Diagnostic performance of ultrasound elastography alone and in combination with conventional ultrasonography for Bethesda III–IV thyroid nodules: a systematic review and meta-analysis

Introduction

With an increasing incidence, thyroid nodules became the most common endocrine tumor in 2022. Moreover, thyroid cancer has also become the most common endocrine cancer, ranking seventh among all newly diagnosed cancers, with a male-to-female ratio of approximately 1:3 (1-3). When ultrasound detects suspicious thyroid nodules, fine needle aspiration (FNA) is the most accurate and cost-effective method for evaluating thyroid nodules (4).

Despite this, approximately 5–19% of lesions remain unidentified as benign or malignant through FNA (5). These typically include atypia of undetermined significance and follicular neoplasms, which the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), Royal College of Pathologists, British Thyroid Association, and Italian Society of Endocrinology categorize as Bethesda III–IV (6), Thy3 class (Thy3a, 3f) (7,8), and TIR3 class (3A-3F) (9). On the basis of FNA classification and ultrasound findings, the recommended management approach includes repeated FNA, molecular testing, and diagnostic lobectomy (10). However, some nodules may remain undiagnosed even after repeated FNA, necessitating close follow-up. Molecular testing poses challenges, particularly in certain regions, and the malignancy rate is relatively low, with approximately 70% of postoperative pathologies revealing benign conditions. Therefore, developing simple and effective noninvasive methods for accurate diagnosis becomes particularly crucial.

Ultrasound elastography is a noninvasive technique that, on the basis of its different working principles, is categorized into strain elastography and shear wave elastography (SWE) (11). It was first applied to thyroid scanning by Lyshchik et al. in 2005 (12). Currently, the World Federation for Ultrasound in Medicine and Biology recommends elastography as a supplementary method to conventional thyroid ultrasound and its use in guiding follow-up for patients diagnosed with benign lesions through FNA biopsy (13). Conventional ultrasound typically evaluates key morphological features such as composition, echogenicity, shape, margin, echogenic foci, and color Doppler flow imaging (CDFI), among others. However, the value of elastography in the treatment of Bethesda III–IV nodules remains controversial, with sensitivity ranging from 13% to 100% and specificity varying from 33% to 100% (14-17).

Therefore, we conducted a meta-analysis to explore the diagnostic efficacy of ultrasound elastography in detecting Bethesda III–IV thyroid nodules. Furthermore, we compared it with the combination of ultrasound elastography and conventional ultrasonography to analyze its practical value. We present this article in accordance with the PRISMA reporting checklist (18) (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-553/rc).

Methods

As this study was a meta-analysis and a retrospective study, ethical approval was not needed. This study has been registered on the Prospero website (https://www.crd.york.ac.uk/prospero/) with the ID CRD42024618764.

Literature search

A literature search was conducted by two independent members across databases including PubMed, Embase, Web of Science, the Cochrane Library, and Ovid. The specific search strategy is detailed in Table 1. Duplicate articles were manually excluded. Unpublished relevant data were also considered, but no suitable studies were found. The search concluded on 6 October 2024, with no stipulated starting date.

Inclusion and exclusion criteria

The criteria for the literature search were formulated by 2 independent members. The inclusion criteria were as follows: (I) elastic imaging was performed, and the patient was definitively diagnosed with Bethesda III–IV or other corresponding pathological classifications (Thy 3, TIR 3) on the basis of BSRTC criteria; (II) the complete report data in the article can be used to calculate the true positive (TP), false positive (FP), false negative (FN), and true negative (TN) cases; (III) postoperative histopathology and/or FNA cytology results served as the reference standards. The exclusion criteria were as follows: (I) comments, case reports, letters, meeting reports, editorial comments, and reviews; (II) articles that were not written in English; (III) effective data could not be extracted from the articles; (IV) for two articles published by the same institute using the same set of data at the same time, earlier or fewer data-rich articles were excluded; (V) for some studies with incomplete data, the corresponding author was sent an e-mail request to provide the original data, and no reply was received within 15 days.

Data extraction

The data extraction was completed by two members independently. When disagreements arose, a third member reviewed the articles, which were then resolved through consensus. During the data extraction process, the two researchers independently browsed all the retrieved literature and selected articles eligible for inclusion in this study. All pertinent data, including the first author, country of study, year of publication, study type, number of patients included, age range of patients, sex ratio of patients, number of lesions, reference standard, FNA classification, ultrasound system, type of ultrasound elastography, cut-off value, and the numbers of TPs, FPs, FNs, and TNs, were extracted from each article. If the article included both conventional ultrasonography and/or ultrasound elastography combined with conventional ultrasonography, the corresponding numbers of TPs, FPs, FNs, and TNs were also extracted. If the article mentioned more than 1 set of cut-off values and their corresponding data, all team members collaborated to extract the data via consultation. If not explicitly stated by the authors, cut-off values were determined on the basis of the Youden index.

