Prevalence of thyroid diffuse goiter and its association with body mass index and the presence of cysts and nodules in children and adolescents: the Fukushima Health Management Survey.

The main cause of diffuse thyroid goiter is autoimmune chronic thyroiditis, otherwise known as Hashimoto's thyroiditis. Thyroid hormones play pivotal roles in growth and development during childhood. However, the prevalence of diffuse goiter and the relationships between diffuse goiter, thyroid volume, cysts and nodules, and anthropometric measurements in children are not well known. Among 789,459 participants who participated in thyroid ultrasound examinations, 320,206 participants (male: 161,728; female: 158,478) aged 1-23 years were analyzed. Logistic regression analyses were conducted to calculate the odds ratios of the standard deviation score of body mass index (BMI-SDS), the SDS of bilateral width multiplied thickness area (BWTAR-SDS) as a provisional determination of thyroid volume, and the presence of nodules or cysts for positive diffuse goiter compared with negative diffuse goiter after correction for sex and age. The prevalence of diffuse goiter increased in a female-dominant manner with aging. Compared with the absence of diffuse goiter, the age- and sex-adjusted odds ratios (95% confidence intervals) for BMI-SDS (1 SD), BWTAR-SDS (1 SD), cysts, and nodules were 1.24 (1.21-1.27), 3.21 (3.13-3.29), 0.53 (0.50-0.58), and 1.38 (1.17-1.64), respectively. The odds ratios of nodules for positive diffuse goiter were 4.18 (1.08-16.08), 1.76 (1.01-3.07), 1.80 (1.32-2.45), and 1.34 (1.08-1.67) in the age groups 1-7, 8-11, 12-15, and 16-23 years, respectively. The age-dependent increase in the prevalence of diffuse goiter was independently associated with increased BMI and positive prevalence of nodules in young individuals.

The role of elastography in the assessment of thyroid nodules in acromegaly.

BACKGROUND: Nodular thyroid disease is a frequent finding seen in patients with acromegaly. Ultrasound-elastography (US-E) appears to be a helpful tool for the diagnosis of thyroid cancer. The aims of this study were to evaluate thyroid nodules in acromegaly and to assess the diagnostic accuracy of US-E in detecting thyroid cancer in this population. METHODS: US-E was applied to 166 nodules detected in 102 acromegalic patients and to 105 nodules found in 95 nonacromegalic subjects. The lesions were classified according to the elasticity scores (ES) as soft (ES 1-2) or hard (ES 3-4). RESULTS: : Mean age was 55.1 ± 12.47 years [59 (58%) women]. The prevalence of hard nodules (ES 3 and 4) was significantly higher in the group of acromegalic patients than in control subjects (48% to 20%, p < 0.001). Mean ES was higher in patients with acromegaly (2.45 to 2.22, p: 0.001), however, the mean strain index (SI) was similar between groups (1.53 to 1.65, p: 0.204). DISCUSSION: Thyroid nodules in acromegaly patients have a higher elasto score and the prevalence of hard nodules is higher in active disease. However, increased stiffness of nodules by US-E in patients with acromegaly does not seem to estimate the malignancy of the nodules.

Thyroid nodules: Global, economic, and personal burdens.

Thyroid nodules have garnered attention due to changes in population surveillance systems and rising concerns about the associated financial burden on healthcare systems, payers, and patients. In this review, we find that prevalence rates vary widely based on method of detection and may particularly pronounced in asymptomatic patients undergoing routine screening. Incidence rates may be particularly rising in lower-income and middle-income countries and may be declining in higher-income countries. Despite high incidence rates, survival rates continue to be as high as 97% for papillary thyroid cancer. Over the last few decades, thyroid nodule workup and management has grown more sophisticated with the advent of fine-needle aspiration biopsy, specialized biomarkers, and molecular testing. However, gaps remain in risk stratification that can lead to substantial costs of care. Certain molecular tests, such as the Afirma Gene Sequencing Classifier can lead to a cost per diagnosis of $17,873 while achieving only mild decreases in diagnostic lobectomies for patients (11.6% to 9.7% in one study). Out-of-pocket costs associated with thyroid nodule management continue to drive significant financial toxicity for patients, especially for individuals with thyroid cancer. Financial toxicity has been defined as a term that describes how direct and indirect medical costs of cancer care strain patients and households via decreased income, assets, and spending on basic necessities. Recent studies suggest that such toxicity can lead to adverse financial outcomes, such as foreclosure and bankruptcy. Additional cost-effectiveness analyses are needed to improve existing thyroid nodule management systems and new clinical tools are needed to avoid unnecessary workup and management.

