Abstract
Objective
Thyroid nodule (TN) is usually managed according to Thyroid Imaging And Reporting Data Systems (TIRADS) with the major aim to reduce as much as possible unnecessary fine-needle aspiration cytologies (UN-FNACs). Since the assessment of autonomously functioning thyroid nodule (AFTN) according to TIRADS is heterogeneous, that virtually benign entity may increase the rate of UN-FNAC. This study retrospectively analyzed the appropriateness of TIRADS-based FNAC indication in AFTNs, also looking at the impact of TSH and nodule size.
Methods
Cases diagnosed with AFTN on scintigraphy were searched. Patients who had undergone AFTN treatment, were on medications or supplementation that could affect thyroid function, or had multiple AFTNs were excluded. The AFTNs were assessed according to ACR-TIRADS.
Results
Forty-eight AFTNs were included of which 37.5% had FNAC indication according to TIRADS. The FNAC indication rate in the case of TSH lower than 0.4 mIU/L was significantly higher than in other cases (P = 0.0078). The most accurate TSH cut-off and AFTN size associated with UN-FNAC were ≤ 0.41 mIU/L and > 22 mm, respectively. The multivariate analysis showed that both TSH and nodule size were independent predictors of UN-FNAC with OR of 6.65 and 6.46, respectively. According to these data, the rate of FNAC indication dropped to 4.16%.
Conclusion
Inappropriate FNACs in AFTNs are primarily observed in patients with low TSH and large AFTN. Since these cases typically undergo scintigraphy, the risk of TIRADS-based UN-FNAC is clinically negligible. There is no need for integrating other imaging procedures into the TIRADS model.
Introduction
Thyroid nodule (TN) is a common pathological condition requiring a specific diagnostic workup (1). The first step in diagnosing thyroid disorders is to conduct a physical examination of the thyroid gland, followed by laboratory tests and a neck ultrasound, if necessary. Thyroid function tests, such as TSH measurement, are used to assess thyroid function, while ultrasound can help to determine the risk of malignancy of any detected lesions. This diagnostic process is highly reliable and recommended by thyroid experts (2, 3). Over the past decade, Thyroid Imaging and Reporting Data Systems (TIRADS) have achieved wide global adoption (4). One of their primary objectives is to standardize the lexicon used in thyroid ultrasound reports. They also aim to improve the indication of fine-needle aspiration cytology (FNAC) by evaluating TNs based on category-risk assessment and category-specific dimensional cut-offs. Although the different TIRADS were developed with varying geographical and cultural contexts in mind, their accuracy has been demonstrated to be high enough to reduce the need for other imaging procedures over time (5). The reliability of TIRADS can be measured by the rate of unnecessary FNAC (UN-FNAC), which refers to biopsies that yield a final benign cytological/histological outcome. The lower the rate of UN-FNAC, the higher the reliability of TIRADS (6).
Autonomously functioning thyroid nodule (AFTN) is a thyroid nodule that can produce hormones independently of the body’s needs. While hyperplasia and neoplasm can occur in AFTNs (7), they are typically considered benign despite rare reports of malignant AFTNs (8, 9), and FNAC is not usually recommended (2, 3). However, since AFTNs have a heterogeneous ultrasound appearance and are generally larger than the TIRADS category-specific size (10, 11, 12), they can increase the number of UN-FNACs and potentially lead to unnecessary diagnostic surgery (13). Since thyroid scintigraphy (TS) is still recognized as the gold standard for detecting AFTN, authors suggested integrating TS in the TIRADS model to prevent UN-FNACs (10, 12, 13). However, the TIRADS-based strategy was proven highly accurate and guidelines recommend TS only in TN patients with suspicious subclinical hyperthyroidism (i.e. TSH levels lower than 1.0 mIU/L) (2, 3).
This study aims to evaluate the appropriateness of TIRADS-based FNAC indications in patients with TS-proven AFTN. It retrospectively analyzes a series of AFTNs using ACR-TIRADS (14) and calculates their indication for FNAC. The study also explores the impact of major clinical data, such as TSH levels and nodule size.
