Associazione Medici Endocrinologi Research Articles

Italian Guidelines for the Management of Prolactinomas.

This guideline (GL) is aimed at providing a reference for the management of prolactin (PRL)-secreting pituitary adenoma in adults. However, pregnancy is not considered. This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinologi (AME) has identified potentially relevant outcomes, which have then been rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" have been considered in the systematic review of evidence and only those classified as "critical" have been considered in the formulation of recommendations. The present GL provides recommendations regarding the role of pharmacological and neurosurgical treatment in the management of prolactinomas. We recommend cabergoline (Cab) vs. bromocriptine (Br) as the firstchoice pharmacological treatment to be employed at the minimal effective dose capable of achieving the regression of the clinical picture. We suggest that medication and surgery are offered as suitable alternative first-line treatments to patients with non-invasive PRL-secreting adenoma, regardless of size. We suggest Br as an alternative drug in patients who are intolerant to Cab and are not candidates for surgery. We recommend pituitary tumor resection in patients 1) without any significant neuro-ophthalmologic improvement within two weeks from the start of Cab, 2) who are resistant or do not tolerate Cab or other dopamine-agonist drugs (DA), 3) who escape from previous efficacy of DA, and 4) who are unwilling to undergo a chronic DA treatment. We recommend that patients with progressive disease notwithstanding previous tumor resection and ongoing DA should be managed by a multidisciplinary team with specific expertise in pituitary diseases using a multimodal approach that includes repeated surgery, radiotherapy, DA, and possibly, the use of temozolomide. The present GL is directed to endocrinologists, neurosurgeons, and gynecologists working in hospitals, in territorial services or private practice, and to general practitioners and patients.

Impact of the introduction of minimally invasive treatments of the thyroid (MITT) for benign thyroid nodules in an Italian hospital: a cost-minimization analysis.

Prevalence of thyroid nodules is high in the adult population, approaching 60% in women and older people. Most thyroid nodules are benign and asymptomatic. However, a not negligible part of them causes compressive symptoms and/or cosmetic concerns and need to be treated. In the last two decades, minimally-invasive treatments of the thyroid (MITT) have been proposed in routine clinical practice as a reliable cost-effective alternative to surgery in patients with symptomatic benign thyroid nodules (SBTNs). To perform a cost-minimization analysis comparing direct, indirect and intangible costs of radiofrequency (RFA) and laser thermal ablation (LTA) with traditional surgery in patients with SBTNs. Data of patients treated by MITT for SBTNs from October 1st 2019 to September 30th 2022 in a single Italian tertiary Center were analyzed. Costs were compared to those of traditional surgery reported in the 2022 Associazione Medici Endocrinologi Guidelines on the Management of SBTNs. In the study lapse, 157 MITT of SBTNs were performed in 148 patients, 114 females and 34 males (mean age: 59 yrs; median age: 57 yrs). Before MITT, the mean thyroid nodule volume was 19 ml; 1 year after MITT, volume reduction rate >50% and symptom relief were achieved in 89% and 93% of patients, respectively. No major complications occurred. Adding up pre-operative, operative and post-operative costs, total direct costs per single procedure are the following: 1361.43 € for LTA when using one optic fiber; 1761.43 € for LTA when using two optic fibers; 1968.53 € for RFA; 3338.39 € for hemithyroidectomy plus isthmectomy; 4034.99 € for total thyroidectomy. Surgery was impactful on direct-i.e., preoperative, operative and postoperative-costs, due to longer operating room occupation time and hospital stay. Overall, a total saving for the Italian National Health Service of 285,377.15 € has been obtained treating the 148 patients by MITT instead of surgery. Likewise, MITT was advantageous also for indirect costs-i.e., those related to "loss of productivity" caused by time off work due to hospital stay and recovery time-, for both the self-employed workers and the Government, the latter saving 53,838.50 € overall. Finally, intangible costs, related to patients' quality of life-e.g., residual surgical scar, stress related to general anesthesia, convalescence, and life-long intake of L-Thyroxine replacement therapy-were all in favor of MITT. This real-life cost-minimization analysis demonstrates that LTA and RFA are safe and cost-effective procedures for the treatment of SBTNs. In our 3 years experience, adding the savings of 285,377.15 € for direct costs to those of 53.838,50 € for indirect costs, in total 339,215.65 € were saved. The saving concern patients, the National Health System and the Government.

An International Survey on Utilization of Five Thyroid Nodule Risk Stratification Systems: A Needs Assessment with Future Implications.