Quality assessment

The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was used as the assessment tool in this study (19). The QUADAS-2 tool consists of four main components: case selection, trials to be evaluated, the gold standard, and case flow and progression. All the components are evaluated for risk of bias, and the first 3 components are also assessed for clinical applicability. On the basis of the answers ‘yes’, ‘no’, or ‘unclear’ to the relevant landmark questions included in each section, the risk of bias can be classified as ‘low’, ‘high’, or ‘unclear’. The quality assessment was conducted by two members independently. In the case of disagreement, a third member reviewed the article, and resolution was achieved through consensus.

Statistical analysis

The statistical software utilized in this study included Meta-Disc (Version 1.4, Unit of Clinical Biostatistics, Ramón y Cajal Hospital, Madrid, Spain), STATA (Version 18.0 for Windows, Stata Corp., College Station, TX, USA), and SPSS Statistics (Version 29.0, IBM Corp., Armonk, NY, USA). Cochran Q and I² statistics were employed to assess the statistical heterogeneity among the studies, whereas Spearman’s correlation coefficient was utilized to analyze threshold effects. When the P value of heterogeneity was less than 0.05 and I² was less than 50%, the fixed effects model was applied; otherwise, the random effects model was utilized. STATA software was used to investigate the stability of the results through sensitivity analysis, and funnel plots and Egger tests were employed to analyze potential publication bias. Meta-Disc was used to calculate the overall sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR−), diagnostic odds ratio (DOR), area under the curve (AUC), and the Q* index. Meta-regression analysis was employed to explore potential sources of heterogeneity and identify factors that may affect diagnostic value through subgroup analysis. Cohen’s κ analysis was conducted via SPSS software to evaluate interobserver consistency. The Z test was used to compare the overall sensitivity, specificity, DOR, and AUC between ultrasound elastography and conventional ultrasonography or the combined application of the two.

Results

Search results and study characteristics

After excluding duplicate results and conducting title and abstract screening, the full texts of potentially eligible studies were read. Ultimately, this analysis included a total of 27 studies, covering the period from 2012 to 2024. These studies included a total of 2,356 nodules, as illustrated in Figure 1. Detailed information on all the included studies can be found in Tables 2,3.

Figure 1 Flow diagram of study selection.

Ragazzoni et al. (20) and Garino et al. (27) published two articles from the same institute, with research periods of 2010 and 2011–2013. Cantisani et al. (22,29) and Celletti et al. (38) published 3 articles from the same institute, with research periods of 2009–2011, 2012–2014, and 2017–2018. Stoian et al. (33), Borlea et al. (36), and Latia (42) published 3 articles from the same institute, with the following research periods and subjects: 2018 (Bethesda III), 2019 (Bethesda III, IV), and 2013–2023 (Bethesda IV). After independent assessments by two members and subsequent consultation with the research team, it was determined that the research time and subjects of Borlea et al. (36) and Latia et al. (42) had minimal overlap. Consequently, both articles were unanimously agreed upon for inclusion in this study. Good interobserver consistency was observed when studies were excluded on the basis of their titles and abstracts (κ=0.886). In the other procedures, there was no disagreement between the two observers (κ=1).

Quality assessment

The quality assessment results of each study are shown in Figure 2. Some articles did not mention whether patients were included consecutively, nor did they specify whether the interpretation of the results of the trials to be evaluated was conducted without knowledge of the results of the gold standard trials. For articles utilizing semiquantitative or quantitative methods, it remains unclear whether the diagnostic threshold was established prior to the experiment. Overall, the quality assessment results of the included studies were positive. The interobserver agreement between the two researchers was high (κ=0.825).

Figure 2 Quality assessment of the included studies according to the QUADAS-2 criteria. (A) Each included study and (B) the overall judgment. QUADAS-2, Quality Assessment of Diagnostic Accuracy Studies 2.

Threshold effect

The Spearman correlation coefficient was –0.329 (P=0.094), indicating the absence of a threshold effect. The Cochran Q, I², and P values for DOR in ultrasound elastography were 140.98, 81.6%, and <0.001, respectively, suggesting a high degree of heterogeneity in this study. Therefore, we adopted a random effects model for analysis.

Diagnostic accuracy of ultrasound elastography

Under the random effects model, the overall sensitivity of ultrasound elastography for the diagnosis of benign and malignant Bethesda III–IV thyroid nodules was 0.81 [95% confidence interval (CI): 0.78–0.84], the overall specificity was 0.83 (95% CI: 0.81–0.84), the LR+ was 4.11 (95% CI: 2.73–6.21), the LR− was 0.28 (95% CI: 0.19–0.43), and the DOR was 16.40 (95% CI: 8.61–31.24). The summary receiver operating characteristic (SROC) curve indicated overall good accuracy, with an AUC of 0.87 (Q* =0.80) (Figure 3).