Materials and methods
Institutional context and flow of thyroid nodule patients
Our institution is the major healthcare organization in Tessin Canton and comprises four regional hospitals. The institutional service of endocrinology is present in all these hospitals. Ours is a major nuclear medicine service in the canton. Patients with thyroid nodules diagnosed by non-thyroid specialists are generally referred to our endocrinology service. In addition, patients with large multinodular goiters may be referred by their general practitioners for TS with the aim of ruling out AFTN regardless of TSH levels. Since our database includes patients undergoing both thyroid ultrasound and scintigraphy, this institutional context represents a good setting to explore retrospective series of AFTN and thus meet the aim of the study.
Case selection
Our endocrinology clinic’s database was searched to retrieve patients diagnosed with AFTN who were seen at our center between January 2019 and March 2024. We included cases with a confirmed AFTN diagnosis through TS and available data on thyroid ultrasound and laboratory tests. Patients who had undergone AFTN treatment (such as surgery, radioiodine, and thermal ablation) before our visit, were on medications or supplements that could affect thyroid function (such as thyroid hormones, anti-thyroid drugs, amiodarone, and iodine), or had multiple AFTNs were excluded from the study.
Measures
One expert radiologist (AL) and one expert endocrinologist (PT) reviewed the ultrasound images of the selected patients to classify the AFTNs using the 5-tiered ACR-TIRADS (American College of Radiology Thyroid Imaging Reporting and Data System) classification system, which ranges from TR1 (benign) to TR5 (highly suspicious) (14). According to ACR-TIRADS, FNAC is indicated in cases of nodules ≥ 1 cm and assessed as TR5, or ≥ 1.5 cm and TR4, or ≥ 2.5 cm and TR3 (14). In addition, ACR-TIRADS recommends follow-up of nodules assessed as TR5 and sized 0.5–1 cm, or TR4 and sized 1–1.5 cm, or TR3 and sized 1.5–2.5 cm. The inter-observer agreement between the two raters was previously known as very good because of their strict collaboration in clinical activity. The present series of AFTNs represents a part of a larger series of thyroid nodules that were independently reviewed by the two raters for study purposes. Thus, when the two raters re-assessed the nodules included in the present study, they were not aware that the lesions were AFTNs. In any case, their inter-observer variation in the present series was 6.25%, and the discrepant cases were resolved in a meeting.
The FNAC indication was established based on the ACR-TIRADS category and the category-specific dimensional threshold. As the present study was a retrospective analysis, the results were independent of the indication for FNAC in real life during clinical practice. Data of TSH (and free-T3/free-T4) were extracted from patient’s records. In patients with multiple TSH evaluations, the lowest TSH value was considered.
Thyroid tests were performed with chemiluminescence immunoassay technology. Their normal ranges in clinical practice are the following: TSH between 0.40 and 4.0 mIU/L, free-T3 between 3.8 and 6.8 pmol/L, and free-T4 between 12 and 22 pmol/L.
Statistical analysis
The manuscript reported the results of continuous parameters as the median and interquartile range (IQR). The Mann–Whitney U test was used to compare continuous parameters from subgroups. The Pearson test was used to analyze the correlation between continuous parameters. The frequency of dichotomous parameters from subgroups was compared using the Fisher or Chi-square test. A lesion-based analysis was used to determine the performance of ACR-TIRADS in assessing AFTNs and indicating FNAC. The ROC curve analysis was used to analyze the influence of TSH value and AFTN diameter on ACR-TIRADS, calculating the area under the curve (AUC) and identifying the best cut-off point and its related sensitivity and specificity with a 95% confidence interval (95% CI). A multivariate logistic regression analysis was performed to identify independent predictors of UN-FNAC. The Odds Ratios (OR) with 95% CI were used to estimate the association between variables and UN-FNAC. The statistical significance level was set at P < 0.05. The statistical analyses were performed using GraphPad Prism version 7 or MedCalc (MedCalc Software Ltd, Belgium).
Ethics
The protocol of this retrospective study was approved by the Ethics Committee of Cantone Ticino. Accordingly, patients gave informed consent for their inclusion. All procedures comply with the 1964 Helsinki Declaration.
Results
Patient features
Based on the predefined selection criteria, the study included 48 patients with single AFTN, of which 89.6% were female. The median age of the patients was 63 years, and the median size of the AFTN was 21 mm. Of these patients, 28 (58.3%) had TSH lower than the lower reference limit (LRL) (ranging from 0.005 to 0.39 mIU/L), with 15/28 (53.6%) having suppressed TSH levels, while the remaining 20 (41.7%) had normal TSH values (ranging from 0.41 to 2.3 mIU/L). One patient had free-T3 levels higher than the upper reference limit, and the other five patients had free-T4 levels higher than the upper reference limit. No patients underwent FNAC during real clinical practice. The study series is described in detail in Table 1.
