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Tommaso Piticchio Endocrinology Section, Department of Clinical and Experimental Medicine, Garibaldi Nesima Hospital, University of Catania, Catania, Italy
Servizio di Endocrinologia e Diabetologia, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland

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Gilles Russ Department of Thyroid and Endocrine Tumor Diseases, La Pitie-Salpetriere Hospital, 83 Bd de l’Hopital, Paris, France

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Maija Radzina Riga Stradins University, Radiology Research Laboratory, Riga, Latvia
University of Latvia, Faculty of Medicine, Riga, Latvia

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Francesco Frasca Endocrinology Section, Department of Clinical and Experimental Medicine, Garibaldi Nesima Hospital, University of Catania, Catania, Italy

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Cosimo Durante Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

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Pierpaolo Trimboli Servizio di Endocrinologia e Diabetologia, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland
Facoltà di Scienze Biomediche, Università della Svizzera Italiana (USI), Lugano, Switzerland

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Context

Ultrasound-based risk stratification systems (Thyroid Imaging Reporting and Data Systems (TIRADSs)) of thyroid nodules (TNs) have been implemented in clinical practice worldwide based on their high performance. However, it remains unexplored whether different TIRADSs perform uniformly across a range of TNs in routine practice. This issue is highly relevant today, given the ongoing international effort to establish a unified TIRADS (i.e. I-TIRADS), supported by the leading societies specializing in TNs. The study aimed to conduct a direct comparison among ACR-, EU-, and K-TIRADS in the distribution of TNs: (1) across the TIRADS categories, and (2) based on their estimated cancer risk.

Methods

A search was conducted on PubMed and Embase until June 2023. Original studies that sequentially assessed TNs using TIRADSs, regardless of FNAC indication, were selected. General study characteristics and data on the distribution of TNs across TIRADSs were extracted.

Results

Seven studies, reporting a total of 41,332 TNs, were included in the analysis. The prevalence of ACR-TIRADS 1–2 was significantly higher than that of EU-TIRADS 2 and K-TIRADS 2, with no significant difference observed among intermediate- and high-risk categories of TIRADSs. According to malignancy risk estimation, K-TIRADS often classified TNs as having more severe risk, ACR-TIRADS as having moderate risk, and EU-TIRADS classified TNs as having lower risk.

Conclusion

ACR-, EU-, and K-TIRADS assess TNs similarly across their categories, with slight differences in low-risk classifications. Despite this, focusing on cancer risk estimation, the three TIRADSs assess TNs differently. These findings should be considered as a prerequisite for developing the I-TIRADS.

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Gilles Russ Thyroid and Endocrine Tumors, Institute of Endocrinology, Pitié Salpêtrière Hospital, Pierre and Marie Curie University, Paris, France

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Steen J. Bonnema Department of Endocrinology, Odense University Hospital, Odense, Denmark

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Murat Faik Erdogan Department of Endocrinology and Metabolism, University of Ankara School of Medicine, İbni Sina Hastanesi, Ankara, Turkey

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Cosimo Durante Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy

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Rose Ngu Head Neck and Thyroid Imaging, Department of Radiology, Guy’s and St Thomas’ Hospitals NHS Foundation Trust, London, United Kingdom

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Laurence Leenhardt Thyroid and Endocrine Tumors, Institute of Endocrinology, Pitié Salpêtrière Hospital, Pierre and Marie Curie University, Paris, France

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Thyroid ultrasound (US) is a key examination for the management of thyroid nodules. Thyroid US is easily accessible, noninvasive, and cost-effective, and is a mandatory step in the workup of thyroid nodules. The main disadvantage of the method is that it is operator dependent. Thyroid US assessment of the risk of malignancy is crucial in patients with nodules, in order to select those who should have a fine needle aspiration (FNA) biopsy performed. Due to the pivotal role of thyroid US in the management of patients with nodules, the European Thyroid Association convened a panel of international experts to set up European guidelines on US risk stratification of thyroid nodules. Based on a review of the literature and on the American Association of Clinical Endocrinologists, American Thyroid Association, and Korean guidelines, the panel created the novel European Thyroid Imaging and Reporting Data System, called EU-TIRADS. This comprises a thyroid US lexicon; a standardized report; definitions of benign and low-, intermediate-, and high-risk nodules, with the estimated risks of malignancy in each category; and indications for FNA. Illustrated by numerous US images, the EU-TIRADS aims to serve physicians in their clinical practice, to enhance the interobserver reproducibility of descriptions, and to simplify communication of the results.