SFE-AFCE-SFMN 2022 consensus on the management of thyroid nodules: Epidemiology and challenges in the management of thyroid nodules.

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with epidemiology and challenges in the management of thyroid nodules.

Point of Care Measurement of Body Mass Index and Thyroid Nodule Malignancy Risk Assessment.

Background: Large scale epidemiology studies have suggested obesity may increase the risk of thyroid cancer, though no prospective analyses using real-world measurement of BMI at a time proximate to initial thyroid nodule evaluation have been performed. Methods: We performed a prospective, cohort analysis over 3 years of consecutive patients presenting for thyroid nodule evaluation. We measured BMI proximate to the time of initial evaluation and correlated this with the final diagnosis of benign or malignant disease. We further correlated patient BMI with aggressivity of thyroid cancer, if detected. Results: Among 1,259 consecutive patients with clinically relevant nodules, 199(15%) were malignant. BMI averaged 28.6 kg/m2 (SD: 6.35, range:16.46-59.26). There was no correlation between the measurement of BMI and risk of thyroid cancer (p=0.58) as mean BMI was 28.9 kg/m2 and 28.6 kg/m2 in cancerous and benign cohorts, respectively. Similarly, BMI did not predict aggressive thyroid cancer (p=0.15). While overall nodule size was associated with increased BMI (p<0.01), these data require further validation as obesity may hinder nodule detection until large. Conclusion: In contrast to findings published from large scale association studies drawn from national databases, these prospective data of consecutive patients presenting for nodule evaluation detect no association of obesity (as measured by BMI) with thyroid cancer. Real time measurement of BMI at the time of thyroid nodule evaluation does not contribute to cancer risk assessment.

Testing telediagnostic thyroid ultrasound in Peru: a new horizon in expanding access to imaging in rural and underserved areas.

PURPOSE: Thyroid ultrasound is a key tool in the evaluation of the thyroid, but billions of people around the world lack access to ultrasound imaging. In this study, we tested an asynchronous telediagnostic ultrasound system operated by individuals without prior ultrasound training which may be used to effectively evaluate the thyroid and improve access to imaging worldwide. METHODS: The telediagnostic system in this study utilizes volume sweep imaging (VSI), an imaging technique in which the operator scans the target region with simple sweeps of the ultrasound probe based on external body landmarks. Sweeps are recorded and saved as video clips for later interpretation by an expert. Two operators without prior ultrasound experience underwent 8 h of training on the thyroid VSI protocol and the operation of the telemedicine platform. After training, the operators scanned patients at a health center in Lima. Telediagnostic examinations were sent to the United States for remote interpretation. Standard of care thyroid ultrasound was performed by an experienced radiologist at the time of VSI examination to serve as a reference standard. RESULTS: Novice operators scanned 121 subjects with the thyroid VSI protocol. Of these exams, 88% were rated of excellent image quality showing complete or near complete thyroid visualization. There was 98.3% agreement on thyroid nodule presence between VSI teleultrasound and standard of care ultrasound (Cohen's kappa 0.91, P < 0.0001). VSI measured the thyroid size, on average, within 5 mm compared to standard of care. Readers of VSI were also able to effectively characterize thyroid nodules, and there was no significant difference in measurement of thyroid nodule size (P = 0.74) between VSI and standard of care. CONCLUSION: Thyroid VSI telediagnostic ultrasound demonstrated both excellent visualization of the thyroid gland and agreement with standard of care thyroid ultrasound for nodules and thyroid size evaluation. This system could be deployed for evaluation of palpable thyroid abnormalities, nodule follow-up, and epidemiological studies to promote global health and improve the availability of diagnostic imaging in underserved communities.

