Incidence of Microcarcinoma and Non-Microcarcinoma in Ultrasound-Found Thyroid Nodules

Incidence of Microcarcinoma and Non-Microcarcinoma in Ultrasound-Found Thyroid Nodules | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Incidence of Microcarcinoma and Non-Microcarcinoma in Ultrasound-Found Thyroid Nodules Zhi Chen, Singla Sethiel Mosha, Tong Zhang, Ming Xu, Yanli Li, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-150354/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Mar, 2021 Read the published version in BMC Endocrine Disorders → Version 1 posted 9 You are reading this latest preprint version Abstract Backgrounds: The incidence of thyroid nodules is increasing year by year around the world. However, ultrasound is not recommended as a screening test for the general population or patients with a normal thyroid on palpation by the American Association of Clinical Endocrinologists (AACE). In practice, some individuals with normal thyroid palpation have nodules that can just be found out by ultrasound. No studies have directly described the risk of nodules found by ultrasound or by palpation up to now. More evidence is needed to carry out for helping us balance the over diagnosis and missed diagnosis of malignant lesions. Therefore, we carried out a retrospective study to investigate the incidence of malignant lesions in ultrasound-found nodules in a large cohort. Methods: We conducted a retrospective analysis involving 2957 patients who underwent thyroid ultrasound evaluation and fine-needle aspiration (FNA) between Jan 2013 and Dec 2019. The cytologic examinations were analyzed based on the Bethesda system. For nodules suspected to be follicular neoplasm or other malignant tumors by cytological tests, patients were recommended for surgery and histopathology examinations. Results: Compared with palpation-found nodules, ultrasound-found nodules were presenting less as purely cystic nodules (10.1% vs 39.9%, x 2 =355.69, p=0.000), smaller size (17.5±9.9 mm vs 28.0±12.5 mm, t=23.876 p=0.000), and higher TI-RADS score (5.5±2.9 vs 3.4±3.3, t=18.084, p=0.000), respectively. More ultrasound-found nodules were diagnosed as carcinoma by histology examinations [136 (11.2%) nodules found by ultrasound vs 68 (3.9%) by palpation, x 2 =59.737, p=0.000], and 88 (64.7%) nodules found by ultrasound were non-microcarcinoma. Among the malignant nodules confirmed by histopathology, a higher proportion of microcarcinoma was detected in ultrasound-found nodules [35.3% (48/136) vs 16.2% (11/68), x 2 =8.183, p=0.004]. Conclusions: In view of the results observed in our research that malignant nodules were more common screened out by ultrasound, and nearly two thirds of them were non-microcarcinoma. We recommend reassessment of the recommendations for thyroid nodule screening. Endocrinology & Metabolism Thyroid nodules Ultrasound Carcinomas Screen Figures Figure 1 Figure 2 Background The incidence rate of thyroid nodules has an annual increasing trend worldwide. The overall prevalence rate was 49%-68% in general population of China, Europe and America by using ultrasound [ 1 – 3 ]. As thyroid nodules are usually the first sign of cancer, the primary goal of treatment is to distinguish between malignant and benign lesions. In practice, more and more physicians took thyroid ultrasound as the preferred examination because of its noninvasive and inexpensive. However, rencent researches reported that screening for thyroid cancer has led to a significant increase in the global diagnosis rate of the disease, but no change in mortality [ 4 , 5 ]. Therefore, the American Association of Clinical Endocrinologists (AACE) does not recommend ultrasound as a screening test for the general population or patients with a normal thyroid on palpation and a low clinical risk of thyroid disease [ 6 ]. Similarly, The United States Preventive Services Task Force recommends against screening for thyroid cancer in asymptomatic adults [ 7 ]. Nevertheless, the AACE prescription standard for ultrasound screening is only at a level 4 evidence and GRADE C recommendation, which means it is based on expert experience with no conclusive risks or benefits [ 6 ]. It is necessary to investigate the characteristics of thyroid nodules only detected by ultrasound, therefore to determine whether it is necessary to conduct ultrasound examination for patients with no nodules found by palpation. Up to now, no studies have directly compared the risk of ultrasound-found and palpation-found nodules. More researches evidence is needed to carry out for accumulating evidence to help us balance the over diagnosis and missed diagnosis of malignant lesions. The purpose of this retrospective study was to investigate the incidence of malignant lesions in ultrasound-found nodules. Methods Patients We conducted a retrospective analysis involving 2957 patients who underwent thyroid ultrasound evaluation and fine-needle aspiration (FNA) between January 2013 and December 2019. Patients were divided into two groups according to the detection way of the nodules. The ultrasound-found group refers to nodules discovered by ultrasound examination. The palpation-found group means that the nodules were found by patients themselves or by physicians when performing physical examination. Ultrasound Evaluation Risk of nodules was reported by ACR thyroid imaging, reporting and data system (TI-RADS) [ 8 ]. The characteristics of thyroid nodules