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Cosimo Durante Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

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Laszlo Hegedüs Department of Endocrinology, Odense University Hospital, Odense, Denmark

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Agnieszka Czarniecka M. Sklodowska-Curie National Research, Institute of Oncology Gliwice Branch, Gliwice, Poland

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Ralf Paschke Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

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Gilles Russ Thyroid and Endocrine Tumors Department, Pitié-Salpêtrière Hospital, Sorbonne University GRC N°16, Paris, France

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Fernando Schmitt Faculty of Medicine of University of Porto, CINTESIS@RISE and Institute of Molecular Pathology and Immunology, University of Porto (Ipatimup), Porto, Portugal

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Paula Soares Institute of Investigation and Innovation in Health (I3S), Faculty of Medicine of the University of Porto, Porto, Portugal

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Tamas Solymosi Endocrinology and Metabolism Clinic, Bugat Hospital, Gyöngyös, Hungary

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Enrico Papini Department of Endocrine and Metabolic Diseases, Regina Apostolorum Hospital, Albano, Rome, Italy

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With the widespread use of sensitive imaging techniques, which include neck visualization, a conspicuous number of thyroid nodules emerge and demand attention. Most lesions are benign, asymptomatic, and do not warrant treatment. In the case of cancer diagnosis, most are small, intrathyroidal and indolent neoplasms that can safely be managed conservatively. There is a pronounced need for more cost-effective, risk-adapted approaches to the management of this highly prevalent condition, taking the wishes of the patient into consideration. Thus, the present guidelines aim at providing a clinical practice guide for the initial workup and the subsequent management of adult individuals harboring thyroid nodules. Importantly, these guidelines are not intended to cover the management of thyroid malignancy. The manuscript and the specific recommendations were developed by reconciling the best available research evidence with the knowledge and clinical experience of the panelists and updating aspects of a number of previous European Thyroid Association guidelines.

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Giorgio Grani Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy

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Livia Lamartina Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy

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Valeria Ramundo Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy

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Rosa Falcone Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy

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Cristiano Lomonaco Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy

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Laura Ciotti Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy

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Martina Barone Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy

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Marianna Maranghi Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy

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Vito Cantisani Diagnostic and Ultrasound Innovations Unit, Azienda Ospedaliera Universitaria Policlinico Umberto I, “Sapienza” University of Rome, Rome, Italy

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Sebastiano Filetti Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy

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Cosimo Durante Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy

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Introduction: A taller-than-wide (TTW) shape is a suspicious feature of thyroid nodules commonly defined as an anteroposterior/transverse diameter (AP/T) ratio >1. An intraobserver variability of up to 18% in AP diameter evaluations has been described, which may lead to overreporting of this feature. To potentially improve the reliability of the TTW definition, we propose an arbitrary ratio of ≥1.2. Objective: The aim of this study was to estimate the impact of this definition on diagnostic performance. Methods: We prospectively analyzed 553 thyroid nodules referred for cytology evaluation at an academic center. Before fine-needle aspiration, two examiners jointly defined all sonographic features considered in risk stratification systems developed by the American Thyroid Association (ATA), the American Association of Clinical Endocrinologists (AACE), the American College of Radiology (ACR TIRADS), the European Thyroid Association (EU-TIRADS), and the Korean Society of Thyroid Radiology (K-TIRADS). TTW was defined according to the current definition (AP/T diameter ratio >1) and an arbitrary alternative definition (AP/T ratio >1.2). Results: The alternative definition classified fewer nodules as TTW (28, 5.1% vs. 94, 17%). The current and proposed definitions have a sensitivity of 26.2 and 11.9% (p = 0.03) and a specificity of 83.8 and 95.5% (p < 0.001). Thus, as a single feature, the arbitrary definition has a lower sensitivity and a higher specificity. When applied to sonographic risk stratification systems, however, the proposed definition would increase the number of avoided biopsies (up to 58.2% for ACR TIRADS) and the specificity of all systems, without negative impact on sensitivity or diagnostic odds ratio. Conclusions: Re-defining TTW nodules as those with an AP/T ratio ≥1.2 improves this marker’s specificity for malignancy. Using this definition in risk stratification systems will increase their specificity, reducing the number of suggested biopsies without significantly diminishing their overall diagnostic performance.