Thyroid fine-needle aspiration trends before, during, and after the lockdown: what we have learned so far from the COVID-19 pandemic.

PURPOSE: Nowadays, the clinical management of thyroid nodules needs to be multi-disciplinary. In particular, the crosstalk between endocrinologists and cytopathologists is key. When FNAs are properly requested by endocrinologists for nodules characterised by relevant clinical and ultrasound features, cytopathologists play a pivotal role in the diagnostic work-up. Conversely, improper FNA requests can lead to questionable diagnostic efficiency. Recently, recommendations to delay all non-urgent diagnostic procedures, such as thyroid FNAs, to contain the spread of COVID-19 infection, have made the interplay between endocrinologists and cytopathologists even more essential. The objective of this study was to assess the impact of COVID-19 pandemic on our practice by evaluating the total number of FNAs performed and the distribution of the Bethesda Categories before, during, and after the lockdown. METHODS: We analysed the FNA trends before (1st January 2019 to March 13th 2020), during (March 14th to May 15th), and after (May 16th to July 7th) the lockdown. RESULTS: Although the total number of weekly FNAs dropped from 62.1 to 23.1, our referring endocrinologists managed to prioritise patients with high-risk nodules. In fact, in the post-lockdown, the weekly proportion of benign diagnoses dropped on average by 12% and that of high-risk diagnoses increased by 6%. CONCLUSIONS: The lesson we have learned so far from this pandemic is that by applying safety protocols to avoid contagion and by increasing the threshold for FNA requests for thyroid nodules, we can continue to guarantee our services to high-risk patients even in times of a health crisis.

Cost-effectiveness of fine-needle aspiration cytology (FNAC) and watchful observation for incidental thyroid nodules.

OBJECTIVES: A trial-based comparison of the use of resources, costs and health utility outcomes of fine-needle aspiration cytology (FNAC), and watchful observation for incidental small (< 2 cm) thyroid nodules was performed using data from the randomized controlled trial (RCT). METHODS: Using data from 314 patients, healthcare-related use of resources, costs, health utility, and quality-adjusted life years (QALYs) were estimated at 12 months after first presentation of incidental thyroid nodule(s) on an intention-to-treat basis with adjustment for covariates. Uncertainty about the incremental cost-effectiveness ratio for FNAC versus watchful management at 12 months of follow-up was incorporated using bootstrapping. Multiple imputation methods were used to deal with missing data. RESULTS: FNAC management was associated with greater use of healthcare resources and mean direct healthcare costs per patient (US$542.47 vs US$411.55). Lower mean 12-month QALYs per patient in FNAC was observed in comparison to watchful observation (0.752 versus 0.758). The probability that FNAC management was cost-effective compared with watchful management at a willingness-to-pay threshold of US50,000 per QALY gained was 26.5%. CONCLUSION: Based on 12-month data from RCT, watchful observation appeared cost-saving compared to FNAC in patients with incidental thyroid nodules that have a low-suspicion sonographic pattern and measure between 1.0 and 2.0 cm from healthcare provider perspective. CLINICALTRIALS. GOV IDENTIFIER: NCT02398721.

Development and Internal Validation of a Predictive Model for Individual Cancer Risk Assessment for Thyroid Nodules.

