Diagnostic Work-up Of Thyroid Nodules Research Articles

Efficacy of an Integrated Hands-On Thyroid Ultrasound Session for Medical Student Education.

As ultrasound has gained popularity with improving technology and ease-of-use, a push has been made to integrate ultrasound into the medical school curriculum. Many institutions are reporting one- to four-year integrated ultrasound curricula to augment anatomy and pathophysiology teaching. Our goal was to integrate a thyroid ultrasound scanning session into the endocrinology block of our institution’s medical school curriculum to enhance medical student understanding of thyroid anatomy and pathophysiology. We conducted a prospective, single-center cohort (pre-experimental) study to evaluate student performance and knowledge acquisition using a pretest-posttest design. These multimodal sessions, consisting of a didactic, hands-on scanning sessions, and knowledge integration tests, covered ultrasound technique and thyroid evaluation and advanced to diagnosing an abnormal thyroid and working up a thyroid nodule. There were 26 to 27 second-year medical students per session who rotated between three stations proctored by credentialled physicians. Students participated in hands-on scanning of patients with or without thyroid pathology at each station. Out of the 209 students who participated in the ultrasound sessions, 114 (54.5%) consented to participate in the research project and completed both the pretest and posttest. Test data from the 114 students showed a mean pretest score of 57.5% ± 14.6% and the mean posttest score of 73.9% ± 17.4%. They had a 16.5% ± 19.6% (p < 0.001) increase in score between the two tests. Our study demonstrates that a multimodal thyroid ultrasound scanning session is an effective tool to augment the medical school endocrinology curriculum and to improve students’ knowledge of thyroid anatomy, pathophysiology, and diagnostic workup of thyroid nodules.

Ultrasound-guided fine-needle aspiration biopsy of thyroid nodules.

Fine needle aspiration biopsy (FNAB) remains crucial in the evaluation of thyroid nodules with suspicious clinical findings or ultrasound (US) features suggestive of malignancy. The use of US-guidance for FNAB allows real-time visualization of the needle, but is also highly operator-dependent. Physicians from many specialties (endocrinologists, otolaryngologists/endocrine surgeons, nuclear medicine physicians, radiologists, and pathologists) are involved in the diagnostic workup of thyroid nodules and a standardized and meticulous technique for US-FNAB is essential for lowering the yield of nondiagnostic specimens and false-negative results. This video, therefore, demonstrates a well-proved technique and technical tips to increase the diagnostic results from US-FNAB.

Performance of the ACR TI-RADS and EU TI-RADS scoring systems in the diagnostic work-up of thyroid nodules in a real-life series using histology as reference standard.

The ultrasonographic scores EU TI-RADS and ACR TI-RADS were introduced to give the clinicians indications for fine needle aspiration cytology (FNAC). The predictive role of these scores was never evaluated and compared in a surgical series of patients. The aim of this study was to evaluate the ex post diagnostic accuracy of EU TI-RADS and ACR TI-RADS in a real-life series of thyroidectomized patients and to evaluate the 'missing' thyroid cancer following the operational indications of these scores. Retrospective monocentric cohort study. In total, 255 patients (harboring 304 nodules) undergoing thyroidectomy for benign and malignant thyroid conditions were enrolled. The prevalence of thyroid malignancy for each class of ACR TI-RADS and EU TI-RADS, their diagnostic accuracy, the number of 'unnecessary' FNAC and the number of 'missed' cancers were evaluated. ACR TI-RADS and EU TI-RADS score had similar and satisfactory accuracy values for predicting thyroid malignancy (AUC: 0.835 for ACR TI-RADS vs 0.827 for EU TI-RADS). The ACR TI-RADS and EU TI-RADS categories (suspicious vs non-suspicious), age, sex and presence of a single nodule significantly and independently predicted the presence of malignancy in a logistic regression model. An ex post analysis according to the indications for FNAC for each score indicated that 31 and 16 cases of cancer would have been missed by ACR TI-RADS and EU TI-RADS scores, respectively. ACR TI-RADS and EU TI-RADS display a good performance in predicting thyroid cancer when histology is taken as reference standard, but additional clinical judgement is required to decide the indication for FNAC.

