No focal lesion. Finally, someone has come up with a guide to assist us GPs navigate this difficult but common condition. It has been retrospectively applied to thyroidectomy specimens, which is clearly not representative of the patient presenting with a thyroid nodule [34-36], and has even been used on the same data set used for TIRADS development, clearly introducing obvious bias [32, 37]. Based on the 2017 ACR TIRADS classification, the doctor will continue to specify whether the patient needs a biopsy of thyroid cells or not: Thyroid nodule size > 2.5cm: Indication for cytology biopsy. If the nodule got a score of more than 2 in the CEUS schedule, CEUS-TIRADS added 1 category. 5. The 2 examples provide a range of performance within which the real test performance is likely to be, with the second example likely to provide TIRADS with a more favorable test performance than in the real world. Depending on the constellation or number of suspicious ultrasound features, a fine-needle biopsy is . That particular test is covered by insurance and is relatively cheap. Shin JH, Baek JH, Chung J, et al. The Value of Chinese Thyroid Imaging Report and Data System Combined With Contrast-Enhanced Ultrasound Scoring in Differential Diagnosis of Benign and Malignant Thyroid Nodules. Sometimes a physician may refer you to a specialist (doctor) at a clinic that specializes in thyroid cancer. Mao S, Zhao LP, Li XH, Sun YF, Su H, Zhang Y, Li KL, Fan DC, Zhang MY, Sun ZG, Wang SC. Diagnosis and Management of Small Thyroid Nodules: A Comparative Study with Six Guidelines for Thyroid Nodules. 2011;260 (3): 892-9. Thyroid imaging reporting and data system (TI-RADS). Any additional test has to perform exceptionally well to surpass this clinicians 95% negative predictive performance, without generating false positive results and consequential harm. Multivariate factors logistic analysis was performed and a CEUS diagnostic schedule was established. no financial relationships to ineligible companies to disclose. PET-positive thyroid nodules have a relatively high malignancy rate of 35%. Tom James Cawood, Georgia Rose Mackay, Penny Jane Hunt, Donal OShea, Stephen Skehan, Yi Ma, TIRADS Management Guidelines in the Investigation of Thyroid Nodules; Illustrating the Concerns, Costs, and Performance, Journal of the Endocrine Society, Volume 4, Issue 4, April 2020, bvaa031, https://doi.org/10.1210/jendso/bvaa031. Here at the University of Florida, we are currently recruiting endocrinologists to work with us to help people with thyroid nodules. A prospective validation study that determines the true performance of TIRADS in the real-world is needed. As noted previously, we intentionally chose the clinical comparator to be relatively poor and not a fair reflection of real-world practice, to make it clearer to what degree ACR TIRADS adds value. 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 Using ACR-TIRADS as a rule-in test to identify a higher risk group that should have FNA is arguably a more effective application. At the time the article was created Praveen Jha had no recorded disclosures. The process of validation of CEUS-TIRADS model. If a guideline indicates that FNA is recommended, it can be difficult to oppose this based on other factors. Until TIRADS is subjected to a true validation study, we do not feel that a clinician can currently accurately predict what a TIRADS classification actually means, nor what the most appropriate management thereafter should be. For those that also have 1 or more TR3, TR4, or TR5 nodules on their scan, they cannot have thyroid cancer ruled out by TIRADS because the possibility that their non-TR1/TR2 nodules may be cancerous is still unresolved. We have detailed the data set used for the development of ACR TIRADS [16] in Table 1, plus noted the likely cancer rates in the real world if one assumes that the data set cancer prevalence (10.3%) is double that in the population upon which the test is intended to be used (pretest probability of 5%). 24;8 (10): e77927. 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. This is likely an underestimate of the number of scans needed, given that not all nodules that are TR1 or TR2 will have purely TR1 or TR2 nodules on their scan. Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW. With the right blood tests, you can see if you have a thyroid nodule, and if so, you can treat it with radioactive iodine. Thyroid nodules are very common and benign in most cases. If your doctor found a hypoechoic nodule during an ultrasound, they may simply do some additional testing to make sure there's . 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 . Now, the first step in T3N treatment is usually a blood test. 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. Endocrine (2020) 70(2):25679. published a simplified TI-RADS that was prospectively validated 5. This is a specialist doctor who specializes in the treatment and diagnosis of thyroid cancer. Save my name, email, and website in this browser for the next time I comment. Whilst our findings have illustrated some of the shortcomings of ACR TIRADS guidelines, we are not able to provide the ideal alternative. Yoon JH, Han K, Kim EK, Moon HJ, Kwak JY. 