Figure 3 Forest plots of the pooled sensitivity (A), specificity (B), and DOR (C) of ultrasound elastography for diagnosis, and SROC curve (D) of their diagnostic accuracy obtained in this paper. The middle curve is the SROC curve. The upper and lower curves show the 95% CI. AUC, area under the curve; CI, confidence interval; DOR, diagnostic odds ratio; OR, odds ratio; SE, standard error; SROC, summary receiver operating characteristic.

Meta-regression and subgroup analysis

To further explore the source of heterogeneity, meta-regression analysis was used to evaluate the article type (Group 1: Prospective; Group 2: Retrospective), elastography type [Group 1: real-time elastography (RTE); Group 2: Strain ratio elastography (SRE); Group 3: shear wave elastography (SWE)], evaluation method (Group 1: qualitative; Group 2: quantitative; Group 3: semiquantitative), region [Group 1: Europe; Group 2: Asia; Group 3: Other (America, Africa)], classification [Group 1: Bethesda; Group 2: Other (Thy, TIR, NA)], reference standard (Group 1: histopathology; Group 2: repeated FNA or Histopathology), number of lesions (Group 1: ≤64; Group 2: >64), and malignant rate (Group 1: ≤28.85%; Group 2: <28.85%). The results indicated that the evaluation method was a significant factor influencing the heterogeneity of the studies (P=0.032). Further analysis revealed that there was no significant difference between qualitative and quantitative evaluations P=0.384), but significant differences were observed between quantitative and semiquantitative evaluations (P<0.001) or between semiquantitative and qualitative evaluations (P=0.023). Compared with qualitative and quantitative evaluation methods, semiquantitative methods performed better (Table 4).

Comparison of the diagnostic value of conventional ultrasonography alone and in combination with elastography

Among the 27 included articles, 20 included conventional ultrasonography, 8 included ultrasound elastography combined with conventional ultrasonography, and 3 (14,15,24) had data that differed from those of elastography. Among the conventional ultrasonography articles, only 6 articles used the risk stratification system (RSS) for evaluation [TI-RADS (14,33), K-TIRADS (38), EU-TIRADS (40), and ACR TI-RADS (41,42)], whereas the other 14 relied on multiparametric image features including grayscale characteristics and color Doppler flow patterns for classification. The Spearman correlation coefficient for conventional ultrasonography was 0.421 (P=0.06), and for ultrasound elastography combined with conventional ultrasonography, it was −0.262 (P=0.53), indicating that there was no threshold effect in either diagnostic test. The Cochran Q, I², and P values for DOR in conventional ultrasonography were 71.76%, 73.5%, and <0.001, respectively. For ultrasound elastography combined with conventional ultrasonography, the Cochran Q, I², and P values for DOR were 15.02, 53.4%, and 0.036, respectively. Therefore, a random effects model was used for analysis. Compared with that of elastography, the overall sensitivity of conventional ultrasonography was 0.43 (Z=−8.54, P<0.001), the overall specificity was 0.83 (Z=0.00, P=0.50), the DOR was 5.48 (Z=−0.13, P=0.45), and the AUC was 0.76 (Z=−0.36, P=0.36) (Figure 4). When ultrasound elastography was combined with conventional ultrasonography, the overall sensitivity increased to 0.87 (Z=0.85, P=0.80), the overall specificity remained at 0.75 (Z=−1.60, P=0.055), the DOR increased to 25.48 (Z=0.04, P=0.51), and the AUC reached 0.90 (Z=0.07, P=0.53) (Figure 5).

Figure 4 Forest plots of the pooled sensitivity (A), specificity (B), and DOR (C) of conventional ultrasonography for diagnosis, and SROC curve (D) of their diagnostic accuracy obtained in this paper. The middle curve is the SROC curve. The upper and lower curves show the 95% CI. AUC, area under the curve; CI, confidence interval; DOR, diagnostic odds ratio; OR, odds ratio; SE, standard error; SROC, summary receiver operating characteristic.

Figure 5 Forest plots of the pooled sensitivity (A), specificity (B), and DOR (C) of ultrasound elastography combined with conventional ultrasonography for diagnosis, and SROC curve (D) of their diagnostic accuracy obtained in this paper. The middle curve is the SROC curve. The upper and lower curves show the 95% CI. AUC, area under the curve; CI, confidence interval; DOR, diagnostic odds ratio; OR, odds ratio; SE, standard error; SROC, summary receiver operating characteristic.

Sensitivity analysis and publication bias

The sensitivity analysis revealed that the stability of the included studies was good, indicating a certain level of reliability in the results (Figure 6). We used a funnel plot (Figure 7) and the Egger test to analyze whether there was any publication bias. The funnel plot appeared largely symmetrical, and the Egger test yielded a P value of 0.66, indicating that there was no significant publication bias in this study.

Figure 6 Sensitivity analysis chart. Three long lines represent the pooled effect size and its 95% CI. The circle behind each study and the short lines on both sides represent the overall effect size and its 95% CI after removing the study. CI, confidence interval.