ENDOCRINOLOGY IN THE TIME OF COVID-19: Management of thyroid nodules and cancer.

Most patients with thyroid nodules and thyroid cancer (TC) referred for diagnostic work-up and treatment are not considered at higher risk of infection from SARS-CoV-2 compared to the general population. On the other hand, healthcare resources should be spared to the maximum extent possible during a pandemic. Indeed, while thyroid nodules are very common, only a small percentage are cancerous and, in turn, most thyroid cancers are indolent in nature. Accordingly, diagnostic work-up of thyroid nodules, thyroid surgery for either benign or malignant thyroid nodules and radioiodine treatment for differentiated thyroid cancers may be safely postponed during SARS-CoV-2 pandemic. Appropriate patient counselling, however, is mandatory and red flags should be carefully identified prompting immediate evaluation and treatment as appropriate. For these selected cases diagnostic work-up (e.g. ultrasound, scintigraphy, fine-needle aspiration), surgery and radioiodine therapy may proceed despite the threat of SARS-CoV-2 infection and COVID-19, after an individual risk-benefit analysis.

Early Diagnosis of Medullary Thyroid Cancer: Are Calcitonin Stimulation Tests Still Indicated in the Era of Highly Sensitive Calcitonin Immunoassays?

Background: Measurements of both basal (b) calcitonin (CT) and calcium (Ca)-stimulated CT (Ca-sCT) levels are performed to identify medullary thyroid cancer (MTC) at an early stage when used as part of the diagnostic workup of thyroid nodules (CT screening). Novel immunochemiluminometric assays, which are highly sensitive and specific for monomeric CT and avoid cross-reactivity, have been introduced over the past decade. No prospectively generated data have so far become available to answer the frequently raised question as to whether Ca-sCT in contrast to bCT alone is helpful and, therefore, still indicated for the early detection of MTC. Methods: Ca-stimulation tests were performed in 149 consecutive patients with thyroid nodules and elevated bCT. Regardless of Ca-sCT levels, all patients had an operation applying a uniform surgical protocol, including thyroidectomy and systematic lymph node dissection. Recently published sex-specific cutoff levels for the differentiation of MTC and other C-cell pathologies (C-cell hyperplasia [CCH]) were used to compare the diagnostic performance of bCT or Ca-sCT alone and in combination using receiver-operating characteristic (ROC) analysis. In addition, CT cutoff levels to predict lateral lymph node metastasis were evaluated for bCT compared with Ca-sCT. Follow-up for all patients was documented and correlated with initial CT levels. Results: MTC was identified in 76 (50.1%) patients, in 21/76 (27.6%) with lymph node and in 4 (5.3%) with distant metastasis. Using predefined cutoff levels, patients could effectively be subdivided into a group above the cutoff level with definitive diagnosis of MTC (100%) and below (gray zone) with a significant overlap of CCH and MTC (all classified as pT1a; males: 19/58 [37.5%], females: 7/41 [17.1%]). The areas under the ROC curve (AUC) were excellent for the diagnosis of MTC in all tests. Determination of bCT proved to be superior for both diagnosing MTC in males (AUC for bCT: 0.894; AUC for Ca-sCT: 0.849) and females (bCT: 0.935; Ca-sCT: 0.868) and also for diagnosing lymph node metastasis in the lateral compartment (males: bCT: 0.925; Ca-sCT: 0.810; females: bCT: 0.797; Ca-sCT: 0.674). Combining both tests did not improve diagnostic accuracy. Using a cutoff level of >85 pg/mL for females and >100 pg/mL for males, the sensitivity for diagnosing lateral neck lymph node metastasis was 100%. Below these cutoff levels, no patient showed persistent or recurrent disease (median follow-up: 46 [ ± 27] months). Conclusions: Predefined sex-specific bCT cutoff levels are helpful for the early detection of MTC and for predicting lateral neck lymph node metastasis. Ca-sCT did not improve preoperative diagnostics. bCT levels >43 and >100 pg/mL for males and of >23 and >85 pg/mL for females are relevant for advising patients and planning the extent of surgery.

