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Maria Mavromati Department of Endocrinology, Diabetology, Nutrition and Therapeutic Education, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva University, Geneva, Switzerland

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Essia Saiji Department of Pathology, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva, Switzerland

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Marco Stefano Demarchi Department of Endocrine Surgery, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva, Switzerland

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Vincent Lenoir Department of Radiology, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva, Switzerland

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Amanda Seipel Department of Pathology, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva, Switzerland

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Paulina Kuczma Department of Endocrine Surgery, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva, Switzerland

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François R Jornayvaz Department of Endocrinology, Diabetology, Nutrition and Therapeutic Education, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva University, Geneva, Switzerland

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Minerva Becker Department of Radiology, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva, Switzerland

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Eugenio Fernandez Department of Oncology, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva, Switzerland

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Claudio De Vito Department of Pathology, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva, Switzerland

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Frédéric Triponez Department of Endocrine Surgery, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva, Switzerland

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Sophie Leboulleux Department of Endocrinology, Diabetology, Nutrition and Therapeutic Education, Geneva University Hospitals, Rue Gabrielle Perret Gentil, Geneva University, Geneva, Switzerland

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Background

Molecular tests for suspicious thyroid nodules decrease rates of unnecessary surgeries but are not widely used due to reimbursement issues. The aim of this study was to assess the rate of unnecessary surgery performed in real-life setting for Bethesda III, IV and V nodules in the absence of molecular testing.

Method

This is a single-center retrospective study of consecutive patients undergoing fine needle aspiration cytology (FNAC) with rapid on-site evaluation between January 2017 and December 2021. Unnecessary surgery was defined as surgery performed because of Bethesda III, IV, or V results in the absence of local compressive symptoms with final benign pathology and as second surgery for completion thyroidectomy.

Results

In the 862 patients (640 females, mean age: 54.2 years), 1010 nodules (median size: 24.4 mm) underwent 1189 FNAC. Nodules were EU-TIRADS 2, 3, 4, and 5 in 3%, 34%, 42%, and 22% of cases, respectively. FNAC was Bethesda I, II, III, IV, V, and VI in 8%, 48%, 17%, 17%, 3%, and 6%, respectively. Surgery was performed in 36% of Bethesda III nodules (benign on pathology: 81%), in 74% of Bethesda IV nodules (benign on pathology: 76%) and in 97% of Bethesda V nodules (benign on pathology: 21%). Surgery was considered unnecessary in 56%, 68%, and 21% of patients with Bethesda III, IV, and V nodules, respectively.

Conclusion

In this real data cohort surgery was unnecessary in more than half of patients with Bethesda III and IV nodules and in 21% of patients with Bethesda V nodules.

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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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Milan Halenka Department of Internal Medicine III – Nephrology, Rheumatology and Endocrinology, University Hospital Olomouc, Olomouc, Czech Republic
Department of Internal Medicine III – Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic

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Hana Munteanu Department of Internal Medicine III – Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic

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Radko Obereigneru Faculty of Arts, Palacky University Olomouc, Olomouc, Czech Republic

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Roman Dohnal Department of Internal Medicine III – Nephrology, Rheumatology and Endocrinology, University Hospital Olomouc, Olomouc, Czech Republic
Department of Internal Medicine III – Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic

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David Karasek Department of Internal Medicine III – Nephrology, Rheumatology and Endocrinology, University Hospital Olomouc, Olomouc, Czech Republic
Department of Internal Medicine III – Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic

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Jan Schovanek Department of Internal Medicine III – Nephrology, Rheumatology and Endocrinology, University Hospital Olomouc, Olomouc, Czech Republic
Department of Internal Medicine III – Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic

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Objective

Ultrasound-guided percutaneous ethanol injection therapy (US-PEIT) is used in patients with recurrent symptomatic thyroid cysts as a credible alternative to surgery. Young patients commonly do not wish to undergo surgery and prefer ethanol ablation, if available. The effect of this approach on quality of life is an essential factor in deciding on the treatment options, especially in the young with a long life expectancy and no comorbidity.

Methods

We performed US-PEIT in a cohort of young patients, 15–30 years, from 2015 to 2020. The patients’ general quality of life (QoL), self-reported compression symptoms and neck appearance were evaluated.

Results

The cohort comprised 59 patients with 63 cysts, more women than men, with a mean age of 23.8 years. About 1.5 mL of injected alcohol were needed to reach a 90.7% mean cyst volume reduction ratio in 12 months. The method did not fail in any of the patients; a single US-PEIT session was undertaken in 46% of them. The procedure significantly improved each of the patients’ symptoms with a significant total score difference (P < 0.001). The total symptom score correlated with the initial cyst volume (P = 0.002; r = 0.395). The mean QoL score by SF-36 6 months after the last US-PEIT was significantly different for physical component summary 56.5 (P < 0.001) but not different for mental component summary 47.7 (P = 0.125), compared to age-corresponding norms.

Conclusions

US-PEIT is a safe and effective method for the young, leading to improvements in cosmetic and subjective complaints, and should also be considered as first-line treatment in the young.

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Radu Mihai Department of Endocrine Surgery, Churchill Cancer Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK

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Objective

The aim of this multicentre study was to investigate the progression of patient-reported outcomes after thyroid surgery, with emphasis on voice and swallowing difficulties.

Methods

An online platform was used to collect replies to standardised questionnaires (voice handicap index, VHI; voice-related quality of life, VrQoL; EAT-10) preoperatively and at 2–6 weeks and 3–6–12 months after surgery.

Results

A total of 236 patients were recruited from five centres that contributed with median of 11 cases (range 2–186 cases). Average symptoms scores showed voice changes lasting up to 3 months: VHI increased from 41 ± 15 (preop) to 48 ± 21 (6 weeks) and returned to 41 ± 15 at 6 months. Similarly, VrQoL increased from 12 ± 4 to 15 ± 6 and returned to 12 ± 4 (6 months). Severe voice changes (VHI > 60) were reported in 12% of patients preop, 22% at 2 weeks, 18% at 6 weeks, 13% at 3 months and 7% at 12 months. Only five patients with normal preoperative voice had persistent severe voice changes after 6–12 months. Those with severe voice changes at 2 weeks (median VHI 70.5, IQR 65–81) had significant improvement by 6 months (median VHI 54, IQR 39–65) (P < 0.001).

Swallowing assessment showed a median preop score of 0 (IQR 0–3) increasing to a median of 2 (IQR 0–8) at 2 weeks and normal values afterwards.

Conclusion

The ThyVoice online platform allows the assessment of patient-reported outcome measures in thyroid surgery. Voice morbidity appears to be more frequent than commonly reported, and this risk should the quoted during informed consent. Swallowing difficulties are mild but significant in the first 2 weeks.

Open access
Tamas Solymosi Endocrinology and Metabolism Clinic, Bugat Hospital, Gyöngyös, Hungary
Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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

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

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Andrea Frasoldati Endocrinology Unit of Arcispedale S Maria Nuova, Reggio Emilia, Italy

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Laszlo Jambor Department of Radiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Zsolt Karanyi Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Gabor L Kovacs 1st Department of Medicine, Flohr Ferenc Hospital, Kistarcsa, Hungary

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Enrico Papini Regina Apostolorum Hospital in Albano, Rome, Italy

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Karoly Rucz 1st Department of Medicine, University of Pecs, Pecs, Hungary

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Gilles Russ Unité Thyroïde et Tumeurs Endocrines – Pr Leenhardt Hôpital La Pitie Salpetriere, Sorbonne Université, Paris, France

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Endre V Nagy Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Objective

Thyroid nodule ultrasound characteristics are used as an indication for fine-needle aspiration cytology, usually as the basis for Thyroid Imaging Reporting and Data System (TIRADS) score calculation. Few studies on interobserver variation are available, all of which are based on analysis of preselected still ultrasound images and often lack surgical confirmation.

Methods

After the blinded online evaluation of video recordings of the ultrasound examinations of 47 consecutive malignant and 76 consecutive benign thyroid lesions, 7 experts from 7 thyroid centers answered 17 TIRADS-related questions. Surgical histology was the reference standard. Interobserver variations of each ultrasound characteristic were compared using Gwet’s AC1 inter-rater coefficients; higher values mean better concordance, the maximum being 1.0.

Results

On a scale from 0.0 to 1.0, the Gwet’s AC1 values were 0.34, 0.53, 0.72, and 0.79 for the four most important features in decision-making, i.e. irregular margins, microcalcifications, echogenicity, and extrathyroidal extension, respectively. The concordance in the discrimination between mildly/moderately and very hypoechogenic nodules was 0.17. The smaller the nodule size the better the agreement in echogenicity, and the larger the nodule size the better the agreement on the presence of microcalcifications. Extrathyroidal extension was correctly identified in just 45.8% of the cases.

Conclusions

Examination of video recordings, closely simulating the real-world situation, revealed substantial interobserver variation in the interpretation of each of the four most important ultrasound characteristics. In view of the importance for the management of thyroid nodules, unambiguous and widely accepted definitions of each nodule characteristic are warranted, although it remains to be investigated whether this diminishes observer variation.

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Eduardo Crespo Vallejo Interventional Radiology, Hospital Universitario Fundacion Jiménez Diaz, Madrid, Spain

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Antonio Hermosin Interventional Radiology, Hospital Universitario Fundacion Jiménez Diaz, Madrid, Spain

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Manuel Gargallo Endocrinology, Hospital Universitario Fundacion Jiménez Diaz, Madrid, Spain

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Álvaro Villalba Interventional Radiology, Hospital Universitario Fundacion Jiménez Diaz, Madrid, Spain

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Eduardo Daguer Interventional Radiology, Hospital Universitario Fundacion Jiménez Diaz, Madrid, Spain

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José Flores Interventional Radiology, Hospital Universitario Fundacion Jiménez Diaz, Madrid, Spain

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Javier Periañez Interventional Radiology, Hospital Universitario Fundacion Jiménez Diaz, Madrid, Spain

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Joaquim Amorín Interventional Radiology, Hospital Universitario Fundacion Jiménez Diaz, Madrid, Spain

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Ernesto Santos Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

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Objective

This study aimed to evaluate the safety and long-term efficacy using the multiple overlapping ablation technique with a novel non-cooled microwave system in benign symptomatic thyroid nodules.

Methods

This prospective cohort single-center study collected complication data from the start of the procedure to 30 days postoperatively and evaluated the safety and effectiveness with a follow-up of 24 months. Ultrasound examinations were performed to determine the volume shrinkage during follow-up. Thyroid function cosmetic and symptoms scores and satisfaction degree were evaluated.

Results

A total of 30 symptomatic benign thyroid nodules were treated by microwave ablation using a power between 15 and 30 W depending on the size of the nodule to be treated. The volume reduction rates in months 1, 3, 6, 9, 12, and 24 after ablation were 32, 59, 67, 69, 73, and 81%, respectively. The mean symptom score and mean cosmetic score before treatment were 4 and 3, respectively, while after treatment they dropped to 3 and 1, respectively. Thyroid function indicators fluctuated in the normal range and those with hyperthyroidism recovered to normal parameters. One case of temporary laryngeal paralysis occurred postoperatively and fully recovered in less than 3 months.

Conclusions

The novel microwave ablation system presented herein can help achieve good clinical success rate in benign thyroid nodules with a satisfying safety profile. The microwave ablation performed with the multiple overlapping ablation technique could be a good alternative to surgery and radiofrequency ablation in the management of benign thyroid nodules.

Open access
Tomohiro Kikuchi Department of Computational Diagnostic Radiology and Preventive Medicine, the University of Tokyo Hospital, Hongo, Bunkyo–ku, Tokyo, Japan
Department of Radiology, Jichi Medical University, School of Medicine, Shimotsuke, Tochigi, Japan

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Shouhei Hanaoka Department of Radiology, The University of Tokyo Hospital, Hongo, Bunkyo–ku, Tokyo, Japan

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Takahiro Nakao Department of Computational Diagnostic Radiology and Preventive Medicine, the University of Tokyo Hospital, Hongo, Bunkyo–ku, Tokyo, Japan

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Yukihiro Nomura Department of Computational Diagnostic Radiology and Preventive Medicine, the University of Tokyo Hospital, Hongo, Bunkyo–ku, Tokyo, Japan
Center for Frontier Medical Engineering, Chiba University, Yayoicho, Inage–ku, Chiba, Japan

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Takeharu Yoshikawa Department of Computational Diagnostic Radiology and Preventive Medicine, the University of Tokyo Hospital, Hongo, Bunkyo–ku, Tokyo, Japan

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Ashraful Alam Department of Computational Diagnostic Radiology and Preventive Medicine, the University of Tokyo Hospital, Hongo, Bunkyo–ku, Tokyo, Japan

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Harushi Mori Department of Radiology, Jichi Medical University, School of Medicine, Shimotsuke, Tochigi, Japan

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Naoto Hayashi Department of Computational Diagnostic Radiology and Preventive Medicine, the University of Tokyo Hospital, Hongo, Bunkyo–ku, Tokyo, Japan

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Objective

This study aimed to determine a standardized cut-off value for abnormal 18F-fluorodeoxyglucose (FDG) accumulation in the thyroid gland.

Methods

Herein, 7013 FDG–PET/CT scans were included. An automatic thyroid segmentation method using two U-nets (2D- and 3D-U-net) was constructed; mean FDG standardized uptake value (SUV), CT value, and volume of the thyroid gland were obtained from each participant. The values were categorized by thyroid function into three groups based on serum thyroid-stimulating hormone levels. Thyroid function and mean SUV with increments of 1 were analyzed, and risk for thyroid dysfunction was calculated. Thyroid dysfunction detection ability was examined using a machine learning method (LightGBM, Microsoft) with age, sex, height, weight, CT value, volume, and mean SUV as explanatory variables.

Results

Mean SUV was significantly higher in females with hypothyroidism. Almost 98.9% of participants in the normal group had mean SUV < 2 and 93.8% participants with mean SUV < 2 had normal thyroid function. The hypothyroidism group had more cases with mean SUV ≥ 2. The relative risk of having abnormal thyroid function was 4.6 with mean SUV ≥ 2. The sensitivity and specificity for detecting thyroid dysfunction using LightGBM (Microsoft) were 14.5 and 99%, respectively.

Conclusions

Mean SUV ≥ 2 was strongly associated with abnormal thyroid function in this large cohort, indicating that mean SUV with FDG–PET/CT can be used as a criterion for thyroid evaluation. Preliminarily, this study shows the potential utility of detecting thyroid dysfunction based on imaging findings.

Open access
Stamatina Ioakim CEDM, Centre of Endocrinology, Diabetes & Metabolism, Limassol, Cyprus
Medical School, University of Milan, Milan, Italy

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Akheel A Syed Department of Diabetes, Endocrinology & Obesity Medicine, Salford Royal NHS Foundation & University Teaching Trust, Salford, UK
Division of Diabetes, Endocrinology & Gastroenterology, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK

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George Zavros CEDM, Centre of Endocrinology, Diabetes & Metabolism, Limassol, Cyprus

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Michalis Picolos Alithias Endocrinology Centre, Nicosia, Cyprus

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Luca Persani Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
Department of Endocrinology and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy

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Angelos Kyriacou CEDM, Centre of Endocrinology, Diabetes & Metabolism, Limassol, Cyprus
Department of Diabetes, Endocrinology & Obesity Medicine, Salford Royal NHS Foundation & University Teaching Trust, Salford, UK
Medical School, European University of Cyprus, Nicosia, Cyprus

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Background

The 2015 American Thyroid Association (ATA) Guidelines recommend the following size cut-offs based on sonographic appearances for subjecting nodules to fine-needle aspiration (FNA) biopsy: low risk: 15 mm and intermediate risk and high risk: 10 mm.

Objective

We conducted a ‘real-world’ study evaluating the diagnostic performance of the ATA cut-offs against increased thresholds, in the interest of safely limiting FNAs.

Methods

We performed a retrospective analysis of prospectively collected data on 604 nodules which were sonographically risk-stratified as per the ATA Guidelines and subsequently subjected to ultrasound-guided FNA. Nodules were cytologically stratified into ‘benign’ (Bethesda class 2) and ‘non-benign’ (Bethesda classes 3–6). We obtained the negative predictive value (NPV), accuracy, FNAs that could be spared, missed ‘non-benign’ cytologies and missed carcinomas on histology, according to the ATA cut-offs compared to higher cut-offs.

Results

In low-risk nodules, the high performance of NPV (≈91%) is unaffected by increasing the cut-off to 25 mm, and accuracy improves by 39.4%; 46.8% of FNAs could be spared at the expense of few missed B3–B6 cytologies (7.9%) and no missed carcinomas. In intermediate-risk nodules, a 15 mm cut-off increases the NPV by 11.3% and accuracy by 40.7%. The spared FNAs approach 50%, while B3–B6 cytologies are minimal, with no missed carcinomas. In high-risk nodules, low NPV (<35%) and accuracy (<46%) were obtained regardless of cut-off. Moreover, the spared FNAs achieved at higher cut-offs involved numerous missed ‘non-benign’ cytologies and carcinomas.

Conclusion

It would be clinically safe to increase the ATA cut-offs for FNA in low-risk nodules to 25 mm and in intermediate-risk nodules to 15 mm.

Open access
Rémy Louvel Head and Neck Surgical Oncology Department, Institut Curie, PSL University, Paris, France

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Nathalie Badois Head and Neck Surgical Oncology Department, Institut Curie, PSL University, Paris, France

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Jerzy Klijanienko Pathology Department, Institut Curie, PSL University, Paris, France

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Ségolène Hescot Medical Oncology Department, Institut Curie, PSL University, Paris, France

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Caroline Hoffmann Head and Neck Surgical Oncology Department, Institut Curie, PSL University, Paris, France

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M Grussendorf Department of Internal Medicine, University Hospital, Düsseldorf, Germany

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I Ruschenburg MVZ Wagnerstibbe Center for Cytology and Pathology, Einbeck, Germany

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G Brabant Department of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, University of Manchester, Manchester, UK

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Objectives

Ultrasound diagnosis of thyroid nodules has greatly increased their detection rate. Their risk for malignancy is estimated between 7 and 15% in data from specialized centers which are used for guidelines recommendations. This high rate causes considerable anxiety to patients upon first diagnosis. Here, we retrospectively analyzed the malignancy rate of sonographically diagnosed nodules larger than 1 cm from a primary/secondary care center when long-term longitudinal follow-up was included.

Patients/methods

In the study, 17,592 patients were diagnosed with a thyroid nodule larger than 1 cm, of whom 7776 were assessed by fine-needle aspiration cytology (FNAC) and 9816 by sonography alone. 9568 patients were initially discharged due to innocent results of FNAC and/or ultrasound. In 1904 patients, definitive histology was obtained, and 6731 cases were included in the long-term follow-up (up to 23 years, median 5 years).

Results

Malignancy was histologically confirmed in 189 patients (1.1% of all) when excluding accidentally diagnosed papillary microcarcinomas. 155 were diagnosed during the first year of management, 25 in years 2–5 of follow-up, 9 in years 6–10 and nil in 1165 patients followed beyond 10 years.

Conclusions

The malignancy rate of thyroid nodules from primary/secondary care was much lower than that previously reported. During follow-up for more than 5 years, their rate rapidly dropped to less than 1/1000 cases. This low malignancy rate may help to reassure patients first confronted with the diagnosis of a thyroid nodule, substantially reduce their anxiety and avoid unwarranted diagnostic and therapeutic procedures.

Open access