were evaluated from five categories: composition, echogenicity, shape, margin, and echogenic foci. Each category has a score, and a total score was obtained by adding the five scores, which is the TI-RADS score. The size of nodules was expressed by the maximum diameter. Cytology And Histology Examinations FNA was performed by a conventional method, and at least two samples were taken per nodule. All our FNA samples were diagnosed at Guangzhou Kingmed Diagnostics which is the first pathology laboratory certified by the College of American Pathologists in China [ 9 ]. Cytology reports were based on the Bethesda system [ 10 ]. Six diagnostic categories include: (I) non-diagnostic or unsatisfactory, (II) benign, (III) atypia or follicular lesion of undetermined significance, (IV) follicular neoplasm, (V) suspicious for malignancy and (VI) malignant. We recommended surgery for patients with the last three categories of cytological reports and obtained corresponding histologic reports. Statistical analysis All grouped data in accordance with normal distribution were described by mean ± standard deviation. The unpaired t test was used to compare the mean nodule size and TI-RADS score between ultrasound-found and palpation-found groups. The comparison of incidence for categorical data between groups was analyzed by chi-square test. Statistical analyses were performed using SPSS Statistics for Windows ver. 18.0. Statistical significance was defined if p < 0.05. Results Characteristics Of Patients The characteristics of two groups of patients were shown in Table 1 . Age, gender, course of disease, and body mass index (BMI) of patients were compared. There were no differences between two groups. Table 1 Characteristics of patients Ultrasound-found (n = 1212) Palpation-found (n = 1745) Male (%) 296 (24.4) 329 (18.9) Age (years) 48.3 ± 13.1 48.0 ± 14.5 Course of disease (months)* 2 (0.1, 240) 3 (0.1, 480) BMI (kg/m 2 ) 23.1 ± 3.7 22.5 ± 2.9 * Median (range) Characteristics Of Two Types Of Nodules In the group of ultrasound-found nodules, less purely cystic nodules were presented (10.1% vs 39.9%). The mean diameter of ultrasound-found nodules was 17.5 ± 9.9 whereas that of palpation-found nodules was 28.0 ± 12.5. A higher TI-RADS score was observed in the group of ultrasound-found nodules (28.0 ± 12.5), respectively. The details were shown in Table 2 . Table 2 Characteristics of two types of nodules Ultrasound-found (n = 1212) Palpation-found (n = 1745) X 2 / t value P value Purely cyst (n/%) 122 (10.1) 697 (39.9) 335.69 0.000 Size (mm) 17.5 ± 9.9 28.0 ± 12.5 23.876 0.000 TI-RADS score 5.5 ± 2.9 3.4 ± 3.3 18.084 0.000 Incidence Of Thyroid Carcinoma On Histology A higher proportion of malignant nodules were confirmed by histopathology in ultrasound group. As shown in Fig. 1, a total of 136 (11.2%) of ultrasound-found nodules and 68 (3.9%) of palpation-found nodules were diagnosed as carcinoma (x 2 = 59.737, p = 0.000). Proportion Of Microcarcinoma And Non-microcarcinoma Among carcinomas in ultrasound group, 35.3% (48/136) nodules were microcarcinomas (with a diameter smaller than 1 cm) and 64.7% (88/136) were non-microcarcinomas. More microcarcinoma was detected in malignant nodules found by ultrasound. 35.3% (48/136) ultrasound-found carcinomas and 16.2% (11/68) palpation-found ones were micro-carcinomas (x2 = 8.183, p = 0.004), respectively (Fig. 2). Discussion Our study indicated that ultrasound-found nodules presented a greater malignancy risk than palpation-found ones. There were several explanations for the results. First, only 10% of ultrasound-found nodules were purely cystic, which are highly likely to be benign [ 6 , 11 ]. In contrast to palpation-found ones, purely cystic nodules were nearly 40%. Second, though ultrasound-found nodules were smaller in size, they had higher TI-RADS score than palpation-found ones. Unlike palpation-found nodules, ultrasound-found nodules were smaller and often located deep in the thyroid tissue. Hence the relation of the nodule size between malignancy risk and prognosis as recommended by AACE became controversial [ 2 ]. Though some studies found that malignant risk is associated with nodule size, for example, a series of observational studies have found that thyroid cancers over 4 cm were associated with more aggressive behavior whereas tumors smaller than 1.5 cm had a good overall prognosis [ 12 , 13 , 14 ]. However, some other researches indicated no correlation between size and risk [ 15 , 16 ]. A recent study found that the impact of nodule size on the malignancy risk differed according to the ultrasound pattern. A large nodule size (≥ 3 cm) showed a higher malignancy risk than smaller nodules in intermediate- and low-suspicion nodules [ 17 ]. We are convinced that our study findings as demonstrated above, highlight a conflict between AACE recommendations and clinical practice in the following aspects: AACE’s recommendation against ultrasound screening for thyroid nodules and the recommendation of FNA based on nodule size [ 6 ]. American Thyroid Association (ATA) also recommends FNA based on nodule size [ 11 ]. In our study, the average diameter of ultrasound-found nodules is 1.75 cm, which was within both of the recommended range of FNA. Another conflict between AACE recommendations and recent reality highlighted in this study is that AACE recommends against ultrasound screening based on a significant increase in global thyroid