Figure 7 Funnel plot for evaluating potential publication bias. Assess whether all studies are symmetrically distributed about the central axis. Each solid circle signifies a study, with the solid line and the dashed lines on either side depicting the 95% CI for the combined effect size. CI, confidence interval; OR, odds ratio; s.e., standard error.

Discussion

Currently, the 2023 BSRTC classifies thyroid FNA results into six categories, namely, nondiagnostic (I), benign (II), atypia of undetermined significance (III), follicular neoplasm (IV), suspicious for malignancy (V), and malignant (VI). According to the updated BSRTC criteria (6), the implied risk of malignancy is 13–30% for Bethesda III and 23–34% for Bethesda IV nodules. Our own meta-analysis included a total of 2,356 nodules from 27 studies, with 1,691 benign and 665 malignant cases and a malignancy rate of 28.23%. This rate aligns closely with the Bethesda IV average risk of malignancy (30%) and falls within the combined III–IV range (13–34%), supporting the representativeness of our pooled data relative to current clinical benchmarks.

Thyroid cytologically indeterminate nodules typically refer to those nodules with unclear pathological characteristics, making it impossible to determine their benign or malignant nature. However, opinions vary regarding which nodules fall under the category of thyroid cytologically indeterminate nodules. Although almost all scholars agree that Bethesda III–IV nodules constitute thyroid cytologically indeterminate nodules, some also consider nodules with suspicious malignancy as falling into this indeterminate category (6,46,47). To exercise caution, this study refrained from using the term “cytological indeterminacy” as the subject of research. Additionally, during the literature screening, articles that merely mentioned cytological indeterminacy without specifying the category were excluded to prevent potential bias.

Meta-analysis revealed that ultrasound elastography has significant diagnostic value for Bethesda III–IV thyroid nodules, with a total sensitivity of 0.81, total specificity of 0.83, and an AUC of 0.87. This study exhibited heterogeneity (I²=81.6%, P<0.001). The meta-regression results indicated that research methodology was a notable factor influencing heterogeneity (P=0.032). The semiquantitative approach was superior to both the qualitative and the quantitative methods. This could be attributed to the fact that the semiquantitative method combines the ease of use inherent to qualitative methods with the high objective accuracy of quantitative methods. No notable disparities were observed among the other subgroups. Additionally, the analysis demonstrated that, compared with ultrasound elastography alone, the combination of ultrasound elastography and conventional ultrasonography exhibited greater sensitivity (0.85 vs. 0.81) and AUC (0.90 vs. 0.87), albeit with a lower specificity (0.75 vs. 0.83). Overall, there was no substantial disparity in diagnostic value between the two methods for Bethesda III–IV thyroid nodules. Compared with ultrasound elastography, conventional ultrasonography exhibited a lower specificity (0.43 vs. 0.81, P<0.001) and AUC (0.76 vs. 0.87) while maintaining a similar sensitivity (0.83 vs. 0.83). Overall, there appears to be no significant difference in diagnostic value between the two for Bethesda III–IV thyroid nodules. To our knowledge, this is the first meta-analysis to assess the diagnostic value of ultrasound elastography specifically for Bethesda III–IV thyroid nodules and the first study to evaluate the diagnostic efficacy of combining ultrasound elastography with conventional ultrasonography.

Recently, a meta-analysis conducted by Xing et al. (48) on the diagnostic efficacy of the RSS for thyroid nodules with uncertain cytology revealed that the overall sensitivity and specificity of the RSS were 0.86 (95% CI: 0.80–0.91) and 0.33 (95% CI: 0.25–0.41), respectively. We conducted a separate analysis of articles (14,33,38,40-42) that employed the ultrasound risk stratification system in conventional ultrasonography and reported that the final overall sensitivity and specificity were 0.73 and 0.66, respectively (I²=40.1%, P=0.138, using a fixed-effects model). In our study, conventional ultrasonography demonstrated higher overall specificity (0.83 vs. 0.73 vs. 0.33) and lower overall sensitivity (0.43 vs. 0.66 vs. 0.86). The reason for the difference may be the different inclusion criteria used in the studies by Xing et al. (Bethesda III–V categories) and our study (Bethesda III–IV categories). Additionally, our study focused primarily on the diagnostic value of ultrasound elastography for Bethesda III–IV thyroid nodules and its comparison with the diagnostic efficacy of conventional ultrasonography in combination, which may have resulted in a less comprehensive search for an ultrasound risk stratification system.

In a meta-analysis of the diagnostic efficacy of ultrasound elastography for thyroid nodules with indeterminate cytology (Bethesda III–V) in 2020, Qiu et al. (49) reported an overall sensitivity of 0.766 (95% CI: 0.686–0.835) and an overall specificity of 0.867 (95% CI: 0.780–0.931). Their subsequent 2023 SWE-focused meta-analysis (50) yielded sensitivity of 0.792 (95% CI: 0.727–0.850) and specificity of 0.845 (95% CI: 0.797–0.887). Crucially, both studies demonstrated systematically higher specificity but lower sensitivity than our findings. We attribute these discrepancies to differences in inclusion criteria: critical review revealed that the 2020 study incorporated one article on non-diagnostic nodules (51) and another lacking indeterminate FNA confirmation (52), whereas the 2023 analysis included Bethesda I and III hybrid cohorts (53).

