Using the Ata and Acr Ti-Rads Sonographic Classifications as Adjunctive Predictors of Malignancy for Indeterminate Thyroid Nodules

Objective: Thyroid nodules with indeterminate cytology pose management challenges in clinical practice. The aim of this study was to determine the efficacy of ultrasound features in navigating clinical decision making in thyroid nodules with indeterminate cytology.Methods: We retrospectively reviewed ultrasound imaging from 186 adult patients with thyroid nodules and indeterminate cytology who underwent thyroidectomy at a quaternary hospital from 2010–2017. All nodules were classified based on the American Thyroid Association (ATA) and 2017 American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS). Nodules were included if good quality pre-operative ultrasound imaging and surgical pathology were available.Results: A total of 202 thyroid nodules were included. The median age was 57 years; 82.8% were female. Risk of malignancy (ROM) in resected nodules with Bethesda 3 and 4 cytology was 19.4% and 30.3%, respectively. ATA high-suspicious and TI-RADS 5 nodules had high ROM, 100% in both systems for Bethesda 3 nodules; 66.7% and 50.0%, respectively, for Bethesda 4 nodules. For ATA very-low suspicious/TI-RADS 1 and 2, ROM was 0%. ROM in ATA low-suspicious/TI-RADS 3 nodules with Bethesda 3 cytology was lower (15.2% and 16.0%, respectively) than Bethesda 4 cytology (33.8% and 34.3%, respectively). ATA intermediate-suspicious/TI-RADS 4 nodules with Bethesda 4 cytology had a lower ROM (11.1% and 18.2%, respectively) than Bethesda 3 cytology (28.6 % and 31.6%, respectively).Conclusion: Using either the ATA or the TI-RADS system to risk-stratify nodules with indeterminate cytology may help clinicians plan better for additional diagnostic testing and treatment.Abbreviations: ACR = American College of Radiology; ATA = American Thyroid Association; AUS = atypia of undetermined significance; FLUS = follicular lesion of undetermined significance; FN = follicular neoplasm; PPV = positive predictive value; ROM = risk of malignancy; SFN = suspicious for follicular neoplasm; TI-RADS = Thyroid Imaging Reporting and Data System     

Comparison of Diagnostic Performance between the American College of Radiology Thyroid Imaging Reporting and Data System and American Thyroid Association Guidelines: A Systematic Review

Objective: We aimed to compare the diagnostic accuracy of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) with the American Thyroid Association (ATA) guidelines in risk stratification of thyroid nodules.Methods: We performed a computerized search of Medline, EMBASE, Web of Science, Cochrane Library, and Google Scholar to identify eligible articles published before July 31, 2019. We included studies providing head-to-head comparison between ACR TI-RADS and ATA guidelines, with fine-needle aspiration biopsy cytology results or pathology results as the reference standard. Quality assessment of included studies was conducted using the Quality Assessment of Diagnostic Accuracy Studies–2 tool. Summary estimates of sensitivity and specificity were calculated by bivariate modeling and hierarchical summary receiver operating characteristic modeling. We also performed multiple subgroup analyses and meta-regression.Results: Twelve original articles with 13,000 patients were included, involving a total of 14,867 thyroid nodules. The pooled sensitivity of ACR TI-RADS and ATA guidelines was 0.84 (95% confidence interval [CI], 0.76–0.89) and 0.89 (95% CI, 0.80–0.95), with specificity of 0.67 (95% CI, 0.56–0.76) and 0.46 (95% CI, 0.29–0.63), respectively. There were no significant differences between the two classification criteria in terms of both sensitivity (P = .26) and specificity (P = .05). For five studies providing direct comparison of ACR TI-RADS, ATA guidelines, and Korean TI-RADS, our analyses showed that the Korean TI-RADS yielded the highest sensitivity (0.89; 95% CI, 0.82–0.94), but at the cost of a significant decline in specificity (0.23; 95% CI, 0.17–0.30).Conclusion: Both classification criteria demonstrated favorable sensitivity and moderate specificity in the stratification of thyroid nodules. However, use of ACR TI-RADS could avoid a large number of biopsies at the cost of only a slight decrease in sensitivity.Abbreviations: ACR = American College of Radiology; ATA = American Thyroid Association; FNAB = fine-needle aspiration biopsy; HSROC = hierarchical summary receiver operating characteristic; SROC = summary receiver operating characteristic; TI-RADS = Thyroid Imaging Reporting and Data System; US = ultrasonography     

Comparison of the Efficacy and Safety of the American Thyroid Association Guidelines and American College of Radiology TI-RADS