cancer prevalence but a constant mortality rate [ 5 , 6 ]. However, latest published study found that in America, incidence-based thyroid cancer mortality rose from 0.40 per 100,000 person-years in 1994–1997 to 0.46 per 100,000 person-years in 2010–2013 [ 18 ]. In China, the mortality increased from 0.30 per 100,000 in 2005 to 0.35 per 100,000 in 2015 [ 19 ]. Under current guidelines, only a small portion of patients could be under active surveillance for micro carcinoma [ 20 ]. Furthermore, in our study of ultrasound-found nodules, there were as high as two thirds that were non-microcarcinoma. For such large nodules, it is generally believed that the benefits of surgery outweigh the risks [ 6 ]. The limitation of this study is that ultrasound evaluations were performed by different operators and machines, so bias may exist. In summary, since malignant nodules were more common in the ultrasound-found nodules, and nearly two thirds of which were non-microcarcinoma, we suggest the recommendation against screening thyroid nodules by ultrasound needs to be re-evaluated. Abbreviations AACE: American Association of Clinical Endocrinologists; ACR: American College of Radiology; ATA: American Thyroid Association; FNA: fine-needle aspiration; TI-RADS: Thyroid imaging reporting and data system Declarations Acknowledgements None. Authors’ contributions L.L. and W.L. constructed the study design, interpreted the data, and drafted the report. Z.C. participated in data analysis and manuscript writing. All the other coauthors contributed to the discussion of the study protocol, data collection, and manuscript revision. All authors read and approved the final manuscript. Funding The present work was supported by grants from the Foundation of Guangdong Medical Science and Technology Research (No. A2019036). Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate The study was submitted to and approved by the Clinical Research Ethics Committee of the Second Affiliated Hospital of Guangzhou Medical University. Every participant signed a voluntary and written informed consent, and all the consents were obtained from the ethics committee. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Authors’ information 1 Department of Endocrinology, The Second Affiliated Hospital, Guangzhou Medical University, No.250 Changgang Road East, Haizhu District, Guangzhou 510260, China. 2 Department of Endocrinology, The Third Affiliated Hospital, Southern Medical University, No.183 Zhongshan Avenue West, Tianhe District, Guangzhou 510630, China. 3 Department of Endocrinology, Affiliated Nanhai Hospital of Southern Medical University, No.40 Foping Road, Nanhai District, Foshan 528200, China. 4 Department of Medical Ultrasound, The Second Affiliated Hospital, Guangzhou Medical University, No.250 Changgang Road East, Haizhu District, Guangzhou 510260, China; References Jiang H, Tian Y, Yan W, et al. The Prevalence of Thyroid Nodules and an Analysis of Related Lifestyle Factors in Beijing Communities. Int J Environ Res Public Health. 2016 Apr 22;13(4):442. Guth S, Theune U, Aberle J, Galach A, Bamberger CM. Very high prevalence of thyroid nodules detected by high frequency (13 MHz) US examination. Eur J Clin Invest. 2009;39:699–706. Davies L, Welch HG. Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg. 2014;140:317–22. Vaccarella S, Franceschi S, Bray F, et al. Worldwide thyroid-cancer epidemic? The increasing impact of overdiagnosis. N Engl J Med. 2016;375:614–7. Ahn HS, Kim HJ, Kim KH, et al. Thyroid cancer screening in South Korea increases detection of papillary cancers with no impact on other subtypes or thyroid cancer mortality. Thyroid. 2016;26:1535–40. Gharib H, Papini E, Garber JR, et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules—2016 update. Endocr Pract. 2016;22(5):622–39. Bibbins-Domingo K, Grossman DC, Curry SJ, et al. US Preventive Services Task Force. Screening for Thyroid Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2017;317:1882–7. Tessler FN, Middleton WD, Grant EG, et al. ACR Thyroid Imaging, Reporting and Data System (TI-RADS): White Paper of the ACR TI-RADS Committee. J Am Coll Radiol. 2017;14(5):587–95. Zheng B, Zarka MA, Chen C, You J, Sun L, Chen L. The largest CAP-certified Chinese reference laboratory experience with the Bethesda system for reporting thyroid cytopathology: correlation with histologic and BRAF data. J Am Soc Cytopathol. 2018;7(1):16–21. Cibas ES, Ali SZ. The Bethesda System for reporting thyroid cytopathology. Thyroid. 2009;19(11):1159–65. Haugen BR, Alexander EK, Bible KC, 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. Cavallo A, Johnson DN, White MG, et al. Thyroid nodule size at ultrasound as a predictor of malignancy and finalpathologic size. Thyroid. 2017;27(5):641–50. Tam S, Amit M, Boonsripitayanon M, et al. Effect of tumor size and minimal extrathyroidal extension in patients with differentiated thyroid cancer. Thyroid. 2018;28:982–90. Ito Y, Miyauchi A, Oda H. Low-risk papillary microcarcinoma of the thyroid: A review of active surveillance trials. Eur J Surg Oncol. 2018;44:307–15. doi: 10.1016/j.ejso.2017.03.004 . McHenry CR, Huh ES, Machekano RN. Is nodule size an independent predictor of thyroid malignancy? Surgery. 2008;144(6):1062–8. Jinih M, Faisal F, Abdalla K, et al. Association between thyroid nodule size and malignancy rate. Ann R Coll Surg Engl. 2020;102(1):43–8. Hong MJ, Na DG, Baek JH, Sung JY, Kim JH. Impact of Nodule Size on Malignancy Risk Differs according to the Ultrasonography Pattern of Thyroid Nodules. Korean J Radiol. 