Imaging and Imaging-Based Management of Pediatric Thyroid Nodules.

Thyroid nodules are less frequent in children than adults. Childhood thyroid nodules carry specific features, including a higher risk of malignancy than nodules in adults, rendering them unique in terms of management. Subsequently, they should be considered a distinct clinical entity with specific imaging recommendations. Initial evaluation requires a thorough workup, including clinical examination, and a detailed personal and familial history to determine the presence of possible risk factors. Laboratory and radiologic evaluation play an integral part in the diagnostic algorithm, with ultrasonography (US) being the first diagnostic test in all patients. US elastography has been recently introduced as an incremental method, reducing the subjectivity of the clinical diagnosis of nodule firmness associated with increased malignancy risk. However, fine-needle aspiration biopsy (FNAB) remains the mainstay in the diagnostic work-up of thyroid nodules and is documented to be best method for differentiating benign from malignant thyroid nodules. In addition, thyroid scintigraphy provides functional imaging information, which has a role both in the diagnostic management of thyroid nodules and during follow up in malignancies. Finally, despite providing additional information in certain clinical scenarios, 18F-fludeoxyglucose Positron Emission Tomography (18F-FDG-PET), computed tomography (CT), and magnetic resonance imaging (MRI) imaging are not routinely recommended for the evaluation of patients with newly detected thyroid nodules or in all cases of thyroid cancer. The objective of this review is to summarize the concepts in imaging and imaging-based management of nodular thyroid disease in the pediatric population, acknowledging the unique features that this patient group carries and the specific approach it requires.

The mutational analysis in the diagnostic work-up of thyroid nodules: the real impact in a center with large experience in thyroid cytopathology

Fine-needle aspiration (FNA) cytology is a mainstay in the evaluation of thyroid nodules, but fails to reach reliable results in 25-30% of cases. The role of molecular markers in helping clinical decisions has been investigated for the last years, but their clinical usefulness is still unsettled. Mutation analysis of BRAF, RAS genes and TERT promoter was performed in a series of 617 consecutive cytological specimens undergoing FNA. The 617 nodules had the following cytological diagnosis: non diagnostic 22 (3.6%), benign 425 (68.9%), indeterminate 114 (18.5%), suspicious 11 (1.8%) and malignant 45 (7.3%). BRAF mutations were found in 31 cases (5.0%), all but two in suspicious and malignant nodules. RAS mutations were detected in 47 samples (7.6%): 25 benign (5.9%) and 19 indeterminate nodules (16.7%). TERT promoter mutation alone was detected in three samples. Histological outcome was available for 167 nodules, 81 of which proved malignant: all the 48 with suspicious or malignant cytology; 25 out of 56 (44.6%) with indeterminate and 8 out of 57 (14%) with benign cytology. BRAF mutations were associated with worse tumors pathological features. The presence of RAS mutations was indicative of follicular-patterned malignancies in 5 out of 8 benign nodules and 9 out of 11 indeterminate nodules. Our study established mutational rates for BRAF and RAS genes in a large series of FNA specimens. BRAF mutations were confirmed as highly specific but not able to improve cytological diagnosis, while RAS testing proved effective in assessing malignancy in nodules with indeterminate and benign cytology.

