the last quartile (p ≤ 0.001). CONCLUSION: Thyrotropin levels were positively associated with the diagnosis of DTC in thyroid nodules.