2018;19(3):534–41. Lim H, Devesa SS, Sosa JA, Check D, Kitahara CM. Trends in thyroid cancer incidence and mortality in the United States, 1974–2013. JAMA. 2017;317:1338–48. Wang J, Yu F, Shang Y, Ping Z, Liu L. Thyroid cancer: incidence and mortality trends in China, 2005–2015. Endocrine. 2020 Jan 30. Ito Y, Miyauchi A, Kudo T, et al. Trends in the implementation of active surveillance for low-risk papillary thyroid microcarcinomas at Kuma Hospital: gradual increase and heterogeneity in the acceptance of this new management option. Thyroid. 2018;28(4):488–95. Cite Share Download PDF Status: Published Journal Publication published 04 Mar, 2021 Read the published version in BMC Endocrine Disorders → Version 1 posted Review # 2 received at journal 20 Jan, 2021 Editorial decision: Major revision 20 Jan, 2021 Reviewer # 2 agreed at journal 18 Jan, 2021 Review # 1 received at journal 16 Jan, 2021 Reviewer # 1 agreed at journal 15 Jan, 2021 Editor assigned by journal 13 Jan, 2021 Reviewers invited by journal 13 Jan, 2021 Submission checks completed at journal 13 Jan, 2021 Editor invited by journal 13 Jan, 2021 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-150354","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":8498680,"identity":"e38d3c10-72ad-4662-9f79-3521f23ce992","order_by":0,"name":"Zhi Chen","email":"","orcid":"","institution":"The Third Affiliated Hospital of Southern Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhi","middleName":"","lastName":"Chen","suffix":""},{"id":8498681,"identity":"7601c7fb-45d4-4b6e-b589-8806a47f13ef","order_by":1,"name":"Singla Sethiel Mosha","email":"","orcid":"","institution":"Guangzhou Medical University 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The overall prevalence rate was 49%-68% in general population of China, Europe and America by using ultrasound [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. As thyroid nodules are usually the first sign of cancer, the primary goal of treatment is to distinguish between malignant and benign lesions.\u003c/p\u003e \u003cp\u003eIn practice, more and more physicians took thyroid ultrasound as the preferred examination because of its noninvasive and inexpensive. However, rencent researches reported that screening for thyroid cancer has led to a significant increase in the global diagnosis rate of the disease, but no change in mortality [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Therefore, the American Association of Clinical Endocrinologists (AACE) does not recommend ultrasound as a screening test for the general population or patients with a normal thyroid on palpation and a low clinical risk of thyroid disease [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Similarly, The United States Preventive Services Task Force recommends against screening for thyroid cancer in asymptomatic adults [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Nevertheless, the AACE prescription standard for ultrasound screening is only at a level 4 evidence and GRADE C recommendation, which means it is based on expert experience with no conclusive risks or benefits [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. It is necessary to investigate the characteristics of thyroid nodules only detected by ultrasound, therefore to determine whether it is necessary to conduct ultrasound examination for patients with no nodules found by palpation.\u003c/p\u003e \u003cp\u003eUp to now, no studies have directly compared the risk of ultrasound-found and palpation-found nodules. More researches evidence is needed to carry out for accumulating evidence to help us balance the over diagnosis and missed diagnosis of malignant lesions.\u003c/p\u003e \u003cp\u003eThe purpose of this retrospective study was to investigate the incidence of malignant lesions in ultrasound-found nodules.\u003c/p\u003e "},{"header":"Methods","content":" \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective analysis involving 2957 patients who underwent thyroid ultrasound evaluation and fine-needle aspiration (FNA) between January 2013 and December 2019. Patients were divided into two groups according to the detection way of the nodules. The ultrasound-found group refers to nodules discovered by ultrasound examination. The palpation-found group means that the nodules were found by patients themselves or by physicians when performing physical examination.\u003c/p\u003e \u003c/div\u003e \n\u003ch2\u003eUltrasound Evaluation\u003c/h2\u003e\n \u003cp\u003eRisk of nodules was reported by ACR thyroid imaging, reporting and data system (TI-RADS) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The characteristics of thyroid nodules were evaluated from five categories: composition, echogenicity, shape, margin, and echogenic foci. Each category has a score, and a total score was obtained by adding the five scores, which is the TI-RADS score. The size of nodules was expressed by the maximum diameter.