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. In the case of thyroid nodules, there are further challenges. Would you like email updates of new search results? doi: 10.3390/diagnostics11081374 Findings of a large, prospective multicenter study from Egypt, published in the August 2019 issue of the European Journal . The CEUS-TIRADS category was 4c. All of the C-TIRADS 4 nodules were re-graded by CEUS-TIRADS. Tessler FN, Middleton WD, Grant EG, et al. Many of these papers share the same fundamental problem of not applying the test prospectively to the population upon which it is intended for use. proposed a system with five categories, which, like BI-RADS, each carried a management recommendation 2. Thyroid nodules are common, affecting around one-half of the population and become increasingly common with advancing age [1, 2]. The Thyroid Imaging Reporting And Data System (TI-RADS) was developed by the American College of Radiology and used by many radiologist in Australia. The. The It might even need surge The system is sometimes referred to as TI-RADS Kwak 6. FOIA This causes the nodules to shrink and signs and symptoms of hyperthyroidism to subside, usually within two to three months. The following article describes the initial iterations proposed by individual research groups, none of which gained widespread use. Anti-thyroid medications. The cost of seeing 100 patients and only doing FNA on TR5 is at least NZ$100,000 (compared with $60,000 for seeing all patients and randomly doing FNA on 1 in 10 patients), so being at least NZ$20,000 per cancer found if the prevalence of thyroid cancer in the population is 5% [25]. This allows patients with a TR1 or TR2 nodule to be reassured that they have a low risk of thyroid cancer, rather than a mixture of nodules (not just TR1 or TR2) not being able to be reassured. K-TIRADS category was assigned to the thyroid nodules. That particular test is covered by insurance and is relatively cheap. (2017) Radiology. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). 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. 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). The arrival time, enhancement degree, enhancement homogeneity, enhancement pattern, enhancement ring, and wash-out time were analyzed in CEUS for all of the nodules. Following ACR TIRADS management guidelines would likely result in approximately one-half of the TR3 and TR4 patients getting FNAs ((0.537)+(0.323)=25, of total 60), finding up to 1 cancer, and result in 4 diagnostic hemithyroidectomies for benign nodules (250.20.8=4). The diagnosis or exclusion of thyroid cancer is hugely challenging. With the right blood tests, you can see if you have a thyroid nodule, and if so, you can treat it with radioactive iodine. These final validation sets must fairly represent the population upon which the test is intended to be applied because the prevalence of the condition in the test population will critically influence the test performance, particularly the positive predictive value (PPV) and negative predictive value (NPV). 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. ", the doctor would like to answer as follows: With the information you provided, you have a homophonic nucleus in the right lobe. The area under the curve was 0.916. Test performance in the TR3 and TR4 categories had an accuracy of less than 60%. Therefore, 60% of patients are in the middle groups (TR3 and TR4), where the US features are less discriminatory. The performance of any diagnostic test in this group has to be truly exceptional to outperform random selection and accurately rule in or rule out thyroid cancer in the TR3 or TR4 groups. 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]. Given that ACR TIRADS test performance is at its worst in the TR3 and TR4 groups, then the cost-effectiveness of TIRADS will also be at its worst in these groups, in particular because of the false-positive TIRADS results. Summary Test Performance of Random Selection of 1 in 10 Nodules for FNA, Compared with ACR-TIRADS. Among the 228 C-TIRADS 4 nodules, 69 were determined as C-TIRADS 4a, 114 were C-TIRADS 4b, and 45 were C-TIRADS 4c. Furuya-Kanamori L, Bell KJL, Clark J, Glasziou P, Doi SAR. Lancet (2014) 384(9957): 1848:184858. In view of their critical role in thyroid nodule management, more improved TI-RADSs have emerged. Castellana M, Castellana C, Treglia G, Giorgino F, Giovanella L, Russ G, Trimboli P. Oxford University Press is a department of the University of Oxford. It is very difficult to know the true prevalence of important, clinically consequential thyroid cancers among patients presenting with thyroid nodules. J Adolesc Young Adult Oncol (2020) 9(2):2868. The main source data set for the ACR TIRADS recommendations was large and consisted of US images and FNA results of more than 3400 nodules [16]. The nodules were scored, measured and assigned to one of five TI-RADS levels (TR): TR1 - benign, TR2 - not suspicious, TR3 - mildly suspicious, TR4 - moderately suspicious, TR5 - highly suspicious. 