ObjectiveTo evaluate the 2015 American Thyroid Association (ATA) guidelines and 2017 American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TI-RADS) for their efficacy in predicting malignant thyroid nodules and safety in recommending fine needle aspiration (FNA).MethodsWe reviewed data of 970 thyroid nodules from 908 patients with core needle biopsy pathology. We calculated the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for each guideline to predict malignancies. We compared the areas under the curve and FNA recommendations between the 2 guidelines.ResultsAccording to the core needle biopsy pathology, 59.9% (581/970) of the thyroid nodules were malignant. Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value was 68%, 91%, 33%, 67%, and 70%, respectively, for the ATA guidelines and 70%, 84%, 49%, 71%, and 68%, respectively, for the ACR TI-RADS. Areas under the curve (ATA: 0.71 vs ACR TI-RADS: 0.74; P = .054) were similar when predicting malignancies. For the 545 nodules with maximum diameter ≥1.0 cm, the ACR TI-RADS recommended FNA less often than the ATA guidelines (83.3% [454/545] vs 87.7% [478/545]; P = .01). For the 321 malignant nodules with maximum diameter ≥1.0 cm, the proportions of FNA recommendations were not significantly different (ACR TI-RADS: 90.7% [291/321] vs ATA: 92.5% [297/321]; P = .06).ConclusionThe 2015 ATA guidelines and 2017 ACR TI-RADS showed a similar ability in predicting malignancies. Reducing FNA recommendations by the ACR TI-RADS would not lead to a significant decrease in the FNA recommendations given for malignancies with maximum diameter ≥1.0 cm.     

Comparison of 5 Thyroid Ultrasound Stratification Systems for Differentiation of Benign and Malignant Nodules and to Avoid Biopsy Using Histology as Reference Standard

ObjectiveWe aimed to compare the thyroid ultrasound risk stratification systems (RSSs) of the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS), European TI-RADS, Korean TI-RADS, and American Thyroid Association (ATA), American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi guidelines to differentiate benign from malignant thyroid nodules and to avoid unnecessary fine needle aspiration (FNA).MethodsThe records of 1143 nodules ≥1 cm that underwent FNA biopsy and thyroidectomy between 2012 and 2020 at our institution were reviewed. Ultrasound categories and FNA recommendation indications of 5 international RSSs were compared with histopathological findings as benign or malignant. The ultrasound categories and recommended FNA indications, the proportion of the avoidable FNA procedures, and false negative rates (FNRs) by different systems were compared with each other.ResultsOf the 1143 nodules, 45% had thyroid malignancy. FNA recommendation and ultrasound risk classification of ATA guidelines had the highest area under curves of 0.619, and 0.715, respectively. ACR TI-RADS, American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi guidelines, European TI-RADS, ATA guidelines, and Korean TI-RADS would have avoided FNA for 34.7%, 31%, 25.7%, 20%, and 6% of nodules with an FNR of 24%, 28.5%, 22%, 7.2%, and 1.9%, respectively.ConclusionOur findings showed that all RSSs classified the nodules appropriately for malignancy. ATA guidelines had the highest area under curves and a low FNR, whereas ACR TI-RADS would have spared more patients from FNA with a high FNR.     

Utility of Afirma Gene Expression Classifier for Evaluation of Indeterminate Thyroid Nodules and Correlation with Ultrasound Risk Assessment: Single Institutional Experience

Objective: We assessed our experience with Afirma gene expression classifier (GEC) combined with sono-graphic risk assessment, using both the American Thyroid Association (ATA) and the Thyroid Imaging Reporting and Data System (TI-RADS) in evaluating indeterminate thyroid nodules.Methods: We identified 98 patients with 101 nodules who had a second fine needle aspiration biopsy (FNA) between January 1, 2014, and September 30, 2017, and sent to Veracyte for cytopathology and subsequent Afirma GEC testing. A second FNA biopsy was performed if the initial cytopathology was either Bethesda III or IV (n = 94) or nondiagnostic (n = 7). We correlated cytopathology, histopathology, and Afirma GEC results with sonographic risk assessment using both the ATA system and TI-RADS.Results: The mean age of the cohort was 57.4 ± 12.3 years; 84% women and 60% white. Repeat FNA was benign in 51 of 101 nodules, and of the remaining 50 nodules, 18 (36%) were GEC-benign and 32 (64%) GEC-suspicious. Eighteen of the 32 GEC-suspicious nodules underwent surgery with the following results: 7 benign (39%), 1 follicular thyroid carcinoma (6%), 6 follicular variant of papillary thyroid cancer (33%), and 4 noninvasive follicular tumor with papillary-like nuclear features (22%). The malignancy rate among the surgical cohort was 39% (without noninvasive follicular tumor with papillary-like nuclear features [NIFTP]) and 61% (with NIFTP) and about 50% and 20% of this group scored in the high suspicion category by ATA and TR5 by TI-RADS, respectively.Conclusion: Afirma GEC was useful in avoiding surgery in one-third of indeterminate nodules and performed similarly to ATA and TI-RADS. However, the use of echogenicity in scoring may underestimate the risk of malignancy in patients with indeterminate nodules.Abbreviations:ATA = American Thyroid Association; AUS = Atypia of Undetermined Significance; FLUS = Follicular Lesion of Undetermined Significance; FN = follicular neoplasm; FNA = fine needle aspiration; FTC = follicular thyroid cancer; FVPTC = follicular variant of papillary thyroid cancer; GEC = Gene Expression Classifier; ND = nondiagnostic; NIFTP = noninvasive follicular tumor with papillary-like nuclear features; TI-RADS = Thyroid Imaging Reporting and Data System; TR = TI-RADS     