Characteristics of the study series. Data are presented as median (IQR).
| Variable | Values |
|---|---|
| Sex (female/male), n | 43/5 |
| Patient’s age (years) | 63 (53.7–72) |
| AFTN major diameter (mm) | 21 (15.5–30.7) |
| TSH (mIU/L) | 0.31 (0.032–0.70) |
| Free-T3 (pmol/L) | 4.9 (4.1–5.2) |
| Free-T4 (pmol/L) | 15.6 (13.7–18.5) |
AFTN, autonomously functioning thyroid nodule; IQR, interquartile range.
TIRADS assessment
Based on the ACR-TIRADS classification system, out of 48 AFTNs, 2 (4.16%) were considered TR5, 9 (18.75%) TR4, 27 (56.25%) TR3, and 10 (20.83%) TR2. Regarding the two TR5 nodules, one was sized 21 mm and was very hypoechoic with irregular margins and peripheral (rim) calcification, while the second one had a major diameter of 8 mm and was solid hypoechoic. The ACR-TIRADS assessment identified that 18 (37.5%) cases required FNAC, while 8 (16.7%) cases required follow-up. Figure 1 illustrates the distribution of the 48 AFTNs across the ACR-TIRADS, with or without FNAC indication and based on normal or low TSH levels.
Results of the assessment of AFTNs across the ACR-TIRADS also consider the TSH value. AFTN, autonomously functioning thyroid nodule; TR is the ACR-TIRADS risk category: TR1, benign; TR2, not suspicious; TR3, mildly suspicious; TR4, moderately suspicious; TR5, highly suspicious.
Citation: European Thyroid Journal 13, 4; 10.1530/ETJ-24-0123
Analysis of TSH and AFTN’s size
Figure 2 illustrates the distribution of AFTN with and without FNAC indication based on their major diameter and TSH levels. The TSH value of patients with an indication for FNAC (median: 0.13 mIU/L, IQR: 0.009–0.32) was found to be significantly lower (P = 0.0097) than those of patients without FNAC indication (0.49 mIU/L, IQR: 0.10–0.76). Even though the ACR-TIRADS assessment was not significantly different between the subgroups of patients with TSH lower than 0.4 mIU/L or normal TSH (P = 0.41) (Fig. 1), the rate of FNAC indication was significantly (P = 0.0078) higher in the former (15/28, 53.6%) than in the latter (3/20, 15%) (Fig. 2). The ROC curve analysis of TSH revealed that the most accurate cut-off point to predict UN-FNAC was ≤ 0.41 mIU/L with 88.9% (65.3–98.6) sensitivity and 54.5% (32.2–75.6) specificity (AUC: 0.66, 95% CI: 0.50–0.81). The nodule size was inversely correlated with TSH levels (P = 0.037), as shown in Fig. 3. The major diameter of the AFTNs of patients with TSH levels below the LRL (25.0 (15.5–31.8) mm) was higher but not significantly different (P = 0.11) from that of patients with normal TSH (19.5 (14.8–23.8) mm). The ROC curve analysis of AFTN diameter revealed that a diameter > 22 mm was the most accurate threshold to predict UN-FNAC. This threshold showed a sensitivity of 72.2% (46.5–90.3) and a specificity of 77.2% (54.6–92.2) with an AUC of 0.79 (95% CI: 0.63–0.90).
Distribution of AFTN with or without FNAC indication according to nodule’s size and TSH value. AFTN, autonomously functioning thyroid nodule; the lower reference limit of TSH is 0.40 mIU/L.
Citation: European Thyroid Journal 13, 4; 10.1530/ETJ-24-0123
Correlation between TSH and AFTN size. AFTN is an autonomously functioning thyroid nodule; LRL has a lower reference limit. The three blue dots indicate the AFTNs of patients with normal TSH who have an FNAC indication according to ACR-TIRADS.