Background: Multiple ultrasound-based risk stratification systems (RSSs) for thyroid nodules are used worldwide. Variations in structure, performance, and recommendations are confusing for physicians and patients and complicate management decisions. The goal of this study was to determine the factors that are associated with choice of RSS and barriers to RSS use. These results are intended to inform development of a universal international thyroid ultrasound RSS. Methods: An online survey with questions about usage of RSSs, ultrasound practice and volumes, training, specialty, practice type, and geographic region was made available to members of five professional societies via email. Subgroup analysis was performed to identify the factors that governed use of one or more of five leading RSSs: American Association of Clinical Endocrinology (AACE), American College of Endocrinology (ACE), and Associazione Medici Endocrinologi (AME) Medical Guidelines, American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS), American Thyroid Association (ATA) guidelines, European Thyroid Association TIRADS (EU-TIRADS), and Korean Society of Thyroid Radiology/Korean Thyroid Association TIRADS (K-TIRADS). Results: There were 875 respondents from 52 countries (response rate not estimated due to overlapping society membership). More than 7 specialties were represented, with most (538; 61.5%) in endocrinology. The choice of RSS was strongly associated with medical specialty and geographic region. Of 692 respondents who indicated that their practice used an RSS, 213 (30.8%) used more than one. The specialties that were more likely to use multiple RSSs were surgery and others (40%), followed by endocrinology (33.0%), and radiology or nuclear medicine (17%) (p < 0.001). Of 271 (31.0%) respondents who indicated that they do not personally use an RSS, the majority (168; 62%) preferred to describe the specific sonographic characteristics/features that they believe are most relevant in a nodule. Conclusions: Almost one third of respondents indicated use of more than one RSS in their practice, potentially leading to confusion, and a similar proportion reported not using an RSS for various reasons. A unified international system that addresses their concerns and simplifies risk classification of thyroid nodules may benefit practitioners and patients. This is particularly important as newer thyroid nodule management options gain acceptance.

Italian Association of Clinical Endocrinologists (Associazione Medici Endocrinologi, AME)

Italian Association of Clinical Endocrinologists (Associazione Medici Endocrinologi, AME)

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.

Malignancy Analyses of Thyroid Nodules in Patients Subjected to Surgery with Cytological- and Ultrasound-Based Risk Stratification Systems

The fine needle aspiration (FNA) cytology is the gold standard for the preoperative diagnosis of thyroid cancer. However, up to 30% of FNA examinations yield nondiagnostic or indeterminate results and this complicates patient management. Clinical features and ultrasound (US) patterns, including US risk stratification systems, could be useful in the preoperative diagnostic workup and prediction of malignancy, but the evidences are not univocal. Methods: 400 consecutive patients subjected to thyroid surgery were retrospectively enrolled at our institution in Calabria, Southern Italy. Preoperative US and FNA cytological descriptions, formulated according to the “Italian consensus for reporting thyroid fine-needle aspiration cytology” (ICCRTC) classification and three US risk stratification systems (those developed by the American Association of Clinical Endocrinologists, American College of Endocrinology and Associazione Medici Endocrinologi (AACE/ACE/AME), American Thyroid Association (ATA), and American College of Radiology (ACR-TIRADS)), were collected, along with histological results. Results: 147 thyroid cancer cases, in large majority papillary carcinomas, were detected on final histological examination. Almost two-thirds of patients subjected to thyroid surgery for either benign or malignant lesions were female. Patient’s age ≤20 years and between 21–30 years were clinical features associated with increased risk of thyroid cancer in logistic regression analyses. US features associated with thyroid cancer included irregular margins, solid composition, microcalcifications, and marked hypoechogenicity. The AACE/ACE/AME, ATA, and ACR-TIRADS risk categories, corresponding to specific US patterns, were strong predictors of malignancy in both genders, but not in nodules with indeterminate cytology. A measured difference between the longitudinal (L) and the anteroposterior (AP) diameter &gt;5 mm, a proxy for a parallel-oriented oval shape of a nodule, emerged as a robust protective factor against thyroid cancer (OR 0.288 (95%CI 0.817–0.443); p &lt; 0.001), regardless of cytological risk. Conclusions: Some, but not all, well-established predictors of TC have been confirmed in this study. Controversy surrounds the diagnostic performance of US risk stratification systems for the detection of thyroid cancer in the subgroup of nodules with indeterminate cytology, suggesting their use only to set the thresholds for FNA. A measured difference between L and AP diameters &gt;5 mm may represent an additional and practical tool for ruling out malignancy in thyroid nodules, with the potential to reduce unnecessary surgical procedures.