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Jaume Capdevila Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), IOB Quiron-Teknon, Barcelona, Spain

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Desiree’ Deandreis Department of Medical Sciences, Nuclear Medicine Unit, University of Turin, AOU Città della Salute e della Scienza, Turin, Italy

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Cosimo Durante Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

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Sophie Leboulleux Service of Endocrinology, Diabetology, University Hospital Geneve, Geneve, Switzerland

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Markus Luster Department of Nuclear Medicine, University Hospital Marburg, Marburg, Germany

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Romana Netea-Maier Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands

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Kate Newbold Royal Marsden Hospital, London, United Kingdom

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Susanne Singer Institute of Medical Biostatistics Epidemiology and Informatics (IMBEI), University Medical Center of Johannes Gutenberg University, Mainz, Germany

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Gerasimos P Sykiotis Service of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

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Beate Bartes Association “Vivre sans Thyroïde”, Léguevin, France

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Kate Farnell Butterfly Thyroid Cancer Trust, Rowlands Gill, Tyne & Wear, UK

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Laura Deborah Locati Medical Oncology Unit, IRCCS ICS Maugeri, Pavia, Italy
Department of Internal Medicine and Therapeutics, University of Pavia, Italy

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Background

Most thyroid cancers of follicular origin have a favorable outcome. Only a small percentage of patients will develop metastatic disease, some of which will become radioiodine refractory (RAI-R). Important challenges to ensure the best therapeutic outcomes include proper, timely, and appropriate diagnosis; decisions on local, systemic treatments; management of side effects of therapies; and a good relationship between the specialist, patients, and caregivers.

Methods

With the aim of providing suggestions that can be useful in everyday practice, a multidisciplinary group of experts organized the following document, based on their shared clinical experience with patients with RAI-R differentiated thyroid cancer (DTC) undergoing treatment with lenvatinib. The main areas covered are patient selection, initiation of therapy, follow-up, and management of adverse events.

Conclusions

It is essential to provide guidance for the management of RAI-R DTC patients with systemic therapies, and especially lenvatinib, since compliance and adherence to treatment are fundamental to achieve the best outcomes. While the therapeutic landscape in RAI-R DTC is evolving, with new targeted therapies, immunotherapy, etc., lenvatinib is expected to remain a first-line treatment and mainstay of therapy for several years in the vast majority of patients and settings. The guidance herein covers baseline work-up and initiation of systemic therapy, relevance of symptoms, multidisciplinary assessment, and patient education. Practical information based on expert experience is also given for the starting dose of lenvatinib, follow-up and monitoring, as well as the management of adverse events and discontinuation and reinitiating of therapy. The importance of patient engagement is also stressed.

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Alessia Cozzolino Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

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Tiziana Filardi Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

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Ilaria Simonelli Service of Medical Statistics and Information Technology, Fatebenefratelli Foundation for Health Research and Education, Rome, Italy
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy

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Giorgio Grani Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

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Camilla Virili Endocrinology Unit, Department of Medico-Surgical Sciences and Biotechnologies, ‘Sapienza’ University of Rome, Latina, Italy

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Ilaria Stramazzo Endocrinology Unit, Department of Medico-Surgical Sciences and Biotechnologies, ‘Sapienza’ University of Rome, Latina, Italy

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Maria Giulia Santaguida Endocrinology Unit, Department of Medico-Surgical Sciences and Biotechnologies, ‘Sapienza’ University of Rome, Latina, Italy

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Pietro Locantore Endocrinology Unit, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy

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Massimo Maurici Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy

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Daniele Gianfrilli Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

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Andrea M Isidori Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

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Cosimo Durante Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

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Carlotta Pozza Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

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on behalf of TALENT Group
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on behalf of TALENT Group

Context

Significant uncertainty exists about the diagnostic accuracy of ultrasonographic (US) features used to predict the risk of thyroid cancer in the pediatric population. Moreover, there are no specific indications for thyroid nodule evaluation in patients during the transition age.

Objective

The meta-analysis aimed to address the following question: which thyroid nodule US features have the highest accuracy in predicting malignancy in the transition age.

Methods

We performed a meta-analysis of observational/cohort/diagnostic accuracy studies dealing with thyroid nodule sonography, reporting US features, and using histology as a reference standard for the diagnosis of malignancy and histology or cytology for the diagnosis of benignity in the transition age (mean/median age 12–21 years).

Results

The inclusion criteria were met by 14 studies, published between 2005 and 2020, including 1306 thyroid nodules (mean size 17.9 mm) from 1168 subjects. The frequency of thyroid cancer was 36.6%. The US features with the highest diagnostic odds ratio (DOR) for malignancy were the presence of suspicious lymph nodes (DOR: 56.0 (95% CI: 26.0–119.0)), a ‘taller than wide’ shape of the nodule (6.0 (95% CI: 2.0–16.0)), the presence of microcalcifications (13.0 (95% CI: 6.0–29.0)) and irregular margins (9.0 (95% CI: 5.0–17.0)). Heterogeneity among the studies was substantial.

Conclusions

Following the diagnosis of a thyroid nodule in the transition age, a thorough US examination of the neck is warranted. The detection of suspicious lymph nodes and/or thyroid nodules with a ‘taller than wide’ shape, microcalcifications, and irregular margins is associated with the highest risk of malignancy in the selection of nodules candidates for biopsy.

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