OBJECTIVE: The objective of this study was to develop and validate a predictive model for the assessment of the individual risk of malignancy of thyroid nodules based on clinical, ultrasound, and analytic variables. METHODS: A retrospective case-control study was carried out with 542 patients whose thyroid nodules were analyzed at our endocrinology department between 2013 and 2018 while undergoing treatment for thyroidectomy. Starting with a multivariate logistic regression analysis, which included clinical, analytic, and ultrasound variables, a predictive model for thyroid cancer (TC) risk was devised. This was then subjected to a cross-validation process, using resampling techniques. RESULTS: In the final model, the independent predictors of the risk of malignancy were: being male, age of the extremes, family history of TC, thyroid-stimulating hormone level >4.7 µU/L, presence of autoimmune thyroiditis, solid consistency, hypoechogenicity, irregular or microlobed borders, nodules that are taller than they are wide, microcalcifications, and suspicious adenopathy. With a cut-off point of 50% probability of thyroid cancer, the predictive model had an area under the receiver operating characteristic curve of 0.925 (95% confidence interval 0.898 to 0.952). Finally, using the 10-fold cross-validation method, the accuracy of the model was found to be 88.46%, with a kappa correlation coefficient of 0.62. CONCLUSION: A predictive model for the individual risk of malignancy of thyroid nodules was developed and validated using clinical, analytic, and ultrasound variables. An online calculator was developed from this model to be used by clinicians to improve decision-making in patients with thyroid nodules.

Diagnostic performance of the American Thyroid Association ultrasound risk assessment of thyroid nodules in endocrinology (the ETIEN 3 study). / Rendimiento diagnóstico del sistema de evaluación de riesgo ecográfico del nódulo tiroideo de la American Thyroid Association en endocrinología (estudio ETIEN 3).

INTRODUCTION: No study has been published to date in Spain about the value of the American Thyroid Association (ATA) ultrasound risk assessment of thyroid nodules applied by endocrinologists. OBJECTIVES: To assess the diagnostic performance of ATA thyroid nodule risk classification applied by endocrinologists with respect to histological results. METHODS: A retrospective, observational study of 317 patients (mean age, 51.7±13.7 years; 83.3% women) with thyroid nodules (maximum diameter: 3.2±1.4cm) who underwent US-guided FNA in endocrinology between October 2015 and December 2018, were classified based on the ATA ultrasound risk assessment. Surgery was performed in all of them. Quality criteria of the ultrasound classification were assessed as compared to histological results. RESULTS: Overall, 61.2% of nodules assessed were classified as benign (n=3) and very low (n=60) or low suspicion (n=131), 11.7% as intermediate suspicion (n=37), and 27.1% as high suspicion (n=86). Benign nodular disease was found in 260 patients, and thyroid cancer in 57 patients. There were 14 incidental papillary microcarcinomas. Classification of thyroid nodules as high suspicion showed a high diagnostic performance to identify malignant nodules (87.7% sensitivity, 86.2% specificity, negative predictive value 97.0%), improving sensitivity (93.0%) and reducing specificity (73.1%) when considering high and intermediate suspicion nodules as a risk for thyroid cancer. CONCLUSIONS: Application by endocrinologists of the ATA ultrasound risk assessment of thyroid nodules shows a high diagnostic performance to identify malignant thyroid nodules before surgery.

Incidence of thyroid cancer and medical cost among patients with newly diagnosed thyroid nodules in Korea: A retrospective cohort study using nationwide data.