Comparison of different systems of ultrasound (US) risk stratification for malignancy in elderly patients with thyroid nodules. Real world experience.

To comparatively assess the performance of three sonographic classification systems, American Thyroid Association (ATA), the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS), and American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE)/Associazione Medici Endocrinologi (AME) in identifying malignant nodules in an elderly population. Cross-sectional study of patients referred for fine needle aspiration biopsy in an academic center for the elderly. One nodule/patient was considered. Nodules classified Bethesda V/VI were considered malignant. Receiver operating characteristics (ROC) curves were established and compared to evaluate diagnostic performance. Malignancy among biopsies below the size cutoff for each ultrasound classification was also compared. One thousand, eight hundred sixty-seven patients (92% females); median (Q1-Q3), age 71 (67-76) years, were studied showing 82.8% benign (Bethesda II) and 2.6% malignant cytology. The three classifications correctly identified malignancy (P < 0.01). Nonetheless, in the ATA and AACE/ACE/AME 16 and 2 malignant nodules, respectively, were unclassifiable. Including unclassified malignant nodules (n = 1234, malignant = 50), comparison of the ROC curves showed lower performance of ATA [area under the curve (AUC) = ATA (0.49) vs. ACR TI-RADS (0.62), p = 0.008 and ATA vs. AACE/ACE/AME (0.59), p = 0.022]. Proportion of below size cutoff biopsies for ATA, ACR TI-RADS, and AACE/ACE/AME was different [16, 42, and 29% (all p < 0.001)], but no differences in malignancy rate were observed in these nodules. The present study is the first to validate in elderly patients these classifications showing that AACE/ACE/AME and ACR TI-RADS can predict thyroid malignancy more accurately than the ATA when unclassifiable malignant nodules are considered. Moreover, in this aged segment of the population, the use of ACR TI-RADS avoided more invasive procedures.

Evaluation of Five Ultrasound Risk-Stratification Systems for Choosing Thyroid Nodules for Fine-Needle Aspiration

Evaluation of Five Ultrasound Risk-Stratification Systems for Choosing Thyroid Nodules for Fine-Needle Aspiration

Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients; the 2019 Italian Survey

Background: The incidence and prevalence of hypothyroidism are increasing and the threshold for the treatment of hypothyroid as well as individuals without evident thyroid disease with thyroid hormone is declining. Objective: To investigate endocrinologists’ use of thyroid hormones in hypothyroid and euthyroid patients in Italy, a country where different formulations of levothyroxine (LT4; tablet, liquid solution and soft-gel capsule) are available on the market. Methods: Members of the Associazione Medici Endocrinologi (Italian Association of Clinical Endocrinologists) were invited to participate in a web-based survey investigating the topic. Results: A total of 797 of 2,028 (39.3%) members completed all the sections of the survey; 98.7% declared that the treatment of choice for hypothyroidism is LT4. A significant minority (37.3%) indicated that LT4 may be considered in infertile euthyroid women seeking pregnancy and harbouring positive thyroperoxidase antibodies (TPOAb) and in goitre increasing in size (18.1%). LT4 + LT3 was considered by 43.2% for LT4-replaced patients and normal TSH, if they reported persistent symptoms. High percentages of respondents chose LT4 in a liquid solution or soft-gel capsules when taken together with other drugs interfering with LT4 absorption (81.8%), in patients with a history of celiac disease, malabsorption, lactose intolerance, intolerance to common excipients (96.6%), or unexplained poor biochemical control of hypothyroidism (74.4%), or in patients not able to adhere to ingesting LT4 fasted and/or separated from food/drink (98.9%). In total, 43.6% of responders would use LT4 in a liquid solution or soft-gel capsules for hypothyroid patients with biochemical euthyroidism on LT4, who had persistent symptoms. Conclusions: The preferred treatment for hypothyroidism is LT4; LT3 + LT4 combination treatment is mainly considered in patients with persistent symptoms. A significant minority would offer LT4 to euthyroid women with positive TPOAb and infertility and to euthyroid patients with progressive simple goitre. Alternative LT4 formulations like liquid solution or soft-gel capsules are largely reserved for specific conditions (interfering drugs, actual or suspected malabsorption, inability to take LT4 in the fasting state, unexplained poor biochemical control of hypothyroidism).