In a meta-analysis of the diagnostic efficacy of RTE for thyroid nodules with indeterminate cytology (Bethesda III–IV) published by Trimboli et al. (54) in 2015, the overall sensitivity was 0.69 (95% CI: 0.59–0.82) and the overall specificity was 0.75 (95% CI: 0.42–0.96). In contrast, this study included 8 additional studies (15) on RTE, with overall sensitivity (0.80) and overall specificity (0.79) that were marginally greater than those of Trimboli et al. (54).

However, our study has several limitations. First, although we included 27 studies, the number of nodules included in the articles was relatively small, with a median of 64. Second, most of the included studies employed RTE (15 out of 27), with fewer articles utilizing SRE and SWE and only one article using acoustic radiation force impulse (31). Third, since we included only English-language literature and were unable to obtain unpublished data, language restrictions prevented the inclusion of some studies (55,56), potentially affecting the reliability of our findings. Fourth, the value of combining ultrasound elastography with the RSS should be evaluated. However, only 4 articles have conducted such research, reporting sensitivities ranging from 0.60 to 0.93 and specificities ranging from 0.31 to 0.93 (38,40-42). Therefore, owing to the limited number of studies, further evaluation has not been conducted. Finally, only two articles adopted repeated FNA/surgery as the reference standard, which may introduce bias.

Conclusions

Ultrasound elastography has significant diagnostic value for Bethesda III–IV thyroid nodules. Semiquantitative methods are superior to both quantitative and qualitative methods and demonstrate higher sensitivity than conventional ultrasonography. Compared with the combination of ultrasound elastography and conventional ultrasonography, although ultrasound elastography has greater specificity, there is no notable difference in its diagnostic value.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-553/rc

