British Thyroid Association Research Articles

MON-580 Diagnostic Accuracy of Different Thyroid Ultrasound Classification Systems and the Added Value of Operator Subjective Impression in Stratifying Nodule Risk

Background and aim. Several ultrasound (US) classifications for thyroid nodules have been proposed. Since most of them are hardly applicable in clinical practice, we set up the Modena US Thyroid Classification (MUT) that stratifies the risk of malignancy based on knowledge derived from scientific literature and on clinician subjective impression. The aim of the present study was to test the diagnostic accuracy of different thyroid US classification systems, AACE/ACE-AME, American Thyroid Association (ATA), British Thyroid Association (BTA), and MUT, and to evaluate inter-classification agreement. Methods. We prospectively enrolled 111 patients (33M, 78F; age 19-75) with indeterminate, suspicious or malignant cytology. All the patients underwent neck US before surgery and a score according to MUT was assigned: 1 not certainly nodular; 2 not suspect; 3 indeterminate; 4 suspect; 5 very suspect. Then, we retrospectively classified nodules according to AACE/ACE-AME, ATA and BTA. US pattern was related to hystology. Sensitivity, specificity, diagnostic cut-off value and accuracy of each classification were calculated. The overall agreement between classifications was quantified by Bland-Altman test. The agreement between single nodule analysis by different classifications was evaluated considering Weighted Cohen's Kappa. Results. Fifteen patients had uninodular and 96 multinodular goiter, for a total of 457 nodules. MUT has the highest accuracy (AUC 0.808) and specificity (89%), followed by ATA and BTA, and finally by AACE/ACE-AME. ATA and BTA are highly interchangeable and MUT is comparable to both of them. AACE/ACE-AME is the least interchangeable with all the other classifications. Considering agreement between single nodule analysis by different classifications, ATA and BTA had the best (k=0.723); AACE/ACE-AME showed slight agreement with BTA (k=0.177) and MUT (k=0.183), and fair agreement with ATA (k=0.282); MUT had fair agreement with both ATA (k=0.291) and BTA (k=0.271). Conclusions. Our findings bring out the limit in specificity of the current reference classifications, which improves when the subjective impression of the clinician is considered.

Radioiodine treatment of differentiated thyroid cancer related to guidelines and scientific literature

In differentiated thyroid cancer (DTC), radioiodine is administered to eliminate residual normal thyroid tissue after thyroidectomy (ablative treatment), to treat residual microscopic disease (adjuvant treatment), and to treat macroscopic or metastatic disease. Currently, treatment of DTC with 131I is still a matter of controversy due to the absence of prospective clinical trials assessing its benefit in terms of overall survival and recurrence-free interval. The current recommendations of the experts are based on observational retrospective data and on their interpretation of the literature. Pending the results of the prospective trials that are currently underway, the use of 131I seems to be justified not only in high-risk patients, but also in intermediate-risk and low-risk patients. The guidelines of The American and British Thyroid Association, European and American Societies of Nuclear Medicine, The European Consensus Group and the latest edition of National Comprehensive Cancer Network (NCCN) were considered in drawing up this continuing education document, we also undertook a review of the related scientific literature.

Can We Discharge Dynamically Risk-Stratified Low-Risk (Excellent Response to Treatment) Thyroid Cancer Patients After 5 Years of Follow-Up?

AimsThe 2014 British Thyroid Association thyroid cancer guidelines recommend lifelong follow-up of thyroid cancer patients. This is probably unnecessary, can cause patient anxiety, is time consuming and places significant demand on National Health Service resources. It has been suggested that low-risk differentiated thyroid cancer (DTC) patients could be discharged to primary care once they are 5 years from diagnosis and treatment. The aim of this study was to investigate the potential safety of this practice. Materials and methodsIn total, 756 patients with dynamically risk-stratified (DRS) low-risk/excellent response to treatment DTC treated over 2001–2013 in the Leeds region were followed after diagnostic surgery and the recurrence rate calculated. ResultsThe median follow-up time was nearly 10 years (5–17 years). Radiological recurrence occurred in 13/756 (1.7%) patients and was always preceded by raised thyroglobulin/ thyroglobulin antibody levels. In all 13 patients elevation of thyroglobulin occurred within 5 years of diagnosis. Two additional patients were found to have rising thyroglobulin at almost 9 and 10.5 years from diagnosis, although to date radiological recurrence has not been detected. Assuming these two patients developed recurrence with longer duration of follow-up, then 0.26% (2/756) of patients would not have their recurrence discovered within 5 years of diagnosis. To detect 100% of patients with a putative recurrence in our cohort would require 10.5 years of follow-up. Four patients had transiently raised thyroglobulin, which became undetectable within 2 years (in three patients), without any treatment and radiological recurrence was not discovered. ConclusionDischarge of DRS low-risk DTC patients to primary care after 5 years of secondary care follow-up is reasonable, accepting that late recurrence may occur in a very small minority of individuals (0.26%, ∼1:400). A more cautious approach would be to continue monitoring for 10 years, although the frequency of assessments could be reduced with increasing duration of follow-up.