Citation: European Thyroid Journal 13, 4; 10.1530/ETJ-24-0123
Multivariate analysis
The multivariate analysis, including the ROC-derived best cut-off of TSH and AFTN size, showed that both were independent predictors of UN-FNAC with OR: 6.65 (95% CI: 1.08–40.76, P = 0.040) and 6.46 (95% CI: 1.39–29.95, P = 0.017), respectively.
Re-evaluation of FNAC indication according to TSH and size
The indication for FNAC might be revised based on TSH levels and AFTN size. If TSH levels are lower than LRL and indicate TS rather than FNAC (2, 3), the rate of FNAC indication in the entire population decreased to 6.25% (3/48). According to the ROC-derived TSH best cut-off, the rate of FNAC indication is 4.16% (2/48). In addition, the frequency of FNAC indication in patients with AFTN smaller than the ROC-derived dimensional threshold was 18.51% (5/27).
Discussion
The impact of TIRADS in clinical practice has been significant. With the advent of these systems, it has been shown that we can adopt a TIRADS-based strategy to manage goiter patients with high accuracy. However, it is important to consider that TIRADS was designed to detect papillary thyroid carcinoma in ultrasound images (15). Therefore, it may not be as effective in detecting other types of cancer or benign lesions (16, 17). In particular, benign lesions like AFTNs may be wrongly identified as cancerous using TIRADS, leading to possible inappropriate FNAC testing (10, 11, 12, 13). To address this issue, the present study was conducted in order to investigate the rate of inappropriate FNAC in AFTNs based on TIRADS guidelines.
More than three-quarters of the AFTNs were assessed as benign/mildly suspicious (i.e. TR2 or TR3), according to ACR-TIRADS. This is initially reassuring because most AFTNs do not require FNAC testing. However, FNAC was indicated in about one-third of AFTNs according to TIRADS recommendations.
The study also found a correlation between TSH levels and AFTN size. This was expected as it is well recognized that the larger the AFTN volume, the higher its inappropriate hormonal production. Furthermore, the analysis showed that specific subgroups of patients had significantly different rates of UN-FNAC. Patients with normal TSH levels and patients with smaller AFTNs had a lower rate of FNAC indication. According to the present findings, a clinically oriented discussion can be addressed.
First, most literature on TIRADS evaluates TN outside the clinical context of patients. This is often due to retrospective studies analyzing cases that have undergone FNAC, histology, or other standards. TIRADS are solely recommendations based on ultrasound characteristics of TN. In AFTN, TS is the reference, recommended for patients with suspected (subclinical) hyperthyroidism in nodular goiter, highlighted by low/very low TSH levels (2, 3). This actually affects studies on inappropriate FNAC in AFTNs. These studies (10, 11, 12, 13) (Table 2), including the current one, correlated ultrasound and scintigraphic data in cases undergoing TS for various reasons (over/subclinical hyperthyroidism, suppressed/low/normal TSH, AFTN suspicion, nodular goiter assessment). However, these retrospective analyses are prone to selection bias and provide theoretical data on FNAC indications for cases actually requiring different management. When dealing with nodular goiter and TSH below the LRL, endocrinologists focus more on hyperthyroidism than TN nature, often recommending TS immediately after ultrasound. Thus, thyroid functional test results are part of the evaluation of the rate of unnecessary FNAC in AFTNs, as this study shows. Moreover, the size threshold for FNAC varies across TIRADS and is debatable (4, 14, 18, 19). The cut-off size for FNAC has yet to be definitively established. Whether to apply the TIRADS dimensional thresholds for each risk category is currently being evaluated (20, 21, 23). Our study shows decreased unnecessary FNAC in smaller lesions when AFTN size is fully considered. This correlation is pivotal as most AFTNs are classified as low-to-intermediate risk by ACR-TIRADS, with higher size thresholds for FNAC compared to high-risk categories. Notably, one study (10) used Kwak-TIRADS that advocates for FNAC in TNs classified 4A or higher, regardless of their size (22). Therefore, considering TSH and nodule size as independent predictors of unnecessary FNAC in AFTNs, we can recommend TS for patients with TSH below the LRL and follow TIRADS for FNAC in other cases. This clinically oriented strategy minimizes the risk of unnecessary FNAC in AFTNs, enabling efficient detection of clinically relevant cases.