\u003c/p\u003e \n\u003ch2\u003eCytology And Histology Examinations\u003c/h2\u003e\n \u003cp\u003eFNA was performed by a conventional method, and at least two samples were taken per nodule. All our FNA samples were diagnosed at Guangzhou Kingmed Diagnostics which is the first pathology laboratory certified by the College of American Pathologists in China [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Cytology reports were based on the Bethesda system [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Six diagnostic categories include: (I) non-diagnostic or unsatisfactory, (II) benign, (III) atypia or follicular lesion of undetermined significance, (IV) follicular neoplasm, (V) suspicious for malignancy and (VI) malignant. We recommended surgery for patients with the last three categories of cytological reports and obtained corresponding histologic reports.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll grouped data in accordance with normal distribution were described by mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. The unpaired \u003cem\u003et\u003c/em\u003e test was used to compare the mean nodule size and TI-RADS score between ultrasound-found and palpation-found groups. The comparison of incidence for categorical data between groups was analyzed by chi-square test. Statistical analyses were performed using SPSS Statistics for Windows ver. 18.0. Statistical significance was defined if p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e "},{"header":"Results","content":"\u003ch2\u003e Characteristics Of Patients\u003c/h2\u003e\n \u003cp\u003eThe characteristics of two groups of patients were shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Age, gender, course of disease, and body mass index (BMI) of patients were compared. There were no differences between two groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUltrasound-found\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1212)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePalpation-found\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1745)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e296 (24.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e329 (18.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e48.3\u0026thinsp;\u0026plusmn;\u0026thinsp;13.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e48.0\u0026thinsp;\u0026plusmn;\u0026thinsp;14.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCourse of disease (months)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (0.1, 240)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (0.1, 480)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e* Median (range)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \n\u003ch2\u003eCharacteristics Of Two Types Of Nodules\u003c/h2\u003e\n \u003cp\u003eIn the group of ultrasound-found nodules, less purely cystic nodules were presented (10.1% vs 39.9%). The mean diameter of ultrasound-found nodules was 17.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.9 whereas that of palpation-found nodules was 28.0\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5. A higher TI-RADS score was observed in the group of ultrasound-found nodules (28.0\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5), respectively. The details were shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of two types of nodules\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUltrasound-found\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1212)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePalpation-found\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1745)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eX\u003csup\u003e2\u003c/sup\u003e / t\u003c/p\u003e \u003cp\u003evalue\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003cp\u003evalue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePurely cyst (n/%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e122 (10.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e697 (39.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e335.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSize (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e28.0\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e23.876\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTI-RADS score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e18.084\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \n\u003ch2\u003eIncidence Of Thyroid Carcinoma On Histology\u003c/h2\u003e\n \u003cp\u003eA higher proportion of malignant nodules were confirmed by histopathology in ultrasound group. As shown in Fig.\u0026nbsp;1, a total of 136 (11.2%) of ultrasound-found nodules and 68 (3.9%) of palpation-found nodules were diagnosed as carcinoma (x\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;59.737, p\u0026thinsp;=\u0026thinsp;0.000).\u003c/p\u003e \n\u003ch2\u003eProportion Of Microcarcinoma And Non-microcarcinoma\u003c/h2\u003e\n \u003cp\u003eAmong carcinomas in ultrasound group, 35.3% (48/136) nodules were microcarcinomas (with a diameter smaller than 1\u0026nbsp;cm) and 64.7% (88/136) were non-microcarcinomas. More microcarcinoma was detected in malignant nodules found by ultrasound. 35.3% (48/136) ultrasound-found carcinomas and 16.2% (11/68) palpation-found ones were micro-carcinomas (x2\u0026thinsp;=\u0026thinsp;8.183, p\u0026thinsp;=\u0026thinsp;0.004), respectively (Fig.\u0026nbsp;2).