Diagnostic performance of ATA, BTA and TIRADS sonographic patterns in the prediction of malignancy in histologically proven thyroid nodules.

We aimed to compare the malignancy risk stratification of histologically proven thyroid nodules using the 2015 American Thyroid Association (ATA) Management Guidelines, 2014 British Thyroid Association (BTA) Guidelines for the Management of Thyroid Cancer and the Thyroid Imaging Reporting and Data System (TIRADS). Thyroid nodules measuring > 1 cm resected over 5.5 years were retrospectively studied. Demographic information as well as cytology and histopathology results were collected. Static ultrasonography (US) images and radiologists' reports of each resected nodules were reviewed and classified based on the above risk classification systems. A total of 167 thyroid nodules from 150 patients were examined. More malignant nodules were solid (78.4% vs. 62.5%; p = 0.049) or hypoechoic (70.6% vs. 28.6%; p < 0.001), and had irregular margins (35.3% vs. 8.0%; p < 0.001), taller-than-wide morphology (9.8% vs. 2.7%; p = 0.031), microcalcifications (33.3% vs. 8.0%; p < 0.001), disrupted rim calcifications (9.8% vs. 0.9%; p = 0.012) or associated abnormal cervical lymphadenopathy (13.7% vs. 0.9%; p = 0.001) compared with benign nodules. The guidelines' diagnostic performance was: ATA - sensitivity 98.0%, specificity 17.3%, positive predictive value (PPV) 35.0%, negative predictive value (NPV) 95.0%; BTA - sensitivity 90%, specificity 50.9%, PPV 45.5%, NPV 91.8%; and TIRADS - sensitivity 94.0%, specificity 28.2%, PPV 37.3%%, NPV 91.2%. Sonographic patterns outlined by the three guidelines displayed high sensitivity and NPV. Although isolated suspicious US features cannot predict malignancy risk, they should be considered when risk stratifying nodules that do not fit into particular sonographic patterns based on current guidelines.

Thy 3F and 3a malignancy rate, a multisite regional retrospective case series.

Introduction The aim of this study was to ascertain the incidence of thyroid cancer for patients categorised as Thy3, 3a or 3f across four tertiary thyroid multidisciplinary centres in the UK. Material and methods This is a retrospective case series examining patients who presented with a thyroid nodule and diagnosed as Thy3, 3a or 3f according to the Royal College of Pathologists modified British Thyroid Association and Royal College of Physicians Thy system. Results In total, 395 patients were included in this study. Of these, 136 turned out to have benign thyroid disease and 24 had micropapillary thyroid carcinomas. The overall rate of thyroid malignancy was 28.8%. For each subcategory, the rate of malignancy was Thy3 24.7.7%, Thy3a 30.4% and Thy3f 29.2. However, the incidence of thyroid malignancy varied considerably between the four centres (Thy 3f 18-54%). Discussion The diagnosis of thyroid cancer is evolving but detection for malignancy for indeterminate nodules remains below 50% for most centres around the world. In 2014, the British Thyroid Association subdivided the original Thy3 category into Thy3a and Thy3f and recommended a more conservative approach to management for Thy3a nodules. Despite this, only two centres yielded a higher conversion rate of malignancy in the new higher graded Thy3f group compared with Thy3a. Conclusion It is debateable whether the new 'Thy3' subcategories are more useful than the original. Local thyroid malignancy rates may also be more useful than national averages to inform treatment decisions.