Sonographically Estimated Thyroid Nodule Malignancy Risk: Strengths and Limitations in Clinical Practice

In recent years, the clinical relevance of thyroid ultra-sound has increased. Due to the development of risk-stratification systems that use a systematic assessment of thyroid nodule sonographic characteristics and tiered categories, such as the Thyroid Imaging Reporting and Data System (TI-RADS), a pattern of morphologic features is easily translated into a specific class, with an associated estimate of malignancy risk and suggestions for clinical management. Currently, scientific societies ( 1. Gharib H. Papini E. Garber J.R. American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules – 2016 update. Endocr Pract. 2016; 22 (et al): 622-639 Abstract Full Text Full Text PDF PubMed Scopus (802) Google Scholar ) recommend using sonographic risk evaluation to guide clinical decisions regarding the need for fine-needle aspiration cytology and the timing of subsequent follow-up evaluations ( 5. Durante C. Grani G. Lamartina L. The diagnosis and management of thyroid nodules: a review. JAMA. 2018; 319 (et al): 914-924 Crossref PubMed Scopus (318) Google Scholar ). The main aim of these systems is to reduce the burden of diagnostic tests performed on thyroid nodules, namely the number of fine-needle aspirations ( 6. Grani G. Lamartina L. Ascoli V. Reducing the number of unnecessary thyroid biopsies while improving diagnostic accuracy: toward the “right” TIRADS. J Clin Endocrinol Metab. 2019; 104 (et al): 95-102 Crossref PubMed Scopus (157) Google Scholar ), since the majority of nodules (>90%) are benign, and others are small, indolent neoplasms. As a consequence, risk-stratification systems are expected to reduce overdiagnosis and overtreatment.

Follow-Up Strategies for Thyroid Nodules with Benign Cytology on Ultrasound-Guided Fine Needle Aspiration: Malignancy Rates of Management Guidelines Using Ultrasound Before and After the Era of the Bethesda System

Background: To evaluate differences in malignancy rates and consequent follow-up strategies for cytologically benign thyroid nodules before and after the introduction of the Bethesda system according to the risk stratification categories of four thyroid management guidelines. Methods: This retrospective study was approved by our institutional review board. In this study, 1716 thyroid nodules with initially benign cytologic diagnosis at ultrasound-guided fine needle aspiration (US-FNA) in 1695 patients were included: 1187 nodules from the pre-Bethesda period and 529 nodules from the post-Bethesda period. Based on US features, the thyroid nodules were categorized into the final assessment categories of the 2015 American Thyroid Association (ATA), the 2016 American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi, the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS), and the European Thyroid Association guidelines for Ultrasound Malignancy Risk Stratification systems. Estimated malignancy rates before and after propensity score matching according to follow-up intervals were obtained. Results: Of the 1716 thyroid nodules benign on initial US-FNA, the malignancy rate was 3.2% (38 of 1187) in the pre-Bethesda period and 2.6% (14 of 529) in the post-Bethesda period (p = 0.641). The 2015 ATA high suspicion pattern and the ACR-TIRADS category 5 had high estimated malignancy rates of >5% in the post-Bethesda period (6.52 and 8.57, respectively). Positive findings that indicated US-FNA in the ACR-TIRADS had estimated malignancy rates of 5.26 and 5.67, respectively, while the remaining guidelines had estimated malignancy rates of <5% in both periods. Conclusions: Immediate diagnostic intervention after benign cytologic diagnosis may not be necessary regardless of the cytologic criteria applied, but it can be considered for the highly suspicious categories in the 2015 ATA or the ACR-TIRADS for benign cytologic diagnosis of the Bethesda system.

Diagnostic Performance Evaluation of a Computer-Assisted Imaging Analysis System for Ultrasound Risk Stratification of Thyroid Nodules.