Cost comparison of initial lobectomy versus fine-needle aspiration for diagnostic workup of thyroid nodules in children

BackgroundThough uncommon in children, pediatric thyroid nodules carry a higher risk of malignancy than adult nodules. While fine-needle aspiration (FNA) has been well established as the initial diagnostic test in adults, it has been more slowly adopted in children. The purpose of this study was to examine the comparative cost of FNA versus initial diagnostic lobectomy (DL) in the pediatric patient with an ultrasound-confirmed thyroid nodule. MethodsA decision tree model was created using an adolescent with an asymptomatic thyroid nodule as the reference case. Probabilities were defined based on review of the pediatric and adult literature. Costs were determined from previous literature and the publicly available Medicare physician fee schedule. Tornado plot and sensitivity analyses were performed to assess sources of cost variation. ResultsUsing decision analysis, FNA was less costly than DL with an estimated cost of $2529 vs. $5680. Tornado analysis demonstrated that the probability of an initial indeterminate FNA result contributed most to cost variation. On sensitivity analysis, when probability of an indeterminate FNA result was increased to 35%, the maximum value found in the literature, FNA remained less costly. In Monte Carlo simulation set to 10,000 iterations, FNA was superior to DL in 74% of cases. ConclusionsIn this theoretical model based on available literature and costs, FNA is less costly than DL for initial diagnostic workup of thyroid nodules in children. Securing resources to offer FNA in the work-up of thyroid nodules may be financially beneficial to hospitals and patients. Level of evidenceLevel 1 cost effectiveness study - using reasonable costs and alternatives used in study with values obtained from many studies, study used multi-way sensitivity analysis.

Predictors of non-diagnostic cytology in surgeon-performed ultrasound guided fine needle aspiration of thyroid nodules.

BackgroundFine needle aspiration (FNA) is the standard of care for the diagnostic work-up of thyroid nodules but despite its proven utility, the non-diagnostic rate for thyroid FNA ranges from 6-36%. A non-diagnostic FNA is problematic for the clinician and patient because it can result in repeated procedures, multiple physician visits, and a delay in definitive treatment. Surgeon-performed FNA has been shown to be safe, cost-effective, as accurate as those performed by other clinicians, and has the added benefit of decreasing wait times to surgery. Several studies have examined rates and factors that may be predictive of a non-diagnostic cytology in non-surgeon FNA, but none have evaluated this in surgeon-performed thyroid FNA. If these factors are unique in surgeon-performed vs. non-surgeon performed thyroid FNA, then patients may be more appropriately triaged to FNA by alternate clinicians.ObjectivesThe purpose of this study was to determine the rate and factors predictive of a non-diagnostic FNA in surgeon performed ultrasound-guided FNA of thyroid nodules.MethodsWe conducted a retrospective review of all adult patients who underwent thyroid FNA by a staff, fellow, or resident Otolaryngologist at the University of Alberta between January 2011 and June 2013. Factors analyzed included patient factors, thyroid characteristics, nodule characteristics, and surgeon level of training and experience. Univariate and multivariate binary logistic regression analysis were performed.Results131 patients (180 nodules) were reviewed. The non-diagnostic rate was 23%. Nodules with predominant cystic component, those less than 1 cm, and resident-performed FNA were associated with non-diagnostic cytology (p = 0.001, p = 0.02, p = 0.04 respectively). A cystic nodule was the only independent predictor of non-diagnostic FNA on multivariate analysis (OR = 4.441, 95% CI [1.785-11.045], p = 0.001).ConclusionsThe rate of non-diagnostic thyroid FNA performed by a surgeon with ultrasound guidance is similar to other clinicians. A cystic nodule is a strong independent predictor of non-diagnostic cytology. Non-cystic nodules may particularly benefit from surgeon-performed thyroid FNA due to the high diagnostic rate and potential for earlier definitive management.

Interobserver Agreement of Thyroid Imaging Reporting and Data System (TIRADS) and Strain Elastography for the Assessment of Thyroid Nodules