Guideline Implementation on Fine-Needle Aspiration for Thyroid Nodules: Focusing on Micronodules

Objective: We investigated patients who were referred to our institution after fine-needle aspiration (FNA) was performed at outside clinics to evaluate how many nodules satisfied the FNA indications of the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and compare that to the number of thyroid nodules that satisfy the FNA indications of the American College of Radiology (ACR)-TIRADS and American Thyroid Association (ATA) guidelines.Methods: Between January 2018 and December 2018, 2,628 patients were included in our study. The included patients were those referred for thyroid surgery after having a suspicious thyroid nodule. We retrospectively applied the three guidelines to each thyroid nodule and determined whether each nodule satisfied the FNA indications. We compared the proportion of nodules satisfying the FNA indications of each guideline using a generalized linear model and generalized estimating equation.Results: The median size of the 2,628 thyroid nodules was 0.9 cm (range, 0.2 to 9.5 cm). We found that FNA was not indicated for 54.1%, 47.7%, and 19.1% of nodules and 87.3%, 99.0%, and 97.8% among them were micronodules (<1 cm) according to the ACR-TIRADS, ATA guideline, and K-TIRADS, respectively. The proportion of micronodules which satisfied the FNA indications was significantly higher for the K-TIRADS (65.1%) compared to the ACR TIRADS (12.1%) and ATA guideline (12.1%) (P<.001).Conclusion: Among patients referred for thyroid surgery to our institutions, about 35% of the micronodules underwent FNA despite not being appropriate for indications by the K-TIRADS. Systematic training for physicians as well as modifications to increase the sensitivity of the guideline may be needed to reduce the overdiagnosis of thyroid cancers, especially for micronodules.     

Can the American Thyroid Association,K-Tirads,and Acr-Tirads Ultrasound Classification Systems Be Used to Predict Malignancy in Bethesda Category IV Nodules?

Objective: Management of thyroid nodules with Bethesda category III and IV cytology on fine needle aspiration (FNA) is challenging as they cannot be adequately classified as benign or malignant. Ultrasound (US) patterns have demonstrated the utility in evaluating the risk of malignancy (ROM) of Bethesda category III nodules. This study aims to evaluate the value of 3 well-established US grading systems (American Thyroid Association &lsqb;ATA], Korean Thyroid Imaging Reporting and Data System &lsqb;Korean-TIRADS], and The American College of Radiology Thyroid Imaging Reporting and Data System &lsqb;ACR-TIRADS]) in determining ROM in Bethesda category IV nodules.Methods: Ninety-two patients with 92 surgically resected thyroid nodules who had Bethesda category IV cytology on FNA were identified. Nodule images were retrospectively graded using the 3 systems in a blinded manner. Associations between US risk category and malignant pathology for each system were analyzed.Results: Of the 92 nodules, 56 (61%) were benign and 36 (39%) were malignant. Forty-seven per cent of ATA high risk nodules, 53% of K-TIRADS category 5 nodules, and 50% of ACR-TIRADS category 5 nodules were malignant. The ATA high-risk category had 25% sensitivity, 82% specificity, 47% positive predictive value (PPV) for malignancy. K-TIRADS category 5 had 25% sensitivity, 85% specificity, 53% PPV for malignancy. ACR-TIRADS category 5 had 25% sensitivity, 84% specificity, 50% PPV for malignancy. None of the 3 grading systems yielded a statistically significant correlation between US risk category and the ROM (P = .30, .72, .28).Conclusion: The ATA, Korean-TIRADS, and ACR-TIRADS classification systems are not helpful in stratifying ROM in patients with Bethesda category IV nodules. Clinicians should be cautious of using ultra-sound alone when deciding between therapeutic options for patients with Bethesda category IV thyroid nodules.     

Implementing Key Changes in The American Thyroid Association 2015 Thyroid Nodules/Differentiated Thyroid Cancer Guidelines Across Practice Types

