A Narrative Review of the 2023 Korean Thyroid Association Management Guideline for Patients with Thyroid Nodules.

The 2023 Korean Thyroid Association (KTA) Management Guideline for Patients with Thyroid Nodules constitute an update of the 2016 KTA guideline for thyroid nodules and cancers that focuses specifically on nodules. The 2023 guideline aim to offer updated guidance based on new evidence that reflects the changes in clinical practice since the 2016 KTA guideline. To update the 2023 guideline, a comprehensive literature search was conducted from January 2022 to May 2022. The literature search included studies, reviews, and other evidence involving human subjects that were published in English in MEDLINE (PubMed), Embase, and other relevant databases. Additional significant clinical trials and research studies published up to April 2023 were also reviewed. The limitations of the current evidence are discussed, and suggestions for areas in need of further research are identified. The purpose of this review is to provide a summary of the 2023 KTA guideline for the management of thyroid nodules released in May 2023 and to give a balanced insight with comparison of recent guidelines from other societies.

Rates of diagnostic and therapeutic procedures in a cohort of patients undergoing first endocrine consultation for thyroid nodular disease.

PURPOSE: This study aimed to evaluate the rates of necessary diagnostic and therapeutic procedures in a cohort of patients undergoing their first endocrine consultation for thyroid nodular disease. METHODS: This was an observational study conducted between January 1 and June 30, 2023, on patients undergoing their first endocrine consultation for thyroid nodular disease. Data were collected, including age, thyroid-stimulating hormone (TSH) concentration, reasons for performing thyroid ultrasound (US), and thyroid US reports. The US was performed at the time of the endocrine consultation according to the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR-TIRADS) risk stratification system. Patients underwent further investigations/treatment or simple US follow-up as necessary. RESULTS: A total of 373 patients with thyroid nodules were evaluated. Reasons for undergoing thyroid US were unrelated to suspected thyroid disease in 126 (33.8%), incidentalomas in 91 (24.4%), dysfunction or positivity for thyroid antibodies in 67 (18%), symptoms or visible nodules in 61 (16.3%), and family history of thyroid disease in 28 (7.5%). A total of 193 diagnostic or therapeutic procedures were performed in 133 (35.7%) patients [fine-needle aspiration (FNA): 121 (62.7%), surgery: 28 (14.5%), percutaneous ethanol injection: 20 (10.4%), scintigraphy: 10 (5.2%); thermal ablation: 7 (3.6%), and radioactive treatment: 7 (3.6%)]. CONCLUSIONS: In the present study only one-third of the patients undergoing endocrine consultation with first detected thyroid nodules required any diagnostic or therapeutic procedures.

Thyroid Nodules: Emerging Trends in Detection and Visualization based on Citespace.

BACKGROUND: Thyroid nodule (TN) is a highly prevalent clinical endocrine disease. Many countries have formed guidelines on the prevention and treatment of TN based on extensive research. However, there is a scarcity of TN-related literature based on bibliometrics. OBJECTIVES: This study aimed to evaluate the scientific achievements and progress of TN research from a global perspective by investigating the literature for 20 years through bibliometrics. METHODS: We searched the literature on TN in the core collection of the Web of Science database from 2002 to 2021 and used the Citespace software to analyze the co-authorship, co-citation, and co-occurrence of countries, institutions, authors, keywords, and co-cited literature. RESULTS: We retrieved 12319 documents related to TN. The literature on TN has been growing since 2002. The United States has contributed the largest proportion of TN papers (20.64%), followed by China, Italy, and South Korea. The United States ranked first in terms of centrality (0.38). Haugen BR, Gharib H, and Cibas ES are the top three most cited authors. The papers published in Thyroid were cited most frequently (7952 times). The most prominent keywords were management, cancer, fine needle aspiration, diagnosis, malignant tumor, thyroid cancer, ultrasound, biopsy, benign, surgery, ablation, and cytology. All keywords could be divided into three categories: diagnosis stratification, treatment, and cancer. As far as potential hot spots are concerned, the keywords that have recently burst strongly and are still continuing are: "Association Guideline" (2018-2021), "Radiofrequency Ablation" (2017-2021), "Classification" (2019-2021), and "Data System" (2017-2021). CONCLUSION: Based on the current trends, the number of publications on TN will continue to increase. The United States is the most active contributor to research in this field. Previous literature focused on stratification, cancer, surgery, and ablation, and there were different opinions on the stratification of diagnosis. There were relatively few studies on pathogenesis and treatment using medicine. More focus will be placed on association guidelines, radiofrequency ablation, classification, and data system, which may be the next popular topics in TN research.

[SFE-AFCE-SFMN 2022 consensus on the management of thyroid nodules: Interest and place of thyroid cytology]. / Consensus SFE-AFCE-SFMN 2022 sur la prise en charge des nodules thyroïdiens : intérêt et place de la cytologie thyroïdienne.

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a symptom that is a frequent reason for consultation in endocrinology. Thyroid nodules are very common and mostly benign. Thyroid ultrasound and thyroid fine-needle aspiration biopsy (FNAB) are the reference tests for the analysis of these nodules. The aim of this article is to describe for the cytopathologist the key points of the SFE-AFCE-SFMN 2022 consensus involving thyroid cytology: the indications for thyroid FNAB, the technique and analysis, and the management (treatment, follow-up) following this cytological screening examination, a key element in the management of the thyroid nodule.

Computer-interpretable guidelines: electronic tools to enhance the utility of thyroid nodule clinical practice guidelines and risk stratification tools.

Clinicians seeking guidance for evaluating and managing thyroid nodules currently have several resources. The principal ones are narrative clinical guidelines and clinical risk calculators. This paper will review the strengths and weaknesses of both. The paper will introduce a concept of computer interpretable guideline, a novel way of transforming narrative guidelines in to a clinical decision support tool that can provide patient specific recommendations at the point of care. The paper then describes an experience of developing an interactive web based computer interpretable guideline for thyroid nodule management, called Thyroid Nodule Management App (TNAPP). The advantages of this approach and the potential barriers for widespread adaptation are discussed.

Cytology and Histology of Thyroid Nodules: Exploring Novel Insights in the Molecular Era for Enhanced Patient Management.

Significant advancements have been made over the past decade in our understanding of thyroid cancers, encompassing histomorphology, cytology, and ancillary techniques, particularly molecular tests. As a result, it is now feasible to put forth a comprehensive histo/cytomolecular approach to treating these tumors, thereby offering patients treatments that are precisely tailored to their unique circumstances.

Current controversies in the management of patients with indeterminate thyroid nodules.

The management of cytologically indeterminate thyroid nodules remains debatable as their malignancy is difficult to establish. Most nodules have benign postoperative histology, but an accurate assessment of their proclivity for malignant transformation is crucial. Numerous studies have investigated the effects of various tools, including clinical, radiological, and cytological features, as well as biochemical and molecular markers, on the management of these heterogeneous nodules. Collectively, strategies aim to treat malignant nodules and avoid unnecessary surgery for asymptomatic benign nodules. Currently, no clear guidelines for the optimal management of cytologically indeterminate thyroid nodules exist to determine whether a conservative approach with long-term observation or surgical intervention should be selected. Thus, personalized approaches have been recommended. Large-scale multicenter prospective studies are needed to elucidate controversial issues. As this topic has not been comprehensively covered based on publications from the Gulf region, this review aims to shed light on remaining controversies.

Artificial Intelligence in Thyroidology: A Narrative Review of the Current Applications, Associated Challenges, and Future Directions.

Background: The use of artificial intelligence (AI) in health care has grown exponentially with the promise of facilitating biomedical research and enhancing diagnosis, treatment, monitoring, disease prevention, and health care delivery. We aim to examine the current state, limitations, and future directions of AI in thyroidology. Summary: AI has been explored in thyroidology since the 1990s, and currently, there is an increasing interest in applying AI to improve the care of patients with thyroid nodules (TNODs), thyroid cancer, and functional or autoimmune thyroid disease. These applications aim to automate processes, improve the accuracy and consistency of diagnosis, personalize treatment, decrease the burden for health care professionals, improve access to specialized care in areas lacking expertise, deepen the understanding of subtle pathophysiologic patterns, and accelerate the learning curve of less experienced clinicians. There are promising results for many of these applications. Yet, most are in the validation or early clinical evaluation stages. Only a few are currently adopted for risk stratification of TNODs by ultrasound and determination of the malignant nature of indeterminate TNODs by molecular testing. Challenges of the currently available AI applications include the lack of prospective and multicenter validations and utility studies, small and low diversity of training data sets, differences in data sources, lack of explainability, unclear clinical impact, inadequate stakeholder engagement, and inability to use outside of the research setting, which might limit the value of their future adoption. Conclusions: AI has the potential to improve many aspects of thyroidology; however, addressing the limitations affecting the suitability of AI interventions in thyroidology is a prerequisite to ensure that AI provides added value for patients with thyroid disease.

[Exploration and management of thyroid nodules]. / Exploration et prise en charge des nodules thyroïdiens.

EXPLORATION AND MANAGEMENT OF THYROID NODULES. Most thyroid nodules are benign (95%) and can benefit from clinical and ultrasound monitoring. Cancers (approximately 5% of nodules) could be suspected, particularly in subjects whose neck was irradiated, in cases of a hard, irregular, evolving nodule, or with very high serum calcitonin (> 100 pg/ml). It is crucial to recognize cancers when nodules exceed the supracentimeter stage. Thyroid ultrasonography is the most common, handy, safe, and cost-effective tool to image thyroid nodules. It classifies thyroid nodules according to the EU-TIRADS score, which comprises 5 categories associated with an increasing risk of malignancy. An ultrasound-guided fine needle aspiration (FNA) biopsy is performed only in nodules staged EU-TIRADS classes 5, 4, and 3 over 1, 1.5, and 2 cm, respectively. Cytologic analysis of FNA material classifies thyroid nodules according to the Bethesda system into 6 classes, each with its own prognostic value. The difficulties in cytological evaluation are related to the uninterpretable (Bethesda I) and indeterminate (especially III and IV) results, for which have to be discussed opportunities of reassessment and follow-up by scintiscans and cytological molecular markers. Management is imperfectly codifiable: from surveillance in the absence of suspicious elements initially to total thyroidectomy in their presence.

EXPLORATION ET PRISE EN CHARGE DES NODULES THYROÏDIENS. La plupart des nodules thyroïdiens sont bénins (95 %) et peuvent bénéficier d'une surveillance clinique et échographique. La malignité (5 % des nodules environ) est à suspecter, particulièrement chez les sujets dont le cou a été irradié, en cas de nodule dur, irrégulier, évolutif, avec une calcitoninémie très élevée (supérieure à 100 pg/mL). C'est au stade de nodule supracentimétrique qu'il importe de reconnaître les cancers. L'échographie est l'examen d'imagerie de référence ; elle permet de classer les nodules selon le score EU-TIRADS, composé de cinq catégories associées à un risque croissant de malignité. Les ponctions échoguidées en vue de l'analyse cytologique sont réservées aux catégories EU-TIRADS 5, 4 et 3 de plus de 1, 1,5 et 2 cm respectivement. Les caractéristiques cytologiques sont présentées selon la nomenclature de Bethesda en six classes dont chacune quantifie aussi le risque de malignité, en complément des données échographiques. Les difficultés de l'évaluation cytologique sont liées aux résultats ininterprétables (Bethesda I) et indéterminés (surtout Bethesda III et IV) pour lesquels se discutent l'opportunité de la réévaluation et de la surveillance, des scintigraphies dites de seconde intention, et également des marqueurs moléculaires sur le produit de cytoponction. La prise en charge est imparfaitement codifiable : de la surveillance en l'absence d'éléments suspects initialement à la thyroïdectomie totale en leur présence.

Evaluation and management of pediatric thyroid nodules and thyroid cancer at a single institution after adoption of the American Thyroid Association 2015 guidelines.