OBJECTIVE. Ultrasound-based stratification of the malignancy risk of thyroid nodules has potential variability. The purpose of this study is to evaluate the diagnostic effectiveness of the first commercially available system for computer-aided diagnosis (CADx) imaging analysis. MATERIALS AND METHODS. Ultrasound images of 300 thyroid nodules (135 of which were malignant) acquired before surgical treatment were retrospectively reviewed by a thyroid expert, and his classification of each image was then compared with the classification rendered by an image analysis program (AmCAD-UT, AmCAD Biomed). The American Thyroid Association (ATA) classification system, the European Thyroid Imaging Reporting and Data System (EU-TIRADS), and the classification system jointly proposed by American and Italian associations of clinical endocrinologists (the American Association of Clinical Endocrinologists [AACE], the American College of Endocrinology [ACE], and Associazione Medici Endocrinologi [AME]) were used for risk stratification. RESULTS. The diagnostic performance of the thyroid expert when the ATA system was used was as follows: sensitivity, 87.0%; specificity, 91.2%; positive predictive value, 90.5%; and negative predictive value, 90.9%. Compared with the expert, the CADx program, when used with the three classification systems, had a similar sensitivity but a lower specificity and positive predictive value. Regarding the negative predictive value, the results of the expert did not differ from those of the CADx program when it applied the ATA classification system (90.9% vs 86.3%; p = 0.07). The ROC AUC value was 0.88 for the expert clinician and 0.72 for the CADx program when the ATA classification system was used. CONCLUSION. The CADx ultrasound image analysis program described in the present study is useful for risk stratification of thyroid nodules, but it does not perform better than a sonography expert.

A Proposal to Stratify the Intermediate-Risk Thyroid Nodules According to the AACE/ACE/AME Guidelines with Ultrasound Features

To propose a risk stratification system for intermediate-risk thyroid nodules (TNs) according to American Association of Clinical Endocrinologists, American College of Endocrinology and Associazione Medici Endocrinologi Medical (AACE/ACE/AME) Guideline with ultrasound (US) features. 1000 patients with 1000 nodules (902 benign nodules and 98 malignant nodules) were included. All the nodules were confirmed with either fine needle aspiration (FNA) cytology and follow-up or histology results after surgery. Univariate analysis and binary multivariate logic regression analysis were applied to analyze the possible risk US features associated with malignancy. Receiver operating characteristic curves (ROC) were drew and compared. Univariate analysis and binary multivariate logistic regression analysis showed that indeterminate hyper-echoic spot (OR = 4.544), slightly ill-defined margin (OR = 2.559), slight hyper-echogenicity (OR = 1.992) and no macro-calcification (OR = 1.921) were risk factors for the intermediate-risk thyroid nodules (TNs). A predicting model was established based on the 4 risk factors. The risk rates of malignancy were 5.7% (26/455) in Stage I, 11.0% (49/445) in Stage II, 23.1% (21/91) in Stage III, 33.3% (3/9) in Stage IV. In conclusion, for the intermediate-risk TNs, special attention should be paid to the TNs with indeterminate hyper-echoic spot, slightly ill-defined margin, slight hyper-echogenicity, or no macro-calcification. The probability of malignancy increased with the number of risk factors increasing.

Ultrasound Risk Categories for Thyroid Nodules and Cytology Results: A Single Institution's Experience after the Adoption of the 2016 Update of Medical Guidelines by the American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi.

Objectives In 2016, the American Association of Clinical Endocrinologists (AACE) and Associazione Medici Endocrinologi (AME) released updated guidelines for the diagnosis and management of thyroid nodules. The aim of this study was to evaluate the AACE/AME recommendations for FNA in clinical practice, by comparing the (US) stratification risk and indications for FNA with cytologic results. Methods From May to December 2016, we collected the cytologic results from FNAs of nodules that were classified using a three-tier US category system (low, intermediate, and high risk). Results We obtained 859 FNAs from 598 patients: 341 (39.7%) from low, 489 (56.9%) from intermediate, and 29 (3.4%) from high risk nodules. Of these, 88.5% and 74.9% of low and intermediate risk nodules, respectively, were cytologically benign, whereas 84.6% of high risk nodules had a moderate-to-elevated risk of malignancy or were malignant. If FNAs had been limited to intermediate risk nodules >20 mm, we would have missed 13/17 (76.5%) nodules that had moderate-to-elevated risk of malignancy or were malignant (11/13 were malignant based on histology). Conclusions A nonnegligible number of cytologically malignant nodules or nodules that were suspected to be malignant would be missed if intermediate US risk nodules <20 mm were not biopsied.

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.