Objective: This article provides suggestions to help clinicians implement important changes in the 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Carcinoma (“ATA 2015”) across diverse settings.Methods: Key ATA 2015 changes are summarized regarding: (1) thyroid nodule management; (2) lobectomy versus thyroidectomy for differentiated thyroid carcinoma (DTC); and (3) surveillance following primary treatment of DTC. Advice to facilitate implementation is based on clinical experience and selected literature.Results: Strategies are described to enhance acquisition of high-quality information that helps identify patients who may possibly avoid fine-needle aspiration (FNA) of thyroid nodules or total thyroidectomy for DTC, or undergo less intense postoperative surveillance. Sonographic imaging of nodules may improve if sonograms are obtained by clinicians ordering or performing FNA or trusted high-volume sonographers. Cytopathologic assessment and reporting can be improved by working with regional or national experts. Pre-operative evaluation by endocrinologists is important so that patients are referred to experienced, proficient surgeons and assisted with well-informed decision-making regarding surgical radicality. Endocrinologists and surgeons should ensure performance of pre-operative neck ultrasonography, voice/laryngeal evaluation, and contrast-enhanced cross-sectional imaging when appropriate. Findings should be disseminated to all healthcare team members, ideally through a comprehensive medical record accessible to the entire team.Conclusion: Optimization of the sequence of specialist visits and assembly of interactive multidisciplinary teams coupled with intensified interdisciplinary and patient communication may enable clinicians to more effectively implement ATA 2015, which calls for more individualized, and often, less “invasive” management of thyroid nodules and DTC.Abbreviations: ATA 2009 = 2009 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Carcinoma; ATA 2015 = 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Carcinoma; DTC = differentiated thyroid carcinoma; FNA = fine-needle aspiration; PET/CT = positron emission tomography/computed tomography     

Drivers of the Decision to Biopsy and Follow-Up of Small Suspicious Thyroid Nodules

Objective: In 2015, the updated American Thyroid Association (ATA) guidelines recommended observation for suspicious subcentimeter thyroid nodules, based on their indolent course. We aimed to evaluate the frequency of biopsy in suspicious thyroid nodules since the introduction of these guidelines, including factors contributing to clinical decision-making in a tertiary care center.Methods: We conducted a retrospective study of patients in the Mayo Clinic, Rochester, Minnesota, with new, subcentimeter suspicious thyroid nodules (by report or by sonographic features) between March, 2015, and November, 2017, not previously biopsied.Results: We identified 141 nodules in 129 patients: mean age 58.1 ± 14.1 years, 74% female, 87% Caucasian. The frequency of biopsy in suspicious thyroid nodules was 39%. Ultrasound features that were the strongest predictors for biopsy on multivariate analysis included: nodule volume (odds ratio [OR] 37.3 [7.5–188.7]), radiology recommendation for biopsy (OR 2.6 [1.8–3.9]) and radiology report of the nodule as “suspicious” (OR 2.1 [1.4–3.2]). Patient’s age and degree of comorbidities did not change the likelihood for biopsy, nor did it vary by clinician type or how the nodule was initially found (incidentally or not incidentally). Among 86 nodules that were not biopsied, 41% had no specific follow-up recommendations.Conclusion: One third of suspicious thyroid nodules underwent biopsy since the release of updated ATA guidelines. Factors driving thyroid biopsy seem to be associated with nodule characteristics but not with patient factors including age and comorbidities. Further studies and development of decision aides may be helpful in providing individualized approaches for suspicious thyroid nodules.Abbreviations: ATA = American Thyroid Association; OR = odds ratio     

Exposure to the Chinese Famine in Early Life and the Thyroid Function and Nodules in Adulthood

Objective: Previous studies found that exposure to famine was associated with a higher risk of metabolic syndrome and fatty liver in adult women. In the present study, we investigated the relationship between exposure to the Chinese famine in early life and thyroid function and nodules in adulthood.Methods: We retrospectively analyzed the data of subjects who underwent routine physical check-up in the Public Health Center of our hospital in 2017. Subjects were divided into 3 groups: post-, pre-, and nonexposed groups. The basal metabolic rate (BMR) was estimated by the revised Harris-Benedict formulation. The serum levels of thyroid hormones were detected. Thyroid ultrasonography was performed by experienced technicians. The diagnosis of thyroid nodules was according to the Thyroid Imaging Reporting and Data System (TI-RADS).Results: Compared to nonexposed subjects, the postnatally exposed subjects had a significantly lower level of thyroxine, and statistically higher ultrasensitive thyroid stimulating hormone (P<.05). There was no significant difference in thyroid autoimmune antibodies between groups exposed to the famine and the nonexposed group (P>.05). There were no statistical differences in heart rate and BMR among these groups (P>.05). Exposure to the famine did not affect either the numbers of thyroid nodules, the TI-RADS score of thyroid nodules, or the maximal diameters of thyroid nodules.Conclusion: Our results indicate a significant association between famine exposure in early life and down-regulated thyroid function in adulthood. Postnatal famine exposure may be more vulnerable to nutrient deficiency and lead to restricted thyroid development in later life.Abbreviations: BMR = basal metabolic rate; FT3 = free triiodothyronine; FT4 = free thyroxine; IDD = iodine deficiency disorder; T3 = triiodothyronine; T4 = thyroxine; TG-Ab = thyroglobulin antibody; TI-RADS = Thyroid Imaging Reporting and Data System; uTSH = ultrasensitive thyroid stimulating hormone     

Additional Surgery for Occult Risk Factors After Lobectomy in Solitary Thyroid Nodules is Predicted by Cytopathology Classification and Tumor Size