Characteristics and general results of the previous studies and the present one.
| Schenke et al. (10) | Castellana et al. (11) | Noto et al. (12) | Kyrilli et al. (13) | Present study | |
|---|---|---|---|---|---|
| AFTN | |||||
| Cases, n | 615 | 87 | 51 | 66 | 48 |
| Size, mm | 23.2 | 22 | 17 | 27 | 21 |
| Patient | |||||
| Age, years | 58.3 | 61 | 54 | 56.3 | 21 |
| TSH, mIU/L | 0.56 | 0.27 | 1.20 | 0.41 | 0.31 |
| ACR-TIRADS assessment, % | |||||
| TR1 | – | 11.5 | 17.6 | – | 0 |
| TR2 | – | 5.7 | 17.6 | – | 20.8 |
| TR3 | – | 49.4 | 33.5 | – | 56.3 |
| TR4 | – | 32.2 | 27.5 | – | 18.8 |
| TR5 | – | 1.2 | 3.9 | – | 4.1 |
| FNAC indicated by TIRADS, % | |||||
| Kwak-TIRADS | 83.5* | – | – | 86.6** | – |
| ACR-TIRADS | – | 44.8 | 25.5 | – | 37.5 |
| EU-TIRADS | – | 60.9** | 43.1** | – | – |
| K-TIRADS | – | 88.9** | – | – | – |
Second, performing FNAC in AFTNs may result in indeterminate reports (i.e. Bethesda III or IV), complicating their management. The prevalence of cancer in patients with toxic nodular goiter is generally estimated at up to 9%, similar to euthyroid multinodular goiter (24). Rare malignant AFTNs have also been reported (8, 9). Thus, FNAC should remain indicated for AFTNs classified as high risk by TIRADS. Surgery is, in any case, an option for treating AFTN (25) and hot indeterminate lesions (2, 3).
Third, performing TS before potentially unnecessary FNAC is controversial (10, 11, 12, 13). Modern medicine emphasizes reducing the costs of inappropriate/unnecessary diagnostic procedures. TIRADS performance is often evaluated by the rate of unnecessary FNAC (5). However, routinely applying TS to reduce unnecessary FNAC is not cost-effective due to TS costs. Data from Noto et al. (12) highlighted that among 449 patients undergoing TS, 81 AFTNs were identified, with a negligible prevalence of AFTN among TNs requiring FNAC (up to 7.6%) regardless of the TIRADS used. This issue may warrant discussion depending on the geographical context and AFTN incidence (26).
Lastly, this study indirectly confirms the variability of TIRADS assessments (4). Different systems have been developed in varied cultural settings (5). Our data, along with previous studies (10, 13), contribute to creating an international TIRADS (I-TIRADS) (27).
The study’s limitations include its retrospective nature, potential selection bias, and small sample size, though they are comparable to other studies in the field. The retrospective re-assessment of static ultrasound images of AFTNs available in RIS-PACS can be seen as a potential bias. In particular, the finest ultrasound features, such as hyperechogenic spots or lobulations, may not be recognized in static images. However, in agreement with the largest part of the 25-year literature about ultrasound in thyroid nodules, the present study design should be the most adequate. It is reassuring that, even if the two ultrasound raters had a good inter-observer agreement, the study design included that eventual discordant cases would have been resolved in a final mutual meeting to achieve a consensus. However, this study uniquely examines UN-FNAC in AFTN, considering clinical data such as TSH levels and nodule size crucial for FNAC recommendations. Derived from clinical practice in a thyroid unit, the results are broadly applicable.
In conclusion, our results collectively state that AFTNs may undergo unnecessary FNAC according to TIRADS recommendations. The novel finding is that inappropriate FNACs in AFTNs are primarily observed in patients with TSH below the LRL and/or large AFTN size. Since these cases typically undergo TS before further examinations, the risk of inappropriate TIRADS-based FNAC in AFTNs is negligible. Therefore, integrating scintigraphy into the TIRADS model is unnecessary. This information is useful in the development of I-TIRADS.
Declaration of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the study reported.
Funding
This work did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.
References
- 1↑
Hegedüs L. Clinical practice. The thyroid nodule. New England Journal of Medicine 2004 351 1764–1771. (https://doi.org/10.1056/NEJMcp031436)
- 2↑
Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, et al.2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016 26 1–133. (https://doi.org/10.1089/thy.2015.0020).