American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules - 2016 Update Appendix

Thyroid nodules are detected in up to 50 to 60% of healthy subjects. Most nodules do not cause clinically significant symptoms, and as a result, the main challenge in their management is to rule out malignancy, with ultrasonography (US) and fine-needle aspiration (FNA) biopsy serving as diagnostic cornerstones. The key issues discussed in these guidelines are as follows: (1) US-based categorization of the malignancy risk and indications for US-guided FNA (henceforth, FNA), (2) cytologic classification of FNA samples, (3) the roles of immunocyto-chemistry and molecular testing applied to thyroid FNA, (4) therapeutic options, and (5) follow-up strategy. Thyroid nodule management during pregnancy and in children are also addressed. On the basis of US features, thyroid nodules may be categorized into 3 groups: low-, intermediate-and high-malignancy risk. FNA should be considered for nodules <10 mm diameter only when suspicious US signs are present, while nodules <5 mm should be monitored rather than biopsied. A classification scheme of 5 categories (nondiagnostic, benign, indeterminate, suspicious for malignancy, or malignant) is recommended for the cytologic report. Indeterminate lesions are further subdivided into 2 subclasses to more accurately stratify the risk of malignancy. At present, no single cytochemical or genetic marker can definitely rule out malignancy in indeterminate nodules. Nevertheless, these tools should be considered together with clinical data, US signs, elastographic pattern, or results of other imaging techniques to improve the management of these lesions. Most thyroid nodules do not require any treatment, and levothyroxine (LT4 suppressive therapy is not recommended. Percutaneous ethanol injection (PEI) should be the first-line treatment option for relapsing, benign cystic lesions, while US-guided thermal ablation treatments may be considered for solid or mixed symptomatic benign thyroid nodules. Surgery remains the treatment of choice for malignant or suspicious nodules. The present document updates previous guidelines released in 2006 and 2010 by the American Association of Clinical Endocrinologists (AACE) and Associazione Medici Endocrinologi (AME).

Thyroid nodule guidelines: agreement, disagreement and need for future research

This article reviews agreement, disagreement and need for future research of the thyroid nodule guidelines published by the British Thyroid Association, National Cancer Institute, American Thyroid Association and the joint, transatlantic effort of three large societies, the American Society of Clinical Endocrinologists, Associazione Medici Endocrinologi and the European Thyroid Association, published in 2010. Consensus exists for most topics in the various guidelines. A few areas of disagreement, such as the use of scintigraphy, are mostly due to differences in disease prevalence in different countries. Most of the discordance, for example, on the use of calcitonin screening or fine-needle aspiration cytology classification, could probably be resolved by further expert discussions, as the basis is the same published evidence. Importantly, owing to a current lack of evidence in many areas, clinically very relevant areas of uncertainty need to be addressed by further research. This situation applies, for instance, to better definition of ultrasound malignancy criteria and the evaluation of emerging new diagnostic and therapeutic techniques, including molecular markers. For clinicians who advise individual patients, these areas of uncertainty can currently only be resolved by sound management on the basis of clinical judgment, experience and patient preference.

Early Diagnosis of Medullary Thyroid Carcinoma: Is Systematic Calcitonin Screening Appropriate in Patients with Nodular Thyroid Disease?

Because of its poor prognosis and high mortality rate, early diagnosis of medullary thyroid carcinoma (MTC) is a challenge. For almost two decades, routine serum calcitonin (CT) measurement has been used as a tool for early MTC diagnosis, with conflicting results. In 2006, the European Thyroid Association (ETA) recommended serum CT measurement in the initial workup of thyroid nodules, whereas the American Thyroid Association (ATA) declined to recommend for or against this approach. In late 2009, the revised ATA guidelines were published, and in June 2010 the ETA released new guidelines for the diagnosis and management of thyroid nodules that had been drafted in collaboration with the American Association of Clinical Endocrinologists and with the Associazione Medici Endocrinologi, and the picture became even more complex. The ATA still takes no stand for or against screening but acknowledges that, if testing is done, a CT value >100 pg/ml should be considered suspicious and an indication for treatment. As for the ETA, it seems to have taken a step back from its 2006 position, and it now advocates CT screening only in the presence of clinical risk factors. These new positions are more cautious and less straightforward because prospective, randomized, large-scale, long-term trial data are lacking. Are such studies feasible? Can they solve the CT dilemma? In the absence of adequate evidence, selective aggressive case finding should be pursued to improve MTC prognosis.

American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules: Executive Summary of recommendations

American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules are systematically developed statements to assist health care professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances.

American Association Of Clinical Endocrinologists, Associazione Medici Endocrinologi, And European Thyroid Association Medical Guidelines For Clinical Practice For The Diagnosis And Management Of Thyroid Nodules

American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules are systematically developed statements to assist health care professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances.