There are a number of additional issues that should be taken into account when examining the ACR TIRADS data set and resultant management recommendations. The NNS for ACR TIRADS is such that it is hard to justify its use for ruling out thyroid cancer (NNS>100), at least on a cost/benefit basis. Thyroid nodules are common, affecting around one-half of the population and become increasingly common with advancing age [1, 2]. Its not something that happens every day, but every day. TR5 in the data set made up 16% of nodules, in which one-half of the thyroid cancers (183/343) were found. Treatment of patients with the left lobe of the thyroid gland, tirads 3 To establish a CEUS-TIRADS diagnostic model to differentiate thyroid nodules (C-TIRADS 4) by combining CEUS with Chinese thyroid imaging reporting and data system (C-TIRADS). 24;8 (10): e77927. TIRADS Management Guidelines in the Investigation of Thyroid Nodules; Illustrating the Concerns, Costs, and Performance TIRADS Management Guidelines in the Investigation of Thyroid Nodules; Illustrating the Concerns, Costs, and Performance J Endocr Soc. Search for other works by this author on: University of Otago, Christchurch School of Medicine, Department of Endocrinology, St Vincents University Hospital, Department of Radiology, St Vincents University Hospital, Dublin 4 and University College Dublin, Biostatistician, Department of Medical & Womens Business Management, Canterbury District Health Board, Thyroid incidentalomas: management approaches to nonpalpable nodules discovered incidentally on thyroid imaging, The prevalence of thyroid nodules and an analysis of related lifestyle factors in Beijing communities, Prevalence of differentiated thyroid cancer in autopsy studies over six decades: a meta-analysis, Occult papillary carcinoma of the thyroid. Unauthorized use of these marks is strictly prohibited. The findings that ACR TIRADS has methodological concerns, is not yet truly validated, often performs no better than random selection, and drives significant costs and potential harm, are very unsettling but result from a rational and scientific assessment of the foundational basis of the ACR TIRADS system. In a clinical setting, this would typically be an unselected sample of the test population, for example a consecutive series of all patients with a thyroid nodule presenting to a clinic, ideally across multiple centers. The following article describes the initial iterations proposed by individual research groups, none of which gained widespread use. Depending on the constellation or number of suspicious ultrasound features, a fine-needle biopsy is . Using TIRADS as a rule-out cancer test would be the finding that a nodule is TR1 or TR2 and hence has a low risk of cancer, compared with being TR3-5. At best, only a minority of the 3% of cancers would show on follow-up imaging features suspicious for thyroid cancer that correctly predict malignancy. The sensitivity, specificity, and accuracy of C-TIRADS were 93.1%, 55.3%, and 74.6% respectively. 4. The ROC curves of C-TIRADS, CEUS, and CEUS-TIRADS of 228 nodules in the diagnostic model. This site needs JavaScript to work properly. Disclosure Summary:The authors declare no conflicts of interest. 5. Diag (Basel) (2021) 11(8):137493. The actual number of inconclusive FNA results in the real-world validation set has not been established (because that study has not been done), but the typical rate is 30% (by this we mean nondiagnostic [ie, insufficient cells], or indeterminate [ie, atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS)/follicular neoplasm/suspicious for follicular neoplasm [Bethesda I, III, IV]). Thyroid surgery, Microvascular reconstruction, Neck surgery, Reconstructive surgery, Facial reconstruction, Parathyroid. To develop a medical test a typical process is to generate a hypothesis from which a prototype is produced. If the nodule got a score of 2 in the CEUS schedule, the CEUS-TIRADS category remained the same as before. TI-RADS 1: normal thyroid gland TI-RADS 2: benign nodule TI-RADS 3: highly probable benign nodule TI-RADS 4a: low suspicion for malignancy TI-RADS 4b: high suspicion for malignancy TI-RADS 5: malignant nodule with more than two criteria of high suspicion Imaging features TI-RADS 2 category Constantly benign patterns include simple cyst -, Zhou J, Yin L, Wei X, Zhang S, Song Y, Luo B, et al. A key factor is the low pretest probability of important thyroid cancer but a higher chance of finding thyroid cancers that are very unlikely to cause ill health during a persons lifetime. The CEUS-TIRADS category was 4c. There are two suspicious signs with the nodule (solid and irregular margin) and it was defined as C-TIRADS 4b. Clinicians should be using all available data to arrive at an educated estimate of each patients pretest probability of having clinically significant thyroid cancer and use their clinical judgment to help advise each patient of their best options. If you do 100 (or more) US scans on patients with a thyroid nodule and apply the ACR TIRADS management guidelines for FNA, this results in costs and morbidity from the resultant FNAs and the indeterminate results that are then considered for diagnostic hemithyroidectomy. Because the data set prevalence of thyroid cancer was 10%, compared with the generally accepted lower real-world prevalence of 5%, one can reasonably assume that the actual cancer rate in the ACR TIRADS categories in the real world would likely be one-half that quoted from the ACR TIRADS data set, which we illustrate in the following section. 6. We have also assumed that all nodules are at least 10 mm and so the TR5 nodule size cutoff of 5 mm does not apply. Instead, it has been applied on retrospective data sets, with cancer rates far above 5%, rather than on consecutive unselected patients presenting with a thyroid nodule [33]. 2013;168 (5): 649-55. eCollection 2022. Whilst our findings have illustrated some of the shortcomings of ACR TIRADS guidelines, we are not able to provide the ideal alternative. The present study evaluated the risk of malignancy in solid nodules>1 cm using ACR TI-RADS. FNA, fine-needle aspiration; US, ultrasound; CEUS, contrast-enhanced, A 38-year-old woman with a nodule in the right-lobe of her thyroid gland., A 35-year-old woman with a nodule in the left-lobe of her thyroid gland., The ROC curves of C-TIRADS, CEUS, and CEUS-TIRADS of 228 nodules in the. Those working in this field would gratefully welcome a diagnostic modality that can improve the current uncertainty. The ACR-TIRADS guidelines also provide easy-to-follow management recommendations that have understandably generated momentum. The flow chart of the study. The TIRADS reporting algorithm is a significant advance with clearly defined objective sonographic features that are simple to apply in practice. Thyroid nodule size from 1.5 - 2.5cm: Periodic follow-up every 6 months. These cutoffs are somewhat arbitrary, with conflicting data as to what degree, if any, size is a discriminatory factor. Cawood T, Mackay GR, Hunt PJ, OShea D, Skehan S, Ma Y. Russ G, Bigorgne C, Royer B, Rouxel A, Bienvenu-Perrard M. Yoon JH, Lee HS, Kim EK, Moon HJ, Kwak JY. no financial relationships to ineligible companies to disclose. The financial costs and surgical morbidity in this group must be taken into account when considering the cost/benefit repercussions of a test that includes US imaging for thyroid cancer. Disclaimer. The chance of finding cancer is 1 in 20, whereas the chance of testing resulting in an unnecessary operation is around 1 in 7. J Med Imaging Radiat Oncol (2009) 53(2):17787. In rare cases, they're cancerous. TIRADS can be welcomed as an objective way to classify thyroid nodules into groups of differing (but as yet unquantifiable) relative risk of thyroid cancer. The more FNAs done in the TR3 and TR4 groups, the more indeterminate FNAs and the more financial costs and unnecessary operations. The results were compared with histology findings. ectomy, Parotid gland surgery, Transoral laser microsurgery, Transoral robotic surgery, Oral surgery, Parotid gland tumor, Skin cancer, Tonsil cancer, Throat cancer, Salivary gland tumor, Salivary gland cancer, Thyroid nodule, Head and neck cancer, Laryngeal cancer, Tongue . Differentiation of Thyroid Nodules (C-TIRADS 4) by Combining Contrast-Enhanced Ultrasound Diagnosis Model With Chinese Thyroid Imaging Reporting and Data System Front Oncol. The proportion of malignancy in Bethesda III nodules confirmed by surgery were significantly increased in proportion relative to K-TIRADS with 60.0% low suspicion, 88.2% intermediate suspicion, and 100% high suspicion nodules (p < 0.001). 