Objective: Clinical practice for differentiated thyroid cancer is moving towards lobectomy rather than total thyroidectomy in patients at low risk of recurrence. However, recurrence risk assessment depends on post-operative findings, while the surgical decision is based on preoperative factors. We determined the preoperative predictors of occult higher-risk pathology and rates of completion thyroidectomy among surgical candidates with nonbenign thyroid nodules 10 to 40 mm and no evidence of extrathyroidal extension or metastasis on preoperative evaluation.Methods: Thyroid surgery cases at a single institution from 2005–2015 were reviewed to identify those meeting American Thyroid Association (ATA) criteria for lobectomy. ATA-based risk stratification from postoperative surgical pathology was compared to preoperative cytopathology, ultrasound, and clinical findings.Results: Of 1,995 thyroid surgeries performed for nonbenign thyroid nodules 10 to 40 mm, 349 met ATA criteria for lobectomy. Occult high-risk features such as tall cell variant, gross extrathyroidal invasion, or vascular invasion were found in 36 cases (10.7%), while intraoperative lymphadenopathy led to surgical upstaging in 13 (3.7%). Intermediate risk features such as moderate lymphadenopathy or minimal extrathyroidal extension were present in an additional 44 cases. Occult risk features were present twice as often in Bethesda class 6 cases (35%) as in lower categories (12 to 17%). In multivariable analysis, Bethesda class and nodule size, but not age, race, sex, or ultrasound features, were significant predictors of occult higher-risk pathology.Conclusion: Most solitary thyroid nodules less than 4 cm and with cytology findings including atypia of undetermined significance through suspicious for papillary thyroid cancer would be sufficiently treated by lobectomy.Abbreviations: ATA = American Thyroid Association; CND = central neck dissection; DTC = differentiated thyroid cancer; ETE = extrathyroidal extension; FNA = fine needle aspiration; FTC/HCC = follicular thyroid carcinoma/Hurthle cell carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; OR = odds ratio; PTC = papillary thyroid cancer; US = ultrasound     

Serial Neck Ultrasound is More Likely to Identify False-Positive Abnormalities than Clinically Significant Disease in Low-Risk Papillary Thyroid Cancer Patients

Objective: American Thyroid Association (ATA) low-risk papillary thyroid cancer (PTC) patients without structural evidence of disease on initial posttreatment evaluation have a low risk of recurrence. Despite this, most patients undergo frequent surveillance neck ultrasound (US). The objective of the study was to evaluate the clinical utility of routine neck US in ATA low-risk PTC patients with no structural evidence of disease after their initial thyroid surgery.Methods: We performed a retrospective review of 171 ATA low-risk PTC patients after total thyroidectomy, with or without radioactive iodine (RAI) ablation, who had a neck US without suspicious findings after therapy. The main outcome measure was a comparison of the frequency of finding false-positive US abnormalities and the frequency of identifying structural disease recurrence.Results: Over a median follow-up of 8 years, 171 patients underwent a median of 5 neck US (range 2–17). Structural recurrence with low-volume disease (≤1 cm) was identified in 1.2% (2/171) of patients at a median of 2.8 years (range 1.6–4.1 years) after their initial diagnosis. Recurrence was associated with rising serum thyroglobulin (Tg) level in 1 of the 2 patients and was detected without signs of biochemical recurrence in the other patient. Conversely, false-positive US abnormalities were identified in 67% (114/171) of patients after therapy, leading to additional testing without identifying clinically significant disease.Conclusion: In ATA low-risk patients without structural evidence of disease on initial surveillance evaluation, routine screening US is substantially more likely to identify false-positive results than clinically significant structural disease recurrence.Abbreviations:18FDG-PET = 18-fluorodeoxyglucose-positron emission testingAJCC = American Joint Committee on CancerATA = American Thyroid AssociationCT = computed tomographyETA = European Thyroid AssociationMRI = magnetic resonance imagingPTC = papillary thyroid cancerRAI = radioactive iodineTg = thyroglobulinTgAb = antithyroglobulin antibodiesTSH = thyroid-stimulating hormoneUS = ultrasound     

Thyroid Nodule Location on Ultrasonography as a Predictor of Malignancy

Objective: The diagnostic capacity of ultrasonography (US) for differentiating between malignant and benign thyroid nodules is crucial in preventing unnecessary invasive procedures. This is the first study to evaluate whether thyroid nodule location on US has predictive value for malignancy.Methods: We retrospectively reviewed data from 219 patients with thyroid nodules who underwent fine-needle aspiration biopsy in 1 year. Patients' demographics as well as nodule's laterality, polarity, morphology, and multinodularity were analyzed. All malignant lesions were confirmed by surgical pathology.Results: The majority of the patients were female (86.2%). Nodules were evenly distributed between the right lobe (46.3%) and left lobe (49.5%). Eight nodules (4.2%) were located in the isthmus. Most nodules (79.3%) were located in the lower pole, while 9.6% were located in the upper pole and 6.9% in the middle pole. Seventy-five patients (39.9%) had multiple nodules. Fourteen nodules were malignant, representing a prevalence of 7.4%. A significantly higher frequency of malignancy was observed in upper pole (22.2%) compared to lower pole (4.7%) and middle pole (15.4%). A multiple logistic regression model confirmed such association after adjusting for age, body mass index, multinodularity, and laterality. The odds of malignancy in the upper pole were 4 times higher than other locations (odds ratio, 4.6; P = .03).Conclusion: Our study is the first showing that thyroid nodules located in the upper pole can be considered as having higher risk for malignancy. It may enhance the predictive value of malignancy if it is included in thyroid nodule ultrasound classification guidelines.Abbreviations: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; BMI = body mass index; FNA = fine-needle aspiration; TMS = total malignancy score; TTW = taller than wide; US = ultrasonography     