- 3↑
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. European Thyroid Journal 2023 12 e230067. (https://doi.org/10.1530/ETJ-23-0067)
- 4↑
Russ G, Trimboli P, & Buffet C. The new era of TIRADSs to stratify the risk of malignancy of thyroid nodules: strengths, weaknesses and pitfalls. Cancers (Basel) 2021 13 4316. (https://doi.org/10.3390/cancers13174316)
- 5↑
Piticchio T, Russ G, Radzina M, Frasca F, Durante C, & Trimboli P. Head-to-head comparison of American, European, and Asian TIRADSs in thyroid nodule assessment: systematic review and meta-analysis. European Thyroid Journal 2024 13 e230242. (https://doi.org/10.1530/ETJ-23-0242)
- 6↑
Kim PH, Suh CH, Baek JH, Chung SR, Choi YJ, & Lee JH. Unnecessary thyroid nodule biopsy rates under four ultrasound risk stratification systems: a systematic review and meta-analysis. European Radiology 2021 31 2877–2885. (https://doi.org/10.1007/s00330-020-07384-6)
- 7↑
Piccardo A, Fiz F, Bottoni G, Massollo M, Puntoni M, Catrambone U, Foppiani L, Bertagna F, Albano D, & Trimboli P. The FDG pattern of autonomously functioning thyroid nodules correlates with thyroid-stimulating hormone and histopathology. Clinical Nuclear Medicine 2023 48 119–125. (https://doi.org/10.1097/RLU.0000000000004396)
- 8↑
Yuang K, Al-Bahadili H, & Chang A. An unexpected finding of poorly differentiated thyroid carcinoma in a toxic thyroid nodule. JCEM Case Reports 2023 1 luad052. (https://doi.org/10.1210/jcemcr/luad052)
- 9↑
Goonoo MS, Arshad MF, Tahir F, & Balasubramanian SP. Toxic adenoma: to biopsy or not to biopsy? Annals of the Royal College of Surgeons of England 2021 103 e319–e323. (https://doi.org/10.1308/rcsann.2021.0008)
- 10↑
Schenke S, Seifert P, Zimny M, Winkens T, Binse I, & Görges R. Risk stratification of thyroid nodules using the thyroid imaging reporting and data system (TIRADS): the omission of thyroid scintigraphy increases the rate of falsely suspected lesions. Journal of Nuclear Medicine 2019 60 342–347. (https://doi.org/10.2967/jnumed.118.211912)
- 11↑
Castellana M, Virili C, Paone G, Scappaticcio L, Piccardo A, Giovanella L, & Trimboli P. Ultrasound systems for risk stratification of thyroid nodules prompt inappropriate biopsy in autonomously functioning thyroid nodules. Clinical Endocrinology 2020 93 67–75. (https://doi.org/10.1111/cen.14204)
- 12↑
Noto B, Eveslage M, Pixberg M, Gonzalez Carvalho JM, Schäfers M, Riemann B, & Kies P. Prevalence of hyperfunctioning thyroid nodules among those in need of fine needle aspiration cytology according to ATA 2015, EU-TIRADS, and ACR-TIRADS. European Journal of Nuclear Medicine and Molecular Imaging 2020 47 1518–1526. (https://doi.org/10.1007/s00259-020-04740-y)
- 13↑
Kyrilli A, Tacelli N, Russo L, Lebrun L, Salmon I, Russ G, Moreno-Reyes R, & Corvilain B. Autonomously functioning thyroid nodules present intermediate malignancy risk according to European Thyroid Imaging Reporting and Data System (EU-TIRADS) and yield indeterminate cytology results. European Thyroid Journal 2023 12 e230135. (https://doi.org/10.1530/ETJ-23-0135)
- 14↑
Tessler FN, Middleton WD, Grant EG, Hoang JK, Berland LL, Teefey SA, Cronan JJ, Beland MD, Desser TS, Frates MC, et al.ACR thyroid imaging, reporting and data system (TI-RADS): white paper of the ACR TI-RADS committee. Journal of the American College of Radiology 2017 14 587–595. (https://doi.org/10.1016/j.jacr.2017.01.046)
- 15↑
Trimboli P, Castellana M, Piccardo A, Romanelli F, Grani G, Giovanella L, & Durante C. The ultrasound risk stratification systems for thyroid nodule have been evaluated against papillary carcinoma. A meta-analysis. Reviews in Endocrine and Metabolic Disorders 2021 22 453–460. (https://doi.org/10.1007/s11154-020-09592-3)