OBJECTIVES: The study purpose is to correlate clinical findings with rates of differentiated thyroid cancer (DTC) in a cohort of children presenting with thyroid nodules at a single institution since the adoption of the 2015 American Thyroid Association (ATA) Guidelines Task Force on Pediatric Thyroid Cancer. METHODS: Clinical, radiographic, and cytopathologic findings were retrospectively analyzed in a pediatric cohort (≤19 years) identified with ICD-10 codes for thyroid nodules and thyroid cancer from January 2017 until May 2021. RESULTS: We analyzed 183 patients with thyroid nodules. The mean patient age was 14 years (interquartile range 11-16) with a female (79.2 %) and white Caucasian (78.1 %) predominance. The overall DTC in our pediatric patient cohort was 12.6 % (23 out of 183). Most of the malignant nodules measured from 1-4 cm (65.2 %) with TI-RADS score of ≥4 (69.6 %). Among the fine-needle aspiration results (n=49), the highest frequency of DTC was within the malignant category (16.33 %), followed by suspicious for malignancy (6.12 %), then atypia or follicular lesion of undetermined significance (8.16 %), and lastly follicular lesion or neoplasm and benign with 4.08 % and 2.04 % respectively. Of the forty-four thyroid nodules that underwent surgical intervention, pathology was remarkable for 19 papillary thyroid carcinoma (43.18 %) and 4 follicular thyroid carcinoma (9.09 %). CONCLUSIONS: Based on the analysis of our pediatric cohort in the southeast region at a single institution, adoption of the 2015 ATA guidelines could lead to an increased accuracy in detecting DTC while reducing the number of patients requiring interventions, such as FNA biopsy and/or surgeries. Further, based on our small cohort, it would be reasonable for thyroid nodules 1 cm or less to be monitored clinically with physical exam and ultrasonography, with further therapeutic or diagnostic intervention considered based on concerning features or parental shared decision making.

Genetic Considerations in the Tumorigenesis, Diagnosis, and Treatment of Differentiated Thyroid Cancer: Current State of the Science.

Thyroid nodules remain a common diagnosis encountered in general and endocrine surgical practice, and thyroid cancer appears to be increasing in incidence in both the United States and worldwide. The understanding of the complex genetics surrounding thyroid neoplasia has increased substantially in recent years and, consequently, has become a consideration in risk stratification, diagnosis, prognosis, and treatment. Molecular genetic analysis of thyroid nodules is now a readily available technology for diagnostic purposes via analysis of fine-needle aspiration biopsy (FNAB) specimens. Although their routine use is controversial, they may aid in selecting which patients require surgery and those who may be safely observed. In the following review, the genetics of the tumorigenesis of thyroid cancer are reviewed, focusing on the most common and clinically relevant of the literally hundreds of known mutations. Following this, the current status of the use of genetic analysis and molecular diagnostics in the workup of thyroid nodules and the diagnosis of differentiated thyroid cancer is explored. Finally, evolving concepts relating to the use of thyroid cancer genetics in individualizing treatment planning, follow-up, and management of recurrent disease is discussed. The goal is to provide the general surgeon with a working knowledge of the most common genetic alterations present in differentiated thyroid cancer, their relevance in clinical practice, and how they impact prognosis and treatment.

Thyroid cancer.

The past 5-10 years have brought in a new era in the care of patients with thyroid cancer, with the introduction of transformative diagnostic and management options. Several international ultrasound-based thyroid nodule risk stratification systems have been developed with the goal of reducing unnecessary biopsies. Less invasive alternatives to surgery for low-risk thyroid cancer, such as active surveillance and minimally invasive interventions, are being explored. New systemic therapies are now available for patients with advanced thyroid cancer. However, in the setting of these advances, disparities exist in the diagnosis and management of thyroid cancer. As new management options are becoming available for thyroid cancer, it is essential to support population-based studies and randomised clinical trials that will inform evidence-based clinical practice guidelines on the management of thyroid cancer, and to include diverse patient populations in research to better understand and subsequently address existing barriers to equitable thyroid cancer care.

Bethesda III and IV Thyroid Nodules Managed Nonoperatively After Molecular Testing With Afirma GSC or Thyroseq v3.