Consistency of Thyroid Imaging Reporting and Data System Reporting in Community-Based Imaging Centers Versus a Large Tertiary Hospital

ObjectiveIn our country, thyroid nodules are sonographically evaluated in health maintenance organization (HMO) imaging centers, and patients are referred to tertiary hospitals for ultrasound-guided fine-needle aspiration (FNA) biopsy when indicated. We evaluated the concordance in Thyroid Imaging Reporting and Data System (TI-RADS) classification reporting between these sites.MethodsWe conducted a retrospective cohort study reviewing the sonographic features of thyroid nodules evaluated both at the HMO and a large tertiary center between January 2018 and December 2019. The primary outcome was concordance between the TI-RADS classification at both sites. Additional endpoints included correlation of TI-RADS to the Bethesda category following FNA and correlation of TI-RADS with malignancy on final pathology at each site.ResultsThe records of 336 patients with 370 nodules were reviewed. The level of concordance was poor (19.8%), with 277 (74.8%) nodules demonstrating higher TI-RADS and 20 (5.4%) lower TI-RADS at the HMO compared to the hospital (P < .001; weighted κ = 0.120). FNA results were available for 236 (63.8%) nodules. The Bethesda category strongly correlated with the hospital TI-RADS (P < .001), yet not with HMO TI-RADS (P = .123). In the surgically removed 57 nodules, a strong correlation was identified between the malignancy on final pathology and TI-RADS documented at the hospital (P < .001), yet not at the HMO (P = .259).ConclusionsThere is poor agreement between TI-RADS classification on ultrasound performed in the HMO compared to a tertiary hospital. The hospital’s TI-RADS strongly correlated with the Bethesda category and the final risk of malignancy, unlike the HMO.     

An Italian Survey of Compliance With Major Guidelines for L-Thyroxine of Primary Hypothyroidism

Objective: The adherence by endocrinologists to guideline regarding levothyroxine (LT4) therapy and the compliance of patients may impact the management of hypothyroidism. The aim of this study was to compare the adherence of Italian endocrinologists to the ATA/AACE and ETA guidelines on the management of newly diagnosed primary hypothyroidism and to validate the Italian version of the Morisky-Green Medical Adherence Scale-8 (MMAS-8) questionnaire as applied to the evaluation of the adherence of patients with hypothyroidism to LT4 treatment.Methods: This was an observational, longitudinal, multicenter, cohort study, involving 12 Italian Units of Endocrinology.Results: The study enrolled 1,039 consecutive outpatients (mean age 48 years; 855 women, 184 men). The concordance of Italian endocrinologists with American Association of Clinical Endocrinologists/American Thyroid Association (AACE/ATA) and European Thyroid Association (ETA) recommendations was comparable (77.1% and 71.7%) and increased (86.7 and 88.6%) after the recommendations on LT4 dose were excluded, considering only the remaining recommendations on diagnosis, therapy, and follow-up. The MMAS-8 was filled out by 293 patients. The mean score was 6.71 with 23.9% low (score <6), 38.6% medium (6 to <8), 37.5% highly (= 8) adherers; the internal validation coefficient was 0.613. Highly adherent patients were not more likely to have good control of hypothyroidism compared with either medium (69% versus 72%, P = .878) or low (69% versus 43%, P = .861) adherers.Conclusion: Clinical management of hypothyroidism in Italy demonstrated an observance of international guidelines by Italian endocrinologists. Validation of the Italian version of the MMAS-8 questionnaire provides clinicians with a reliable and simple tool for assessing the adherence of patients to LT4 treatment.Abbreviations: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; EDIPO = Endotrial SIE: DIagnosis and clinical management of Primitive hypothyrOidism in Italy; eCRF = electronic case report form; ETA = European Thyroid Association; fT3 = free triiodothyronine; fT4 = free thyroxine; LT4 = levothyroxine; MMAS-8 = Morisky-Green Medical Adherence Scale-8; PH = primary hypothyroidism; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone; US = ultrasonography     

Agreement Between American and European Thyroid Imaging,Reporting, and Data System (TIRADS) in the Diagnosis of 473 Thyroid Nodules From a Single Center in Brazil