2018;287(1):29-36. The diagnosis or exclusion of thyroid cancer is hugely challenging. You can then get a more thorough medical evaluation, including a biopsy, which is a small sample of tissue from the nodule to look at under the microscope. Later arrival time, hypo-enhancement, heterogeneous enhancement, centripetal enhancement, and rapid washout were risk factors of malignancy in multivariate analysis. proposed a system with five categories, which, like BI-RADS, each carried a management recommendation 2. Second, the proportion of patients in the different ACR TIRADS (TR) categories may, or may not, reflect the real-world population (Table 1). Tessler F, Middleton W, Grant E. Thyroid Imaging Reporting and Data System (TI-RADS): A Users Guide. ACR TIRADS has not been applied to a true validation set upon which it is intended to be used, and therefore needs to be considered with caution when applying it to the real-world situation. Authors To illustrate the effect of the size cutoffs we have given 2 examples, 1 where the size cutoffs are not discriminatory and the cancer rate is the same above and below the size cutoff, and the second example where the cancer risk of the nodule doubles once the size goes above the cutoff. Other similar systems are in use internationally (eg, Korean-TIRADS [14] and EU-TIRADS [15]). Horvath E, Majlis S, Rossi R et-al. We have also estimated the likely costs associated with using the ACR TIRADS guidelines, though for simplicity have not included the costs of molecular testing for indeterminate nodules (which is not readily available in the New Zealand public health system) nor any US follow-up and associated costs. Therefore, for every 25 patients scanned (100/4=25) and found to be either TR1 or TR2, 1 additional person would be correctly reassured that they do not have thyroid cancer. It is limited by only being an illustrative example that does not take clinical factors into account such as prior radiation exposure and clinical features. This study aimed to assess the performance and costs of the American College of Radiology (ACR) Thyroid Image Reporting And Data System (TIRADS), by first looking for any important issues in the methodology of its development, and then illustrating the performance of TIRADS for the initial decision for or against FNA, compared with an imagined clinical comparator of a group in which 1 in 10 nodules were randomly selected for FNA. Mao S, Zhao LP, Li XH, Sun YF, Su H, Zhang Y, Li KL, Fan DC, Zhang MY, Sun ZG, Wang SC. This is a specialist doctor who specializes in the treatment and diagnosis of thyroid cancer. The Thyroid Imaging Reporting And Data System (TI-RADS) was developed by the American College of Radiology and used by many radiologist in Australia. eCollection 2022. First, 10% of FNA or histology results were excluded because of nondiagnostic findings [16]. Dr. Ron Karni, Chief of the Division of Head and Neck Surgical Oncology at McGovern Medical School at UTHealth Houston discusses Thyroid Nodules. and transmitted securely. Whereas using TIRADS as a rule-in cancer test would be the finding that a nodule is TR5, with a sufficiently high chance of cancer that further investigations are required, compared with being TR1-4. 8600 Rockville Pike Copyright 2022 Zhu, Chen, Zhou, Ma and Huang. To show the best possible performance of ACR TIRADS, we are comparing it to clinical practice in the absence of TIRADS or other US thyroid nodule stratification tools, and based on a pretest probability of thyroid cancer in a nodule being 5%, where 1 in 10 nodules are randomly selected for FNA. Hong MJ, Na DG, Baek JH, Sung JY, Kim JH. Thyroid nodules are lumps that can develop on the thyroid gland. So just using ACR TIRADS as a rule-out test could be expected to leave 99% of undiagnosed cancers amongst the remaining 75% of the population, in whom the investigation and management remains unresolved. Attempts to compare the different TIRADS systems on data sets that are also not reflective of the intended test population are similarly flawed (eg, malignancy rates of 41% [29]). A subdivision into 4a (malignancy between 5 and 10%) and 4b (malignancy between 10 and 80%) was optional. However, the ACR TIRADS flow chart with its sharp cutoffs conveys a degree of certainty that may not be valid and may be hard for the clinician to resist. Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW. The system is sometimes referred to as TI-RADS French 6. For the calculations, we assume an approximate size distribution where one-third of TR3 nodules are25 mm and half of TR4 nodules are15 mm. But the test that really lets you see a nodule up close is a CT scan. in 2009 1. The pathological result was Hashimotos thyroiditis. The implication is that US has enabled increased detection of thyroid cancers that are less clinically important [11-13]. The site is secure. The It might even need surge In CEUS analysis, it reflected as equal arrival time, iso-enhancement, homogeneity, and diffuse enhancement, receiving a score of 0 in the CEUS model. That particular test is covered by insurance and is relatively cheap. All of the C-TIRADS 4 nodules were re-graded by CEUS-TIRADS. We refer to ACR-TIRADS where data or comments are specifically related to ACR TIRADS and use the term TIRADS either for brevity or when comments may be applicable to other TIRADS systems. Methods: Thyroid nodules (566) subclassified as ACR-TIRADS 3 or 4 were divided into three size categories according to American Thyroid Association guidelines. Any test will struggle to outperform educated guessing to rule out clinically important thyroid cancer. View Yuranga Weerakkody's current disclosures, see full revision history and disclosures, American College of Radiology: ACR TI-RADS, Korean Society of Thyroid Radiology: K-TIRADS, iodinated contrast-induced thyrotoxicosis, primary idiopathic hypothyroidism with thyroid atrophy, American Thyroid Association (ATA)guidelines, British Thyroid Association (BTA)U classification, Society of Radiologists in Ultrasound (SRU)guidelines, American College of Radiology:ACR TI-RADS, postoperative assessment after thyroid cancer surgery, ultrasound-guided fine needle aspiration of the thyroid, TIRADS (Thyroid Image Reporing and Data System), colloid type 1:anechoic with hyperechoic spots, nonvascularised, colloid type 2: mixed echogenicity with hyperechoic spots,nonexpansile, nonencapsulated, vascularized, spongiform/"grid" aspect, colloid type 3: mixed echogenicity or isoechoic with hyperechoic spots and solid portion, expansile, nonencapsulated, vascularized, simple neoplastic pattern: solid or mixed hyperechoic, isoechoic, or hypoechoic;encapsulated with a thin capsule, suspicious neoplastic pattern: hyperechoic, isoechoic, or hypoechoic;encapsulated with a thick capsule; hypervascularised; with calcifications (coarse or microcalcifications), malignant pattern A: hypoechoic, nonencapsulated with irregular margins, penetrating vessels, malignant pattern B: isoechoic or hypoechoic, nonencapsulated, hypervascularised, multiple peripheral microcalcifications, malignancy pattern C: mixed echogenicity or isoechoic without hyperechoic spots, nonencapsulated, hypervascularised, hypoechogenicity, especially marked hypoechogenicity, "white knight" pattern in the setting of thyroiditis (numerous hyperechoic round pseudonodules with no halo or central vascularizaton), nodular hyperplasia (isoechoic confluent micronodules located within the inferior and posterior portion of one or two lobes, usually avascular and seen in simple goiters), no sign of high suspicion (regular shape and borders, no microcalcifications), high stiffness with sonoelastography (if available), if >7 mm, biopsy is recommended if TI-RADS 4b and 5 or if patient has risk factors (family history of thyroid cancer or childhood neck irradiation), if >10 mm, biopsy is recommended if TI-RADS 4a or if TI-RADS 3 that has definitely grown (2 mm in two dimensions and >20% in volume). Once the test is considered to be performing adequately, then it would be tested on a validation data set. Diagnostic approach to and treatment of thyroid nodules. It would be unfair to add these clinical factors to only the TIRADS arm or only to the clinical comparator arm, and they would cancel out if added to both arms, hence they were omitted. The optimal investigation and management of the 84% of the population harboring the remaining 50% of cancer remains unresolved. eCollection 2020 Apr 1. The provider may also ask about your risk factors, such as past exposure to radiation and a family history of thyroid cancers. 