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. The sensitivity, specificity, and accuracy of CEUS-TIRADS were 95.7%, 85.7%, and 92.1% respectively. Disclosure Summary:The authors declare no conflicts of interest. There are inherent problems with studies addressing the issue such as selection bias at referral centers and not all nodules having fine needle aspiration (FNA). Some cancers would not show suspicious changes thus US features would be falsely reassuring. Its not something that happens every day, but every day. to propose a simpler TI-RADS in 2011 2. Refer to separate articles for the latest systems supported by various professional societies: A TI-RADS was first proposed by Horvath et al. Tirads 5 thyroid gland: is a thyroid gland with 5 or more lesions, the rate of malignancy accounts for 87.5%. Because we have a lot of people who have been put in a position where they dont have the proper education to be able to learn what were going through, we have to take this time and go through it as normal. A subdivision into 4a (malignancy between 5 and 10%) and 4b (malignancy between 10 and 80%) was optional. The process of establishing of CEUS-TIRADS model. PMC An official website of the United States government. Disclaimer. The detection rate of thyroid cancer has increased steeply with widespread utilization of ultrasound (US) and frequent incidental detection of thyroid nodules with other imaging modalities such as computed tomography, magnetic resonance imaging, and, more recently, positron emission tomography-computed tomography, yet the mortality from thyroid cancer has remained static [10, 11]. The optimal investigation and management of the 84% of the population harboring the remaining 50% of cancer remains unresolved. Doctors use radioactive iodine to treat hyperthyroidism. Hong MJ, Na DG, Baek JH, Sung JY, Kim JH. 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. We aimed to assess the performance and costs of the American College of Radiology Thyroid Image Reporting And Data System (ACR-TIRADS). If one accepts that the pretest probability of a patient presenting with a thyroid nodule having an important thyroid cancer is 5%, then clinicians who tell every patient they see that they do not have important thyroid cancer will be correct 95% of the time. Clipboard, Search History, and several other advanced features are temporarily unavailable. 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. Objective: To determine whether the size of thyroid nodules in ACR-TIRADS ultrasound categories 3 and 4 is correlated with the Bethesda cytopathology classification. For the calculations, we assume an approximate size distribution where one-third of TR3 nodules are25 mm and half of TR4 nodules are15 mm. -, Takano T. Overdiagnosis of Juvenile Thyroid Cancer: Time to Consider Self-Limiting Cancer. 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. 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. Of note, we have not taken into account any of the benefits, costs, or harms associated with the proposed US follow-up of nodules, as recommended by ACR-TIRADS. 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]). TIRADS 5: probably malignant nodules (malignancy >80%). However, most of the sensitivity benefit is due to the performance in the TR1 and TR2 categories, with sensitivity in just the TR3 and TR4 categories being only 46% to 62%, depending on whether the size cutoffs add value (data not shown). Methodologically, the change in the ACR-TIRADS model should now undergo a new study using a new training data set (to avoid replicating any bias), before then undergoing a validation study. To further enhance the performance of TIRADS, we presume that patients present with only 1 TR category of thyroid nodules. The TIRADS reporting algorithm is a significant advance with clearly defined objective sonographic features that are simple to apply in practice. To find 16 TR5 nodules requires 100 people to be scanned (assuming for illustrative purposes 1 nodule per scan). TI-RADS 4b applies to the lesion with one or two of the above signs and no metastatic lymph node is present. Cibas ES, Ali SZ; NCI Thyroid FNA State of the Science Conference. A normal finding in Finland. These appear to share the same basic flaw as the ACR-TIRADS, in that the data sets of nodules used for their development is not likely to represent the population upon which it is intended for use, at least with regard to pretest probability of malignancy (eg, malignancy rate 12% for Korean TIRADS [26]; 18% and 31% for EU TIRADS categories 4 and 5 [27, 28]). -, Zhou J, Yin L, Wei X, Zhang S, Song Y, Luo B, et al. The CEUS-TIRADS category was 4a. Zhang B, Tian J, Pei S, Chen Y, He X, Dong Y, Zhang L, Mo X, Huang W, Cong S, Zhang S. Wildman-Tobriner B, Buda M, Hoang JK, Middleton WD, Thayer D, Short RG, Tessler FN, Mazurowski MA. That particular test is covered by insurance and is relatively cheap. In: Thyroid 26.1 (2016), pp. In CEUS analysis, it reflected as later arrival time, hypo-enhancement, heterogeneous and centripetal enhancement, getting a score of 4 in the CEUS model. The high prevalence of thyroid nodules combined with the generally indolent growth of thyroid cancer present a challenge for optimal patient care. 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. Management of nodules with initially nondiagnostic results of thyroid fine-needle aspiration: can we avoid repeat biopsy? 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. Performance of Contrast-Enhanced Ultrasound in Thyroid Nodules: Review of Current State and Future Perspectives. ; Korean Society of Thyroid Radiology (KSThR) and Korean Society of Radiology. 