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-553/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Baloch ZW, Asa SL, Barletta JA, Ghossein RA, Juhlin CC, Jung CK. LiVolsi VA, Papotti MG, Sobrinho-Simões M, Tallini G, Mete O. Overview of the 2022 WHO Classification of Thyroid Neoplasms. Endocr Pathol 2022;33:27-63. [Crossref] [PubMed]
2. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024;74:229-63. [Crossref] [PubMed]
3. Li M, Dal Maso L, Pizzato M, Vaccarella S. Evolving epidemiological patterns of thyroid cancer and estimates of overdiagnosis in 2013-17 in 63 countries worldwide: a population-based study. Lancet Diabetes Endocrinol 2024;12:824-36. [Crossref] [PubMed]
4. Torregrossa L, Poma AM, Macerola E, Rago T, Vignali P, Romani R, Proietti A, Di Stefano I, Scuotri G, Ugolini C, Basolo A, Antonelli A, Materazzi G, Santini F, Basolo F. The Italian Consensus for the Classification and Reporting of Thyroid Cytology: Cytohistologic and molecular correlations on 37,371 nodules from a single institution. Cancer Cytopathol 2022;130:899-912. [Crossref] [PubMed]
5. Liu Y, Liu H, Zhan J, Chai Q, Zhu J, Ding S, Chen L. Contrast-Enhanced Ultrasound for Diagnosing Thyroid Nodules With Indeterminate Cytology: A Retrospective Study. Clin Endocrinol (Oxf) 2025;102:223-31. [Crossref] [PubMed]
6. Ali SZ, Baloch ZW, Cochand-Priollet B, Schmitt FC, Vielh P, VanderLaan PA. The 2023 Bethesda System for reporting thyroid cytopathology. J Am Soc Cytopathol 2023;12:319-25. [Crossref] [PubMed]
7. Crossley B, Chandrachud L, Herbert A, et al. Guidance on the reporting of thyroid cytology specimens. London: The Royal College of Pathologists; 2025. Available online: https://www.rcpath.org/static/d40af26c-0e49-4d40-8fce4a38f2a5c44b/G089-Guidance-on-the-reporting-of-thyroid-cytology-specimensFor-Publication.pdf
8. Mitchell AL, Gandhi A, Scott-Coombes D, Perros P. Management of thyroid cancer: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol 2016;130:S150-60. [Crossref] [PubMed]
9. Nardi F, Basolo F, Crescenzi A, Fadda G, Frasoldati A, Orlandi F, Palombini L, Papini E, Zini M, Pontecorvi A, Vitti P. Italian consensus for the classification and reporting of thyroid cytology. J Endocrinol Invest 2014;37:593-9. [Crossref] [PubMed]
10. Durante C, Hegedüs L, Czarniecka A, Paschke R, Russ G, Schmitt F, Soares P, Solymosi T, Papini E. 2023 European Thyroid Association Clinical Practice Guidelines for thyroid nodule management. Eur Thyroid J 2023;12:e230067. [Crossref] [PubMed]
11. Cantisani V, De Silvestri A, Scotti V, Fresilli D, Tarsitano MG, Polti G, Guiban O, Polito E, Pacini P, Durante C, Grani G, Isidori AM, Giannetta E, Sorrenti S, Trimboli P, Catalano C, Cirocchi R, Lauro A, D'Andrea V. US-Elastography With Different Techniques for Thyroid Nodule Characterization: Systematic Review and Meta-analysis. Front Oncol 2022;12:845549. [Crossref] [PubMed]
12. Lyshchik A, Higashi T, Asato R, Tanaka S, Ito J, Mai JJ, Pellot-Barakat C, Insana MF, Brill AB, Saga T, Hiraoka M, Togashi K. Thyroid gland tumor diagnosis at US elastography. Radiology 2005;237:202-11. [Crossref] [PubMed]
13. Cosgrove D, Barr R, Bojunga J, Cantisani V, Chammas MC, Dighe M, Vinayak S, Xu JM, Dietrich CF. WFUMB Guidelines and Recommendations on the Clinical Use of Ultrasound Elastography: Part 4. Thyroid. Ultrasound Med Biol 2017;43:4-26. [Crossref] [PubMed]
14. Russ G, Royer B, Bigorgne C, Rouxel A, Bienvenu-Perrard M, Leenhardt L. Prospective evaluation of thyroid imaging reporting and data system on 4550 nodules with and without elastography. Eur J Endocrinol 2013;168:649-55. [Crossref] [PubMed]
15. Pikis G, Kandaraki E, Lamnisos D, Abbara S, Kyriakou K, Economides A, Economides PA. Prevalence of thyroid carcinoma in nodules with thy 3 cytology: the role of preoperative ultrasonography and strain elastography. Thyroid Res 2021;14:7. [Crossref] [PubMed]
16. Shingare A, Maldar AN, Chauhan PH, Wadhwani R. Use of ultrasound elastography in differentiating benign from malignant thyroid nodules: a prospective study. J Diabetes Metab Disord 2023;22:1245-53. [Crossref] [PubMed]
17. Mohey N, Hassan TA, Abdel-Baki S. Role of combined grey scale US and US tissue elastography in differentiating solid thyroid nodules. Egypt J Radiol Nucl Med 2013;44:505-12.
18. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372: [Crossref] [PubMed]
19. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, Leeflang MM, Sterne JA, Bossuyt PM. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 2011;155:529-36. [Crossref] [PubMed]
20. Ragazzoni F, Deandrea M, Mormile A, Ramunni MJ, Garino F, Magliona G, Motta M, Torchio B, Garberoglio R, Limone P. High diagnostic accuracy and interobserver reliability of real-time elastography in the evaluation of thyroid nodules. Ultrasound Med Biol 2012;38:1154-62. [Crossref] [PubMed]
21. Unlütürk U, Erdoğan MF, Demir O, Güllü S, Başkal N. Ultrasound elastography is not superior to grayscale ultrasound in predicting malignancy in thyroid nodules. Thyroid 2012;22:1031-8.
22. Cantisani V, Ulisse S, Guaitoli E, De Vito C, Caruso R, Mocini R, D'Andrea V, Ascoli V, Antonaci A, Catalano C, Nardi F, Redler A, Ricci P, De Antoni E, Sorrenti S. Q-elastography in the presurgical diagnosis of thyroid nodules with indeterminate cytology. PLoS One 2012;7:e50725. [Crossref] [PubMed]
23. Trimboli P, Guglielmi R, Monti S, Misischi I, Graziano F, Nasrollah N, Amendola S, Morgante SN, Deiana MG, Valabrega S, Toscano V, Papini E. Ultrasound sensitivity for thyroid malignancy is increased by real-time elastography: a prospective multicenter study. J Clin Endocrinol Metab 2012;97:4524-30. [Crossref] [PubMed]
24. Rago T, Scutari M, Latrofa F, Loiacono V, Piaggi P, Marchetti I, Romani R, Basolo F, Miccoli P, Tonacchera M, Vitti P. The large majority of 1520 patients with indeterminate thyroid nodule at cytology have a favorable outcome, and a clinical risk score has a high negative predictive value for a more cumbersome cancer disease. J Clin Endocrinol Metab 2014;99:3700-7. [Crossref] [PubMed]
25. Cakir B, Ersoy R, Cuhaci FN, Aydin C, Polat B, Kılıc M, Yazgan A. Elastosonographic strain index in thyroid nodules with atypia of undetermined significance. J Endocrinol Invest 2014;37:127-33. [Crossref] [PubMed]
26. Giusti M, Campomenosi C, Gay S, Massa B, Silvestri E, Monti E, Turtulici G. The use of semi-quantitative ultrasound elastosonography in combination with conventional ultrasonography and contrast-enhanced ultrasonography in the assessment of malignancy risk of thyroid nodules with indeterminate cytology. Thyroid Res 2014;7:9. [Crossref] [PubMed]
27. Garino F, Deandrea M, Motta M, Mormile A, Ragazzoni F, Palestini N, Freddi M, Gasparri G, Sgotto E, Pacchioni D, Limone PP. Diagnostic performance of elastography in cytologically indeterminate thyroid nodules. Endocrine 2015;49:175-83. [Crossref] [PubMed]
28. Samir AE, Dhyani M, Anvari A, Prescott J, Halpern EF, Faquin WC, Stephen A. Shear-Wave Elastography for the Preoperative Risk Stratification of Follicular-patterned Lesions of the Thyroid: Diagnostic Accuracy and Optimal Measurement Plane. Radiology 2015;277:565-73. [Crossref] [PubMed]
29. Cantisani V, Maceroni P, D'Andrea V, Patrizi G, Di Segni M, De Vito C, Grazhdani H, Isidori AM, Giannetta E, Redler A, Frattaroli F, Giacomelli L, Di Rocco G, Catalano C, D'Ambrosio F. Strain ratio ultrasound elastography increases the accuracy of colour-Doppler ultrasound in the evaluation of Thy-3 nodules. A bi-centre university experience. Eur Radiol 2016;26:1441-9. [Crossref] [PubMed]
30. Wojtaszek-Nowicka M, Słowińska-Klencka D, Sporny S, Popowicz B, Kuzdak K, Pomorski L, Kaczka K, Sopiński J, Klencki M. The efficiency of elastography in the diagnostics of follicular lesions and nodules with an unequivocal FNA result. Endokrynol Pol 2017;68:610-22. [Crossref] [PubMed]
31. Zhao CK, Xu HX, Xu JM, Sun CY, Chen W, Liu BJ, Bo XW, Wang D, Qu S. Risk stratification of thyroid nodules with Bethesda category III results on fine-needle aspiration cytology: The additional value of acoustic radiation force impulse elastography. Oncotarget 2017;8:1580-92. [Crossref] [PubMed]
32. Azizi G, Keller JM, Mayo ML, Piper K, Puett D, Earp KM, Malchoff CD. Shear wave elastography and Afirma™ gene expression classifier in thyroid nodules with indeterminate cytology: a comparison study. Endocrine 2018;59:573-84. [Crossref] [PubMed]
33. Stoian D, Borcan F, Petre I, Mozos I, Varcus F, Ivan V, Cioca A, Apostol A, Dehelean CA. Strain Elastography as a Valuable Diagnosis Tool in Intermediate Cytology (Bethesda III) Thyroid Nodules. Diagnostics (Basel) 2019.
34. Wu Q, Li Y, Liu Y, Shen J, Wang Y, Yi X, Hu B. The value of conventional sonography and ultrasound elastography in decision-making for thyroid nodules in different categories of the Bethesda system for reporting thyroid cytopathology. Clin Hemorheol Microcirc 2020;74:255-66. [Crossref] [PubMed]
35. Marturano I, Russo M, Malandrino P, Buscema M, La Rosa GL, Spadaro A, Manzella L, Sciacca L, L'abbate L, Rizzo L. Combined use of sonographic and elastosonographic parameters can improve the diagnostic accuracy in thyroid nodules at risk of malignancy at cytological examination. Minerva Endocrinol 2020;45:3-11. [Crossref] [PubMed]
36. Borlea A, Stoian D, Cotoi L, Sporea I, Lazar F, Mozos I. Thyroid Multimodal Ultrasound Evaluation-Impact on Presurgical Diagnosis of Intermediate Cytology Cases. Appl Sci 2020;10:3439.
37. Moraes PHM, Takahashi MS, Vanderlei FAB, Schelini MV, Chacon DA, Tavares MR, Chammas MC. Multiparametric Ultrasound Evaluation of the Thyroid: Elastography as a Key Tool in the Risk Prediction of Undetermined Nodules (Bethesda III and IV)-Histopathological Correlation. Ultrasound Med Biol 2021;47:1219-26. [Crossref] [PubMed]