CONTEXT: Molecular testing has improved risk stratification and increased nonoperative management for patients with indeterminate thyroid nodules, but data on the long-term outcomes of current molecular tests Afirma Gene Sequencing Classifier (GSC) and Thyroseq v3 are limited. OBJECTIVE: To determine the rate of delayed operation and the false negative rate of the Afirma GSC and Thyroseq v3 in Bethesda III and IV thyroid nodules. METHODS: Prospective follow-up of a single center, randomized, clinical trial comparing the performance of Afirma GSC and Thyroseq v3 in the diagnosis of indeterminate thyroid nodules at the University of California, Los Angeles (UCLA). Consecutive participants who underwent thyroid biopsy in the UCLA health system with Bethesda III and IV cytology from August 2017 to November 2019. The main outcome measure was false negative rate of molecular testing. RESULTS: Of 176 indeterminate nodules with negative or benign molecular test results, 14 (8%) nodules underwent immediate resection, with no malignancies found on surgical pathology. Nonoperative management with active surveillance was pursued for 162 (92%) nodules with benign or negative test results. The median surveillance was 34 months (range 12-60 months), and 44 patients were lost to follow-up. Of 15 nodules resected during surveillance, 1 malignancy was found (overall false negative rate of 0.6%). This was a 2.7 cm minimally invasive Hurthle cell carcinoma that initially tested negative with Thyroseq v3 and underwent delayed resection due to sonographic growth during surveillance. CONCLUSIONS: The majority of Bethesda III/IV thyroid nodules with negative or benign molecular test results are stable over 3 years of follow-up. These findings support the high sensitivity of current molecular tests and their role in ruling out malignancy in indeterminate thyroid nodules.

Diagnostics and treatment of cysts of the neck.

Different congenital and acquired lesions can present as a cystic mass of the neck. The diagnostics and treatment of these is described in this review. Ultrasound and fine-needle aspiration biopsy are essential in the diagnostic workup of neck cysts, and especially cysts located laterally in the neck in adults over 40 years of age require further examination, due to the risk of malignancy. Treatment of the cysts depends on the type and location and can consist of aspiration, surgery, and sclerotherapy. Especially cystic thyroid nodules and macrocystic lymphatic malformations may be treated with schlerotherapy.

Thyroid nodules: Global, economic, and personal burdens.

Thyroid nodules have garnered attention due to changes in population surveillance systems and rising concerns about the associated financial burden on healthcare systems, payers, and patients. In this review, we find that prevalence rates vary widely based on method of detection and may particularly pronounced in asymptomatic patients undergoing routine screening. Incidence rates may be particularly rising in lower-income and middle-income countries and may be declining in higher-income countries. Despite high incidence rates, survival rates continue to be as high as 97% for papillary thyroid cancer. Over the last few decades, thyroid nodule workup and management has grown more sophisticated with the advent of fine-needle aspiration biopsy, specialized biomarkers, and molecular testing. However, gaps remain in risk stratification that can lead to substantial costs of care. Certain molecular tests, such as the Afirma Gene Sequencing Classifier can lead to a cost per diagnosis of $17,873 while achieving only mild decreases in diagnostic lobectomies for patients (11.6% to 9.7% in one study). Out-of-pocket costs associated with thyroid nodule management continue to drive significant financial toxicity for patients, especially for individuals with thyroid cancer. Financial toxicity has been defined as a term that describes how direct and indirect medical costs of cancer care strain patients and households via decreased income, assets, and spending on basic necessities. Recent studies suggest that such toxicity can lead to adverse financial outcomes, such as foreclosure and bankruptcy. Additional cost-effectiveness analyses are needed to improve existing thyroid nodule management systems and new clinical tools are needed to avoid unnecessary workup and management.

The value of second opinions on thyroid nodule management provided via direct-to-consumer telemedicine service.