\u003c/p\u003e "},{"header":"Discussion","content":" \u003cp\u003eOur study indicated that ultrasound-found nodules presented a greater malignancy risk than palpation-found ones. There were several explanations for the results. First, only 10% of ultrasound-found nodules were purely cystic, which are highly likely to be benign [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In contrast to palpation-found ones, purely cystic nodules were nearly 40%. Second, though ultrasound-found nodules were smaller in size, they had higher TI-RADS score than palpation-found ones. Unlike palpation-found nodules, ultrasound-found nodules were smaller and often located deep in the thyroid tissue. Hence the relation of the nodule size between malignancy risk and prognosis as recommended by AACE became controversial [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThough some studies found that malignant risk is associated with nodule size, for example, a series of observational studies have found that thyroid cancers over 4\u0026nbsp;cm were associated with more aggressive behavior whereas tumors smaller than 1.5\u0026nbsp;cm had a good overall prognosis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, some other researches indicated no correlation between size and risk [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. A recent study found that the impact of nodule size on the malignancy risk differed according to the ultrasound pattern. A large nodule size (\u0026ge;\u0026thinsp;3\u0026nbsp;cm) showed a higher malignancy risk than smaller nodules in intermediate- and low-suspicion nodules [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe are convinced that our study findings as demonstrated above, highlight a conflict between AACE recommendations and clinical practice in the following aspects: AACE\u0026rsquo;s recommendation against ultrasound screening for thyroid nodules and the recommendation of FNA based on nodule size [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. American Thyroid Association (ATA) also recommends FNA based on nodule size [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In our study, the average diameter of ultrasound-found nodules is 1.75\u0026nbsp;cm, which was within both of the recommended range of FNA.\u003c/p\u003e \u003cp\u003eAnother conflict between AACE recommendations and recent reality highlighted in this study is that AACE recommends against ultrasound screening based on a significant increase in global thyroid cancer prevalence but a constant mortality rate [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, latest published study found that in America, incidence-based thyroid cancer mortality rose from 0.40 per 100,000 person-years in 1994\u0026ndash;1997 to 0.46 per 100,000 person-years in 2010\u0026ndash;2013 [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In China, the mortality increased from 0.30 per 100,000 in 2005 to 0.35 per 100,000 in 2015 [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eUnder current guidelines, only a small portion of patients could be under active surveillance for micro carcinoma [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Furthermore, in our study of ultrasound-found nodules, there were as high as two thirds that were non-microcarcinoma. For such large nodules, it is generally believed that the benefits of surgery outweigh the risks [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe limitation of this study is that ultrasound evaluations were performed by different operators and machines, so bias may exist.\u003c/p\u003e \u003cp\u003eIn summary, since malignant nodules were more common in the ultrasound-found nodules, and nearly two thirds of which were non-microcarcinoma, we suggest the recommendation against screening thyroid nodules by ultrasound needs to be re-evaluated.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cp\u003eAACE: American Association of Clinical Endocrinologists; ACR: American College of Radiology; ATA: American Thyroid Association; FNA: fine-needle aspiration; TI-RADS: Thyroid imaging reporting and data system\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u2028\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eL.L. and W.L. constructed the study design, interpreted the data, and drafted the report. Z.C. participated in data analysis and manuscript writing. All the other coauthors contributed to the discussion of the study protocol, data collection, and manuscript revision. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe present work was supported by grants from the Foundation of Guangdong Medical Science and Technology Research (No. A2019036).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was submitted to and approved by the Clinical Research Ethics Committee of the Second Affiliated Hospital of Guangzhou Medical University. Every participant signed a voluntary and written informed consent, and all the consents were obtained from the ethics committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Endocrinology, The Second Affiliated Hospital, Guangzhou Medical University, No.250 Changgang Road East, Haizhu District, Guangzhou 510260, China.\u003csup\u003e 2\u003c/sup\u003eDepartment of Endocrinology, The Third Affiliated Hospital, Southern Medical University, No.183 Zhongshan Avenue West, Tianhe District, Guangzhou 510630, China. \u003csup\u003e3\u003c/sup\u003eDepartment of Endocrinology, Affiliated Nanhai Hospital of Southern Medical University, No.40 Foping Road, Nanhai District, Foshan 528200, China. \u003csup\u003e4\u003c/sup\u003eDepartment of Medical Ultrasound, The Second Affiliated Hospital, Guangzhou Medical University, No.250 Changgang Road East, Haizhu District, Guangzhou 510260, China;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eJiang H, Tian Y, Yan W, et al. 