2011;260 (3): 892-9. EU-TIRADS 2 category comprises benign nodules with a risk of malignancy close to 0%, presented on sonography as pure/anechoic cysts ( Figure 1A) or entirely spongiform nodules ( Figure 1B ). Anderson TJ, Atalay MK, Grand DJ, Baird GL, Cronan JJ, Beland MD. Tests and procedures used to diagnose thyroid cancer include: Physical exam. However, if the concern is that this might miss too many thyroid cancers, then this could be compared with the range of alternatives (ie, doing no tests or doing many more FNAs). TIRADS does not perform to this high standard. Clipboard, Search History, and several other advanced features are temporarily unavailable. Among thyroid nodules detected during life, the often quoted figure for malignancy prevalence is 5% [5-8], with UptoDate quoting 4% to 6.5% in nonsurgical series [9], and it is likely that only a proportion of these cancers will be clinically significant (ie, go on to cause ill-health). The sensitivity, specificity, and accuracy of CEUS were 78.7%, 87.5%, and 83.3% respectively. K-TIRADS category was assigned to the thyroid nodules. We found better sensitivity, PPV, and NPV with TIRADS compared with random selection (97% vs 1%, 13% vs 1%, and 99% vs 95%, respectively), whereas specificity and accuracy were worse with TIRADS compared with random selection (27% vs 90%, and 34% vs 85%, respectively (Table 2)[25]. -. It is also relevant to note that the change in nodule appearance over time is poorly predictive of malignancy. Lancet (2014) 384(9957): 1848:184858. The diagnostic schedule of CEUS could get better diagnostic performance than US in the differentiation of thyroid nodules. Unfortunately, the collective enthusiasm for welcoming something that appears to provide certainty has perhaps led to important flaws in the development of the models being overlooked. The probability of malignancy was based on an equation derived from 12 features 2. Perhaps the most relevant positive study is from Korea, which found in a TR4 group the cancer rate was no different between nodules measuring between 1-2 cm (22.3%) and those 2-3 cm (23.5%), but the rate did increase above 3 cm (40%) [24]. Some cancers would not show suspicious changes thus US features would be falsely reassuring. Careers. . Until a well-designed validation study is completed, the performance of TIRADS in the real world is unknown. In a patient with normal life expectancy, a biopsy should be performed for nodules >1cm regardless of the ACR TI-RADS risk category. If the nodule had a regular hyper-enhancement ring or got a score of less than 2 in CEUS analysis, CEUS-TIRADS subtracted 1 category. Shin JH, Baek JH, Chung J, et al. This study has many limitations. Based on the methodology used to acquire the data set, the gender bias, and cancer rate in the data set, it is unlikely to be a fair reflection of the population upon which the test is intended to be applied, and so cannot be considered a true validation set. Thyroid nodules come to clinical attention when noted by the patient; by a clinician during routine physical examination; or during a radiologic procedure, such as carotid ultrasonography, neck or chest computed tomography (CT), or positron emission tomography (PET) scanning. There remains the need for a highly performing diagnostic modality for clinically important thyroid cancers. TI-RADS 1: Normal thyroid gland. A newer alternative that the doctor can use to treat benign nodules in an office setting is called radiofrequency ablation (RFA). 2009;94 (5): 1748-51. The other one-half of the cancers that are missed by only doing FNA of TR5 nodules will mainly be in the TR3 and TR4 groups (that make up 60% of the population), and these groups will have a 3% to 8% chance of cancer, depending upon whether the population prevalence of thyroid cancer in those being tested is 5% or 10%. Bessey LJ, Lai NB, Coorough NE, Chen H, Sippel RS. Results: The costs depend on the threshold for doing FNA. FOIA 7. 4b - Suspicious nodules (10-50% risk of malignancy) Score of 2. Ultimately, most of these turn out to be benign (80%), so for every 100 FNAs, you end up with 16 (1000.20.8) unnecessary operations being performed. They will want to know what to do with your nodule and what tests to take. The more carefully one looks for incidental asymptomatic thyroid cancers at autopsy, the more are found [4], but these do not cause unwellness during life and so there is likely to be no health benefit in diagnosing them antemortem. These nodules are relatively common and are usually harmless, but there is a very low risk of thyroid cancer. The financial cost depends on the health system involved, but as an example, in New Zealand where health care costs are modest by international standards in the developed world, compared with randomly selecting 1 in 10 nodules for FNA, using ACR TIRADS would result in approximately NZ$140,000 spent for every additional patient correctly reassured that he or she does not have thyroid cancer [25]. That particular test is covered by insurance and is relatively cheap. J. Clin. Cystic or almost completely cystic 0 points. 