ObjectiveTo compare 2 ultrasound-based risk stratification systems in malignancy risk assessment of thyroid nodules and the clinical applicability of these guidelines in Brazil.MethodsWe retrospectively reviewed the ultrasound findings of 314 patients (473 thyroid nodules) who underwent fine-needle aspiration (FNA) biopsy and/or surgery between February 2018 and March 2019. All nodules were classified using 2 systems: the Thyroid Imaging, Reporting, and Data System (TIRADS) of the American College of Radiology (ACR-TIRADS) and the TIRADS of the European Thyroid Association (EU-TIRADS). Both risk stratification systems were analyzed. We identified the diagnostic predictive values that yielded optimal sensitivity, specificity, positive predictive value, negative predictive value, and accuracy.ResultsOf the 473 nodules, all underwent FNA, and histopathology was performed for 332 nodules. The agreement between the ACR-TIRADS and EU-TIRADS results and that between cytology and histopathology findings was 92.6% (kappa = 0.84) and 86.7% (kappa = 0.73), respectively. The area under the curve for the ACR-TIRADS and EU-TIRADS was 0.871 and 0.828, respectively (P < .001). The EU-TIRADS had the best sensitivity and negative predictive value, whereas the ACR-TIRADS had the best specificity, positive predictive value, and accuracy. Of the 473 nodules studied, only 158 (33.4%) followed the FNA size criteria suggested by the ACR-TIRADS.ConclusionACR-TIRADS and EU-TIRADS had good diagnostic performances. However, most aspirated nodules did not follow the TIRADS indication; thus, the overuse of FNA as a diagnostic tool was observed.     

No Benefit of Dedicated Thyroid Nodule Screening in Patients with Acromegaly

Objective: Acromegaly results from the excessive production of growth hormone and insulin-like growth factor-1. While there is up to a 2-fold increased prevalence of thyroid nodules in patients with acromegaly, the incidence of thyroid cancer in this population varies from 1.6 to 10.6% in several European studies. The goal of our study was to determine the prevalence of thyroid nodules and thyroid cancer among patients with acromegaly at a large urban academic medical center in the United States (U.S.).Methods: A retrospective chart review was performed of all patients with acromegaly between 2006–2015 within the University of California, Los Angeles health system. Data were collected regarding patient demographics, thyroid ultrasounds, thyroid nodule fine needle aspiration (FNA) biopsy cytology, and thyroid surgical pathology.Results: In this cohort (n = 221, 49.3% women, mean age 53.8 ± 15.2 &lsqb;SD] years, 55.2% Caucasian), 102 patients (46.2%) underwent a thyroid ultrasound, from which 71 patients (52.1% women, mean age 52.9 ± 15.2 &lsqb;SD] years, 56.3% Caucasian) were found to have a thyroid nodule. Seventeen patients underwent a thyroid nodule FNA biopsy and the results revealed 12 benign biopsies, 1 follicular neoplasm, 3 suspicious for malignancy, and 1 papillary thyroid cancer (PTC), from which 6 underwent thyroidectomy; PTC was confirmed by surgical pathology for all cases (8.5% of all nodules observed).Conclusion: In this sample, the prevalence of thyroid cancer in patients with acromegaly and coexisting thyroid nodules is similar to that reported in the general U.S. population with thyroid nodules (7 to 15%). These findings suggest that there is no benefit of dedicated thyroid nodule screening in patients newly diagnosed with acromegaly.Abbreviations: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FNA = fine needle aspiration; GH = growth hormone; IGF-1 = insulin-like growth factor-1; PTC = papillary thyroid cancer; U.S. = United States     

The Risk of Thyroid Cancer in Patients with Thyroid Nodule 3 Cm Or Larger

Objective: There are conflicting data on the risk of thyroid cancer in thyroid nodules 3 cm or larger, and few such studies on this issue have been conducted in Asia. This study aimed to examine the risk of thyroid cancer in patients with thyroid nodules 3 cm or larger.Methods: This was a 7-year retrospective study conducted in a tertiary referral hospital in Taiwan. All patients with a thyroid nodule measuring ≥3 cm who underwent thyroid operation with or without fine-needle aspiration biopsy (FNAB) were included. The prevalence rate of thyroid cancer, as well as the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and false-negative rate of FNAB for thyroid nodule ≥3 cm were also examined.Results: A total of 132 patients were included in this study. Thyroid cancer was detected in 19 of 132 (14.4%) thyroid nodules measuring ≥3 cm. The performance of FNAB for detecting cancer in nodules 3 cm or larger without considering other ultrasonography parameters was relatively poor with a sensitivity of 50%, but the specificity (100%), PPV (100 %), and NPV (93.4 %) were excellent.Conclusion: The risk of thyroid cancer for thyroid nodules ≥3 cm in this study was low. The PPV and NPV of FNAB were high for the detection of cancer in large nodules. The decision to perform thyroidectomy should not be solely based on nodule size and should include other factors, such as ultrasound characteristics and surgical risk.     