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ACR Thyroid Imaging, Reporting and Data System (TI-RADS): White Paper of the ACR TI-RADS Committee. J Am Coll Radiol. 2017;14(5):587\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZheng B, Zarka MA, Chen C, You J, Sun L, Chen L. The largest CAP-certified Chinese reference laboratory experience with the Bethesda system for reporting thyroid cytopathology: correlation with histologic and BRAF data. J Am Soc Cytopathol. 2018;7(1):16\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCibas ES, Ali SZ. The Bethesda System for reporting thyroid cytopathology. Thyroid. 2009;19(11):1159\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaugen BR, Alexander EK, Bible KC, 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\u0026ndash;133.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCavallo A, Johnson DN, White MG, et al. Thyroid nodule size at ultrasound as a predictor of malignancy and finalpathologic size. Thyroid. 2017;27(5):641\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTam S, Amit M, Boonsripitayanon M, et al. Effect of tumor size and minimal extrathyroidal extension in patients with differentiated thyroid cancer. Thyroid. 2018;28:982\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIto Y, Miyauchi A, Oda H. Low-risk papillary microcarcinoma of the thyroid: A review of active surveillance trials. Eur J Surg Oncol. 2018;44:307\u0026ndash;15. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ejso.2017.03.004\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcHenry CR, Huh ES, Machekano RN. Is nodule size an independent predictor of thyroid malignancy? Surgery. 2008;144(6):1062\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJinih M, Faisal F, Abdalla K, et al. Association between thyroid nodule size and malignancy rate. Ann R Coll Surg Engl. 2020;102(1):43\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHong MJ, Na DG, Baek JH, Sung JY, Kim JH. Impact of Nodule Size on Malignancy Risk Differs according to the Ultrasonography Pattern of Thyroid Nodules. Korean J Radiol. 2018;19(3):534\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLim H, Devesa SS, Sosa JA, Check D, Kitahara CM. Trends in thyroid cancer incidence and mortality in the United States, 1974\u0026ndash;2013. JAMA. 2017;317:1338\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang J, Yu F, Shang Y, Ping Z, Liu L. Thyroid cancer: incidence and mortality trends in China, 2005\u0026ndash;2015. Endocrine. 2020 Jan 30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIto Y, Miyauchi A, Kudo T, et al. Trends in the implementation of active surveillance for low-risk papillary thyroid microcarcinomas at Kuma Hospital: gradual increase and heterogeneity in the acceptance of this new management option. Thyroid. 2018;28(4):488\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Thyroid nodules, Ultrasound, Carcinomas, Screen","lastPublishedDoi":"10.21203/rs.3.rs-150354/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-150354/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackgrounds: \u003c/strong\u003eThe incidence of thyroid nodules is increasing year by year around the world. However, ultrasound is not recommended as a screening test for the general population or patients with a normal thyroid on palpation by the American Association of Clinical Endocrinologists (AACE). In practice, some individuals with normal thyroid palpation have nodules that can just be found out by ultrasound. No studies have directly described the risk of nodules found by ultrasound or by palpation up to now. More evidence is needed to carry out for helping us balance the over diagnosis and missed diagnosis of malignant lesions. Therefore, we carried out a retrospective study to investigate the incidence of malignant lesions in ultrasound-found nodules in a large cohort.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe conducted a retrospective analysis involving 2957 patients who underwent thyroid ultrasound evaluation and fine-needle aspiration (FNA) between Jan 2013 and Dec 2019. The cytologic examinations were analyzed based on the Bethesda system. For nodules suspected to be follicular neoplasm or other malignant tumors by cytological tests, patients were recommended for surgery and histopathology examinations.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Compared with palpation-found nodules, ultrasound-found nodules were presenting less as purely cystic nodules (10.1% vs 39.9%, x\u003csup\u003e2\u003c/sup\u003e=355.69, p=0.000), smaller size (17.5±9.9 mm vs 28.0±12.5 mm, t=23.876 p=0.000), and higher TI-RADS score (5.5±2.9 vs 3.4±3.3, t=18.084, p=0.000), respectively. More ultrasound-found nodules were diagnosed as carcinoma by histology examinations [136 (11.2%) nodules found by ultrasound vs 68 (3.9%) by palpation, x\u003csup\u003e2\u003c/sup\u003e=59.737, p=0.000], and 88 (64.7%) nodules found by ultrasound were non-microcarcinoma. Among the malignant nodules confirmed by histopathology, a higher proportion of microcarcinoma was detected in ultrasound-found nodules [35.3% (48/136) vs 16.2% (11/68), x\u003csup\u003e2\u003c/sup\u003e=8.183, p=0.004]. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e In view of the results observed in our research that malignant nodules were more common screened out by ultrasound, and nearly two thirds of them were non-microcarcinoma. We recommend reassessment of the recommendations for thyroid nodule screening.