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. Haugen BR, Alexander EK, Bible KC, et al. 6. It is this proportion of patients that often go on to diagnostic hemithyroidectomies, from which approximately 20% are cancers [12, 17, 21], meaning the majority (80%) end up with ultimately unnecessary operations. Anderson TJ, Atalay MK, Grand DJ, Baird GL, Cronan JJ, Beland MD. Compared with randomly doing FNA on 1 in 10 nodules, using ACR TIRADS and doing FNA on all TR5 requires NNS of 50 to find 1 additional cancer. Radiology. 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]. Cavallo A, Johnson DN, White MG, et al. Radiofrequency ablation uses a probe to access the benign nodule under ultrasound guidance, and then treats it with electrical current and heat that shrinks the nodule. Russ G, Bonnema SJ, Erdogan MF, Durante C, Ngu R, Leenhardt L. Middleton WD, Teefey SA, Reading CC, et al. The flow chart of the study. Your health care provider will examine your neck to feel for changes in your thyroid, such as a lump (nodule) in the thyroid. Cao H, Fan Q, Zhuo S, Qi T, Sun H, Rong X, Xiao X, Zhang W, Zhu L, Wang L. J Ultrasound Med. 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. If your doctor is not sure what to do with your nodule, lets say its just a very small, non-cancerous, nodule, you may need to go to an endocrinologist. The test that really lets you see a nodule up close is a CT scan. 3. Whilst we somewhat provocatively used random selection as a clinical comparator, we do not mean to suggest that clinicians work in this way. 2021 Dec 7;101(45):3748-3753. doi: 10.3760/cma.j.cn112137-20210401-00799. Haymart MR, Banerjee M, Reyes-Gastelum D, Caoili E, Norton EC. In 2013, Russ et al. 5 The modified TI-RADS was composed of seven ultrasound features in identifying benign and malignant thyroid nodules, such as the nodular texture, nodular The ACR TIRADS white paper [22] very appropriately notes that the recommendations are intended to serve as guidance and that professional judgment should be applied to every case including taking into account factors such as a patients cancer risk, anxiety, comorbidities, and life expectancy. For a rule-out test, sensitivity is the more important test metric. The diagnostic performance of CEUS-TIRADS was significantly better than CEUS and C-TIRADS. Thyroid imaging reporting and data system for US features of nodules: a step in establishing better stratification of cancer risk. Thyroid nodule size from 1.5 - 2.5cm: Periodic follow-up every 6 months. A proposal for a thyroid imaging reporting and data system for ultrasound features of thyroid carcinoma. In a cost-conscious public health system, one could argue that after selecting out those patients that clearly raise concern for a high risk of cancer (ie, from history including risk factors, examination, existing imaging) the clinician could reasonably inform an asymptomatic patient that they have a 95% chance of their nodule being benign. If a clinician does no tests and no FNAs, then he or she will miss all thyroid cancers (5 people per 100). TIRADS does not perform to this high standard. The health benefit from this is debatable and the financial costs significant. The ACR-TIRADS guidelines also provide easy-to-follow management recommendations that have understandably generated momentum. ADVERTISEMENT: Radiopaedia is free thanks to our supporters and advertisers. 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). These cutoffs are somewhat arbitrary, with conflicting data as to what degree, if any, size is a discriminatory factor. TIRADS ( T hyroid I maging R eporting and D ata S ystem) is a 5-point scoring system for thyroid nodules on ultrasound, developed by the American College of Radiology ( hence also termed as ACR- TIRADS). It should also be on an intention-to-test basis and include the outcome for all those with indeterminate FNAs. Such data should be included in guidelines, particularly if clinicians wish to provide evidence-based guidance and to obtain truly informed consent for any action that may have negative consequences. TIRADS 4: suspicious nodules (5-80% malignancy rate). Unauthorized use of these marks is strictly prohibited. Thyroid Tirads 4: Thyroid lesions with suspicious signs of malignancy. Thyroid nodules are detected by ultrasonography in up to 68% of healthy patients. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. 4. Symptoms and Causes Diagnosis and Tests Management and Treatment Prevention Outlook / Prognosis Living With Frequently Asked Questions Overview The American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) has achieved high accuracy in categorizing the malignancy status of nearly 950 thyroid nodules detected on thyroid ultrasonography. The Thyroid Imaging Reporting and Data System (TI-RADS) of the American College of Radiology (ACR) was designed in 2017 with the intent to decrease biopsies of benign nodules and improve overall . The truth is, most of us arent so lucky as to be diagnosed with all forms of thyroid cancer, but we do live with the results of it. in 2009 1. 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. The risk of malignancy was derived from thyroid ultrasound (TUS) features. Thyroid surgery, Microvascular reconstruction, Neck surgery, Reconstructive surgery, Facial reconstruction, Parathyroid. The ROC curves of C-TIRADS, CEUS, and CEUS-TIRADS of 228 nodules in the diagnostic model. Bastin S, Bolland MJ, Croxson MS. Role of Ultrasound in the Assessment of Nodular Thyroid Disease.
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