Differentiated thyroid cancer: A retrospective evaluation of the impact of changes to disease management guidelines on patients in South East Scotland

BackgroundThe British Thyroid Association (BTA) updated guidelines for the management of differentiated thyroid cancer (DTC) in 2014. A key update was that patients with unifocal disease >10–≤40 mm in diameter, aged <45 years and with no other risk factors could be considered for lobectomy alone. The aim of this study was to retrospectively evaluate the potential impact of these changes on the management of DTC in South East Scotland, and to analyse the characteristics of lobes now potentially considered for observation rather than resection. MethodsConsecutive patients were identified through prospectively held regional MDT minutes from 2009 to 13. Data included age, pT, pN, M stage, tumour size, vascular invasion and extra-thyroidal extension. ResultsFrom a cohort of 281 patients, 22 (8%) could now be considered for lobectomy alone. Of these, 4 had disease in the contralateral lobe (18%), all of which were low-risk tumours with no influence on recommendation for radioactive remnant ablation (RRA). Analysis of all patients, regardless of age, with pT1-2N0M0 disease (n = 50) revealed 11 (22%) had contralateral disease. The presence of index multifocal disease was predictive of disease in the contralateral lobe. One patient (2%) had a finding in the contralateral lobe which may potentially influence the recommendation for RRA. In no cases did findings in the contralateral lobe elevate a patient to a group where RRA was routinely recommended by BTA guidelines. DiscussionThe updated BTA guidelines are likely to affect only 8% of our cohort. Further analysis questions the role of age in excluding patients from a conservative approach.

Implementation of the British Thyroid Association thyroid nodule classification: a general UK hospital perspective

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Ensuring patient safety when implementing a new diagnostic pathway for thyroid nodules.

Introduction The aim of this study was to determine whether ultrasound alone is sufficient to safely exclude malignancy in thyroid nodules in a district general hospital setting, to comply with the latest British Thyroid Association guidelines. Methods This retrospective study investigated the quality of ultrasound reporting and the correlation between ultrasound report and histology for individual thyroid nodules. Cases were selected from the thyroid multidisciplinary meeting and included all patients having undergone surgery for a thyroid malignancy in a one-year period. Results Forty-seven patients were included in the study. Ultrasound reports were reviewed and assessed, in which 21 clinicians were involved; 36% of scans included a summary of whether the nodule(s) overall appeared benign, equivocal, suspicious or malignant; 4% of reports included a U classification; 81% of reports commented on cervical lymph nodes. Ultrasound was compared with histology. The sensitivity of ultrasound in correctly identifying nodules requiring further investigation was of 56% and specificity was 81%. Positive predictive value was 81% and negative predictive value was 56%. Discussion These findings suggest that, in a district general hospital setting without a dedicated head and neck radiologist, using only ultrasound and limiting fine-needle aspiration cytology to identify suspicious nodules may not be safe, as a high number of nodules appearing benign on ultrasound may ultimately prove to be malignant.

Appraisal of clinical practice guidelines on the management of hypothyroidism in pregnancy using the Appraisal of Guidelines for Research and Evaluation II instrument.

This study aimed to systematically evaluate the quality of guidelines for the management of hypothyroidism in pregnancy. Systematic searches were conducted to identify hypothyroidism in pregnancy guidelines published in electronic databases and developers' websites. Four reviewers independently evaluated eligible guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. Agreement among reviewers was measured using the intraclass correlation coefficient (ICC). The number of recommendations, strength of recommendations, and levels of evidence were determined. The software used for analysis was SPSS version 12.0. Nine guidelines met the inclusion criteria and were appraised. The scope and purpose (65%) and clarity of presentation (70%) domains achieved relatively high scores, whereas the stakeholder involvement (41%), rigor of development (33%), applicability (36%), and editorial independence (31%) domains yielded low scores. The American Thyroid Association (ATA) guideline ranked the highest, whereas the 2012 Chinese Society of Endocrinology (CSE) guideline ranked the lowest among all the guidelines. The British Thyroid Association (BTA) and ATA guidelines were strongly recommended as dependable and helpful references to aid clinical decisions for medical providers, whereas the CSE guideline was not recommended. Most recommendations of the guidelines were relatively consistent. However, the nine guidelines varied with respect to their recommendations on thyroid scanning, dose of levothyroxine (L-T4) treatment, and target thyroid-stimulating hormone(TSH) level of L-T4 therapy. The quality of the guidelines on the management of hypothyroidism in pregnancy is highly variable. Additionally, these guidelines need significant improvement, especially in the rigor of development and applicability domains. Some improvements should be made to promote the development and implementation of guidelines, for example, conducting a comprehensive search strategy to include more potential evidence and establishing a standard grading system to evaluate the quality of evidence.