\u003c/p\u003e","manuscriptTitle":"Incidence of Microcarcinoma and Non-Microcarcinoma in Ultrasound-Found Thyroid Nodules","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-01-20 18:47:19","doi":"10.21203/rs.3.rs-150354/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2021-01-21T00:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after discretionary revisions\nForm responses:\n---\n\nComments to Author:\n---\nDear authors,\n\nWith great interest I read the first Revision of the manuscript \"Incidence of Microcarcinoma and Non-microcarcinoma in Ultrasound-found Thyroid Nodules\" submitted to BMC Endocrine Disorders. The study evaluates the incidence of microcarcinoma and non-microcarcinoma in ultrasound-found thyroid nodules in a large study cohort of 2957 patients.\n\nThe submitted manuscript is well designed and its methodology and statistical analysis are appropriate for its stated aim. The intention for the study is presented adequately and the results are clear-cut.\n\nTherefore, I have only minor revisions concerning the manuscript.\n\nDiscussion\nThis section is well written and clearly to the point. However, I would suggest to shortly consider the following recently published valuable references according to their importance on this topic:\n\n2020 Chinese guidelines for ultrasound malignancy risk stratification of thyroid nodules: the C-TIRADS.\nZhou J, Yin L, Wei X, Zhang S, Song Y, Luo B, Li J, Qian L, Cui L, Chen W, Wen C, Peng Y, Chen Q, Lu M, Chen M, Wu R, Zhou W, Xue E, Li Y, Yang L, Mi C, Zhang R, Wu G, Du G, Huang D, Zhan W.\nEndocrine. 2020 Nov; 70(2): 256-279\n\nThyroid imaging reporting and data system (TIRADS) for ultrasound features of nodules: multicentric retrospective study in China\nJianQiao Zhou, YanYan Song, WeiWei Zhan, Xi Wei, Sheng Zhang, RuiFang Zhang, Ying Gu, Xia Chen, Liying Shi, XiaoMao Luo, LiChun Yang, QiaoYing Li, BaoYan Bai, XinHua Ye, Hong Zhai, Hua Zhang, XiaoHong Jia, YiJie Dong, JingWen Zhang, ZhiFang Yang, HuiTing Zhang, Yi Zheng, WenWen Xu, LiMei Lai, LiXue Yin.\nEndocrine. 2020 Aug 27. doi: 10.1007/s12020-020-02442-x. Online ahead of print.\n\nComparison among TIRADS (ACR TI-RADS and KWAK- TI-RADS) and 2015 ATA Guidelines in the diagnostic efficiency of thyroid nodules\nLuying Gao, Xuehua Xi, Yuxin Jiang, Xiao Yang, Ying Wang, Shenling Zhu, Xingjian Lai, Xiaoyan Zhang, Ruina Zhao, Bo Zhang.\nEndocrine. 2019 Apr;64(1):90-96. doi: 10.1007/s12020-019-01843-x. Epub 2019 Jan 18.\n\nEditorial points:\nLine 54: recent\nLine 125: more microcarcinoma were detected\n\nIn my opinion the manuscript is, after the above mentioned minor revisions, ready for final acceptance in BMC Endocrine Disorders.\n\nThank you for your fine contribution\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Declaration of competing interests: **'I declare that I have no competing interests'**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"decision","content":"Major revision","date":"2021-01-21T00:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-01-19T00:00:00+00:00","index":2,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-01-17T00:00:00+00:00","index":1,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nIn this study, the authors aimed at evaluating the incidence of malignant lesions (i.e., both microcarcinomas non-microcarcinomas) by a retrospective analysis involving 2957 patients who underwent thyroid ultrasound evaluation. The subject is interesting, but I recommend a thorough linguistic revision by a native speaker. In addition, the discussion section should be more extensive and detailed.\nMinor comments\nLines 63-66. This sentence is unclear. Please rephrase for better clarity.\nLine 125. Please change \"microcarcinoma\" to \"microcarcinomas\" and \"was\" to \"were\".\nLines 133-134. Please rephrase as follows: \"In contrast, purely cystic nodules were nearly 40%in palpation-found ones.\nLine 135. Please add \"and\" before \"they\" and delete the comma.\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **No**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"reviewerAgreed","content":"","date":"2021-01-16T00:00:00+00:00","index":1,"fulltext":""},{"type":"editorAssigned","content":"","date":"2021-01-14T00:00:00+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-01-14T00:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2021-01-13T23:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2021-01-13T23:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3082b208-70f7-48f7-b634-9545f0ca2f8b","owner":[],"postedDate":"January 20th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":1984832,"name":"Endocrinology \u0026 Metabolism"}],"tags":[],"updatedAt":"2021-03-07T15:07:12+00:00","versionOfRecord":{"articleIdentity":"rs-150354","link":"https://doi.org/10.1186/s12902-021-00700-1","journal":{"identity":"bmc-endocrine-disorders","isVorOnly":false,"title":"BMC Endocrine Disorders"},"publishedOn":"2021-03-04 15:05:35","publishedOnDateReadable":"March 4th, 2021"},"versionCreatedAt":"2021-01-20 18:47:19","video":"","vorDoi":"10.1186/s12902-021-00700-1","vorDoiUrl":"https://doi.org/10.1186/s12902-021-00700-1","workflowStages":[]},"version":"v1","identity":"rs-150354","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-150354","identity":"rs-150354","version":["v1"]},"buildId":"omnImTCwR2MFx8CMYfrG7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}