PURPOSE: Second medical opinions (SMO) can improve patient outcomes and change medical decision-making. The purpose was to determine the concordance of initial management of thyroid nodules for patients seeking SMO to established management guidelines. MATERIALS AND METHODS: Cases of patients consulting a single provider via telemedicine for SMO on the workup and management of thyroid nodule(s) were reviewed from September 2011 to February 2022. The primary outcome was the overall rate of adherence to 2015 ATA guidelines (correct/incorrect) and complete agreement (yes/no) between SMO and initial treatment team. RESULTS: Most sought a second opinion for treatment options. Only 14 (29.2 %) cases had followed all the guidelines correctly. Living in North America compared to Asia (10/18 vs. 4/25, p = 0.004) and consulting endocrinology (11/21 vs. 3/26, p = 0.004) was associated with correct following of all guidelines. The most common violations of the guidelines were a lack of Bethesda scoring in pathology reports (31.8 %) and inappropriate initial FNA (25.5 %). The SMO was in complete agreement with the initial treatment recommendation in 31 cases (64.6 %), in partial agreement in 12 cases (25 %), and in disagreement in 5 cases (10.4 %). CONCLUSIONS: In our study, adherence to guidelines was low. However, the SMO agreed with the workup and management of most patients, as most of this discordance with guidelines did not affect the overall treatment. The virtual second opinion consult was valuable in addressing patient-specific concerns, explaining additional treatment options, and, in a few cases, recommending against inappropriate surgical intervention.

Ultrasound imaging in thyroid nodule diagnosis, therapy, and follow-up: Current status and future trends.

Ultrasound, the primary imaging modality in thyroid nodule management, suffers from drawbacks including: high inter- and intra-observer variability, limited field-of-view and limited functional imaging. Developments in ultrasound technologies are taking place to overcome these limitations, including three-dimensional-Doppler, -elastography, -nodule characteristics-extraction, and novel machine-learning algorithms. For thyroid ablative treatments and biopsies, perioperative use of three-dimensional ultrasound opens a new field of research. This review provides an overview of the current and future applications of ultrasound, and discusses the potential of new developments and trends that may improve the diagnosis, therapy, and follow-up of thyroid nodules.

Thyroid cancer in pregnancy: diagnosis, management, and treatment.

The evaluation and management of cancer during pregnancy requires special care to assure the health and safety of both the mother and fetus. The diagnosis and treatment of thyroid cancer in the non-pregnant patient often involves radioactive iodine exposure. However, radioactive iodine is contraindicated in pregnancy and surgical interventions pose risks to both the mother and fetus. Thus, the management of thyroid cancer during pregnancy is a unique clinical challenge. In this review, we discuss the imaging of thyroid nodules during pregnancy, including the role of CT, MRI, and nuclear Imaging, as well as that of Ultrasound and FNA. The staging and prognosis are discussed along with the management, treatment, and surveillance of thyroid cancer in pregnancy. Finally, the risks to the fetus through treatment are examined. Case examples are provided with an emphasis on the appropriate direction of care from a radiologist's perspective.

Establishing a Multicenter Network for Patients With Thyroid Nodules and Cancer: Effects on Referral Patterns.

OBJECTIVE: To perform a qualitative evaluation of the Thyroid Network, with a quantitative analysis of second opinion referrals for patients in the southwestern part of the Netherlands who have thyroid nodules and cancer. METHODS: This prospective observational study registered all patients with thyroid nodules and cancer who were referred to the academic hospital from 2 years before and 4 years after the foundation of the Thyroid Network. We implemented biweekly regional multidisciplinary tumor boards using video conference and a regional patient care pathway for patients with thyroid nodules and cancer. For qualitative evaluation, interviews were conducted with a broad selection of stakeholders via maximum variation sampling. The primary outcome was the change in second opinions after the foundation of the Thyroid Network. RESULTS: Second opinions from Thyroid Network hospitals to the academic hospital decreased from 10 (30%) to 2 (7%) two years after the start of the Thyroid Network (P = .001), while patient referrals remained stable (n = 108 to 106). Qualitative evaluation indicated that the uniform care pathway and the regional multidisciplinary tumor board were valued high. DISCUSSION: Establishing a regional network, including multidisciplinary tumor boards and a care pathway for patients with thyroid nodules and cancer, resulted in a decrease in second opinions of in-network hospitals and high satisfaction of participating specialists. IMPLICATIONS FOR PRACTICE: The concept of the Thyroid Network could spread to other regions as well as to other specialties in health care. Future steps would be to assess the effect of regional collaboration on quality of care and patient satisfaction.