- 16↑
Castellana M, Piccardo A, Virili C, Scappaticcio L, Grani G, Durante C, Giovanella L, & Trimboli P. Can ultrasound systems for risk stratification of thyroid nodules identify follicular carcinoma? Cancer Cytopathology 2020 128 250–259. (https://doi.org/10.1002/cncy.22235)
- 17↑
Ferrarazzo G, Camponovo C, Deandrea M, Piccardo A, Scappaticcio L, & Trimboli P. Suboptimal accuracy of ultrasound and ultrasound-based risk stratification systems in detecting medullary thyroid carcinoma should not be overlooked. Findings from a systematic review with meta-analysis. Clinical Endocrinology 2022 97 532–540. (https://doi.org/10.1111/cen.14739)
- 18↑
Russ G, Bonnema SJ, Erdogan MF, Durante C, Ngu R, & Leenhardt L. European Thyroid Association guidelines for ultrasound malignancy risk stratification of thyroid nodules in adults: the EU-TIRADS. European Thyroid Journal 2017 6 225–237. (https://doi.org/10.1159/000478927)
- 19↑
Ha EJ, Chung SR, Na DG, Ahn HS, Chung J, Lee JY, Park JS, Yoo RE, Baek JH, Baek SM, et al.2021 Korean thyroid imaging reporting and data system and imaging-based management of thyroid nodules: Korean society of thyroid radiology consensus statement and recommendations. Korean Journal of Radiology 2021 22 2094–2123. (https://doi.org/10.3348/kjr.2021.0713)
- 20↑
Li W, Chen J, Ye F, Xu D, Fan X, & Yang C. The diagnostic value of ultrasound on different-sized thyroid nodules based on ACR TI-RADS. Endocrine 2023 82 569–579. (https://doi.org/10.1007/s12020-023-03438-z)
- 21↑
Shayganfar A, Hashemi P, Esfahani MM, Ghanei AM, Moghadam NA, & Ebrahimian S. Prediction of thyroid nodule malignancy using thyroid imaging reporting and data system (TIRADS) and nodule size. Clinical Imaging 2020 60 222–227. (https://doi.org/10.1016/j.clinimag.2019.10.004)
- 22↑
Amendola S, Wolde Sellasie S, Pedicini F, Carlini M, Russo G, Ossola N, Leoncini A, Botti F, Bonanno E, Trimboli P, et al.Evaluation of the performance of ACR TI-RADS also considering those nodules with no indication of FNAC: a single-center experience. Journal of Clinical Medicine 2023 12 398. (https://doi.org/10.3390/jcm12020398)
- 23↑
Kwak JY, Han KH, Yoon JH, Moon HJ, Son EJ, Park SH, Jung HK, Choi JS, Kim BM, & Kim EK. Thyroid imaging reporting and data system for US features of nodules: a step in establishing better stratification of cancer risk. Radiology 2011 260 892–899. (https://doi.org/10.1148/radiol.11110206)
- 24↑
Cerci C, Cerci SS, Eroglu E, Dede M, Kapucuoglu N, Yildiz M, & Bulbul M. Thyroid cancer in toxic and non-toxic multinodular goiter. Journal of Postgraduate Medicine 2007 53 157–160. (https://doi.org/10.4103/0022-3859.33855)
- 25↑
Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, Rivkees SA, Samuels M, Sosa JA, Stan MN, et al.2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016 26 1343–1421. (https://doi.org/10.1089/thy.2016.0229). Erratum in: Thyroid 2017 27 1462. (https://doi.org/10.1089/thy.2016.0229.correx)
- 26↑
Trimboli P, Bojunga J, Deandrea M, Frasca F, Imperiale A, Leoncini A, Paone G, Pitoia F, Rotondi M, Sadeghi R, et al.Reappraising the role of thyroid scintigraphy in the era of TIRADS: a clinically-oriented viewpoint. Endocrine 2024. (https://doi.org/10.1007/s12020-024-03825-0)
- 27↑
Durante C, Hegedüs L, Na DG, Papini E, Sipos JA, Baek JH, Frasoldati A, Grani G, Grant E, Horvath E, et al.International expert consensus on US lexicon for thyroid nodules. Radiology 2023 309 e231481. (https://doi.org/10.1148/radiol.231481)