Predictive Value of Malignancy of Thyroid Nodule Ultrasound Classification Systems: A Prospective Study.

British Thyroid Association (BTA), American Thyroid Association (ATA), and American Association of Clinical Endocrinologists (AACE/ACE/AME) recommend for thyroid nodules an ultrasound (US)-based stratification of risk of malignancy. Aim of our study was to assess the diagnostic accuracy of US classification systems and their reliability for indication to fine-needle aspiration (FNA). Prospective study on 987 thyroid nodules consecutively referred for FNA. US images were independently reviewed by four experts for assignment of malignancy risk. Cytologically benign nodules had confirmation with a second FNA, whereas Bethesda class IV, V, and VI nodules were operated upon. Class III nodules had surgery or follow-up on the basis of clinical, immunocytochemical, and US features. BTA: Malignancy rate was 2.8% in benign, 10.0% in indeterminate, 51.3% in suspicion, and 80.9% in malignant US class. Sensitivity was 0.74, specificity was 0.92, and accuracy was 0.89. ATA: Malignancy rate was 0.0% in benign, 2.2% in very low suspicion, 3.0% in low suspicion, 5.8% in intermediate, and 55.0% in high suspicion US class. Sensitivity was 0.81, specificity was 0.87, and accuracy was 0.86. AACE/ACE/AME: Malignancy rate was 1.1% in low-risk, 4.4% in intermediate-risk, and 54.9% in high-risk US class. Sensitivity was 0.82, specificity was 0.87, and accuracy was 0.86. K correlation coefficient was 78.9%, 76.9%, and 82.0% for BTA, ATA, and AACE/ACE/AME classifications. Classification systems had elevated predictive value of malignancy in high-risk classes. ATA and AACE/ACE/AME systems were effective for ruling out indication to FNA in low-US-risk nodules. A similar diagnostic accuracy and a substantial interobserver agreement was provided by the three- and the five-category classifications.

Differentiated thyroid cancer: A retrospective evaluation of the impact of changes to disease management guidelines on patients in South East Scotland

Abstract Background The British Thyroid Association (BTA) updated guidelines for the management of differentiated thyroid cancer (DTC) in 2014. A key update was that patients with unifocal disease >10–≤40 mm in diameter, aged Methods Consecutive patients were identified through prospectively held regional MDT minutes from 2009 to 13. Data included age, pT, pN, M stage, tumour size, vascular invasion and extra-thyroidal extension. Results From a cohort of 281 patients, 22 (8%) could now be considered for lobectomy alone. Of these, 4 had disease in the contralateral lobe (18%), all of which were low-risk tumours with no influence on recommendation for radioactive remnant ablation (RRA). Analysis of all patients, regardless of age, with pT1-2N0M0 disease (n = 50) revealed 11 (22%) had contralateral disease. The presence of index multifocal disease was predictive of disease in the contralateral lobe. One patient (2%) had a finding in the contralateral lobe which may potentially influence the recommendation for RRA. In no cases did findings in the contralateral lobe elevate a patient to a group where RRA was routinely recommended by BTA guidelines. Discussion The updated BTA guidelines are likely to affect only 8% of our cohort. Further analysis questions the role of age in excluding patients from a conservative approach.

Predictive value of U and Thy classification in the assessment of thyroid nodules: A retrospective study (2015-2016)

Introduction: The British Thyroid Association (BTA) Guidelines for the Management of Thyroid Cancer regard ultrasound as a sensitive examination that can be specific for the diagnosis of thyroid cancer. The guidelines recommend the ultrasound classification of thyroid nodules (U) be used in combination, where necessary, with fine needle aspiration cytology (FNAC) reported to The Royal College of Pathologists’ numerical category (Thy), to assess the risk of malignancy.