AIMS: The frequency of newly diagnosed thyroid nodules is increasing in South Korea. However, few studies have investigated the incidence of thyroid cancer in patients with thyroid nodules using national data. Therefore, this study was conducted to investigate the incidence of thyroid cancer and medical costs among patients newly diagnosed with thyroid nodules in South Korea. SETTINGS AND DESIGN: This was a retrospective cohort study. Subjects and Methods: We analyzed the national health claim database, which includes all hospital records and covers almost every population managed by the National Health Insurance System. We selected patients aged 20-120 years with new thyroid nodules in 2008 using the International Classification of Diseases, Tenth Edition codes. We followed the selected cases for at least 2 years after thyroid nodule diagnosis to investigate cancer development and medical costs. STATISTICAL ANALYSIS USED: Frequency analysis was used. RESULTS: We identified 283,844 eligible patients with thyroid nodules. Their mean age was 48 ± 13.2, and 234,388 (82.58%) cases were female. During the median follow-up of 2.4 years, 21,538 (7.6%) patients were diagnosed with thyroid cancer, and 93.5% of them underwent treatment such as thyroidectomy, chemotherapy, or radiotherapy. The average medical cost was 3,996,391 KRW after diagnosis of thyroid cancer. CONCLUSIONS: Here, national representative statistics regarding the incidence and medical costs of thyroid nodule and thyroid cancer are presented. The information provided herein will improve understanding of the natural course of thyroid nodules in Asians. Further study is needed to identify the risk factors of thyroid cancer in patients with thyroid nodules.

An assessment of the relationship between thyroid nodule characteristics, insulin resistance and arterial stiffness in euthyroid nodular goiter.

OBJECTIVES: Publications suggesting that thyroid nodule might be associated with insulin resistance and metabolic syndrome are quite interesting. There is a need for studies assessing the relationship between nodule presence and cardiovascular risk in individuals with non-functioning nodular goiter. The purpose of the present study is to reveal whether or not insulin resistance, nodule presence, and nodule stiffness affect arterial stiffness, which is a reliable and valid cardiovascular risk indicator, in individuals with euthyroid nodular goiter using the pulse wave analysis (PWA). MATERIALS AND METHODS: 50 patients with euthyroid nodular goiter and 50 healthy volunteers were included in the study. All participants were examined by B-mode thyroid ultrasound, and the participants in the nodular goiter group were also examined by strain elastography (SE). The strain index of nodules was calculated according to the Rago scoring. Also, fasting plasma glucose (FPG) and insulin levels were measured, and HOMA-IR. Arterial stiffness measurements of the participants were performed using a PWA device which employs a cuff-based oscillometric method from the brachial artery. RESULTS: PWV was found to be significantly higher in the euthyroid nodular goiter group (p < 0.001). PWV was found to be positively correlated with FPG and waist circumference. Fasting plasma glucose was found to be higher in the group with nodular goiter (p = 0.03). However, no difference was found between the groups in terms of HOMA-IR and insulin level. HOMA-IR was not correlated with thyroid volume, nodule volume, and nodule count. Also, HOMA-IR was not correlated with strain index value and PWA data. CONCLUSION: We found that PWV was significantly higher in patients with euthyroid nodular goiter. This result suggests that these patients may be at risk for cardiovascular disease.

INCIDENTAL THYROID NODULES: RACE/ETHNICITY DISPARITIES AND OUTCOMES.

OBJECTIVE: Black patients have a significantly lower incidence of well-differentiated thyroid cancer (WDTC) compared to all other race/ethnic groups, while white patients appear to be at greater risk. This study examines incidental thyroid nodules (ITNs) to assess whether racial disparities in WDTC arise from a differential discovery of ITNs-perhaps due to socioeconomic disparities-or reflect true differences in thyroid cancer rates. METHODS: A retrospective review was performed of all patients who underwent fine-needle aspiration (FNA) of thyroid nodules by our academic medical center's endocrinology division between January 2006 and December 2010. Medical records were reviewed to identify whether the biopsied thyroid nodule was discovered incidentally through nonthyroid-related imaging or identified by palpation. RESULTS: FNAs were performed on 1,369 total thyroid nodules in 1,141 study patients; 547 (48%) were classified as white, and 593 (52%) were classified as nonwhite. Among this cohort, 36.6% of patients underwent biopsy for an ITN. White patients were 1.6 times more likely to have undergone a biopsy for a nodule that was incidentally identified compared to nonwhites ( P<.0001). Indicators of socioeconomic status (SES) did not have a significant association with ITNs. Within the ITN cohort, 4.9% of nonwhite patients were found to have a thyroid malignancy compared to 12.9% of white patients ( P<.01). CONCLUSION: The higher incidence of thyroid cancer in white patients appears to be not only due to diagnostic bias, but also to a true difference in cancer prevalence. ABBREVIATIONS: FNA = fine-needle aspiration; ITN = incidental thyroid nodule; SEER = Surveillance Epidemiology and End Results; SES = socioeconomic status; WDTC = well-differentiated thyroid cancer.