38. Celletti I, Fresilli D, De Vito C, Bononi M, Cardaccio S, Cozzolino A, Durante C, Grani G, Grimaldi G, Isidori AM, Catalano C, Cantisani V. TIRADS, SRE and SWE in INDETERMINATE thyroid nodule characterization: Which has better diagnostic performance? Radiol Med 2021;126:1189-200. [Crossref] [PubMed]
39. Uçan B, Şahin M, Önal B, Kızılgül M, Düğer H, Sencar ME, Çakal E, Özbek M. Assessment of diagnostic value of preoperative elastography in thyroid nodules having indeterminate cytology results. Turk J Med Sci 2021;51:2924-30. [Crossref] [PubMed]
40. Chambara N, Lo X, Chow TCM, Lai CMS, Liu SYW, Ying M. Combined Shear Wave Elastography and EU TIRADS in Differentiating Malignant and Benign Thyroid Nodules. Cancers (Basel) 2022.
41. Appanraj P, Kaur J, George NA, Chinniah PK. Role of Ultrasound Elastography in Evaluating Suspicious Thyroid Nodules. Indian J Surg Oncol 2024;15:646-51. [Crossref] [PubMed]
42. Latia M, Borlea A, Mihuta MS, Neagoe OC, Stoian D. Impact of ultrasound elastography in evaluating Bethesda category IV thyroid nodules with histopathological correlation. Front Endocrinol (Lausanne) 2024;15:1393982. [Crossref] [PubMed]
43. Rago T, Santini F, Scutari M, Pinchera A, Vitti P. Elastography: new developments in ultrasound for predicting malignancy in thyroid nodules. J Clin Endocrinol Metab 2007;92:2917-22. [Crossref] [PubMed]
44. Giusti M, Massa B, Balestra M, Calamaro P, Gay S, Schiaffino S, Turtulici G, Zupo S, Monti E, Ansaldo G. Retrospective cytological evaluation of indeterminate thyroid nodules according to the British Thyroid Association 2014 classification and comparison of clinical evaluation and outcomes. J Zhejiang Univ Sci B 2017;18:555-66. [Crossref] [PubMed]
45. Anvari A, Dhyani M, Stephen AE, Samir AE. Reliability of Shear-Wave Elastography Estimates of the Young Modulus of Tissue in Follicular Thyroid Neoplasms. AJR Am J Roentgenol 2016;206:609-16. [Crossref] [PubMed]
46. Zhang WB, Deng WF, He BL, Wei YY, Liu Y, Chen Z, Xu RY. Diagnostic value of CEUS combined with C-TIRADS for indeterminate FNA cytological thyroid nodules. Clin Hemorheol Microcirc 2024;88:475-83. [Crossref] [PubMed]
47. Riccio IR, LaForteza AC, Hussein MH, Linhuber JP, Issa PP, Staav J, Fawzy MS, Toraih EA, Kandil E. Diagnostic utility of RAS mutation testing for refining cytologically indeterminate thyroid nodules. EXCLI J 2024;23:283-99. [Crossref] [PubMed]
48. Xing Z, Qiu Y, Zhu J, Su A, Wu W. Diagnostic performance of ultrasound risk stratification systems on thyroid nodules cytologically classified as indeterminate: a systematic review and meta-analysis. Ultrasonography 2023;42:518-31. [Crossref] [PubMed]
49. Qiu Y, Xing Z, Liu J, Peng Y, Zhu J, Su A. Diagnostic reliability of elastography in thyroid nodules reported as indeterminate at prior fine-needle aspiration cytology (FNAC): a systematic review and Bayesian meta-analysis. Eur Radiol 2020;30:6624-34. [Crossref] [PubMed]
50. Qiu Y, Xing Z, Yang Q, Luo Y, Ma B. Diagnostic performance of shear wave elastography in thyroid nodules with indeterminate cytology: A systematic review and meta-analysis. Heliyon 2023;9:e20654. [Crossref] [PubMed]
51. Cappelli C, Pirola I, Gandossi E, Agosti B, Cimino E, Casella C, Formenti A, Castellano M. Real-time elastography: a useful tool for predicting malignancy in thyroid nodules with nondiagnostic cytologic findings. J Ultrasound Med 2012;31:1777-82. [Crossref] [PubMed]
52. Yang BR, Kim EK, Moon HJ, Yoon JH, Park VY, Kwak JY. Qualitative and Semiquantitative Elastography for the Diagnosis of Intermediate Suspicious Thyroid Nodules Based on the 2015 American Thyroid Association Guidelines. J Ultrasound Med 2018;37:1007-14. [Crossref] [PubMed]
53. Chen L, Shi YX, Liu YC, Zhan J, Diao XH, Chen Y, Zhan WW. The values of shear wave elastography in avoiding repeat fine-needle aspiration for thyroid nodules with nondiagnostic and undetermined cytology. Clin Endocrinol (Oxf) 2019;91:201-8. [Crossref] [PubMed]
54. Trimboli P, Treglia G, Sadeghi R, Romanelli F, Giovanella L. Reliability of real-time elastography to diagnose thyroid nodules previously read at FNAC as indeterminate: a meta-analysis. Endocrine 2015;50:335-43. [Crossref] [PubMed]
55. Liu JF, Chen YX, Zheng YJ, Wen DH, Wang YC, Xue G. The role of SWE and ATA(2015) guidelines combined mode in differentiation malignant from benign of Bethesda III thyroid nodules. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2018;32:1400-5. [Crossref] [PubMed]
56. Wang J, Yu F, Hu J, Rong R, Hang J. Combined Analysis of TIRADS and Shear Wave Elastography for the Diagnosis of Bethesda Category III Nodules. Chinese Journal of Medical Imaging 2021;29:993-7.