Predictive Value of Somatic Mutations for the Development of Malignancy in Thyroid Nodules by Cytopathology

Objective: The purpose of our prospective longitudinal study was to evaluate the predictive efficacy of genetic testing for malignancies in fine-needle aspiration biopsy samples that are cytologically benign at the time of biopsy.Methods: A total of 779 aspirated cytological samples collected from thyroid nodules of 626 patients were included in a 3-year follow-up study. Consecutive patients with cytologically benign thyroid nodules by the Bethesda System for Reporting Thyroid Cytopathology were enrolled in the study. At enrollment, somatic 1-point nucleotide polymorphisms of BRAF and RAS family genes were tested by melting-point analysis, while RET/PTC and PAX8/PPAR-gamma rearrangements were examined by real-time polymerase chain reaction. The genetic test was considered to be positive if a somatic mutation was found. Malignant cytopathologic diagnoses were confirmed by histopathology.Results: In samples collected from 779 thyroid nodules, there were 39 BRAF, 33 RAS mutations, and 1 RET/PTC rearrangements found at the beginning of the study. No PAX8/PPAR-gamma rearrangement was identified. There were 52 malignant thyroid tumors removed during follow-up, out of which 24 contained a somatic mutation. The specificity of the presence of somatic mutations for malignancies was as high as 93.3%, and sensitivity was 46.2%. The negative predictive value of genetic testing reached 96.0%.Conclusion: Our results show that our set of genetic tests can predict the appearance of malignancy in benign thyroid nodules (at the beginning of follow-up) with high specificity and strong negative predictive value.Abbreviations:BRAF = v-raf murine sarcoma viral oncogene homolog B1FLUS = follicular lesion of undetermined significanceFNAB = fine-needle aspiration biopsyFTC = follicular thyroid carcinomaHRAS = homologous to the oncogene from the Harvey rat sarcoma virusKRAS = homologous to the oncogene from the Kirsten rat sarcoma virusNRAS = first isolated from a human neuroblastoma/neuroblastomaRAS = viral oncogene homologPAX8 = paired box 8PCR = polymerase chain reactionPPAR-gamma = peroxisome proliferator-activated receptor gammaPTC = papillary thyroid carcinomaRAS = rat sarcomaRET = rearranged during transfection tyrosine-kinase proto-oncogeneSM = somatic mutationSNP = single-nucleotide polymorphism     

Utility of Ultrasound Versus Gene Expression Classifier in Thyroid Nodules with Atypia of Undetermined Significance

Objective: Thyroid nodules with fine-needle aspiration (FNA) cytology categorized as atypia of undetermined significance (AUS) often undergo additional diagnostic analysis with the Afirma Gene Expression Classifier (GEC), which classifies these as either high probability of being benign (GEC-B) or suspicious for malignancy (GEC-S). Our goal was to assess the clinical validity and utility of GEC in the evaluation of AUS cytology and evaluate the performance of ultrasonography (USG) for predicting malignancy in this subset.Methods: We conducted a study with a retrospective cohort of patients from January 2012 to January 2014 who had FNA of thyroid nodules >1 cm in size with AUS cytology.Results: Cleveland Clinic Florida has an overall prevalence of AUS of 5%. A total of 119 cases with nodules >1 cm in size were reported as AUS. Forty-eight (40.3%) had a GEC performed after the first FNA (AUS-1), and 27 of these were GEC-S. Of those 27, 21 went for surgery and 14 (66.6%) had thyroid cancer on histopathology. The remaining 71 with AUS-1 were sent for a second FNA: 19 nodules were benign and did not undergo further evaluation, while the remaining 52 were reported as AUS for the second consecutive time (AUS-2). AUS-2 samples were sent for GEC. Of these 52 AUS-2, 38 (73.1%) were reported as GEC-S. Thirty-five went for surgery and 32 (91.4%) had confirmed malignancy on histopathology. Positive predictive value (PPV) was 91.4% for AUS-2 and 66.6% for AUS-1. Moreover, AUS-2 nodules that were hypoechoic and solid on USG showed a PPV of 92% for malignancy.Conclusion: In our practice, the diagnostic accuracy to predict malignancy with GEC for AUS-1 nodules was poor (PPV, 66.6%). The PPV of GEC testing was markedly higher at 91.4% performed after two consecutive AUS cytologies. AUS-2 nodules that were solid and hypoechoic on USG also had a high probability to be malignant (PPV, 92%). We recommend repeat FNA on AUS-1 nodules rather than proceeding directly to GEC testing. Also, we suggest that among AUS-2 nodules, surgery can be recommended when USG shows solid and hypoechoic features with GEC testing reserved for the remainder.Abbreviations:AUS = atypia of undetermined significanceFNA = fine-needle aspirationGEC = gene expression classifierGEC-B = GEC-benignGEC-S = GEC-suspicious for malignancyNPV = negative predictive valuePPV = positive predictive valueUSG = ultrasonography