Incidental Thyroid Nodules in the National Lung Screening Trial: Estimation of Prevalence, Malignancy Rate, and Strategy for Workup.

RATIONALE AND OBJECTIVES: There is limited research on the prevalence of incidental thyroid nodules (ITNs) in the United States screening population and on the appropriate evaluation of computed tomography (CT)-detected ITNs. The purpose of this study is to determine the prevalence of ITNs in the National Lung Screening Trial (NLST) and develop a workup strategy for ITNs. MATERIALS AND METHODS: CT images were obtained for subjects with documented thyroid abnormalities in the CT screening arm of the NLST, subjects diagnosed with thyroid malignancies, and control subjects. Several size thresholds were compared to determine how many nodules would be further evaluated and how many thyroid malignancies would be missed had each threshold been applied at the time of workup. RESULTS: Thyroid nodules were reported in 0.7% (117 of 17,309 subjects). In 663 control subjects without reported thyroid nodules, thyroid nodules were identified in 78 (11.8%). Reported nodules were larger than unreported nodules (21.3 vs 16.9 mm, P = .03). Thyroid malignancies were diagnosed in 0.1% (22 of 17,309). If a 20-mm rather than a 10-mm cutoff were used to determine which nodules should be further evaluated, all malignancies would be detected, but 24 rather than 62 patients would require workup, for a workup reduction rate of 48.7% (38 of 78). CONCLUSIONS: Less than 1% of subjects in the NLST had reported ITNs. The true prevalence of ITNs was estimated to be 11.8%, which provides a better approximation of the number of patients who could potentially receive workup. A 20-mm rather than a 10-mm cutoff would reduce the workup rate by almost 50% while still capturing all malignancies.

Bayesian dose-response analysis for epidemiological studies with complex uncertainty in dose estimation.

Most conventional risk analysis methods rely on a single best estimate of exposure per person, which does not allow for adjustment for exposure-related uncertainty. Here, we propose a Bayesian model averaging method to properly quantify the relationship between radiation dose and disease outcomes by accounting for shared and unshared uncertainty in estimated dose. Our Bayesian risk analysis method utilizes multiple realizations of sets (vectors) of doses generated by a two-dimensional Monte Carlo simulation method that properly separates shared and unshared errors in dose estimation. The exposure model used in this work is taken from a study of the risk of thyroid nodules among a cohort of 2376 subjects who were exposed to fallout from nuclear testing in Kazakhstan. We assessed the performance of our method through an extensive series of simulations and comparisons against conventional regression risk analysis methods. When the estimated doses contain relatively small amounts of uncertainty, the Bayesian method using multiple a priori plausible draws of dose vectors gave similar results to the conventional regression-based methods of dose-response analysis. However, when large and complex mixtures of shared and unshared uncertainties are present, the Bayesian method using multiple dose vectors had significantly lower relative bias than conventional regression-based risk analysis methods and better coverage, that is, a markedly increased capability to include the true risk coefficient within the 95% credible interval of the Bayesian-based risk estimate. An evaluation of the dose-response using our method is presented for an epidemiological study of thyroid disease following radiation exposure.

Incidental thyroid nodules and thyroid cancer: considerations before determining management.