Adoption of the British Thyroid Association guidelines for the investigation of thyroid nodules: a district general hospital experience

Adoption of the British Thyroid Association guidelines for the investigation of thyroid nodules: a district general hospital experience

Meeting abstracts from the 65th British Thyroid Association Annual Meeting

Meeting abstracts from the 65th British Thyroid Association Annual Meeting

Retrospective cytological evaluation of indeterminate thyroid nodules according to the British Thyroid Association 2014 classification and comparison of clinical evaluation and outcomes.

The cytology of 130 indeterminate nodules (Thy 3) was retrospectively reviewed according to the British Thyroid Association 2014 classification. Nodules were divided into Thy 3a (atypical features) and Thy 3f (follicular lesion) categories. Histology was available as a reference for 97 nodules. Pre-surgical evaluations comprised biochemical tests, color-Doppler ultrasonography (US), semi-quantitative elastography-US (USE), contrast-enhanced US (CEUS), and mutation analysis from cytological slides. Thyroid malignancy was the final diagnosis for 19% of surgically-treated nodules. No statistically significant difference in the risk of malignancy was found between Thy 3a (26%) and Thy 3f (14%) nodules. Histology of the Thy 3a and Thy 3f nodules showed a higher incidence of Hurtle cell adenomas in Thy 3f (29%) than in Thy 3a (3%) nodules (P=0.01). The only pre-surgical difference concerned the BRAF V600E mutation, which was positive in some Thy 3a but not in any Thy 3f nodules (P=0.04). Receiver-operating characteristic (ROC) analysis was used to obtain cut-off values from US (score), USE (ELX 2/1 strain index), and CEUS (time-to-peak index and peak index) data. The cut-off values were similar for Thy 3a and Thy 3f nodules. Data showed that malignancy can be suspected if the US score is >2, ELX 1/2 strain index >1, time-to-peak index >1, and peak index <1. In a sub-group of 24 revised nodules (12 Thy 3a and 12 Thy 3f) with histology as a reference, the diagnostic power of cumulative pre-surgical analysis by means of US, USE, and CEUS showed high positive and negative predictive values (83% and 100%, respectively) for the presence of malignancy in Thy 3a and Thy 3f nodules. In conclusion, in our series of revised Thy 3 nodules, malignancy was low and displayed no significant differences between Thy 3a and Thy 3f categories. The use of cut-offs based on histology as a reference could reduce surgery. Our data support the conviction that, in mutation-negative Thy 3a and Thy 3f nodules, observation should be the first choice when not all instrumental results are suspect.

Sonographic differences between conventional and follicular variant papillary thyroid carcinoma.

Follicular variant papillary thyroid carcinoma (FVPTC) may pose a diagnostic challenge due to higher likelihood of lower risk cytology compared to conventional papillary thyroid carcinoma (CPTC). Recent guidelines have recommended the use of sonographic features to guide decisions to biopsy thyroid nodules. The purpose of this study was to evaluate the sonographic features of CPTC and FVPTC. This is a retrospective study design done in an Academic teaching hospital setting. Preoperative ultrasounds of 79 patients with conventional CPTC (48) and FVPTC (31) were reviewed by a radiologist blinded to histological diagnosis. Sonographic features of nodules were classified according to the British Thyroid Association (BTA) U-classification system as normal (U1), benign (U2), indeterminate (U3), suspicious (U4), and malignant (U5). Pathology slides of patients with FVPTC were reviewed by two pathologists and subclassified into encapsulated, well circumscribed/partly encapsulated, and infiltrative subtypes. FVPTC had a significantly lower incidence of any calcifications (p=0.0005), microcalcifications (p=0.002), and irregular or lobulated margins (p=0.03) than CPTC. Differences in hypoechogenicity (p=0.06), taller>wide shape (p=0.17) and presence of halo (p=0.07) were not significant. FVPTC was significantly less likely to be classified sonographically as malignant (U5) (p=0.006) or suspicious/malignant (U4/5) (p=0.009) than conventional PTC. Among FVPTC cases, infiltrative FVPTC were more likely to be sonographically classified as suspicious/malignant (U4/5) than non-infiltrative FVPTC. FVPTC nodules are less likely to show sonographic features of malignancy than conventional PTC. Reliance solely on sonographic features for thyroid nodule evaluation may not be sufficient to exclude FVPTC.