BackgroundThyroid Imaging Reporting and Data System (TIRADS) was developed to improve patient management and cost-effectiveness by avoiding unnecessary fine needle aspiration biopsy (FNAB) in patients with thyroid nodules. However, its clinical use is still very limited. Strain elastography (SE) enables the determination of tissue elasticity and has shown promising results for the differentiation of thyroid nodules.MethodsThe aim of the present study was to evaluate the interobserver agreement (IA) of TIRADS developed by Horvath et al. and SE. Three blinded observers independently scored stored images of TIRADS and SE in 114 thyroid nodules (114 patients). Cytology and/or histology was available for all benign (n = 99) and histology for all malignant nodules (n = 15).ResultsThe IA between the 3 observers was only fair for TIRADS categories 2–5 (Coheńs kappa = 0.27,p = 0.000001) and TIRADS categories 2/3 versus 4/5 (ck = 0.25,p = 0.0020). The IA was substantial for SE scores 1–4 (ck = 0.66,p<0.000001) and very good for SE scores 1/2 versus 3/4 (ck = 0.81,p<0.000001). 92–100% of patients with TIRADS-2 had benign lesions, while 28–42% with TIRADS-5 had malignant cytology/histology. The negative-predictive-value (NPV) was 92–100% for TIRADS using TIRADS-categories 4&5 and 96–98% for SE using score ES-3&4 for the diagnosis of malignancy, respectively. However, only 11–42% of nodules were in TIRADS-categories 2&3, as compared to 58–60% with ES-1&2.ConclusionsIA of TIRADS developed by Horvath et al. is only fair. TIRADS and SE have high NPV for excluding malignancy in the diagnostic work-up of thyroid nodules.

Medullary carcinoma of the thyroid: an update

Medullary carcinoma of the thyroid (MTC) represents 5-10% of differentiated thyroid cancers. It derives from the thyroid C-cells which produce calcitonin and are of neuroendocrine origin. It is a rather rare tumour and is accompanied by considerable mortality as it has frequently already metastasised at diagnosis and is not sensitive to either radiation or chemotherapy. Recently it has been shown that MTC is not infrequent in multinodular thyroid disease and thus universal calcitonin screening has been suggested in the diagnostic workup of thyroid nodules. The prognosis of the disease has recently improved as many of the newly diagnosed cases are now small, non-invasive tumours, that probably were previously missed. MTC is an interesting tumour as it occurs in a familial form in >25% of the cases, as part of the multiple endocrine neoplasia 2 syndromes (MEN2). When familial MTC may occur in combination with pheochromocytomas and, more rarely, with primary hyperparathyroidism. Recent advances in MTC management include preclinical diagnosis using molecular techniques in the case of familial disease and prophylactic thyroidectomy in asymptomatic gene carriers. The gene responsible for transmission of the MEN2 is the ret proto-oncogene, which is a membrane receptor tyrosine kinase; its physiological role is the transmission of neural signals during development. Most of the mutations which are found in MEN2 syndromes are clustered in the cysteine rich extracellular domain of the protein and either cause dimerisation or ligand-independent activation. Novel previously unknown ret mutations across many regions of the gene are currently being recognized. Mutation analysis should be performed in all cases of MTC because these sometimes represent unrecognized familial disease. When a mutation is identified, family members are screened and carriers are offered prophylactic thyroidectomy at a young age. The type of mutation is classified into more or less aggressive and it is important for the penetrance of the disease. The majority of experts suggest prophylactic surgery at 5-10 years, especially when the specific mutation associates with risk for earlier MTC development and more aggressive disease. Several recent publications have examined the success/cure rate of prophylactic treatment. One important development in the field of MTC concerns the use of newer antineoplastic agents, including agents targeting the molecular pathways involved in its pathogenesis. Novel multi targeted tyrosine kinase inhibitors are being tested in advanced disease in the context of clinical trials. Recent publications indicate that a substantial proportion of patients with advanced disease will stabilize with the use of these promising agents. Patients with familial disease appear to respond better to therapy with tyrosine kinase inhibitors. Combination therapies are also being tested.