The worldwide incidence of thyroid cancer is increasing substantially, almost exclusively attributable to small papillary thyroid cancers. Increased use of diagnostic imaging is considered the most likely explanation for this reported rise, but other factors may also be contributing. The increase in health care expenditures related to managing these presumably low-risk cancers, without a clear patient benefit, has resulted in a backlash against the early detection of thyroid cancer. Currently, there is no way to confidently predict which incidentally detected thyroid nodule may be the precursor to a more aggressive process. Predictions such as these would require more accurate characterization of the biology of individual thyroid cancers than is currently possible. With time, we might prove our ability to confidently differentiate low-risk from high-risk thyroid cancers, but until that happens, routine screening for thyroid cancer by imaging billed as a "health checkup" should not be performed. However, incidentally detected thyroid nodules should be reported, and a clear medical team management plan should be developed. Our ethical responsibility is to provide patients with objective, evidence-based information about their disease status, not to assume that we know what is best for them by selectively withholding information. In addition, providing patients with psychosocial assistance will help them process the information necessary to make informed decisions that will provide them with the most value when a small thyroid nodule or cancer is incidentally identified. Herein, we summarize the epidemiological data for disease incidence, discuss some controversies in disease management, and outline the key elements and ethical considerations of informed decision making as they apply to managing incidentally detected thyroid nodules and thyroid cancer.

TIRADS for sonographic assessment of hypofunctioning and indifferent thyroid nodules.

AIM: To test the feasibility of the Thyroid Imaging Reporting And Data System (TIRADS) according to Horvath and Kwak for the assessment of thyroid nodules. PATIENTS, METHOD: Retrospective analysis of patients with thyroid nodules applying the following inclusion criteria: B-mode-ultrasound, surgery and histological results. Thyroid nodules were classified as TIRADS 2, 3, 4A, 4B, 4C, 5 and 6. RESULTS: A total of 172 patients were included (133 women, 48 ± 13 years, 39 men, 49 ± 11 years) with 222 thyroid nodules (24.9 ± 11.5 mm). Final histological diagnosis revealed 203 benign nodules (91%) and 19 malignant nodules (9%; 18 papillary thyroid carcinoma, PTC, and one medullary thyroid carcinoma, MTC). One hundred and sixty thyroid nodules were hypofunctioning in 99mTc-pertechnetate-scintigraphy, 14 nodules were hyperfunctioning and 46 nodules were classified as indifferent. In two cases with small carcinoma < 1 cm 99mTc-pertechnetate-scintigraphy was not performed. According to Horvath, the prevalence of malignancy was 6.7% in TIRADS 2, 0% in 3, 1.9% in 4A, 33% in 4B, 12.5% in 5 and 100% in 6; 73 nodules (39%) were not clearly classifiable, including 3 carcinoma (4.1%). According to Kwak, the prevalence of malignancy was 6.9% in TIRADS 2, 0% in 3, 2% in 4A, 4.1% in 4B, 23.1% in 4C, and 100% in 5 and 6, respectively. Notably, in the subgroup of hot nodules, 11 (79%) were graded as TIRADS 4A or higher, and thus advisable for fine-needle aspiration biopsy in both TIRADS. CONCLUSION: The TIRADS described by Horvath is not practicable due to numerous unclassifiable nodules. The revised TIRADS published by Kwak is feasible and suitable to assess the prevalence of malignancy, but it cannot replace scintigraphic imaging. Fine-needle-biopsy is not necessary in nodules categorized as (K)TIRADS 3, 4A and 5.

Cost-effectiveness of molecular testing for thyroid nodules with atypia of undetermined significance cytology.