2022 Jun 30;12:840819. doi: 10.3389/fonc.2022.840819. Performance of Contrast-Enhanced Ultrasound in Thyroid Nodules: Review of Current State and Future Perspectives. The summary of test performance of random selection, ACR TIRADS as a rule-out test, ACR TIRADS as a rule-in test, and ACR TIRADS applied across all TIRADS categories are detailed in Table 2, and the full data, definitions, and calculations are given elsewhere [25]. Update of the Literature. Accessibility However, in the data set, only 25% of all nodules were categorized as TR1 or TR2 and these nodules harbored only 1% of all thyroid cancers (9 of 343). We realize that such factors may increase an individuals pretest probability of cancer and clinical decision-making would change accordingly (eg, proceeding directly to FNA), but we here ascribe no additional diagnostic value to avoid overestimating the performance of the clinical comparator. Kwak JY, Han KH, Yoon JH et-al. Russ G, Royer B, Bigorgne C et-al. Thyroid nodules are solid or fluid-filled lumps that form within your thyroid, a small gland located at the base of your neck, just above your breastbone. The area under the curve was 0.916. The test that really lets you see a nodule up close is a CT scan. Recently, the American College of Radiology (ACR) proposed a Thyroid Imaging Reporting and Data System (TI-RADS) for thyroid nodules based on ultrasonographic features. The challenge of appropriately balancing the risks of missing an important cancer versus the chance of causing harm and incurring significant costs from overinvestigation is major. Thyroid nodules are detected by ultrasonography in up to 68% of healthy patients. The low pretest probability of important thyroid cancer and the clouding effect of small clinically inconsequential thyroid cancers makes the development of an effective real-world test incredibly difficult. Objectives: If a guideline indicates that FNA is recommended, it can be difficult to oppose this based on other factors. A normal finding in Finland. Now you can go out and get yourself a thyroid nodule. It is important to validate this classification in different centres. Would you like email updates of new search results? doi: 10.12659/MSM.936368. Given the need to do more than 100 US scans to find 25 patients with just TR1 or TR2 nodules, this would result in at least 50 FNAs being done. Endocrine (2020) 70(2):25679. EU-TIRADS 1 category refers to a US examination where no thyroid nodule is found; there is no need for FNAB. A meta-analysis, This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (, Mitoguardin2 is Associated with Hyperandrogenism and Regulates Steroidogenesis in Human Ovarian Granulosa Cells, Factors Associated with Diabetes Distress among Patients with Poorly Controlled Type 2 Diabetes, Serum adiponectin and leptin is not related to skeletal muscle morphology and function in young women, Association Between Metabolic Syndrome Inflammatory Biomarkers and COVID-19 Severity, Long-term outcome of body composition, ectopic lipid and insulin resistance changes with surgical treatment of acromegaly, Volume 7, Issue 4, April 2023 (In Progress), The Journal of Clinical Endocrinology & Metabolism, https://www.uptodate.com/contents/diagnostic-approach-to-and-treatment-of-thyroid-nodules, https://doi.org/10.6084/m9.figshare.11640168.v, http://creativecommons.org/licenses/by-nc-nd/4.0/, Receive exclusive offers and updates from Oxford Academic, 1 in 10 nodules having FNA, assuming pretest probability of cancer of 5%, Negative test being TR1 or TR2; positive test meaning TR3, TR4, or TR5, Positive test meaning TR5; negative test meaning TR1-4, Positive test meaning TR5, TR4 above size cutoff and TR3 above size cutoff; negative test meaning TR1, TR2, TR3 Below Size Cutoff or TR4 below size cutoff, Positive Test Meaning TR5, TR4 Above Size Cutoff and TR3 Above Size Cutoff; negative test meaning TR1, TR2, TR3 below size threshold or TR4 below size cutoff. The common first step when you have a thyroid nodule is to go to your health care provider and get a referral.