Value of virtual touch tissue quantification technique in the diagnosis of small solid thyroid nodules

Objective To explore the application value of virtual touch tissue quantification(VTQ) technique in differentiating small solid thyroid nodules.Methods The patients with suspiciously malignant thyroid nodules(solitary,size range 5-15 mm),homogeneous and normal color Doppler flow imaging in the rest of thyroid parenchyma,were enrolled in this study.Five repeated measurements were performed on both nodules and extra-nodular tissues using VTQ.A receiver-operating characteristic (ROC) curve was drew according to shear wave velocity(Vs).Results 62 patients with a total of 67 lesions were included in this study,turned out to be 39 malignant and 28 benign.The Vs of malignant group nodules,malignant group extra-nodular tissues,benign group nodules and benign group extra-nodular tissues were (3.91 ±1.85) m/s,(2.03 ± 0.42)m/s,(2.29 ± 0.56)m/s,(1.84 ± 0.45)m/s,respectively.The Vs difference between malignant and benign nodules was statistically significant (P =0.000),while the Vs difference between malignant and benign extra-nodular tissues had no statistical significance (P =0.07).The best cutoff Vs value for distinguishing malignant from benign nodules was 2.78 m/s,with the sensitivity,specificity and accuracy of 76.9％,78.6％ and 80.6％ respectively.The area under ROC curve was 0.84.Conclusions VTQ could evaluate the elasticity of thyroid nodules,and was helpful in the diagnostic work-up of thyroid nodules. Key words: Ultrasonography; Thyroid neoplasms; Virtual touch tissue quantification

Shear wave elastography in the diagnosis of thyroid nodules: feasibility in the case of coexistent chronic autoimmune Hashimoto’s thyroiditis

ShearWave™ Elastography (SWE) is real-time, quantitative and user-independent technique, recently introduced in the diagnostic work-up of thyroid nodules. Hashimoto's thyroiditis (HT), characterized by variable degrees of lymphocytic infiltration and fibrosis, might affect shear wave propagation. The aim of this study was to assess the feasibility of SWE in cytologically benign thyroid nodules within both Hashimoto's and nonautoimmune thyroid glands. The effect of autoimmunity on the gland stiffness was also evaluated. longitudinal study in a single centre. SWE was performed in 75 patients with a benign thyroid nodule at cytology: 33 with Hashimoto's thyroiditis (HT group) and 42 with uni- or multi-nodular goitre, negative for thyroid autoimmunity (non-HT group). The elasticity index (EI) of the extra-nodular tissue was greater, though not statistically significant, in the HT than in the non-HT group (24·0 ± 10·5 kPa vs 20·8 ± 10·4 kPa; P = 0·206). However, the EI of extra-nodular tissue was related to the TPOAb titre in the HT group (P = 0·02) and was significantly higher in patients with HT receiving L-thyroxine than in the euthyroid subjects (P = 0·02). The EI of thyroid nodules was similar in HT and non-HT groups. In both groups, the stiffness of nodules was significantly higher than that of the embedding tissue. Our data indicate that SWE correctly defines the elasticity of thyroid nodules independently from the coexistence of autoimmune thyroiditis, always being able to differentiate nodular tissue from the surrounding parenchyma. In HT, the stiffness of extra-nodular tissue increases in relation to both the thyroid antibody titre and the degree of impairment of thyroid function.

Thyroid nodule evaluation: what have we really learned from recent clinical guidelines?

Recent guidelines for the evaluation of thyroid nodules clarify the diagnostic algorithm while also reporting important differences. The performance of fine needle aspiration (FNA) for cytological examination follows serum TSH determination and thyroid ultrasonography. Thyroid scintigraphy is recommended following a low TSH value and/or FNA yielding an indeterminate follicular cytology. The use of thyroid ultrasonography is the source of some controversy: though it is recommended as a principal first test, its real-time use to guide FNA ranges from routine to only following an FNA yielding an inadequate or nondiagnostic cytological result. In clinical practice, the proportion of physicians utilizing ultrasonography, scintigraphy and FNA varies and frequently deviates from recommended guidelines. The development of guidelines is necessary to bring about consistency and optimization to the diagnostic work-up of thyroid nodules. It is likely that novel diagnostic procedures, such as molecular markers, large needle aspiration biopsy and thyroid imaging with tracers beyond conventional radioactive iodine or 99mTc pertechnetate, will lead to improved performance and implementation of guidelines.