CONTEXT: Novel molecular diagnostics, such as the gene expression classifier (GEC) and gene mutation panel (GMP) testing, may improve the management for thyroid nodules with atypia of undetermined significance (AUS) cytology. The cost-effectiveness of an approach combining both tests in different practice settings in North America is unknown. OBJECTIVE: The aim of the study was to determine the cost-effectiveness of two diagnostic molecular tests, singly or in combination, for AUS thyroid nodules. DESIGN AND SETTING: We constructed a microsimulation model to investigate cost-effectiveness from US (Medicare) and Canadian healthcare system perspectives. PATIENTS: Low-risk patients with AUS thyroid nodules were simulated. INTERVENTIONS: We examined five management strategies: 1) routine GEC; 2) routine GEC + selective GMP; 3) routine GMP; 4) routine GMP + selective GEC; and 5) standard management. MAIN OUTCOME MEASURES: Lifetime costs and quality-adjusted life-years were measured. RESULTS: From the US perspective, the routine GEC + selective GMP strategy was the dominant strategy. From the Canadian perspective, routine GEC + selective GMP cost and additional CAN$24 030 per quality-adjusted life-year gained over standard management, and was dominant over the other strategies. Sensitivity analyses reported that the decisions from both perspectives were sensitive to variations in the probability of malignancy in the nodule and the costs of the GEC and GMP. The probability of cost-effectiveness for routine GEC + selective GMP was low. CONCLUSIONS: In the US setting, the most cost-effective strategy was routine GEC + selective GMP. In the Canadian setting, standard management was most likely to be cost effective. The cost of these molecular diagnostics will need to be reduced to increase their cost-effectiveness for practice settings outside the United States.

BRAF(V600E) assessment by pyrosequencing in fine needle aspirates of thyroid nodules with concurrent Hashimoto's thyroiditis is a reliable assay.

Detection of BRAF mutation in cytology specimens has been proposed as a diagnostic adjunctive tool in evaluation of thyroid nodules with indeterminate cytology findings. Concurrent papillary thyroid carcinoma and Hashimoto's thyroiditis (HT), a disease characterized by thyroid lymphocytic infiltration, is a frequent occurrence. A large lymphocytic infiltrate might reduce the sensitivity of methods employed to detect BRAF mutation in thyroid cytology specimens. To determine whether testing for BRAF mutational status in fine needle aspirates (FNA) is reliable also in the presence of HT lymphocytic infiltration, we assessed the BRAF status by direct sequencing and pyrosequencing in a series of FNAs with and without concomitant HT lymphocytic infiltration. We also performed the same assessment by pyrosequencing in the corresponding tissue samples. Pyrosequencing demonstrated to be more sensitive than direct sequencing. The percentage of mutant BRAF(V600E) alleles was higher in FNAs than in the corresponding tissues, probably because of the lower stromal contamination in FNA than in the sections. In the presence of lymphocytic infiltration, the percentage of mutant BRAF(V600E) alleles determined by pyrosequencing was higher in FNAs than in the corresponding tissue samples (P < 0.0001), indicating a minor lymphocytic contamination in FNA. The diagnostic value of BRAF(V600E) in inconclusive FNAs was not hampered by thyroid lymphocytic infiltration. These results indicate that BRAF(V600E) assessment by pyrosequencing is a reliable assay useful to refine inconclusive cytology of thyroid nodules also in the presence of concurrent HT.

Optimization of iodine intake in Belgium.

Mild iodine deficiency (MID) is a long-standing problem in Belgium and was recognized only recently as public health issue by the Ministry of Health (MOH). The main MID-related health problems in Belgium are a high prevalence of thyroid nodules and multinodular goiter. The economic cost of thyroid nodular disease only in Belgium was estimated at about €40 millions per year. The Belgian health authorities adopted a selective strategy to optimize iodine intake through the fortification of bread with iodized salt. A progressive, step-by-step increase of the iodine content of salt was chosen in order to minimize the incidence of hyperthyroidism. MOH monitors this strategy by assessing periodically the urinary iodine concentration in school-aged children and pregnant women, as well as by a yearly follow-up of TSH concentrations in all Belgian newborns. Although the implementation of this strategy was an important step, the main drawback of the current situation is the absence of a legal framework to support the strategy. The utilization of iodized salt in bread on a voluntary basis was endorsed by the bakery industry and MOH. However a legal framework is required to assure the effectiveness and continuity of the program and to avoid a higher than optimal iodine intake in the population.