Meeting abstracts from the 64th British Thyroid Association Annual Meeting

Meeting abstracts from the 64th British Thyroid Association Annual Meeting

Accuracy of international ultrasound risk stratification systems in thyroid lesions cytologically classified as indeterminate

Eminent international societies have published their thyroid ultrasound risk stratification system (US-RSS) to give a friendly tool for thyroidologists. In particular, American Thyroid Association (ATA), American Association Clinical Endocrinologists/American College of Endocrinologists and Associazione Medici Endocrinologi (AACE/ACE/AME), British Thyroid Association (BTA), and Thyroid Imaging Reporting and Data System (TIRADS) are often adopted for clinical practice. The reliability of these US-RSS has not been evaluated in discriminating cancers from benignancy in nodules with indeterminate FNA. Indeterminate thyroid lesions were searched in our database and only those with histology were finally included. The matching of US and histologic data of nodule's location and size were verified. All US images and clips were re-evaluated and nodules classified according to the above US-RSS. A series of 101 indeterminate lesions, diagnosed by FNA were included (mean size 2.4cm) and a 21% of cancers was found at histology. When all lesions were classified by US-RSS, poor accuracy (up to 54%) and specificity (up to 19%) were recorded. Highest sensitivity (91%) and NPV (94%) was obtained by BTA. Of relevance, the rate of nodules with indeterminate US risk recorded by BTA was significantly lower than the other (P<0.001). At nodule's size analysis, cancers had significantly higher estimated volume (P<0.05). When we considered the size thresholds proposed by guidelines, ATA system reached the highest sensitivity in detecting cancers (95%). Even if international US-RSS have suboptimal accuracy in indeterminate thyroid nodules, high sensitivity can be obtained using ATA system with specific dimensional cut-offs. Diagn. Cytopathol. 2017;45:113-117. © 2016 Wiley Periodicals, Inc.

Current recommendations in the management of hypothyroidism: developed from a statement by the British Thyroid Association Executive.

Hypothyroidism is present in about 2–5% of the population and is routinely managed in general practice.1 Uncorrected disease carries significant morbidity and is associated with an increased risk of lipid disorders, cardiovascular disease, osteoporosis, and cognitive dysfunction.2 Most cases are due to chronic autoimmune thyroiditis, and are followed by destructive treatment of the thyroid gland with radioactive iodine or surgery.2 The prevalence of spontaneous hypothyroidism rises with age and is 10 times more common in women than in men.1 In primary hypothyroidism the earliest biochemical abnormality is an increase in serum thyrotropin (TSH) level with normal free T4 (FT4) and free T3 (FT3) concentrations (subclinical hypothyroidism).2 A proportion of individuals with subclinical hypothyroidism (approximately 2–4% per annum) will progress to overt hypothyroidism (decreased FT4 associated with increased serum TSH).1 Patients with overt disease typically manifest symptoms and usually benefit from thyroid hormone treatment. Synthetic levothyroxine (L-T4) remains the treatment of choice for hypothyroidism2–4 and is prescribed to an estimated 1.5 million people in the UK.2 It is simple to administer, and within weeks of initiation most patients achieve normal serum TSH levels, and enjoy restored health.2 However, a proportion of treated patients continue to suffer ill-health even after normalisation of their thyroid hormone levels.5 Most GPs will be familiar with the patient who is persistently dissatisfied with L-T4 therapy or those for whom a stable euthyroid state appears unachievable. The management of such individuals is challenging and sometimes frustrating for patients and clinicians alike. In addition recent community-based surveys have highlighted a series of pressing concerns including the indiscriminate use of thyroid tests,6 overdiagnosis, and excessive treatment of patients with mild hypothyroidism,7 and an …

Variation in the use of definitive treatment options in the management of Graves' disease: a UK clinician survey

BackgroundGraves' disease can be treated with antithyroid drugs (ATDs), radioiodine or surgery. Use of definitive treatments (radioiodine or surgery) varies widely across centres. Specific clinical circumstances, local facilities, patient and...