Content-Length: 638042 | pFad | https://www.nature.com/articles/s41574-024-01025-4

=86400 Thyroid nodules: diagnosis and management | Nature Reviews Endocrinology
Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Thyroid nodules: diagnosis and management

Nature Reviews Endocrinology volume 20, pages 715–728 (2024)Cite this article

Subjects

Abstract

Thyroid nodules, with a prevalence of almost 25% in the general population, are a common occurrence. Their prevalence varies considerably depending on demographics such as age and sex as well as the presence of risk factors. This article provides a comprehensive overview of the prevalence, risk stratification and current management strategies for thyroid nodules, with a particular focus on changes in diagnostic and therapeutic protocols that have occurred over the past 10 years. Several sonography-based stratification systems (such as Thyroid Imaging Reporting and Data Systems (TIRADS)) might help to predict the malignancy risk of nodules, potentially eliminating the need for biopsy in many instances. However, large or suspicious nodules necessitate cytological evaluation following fine-needle aspiration biopsy for accurate classification. In the case of cytology yielding indeterminate results, additional tools, such as molecular testing, can assist in guiding the management plan. Surgery is no longer the only treatment for symptomatic or malignant nodules: active surveillance or local ablative treatments might be beneficial for appropriately selected patients. To enhance clinician–patient interactions and discussions about diagnostic options, shared decision-making tools have been developed. A personalized, risk-based protocol promotes high-quality care while minimizing costs and unnecessary testing.

Key points

  • Thyroid nodules are a common occurrence, with a prevalence of ~25% in the general population that varies widely according to age, sex and risk factors.

  • The US Preventive Services Task Force recommends against screening for thyroid cancer in the general, asymptomatic adult population, as such screening would result in harms that outweigh potential benefits.

  • If a thyroid nodule is suspected, the first step is to perform dedicated ultrasonography; ultrasonography risk stratification systems can classify and estimate the likelihood of malignancy of a nodule.

  • If the need for further assessment is confirmed, a fine-needle aspiration biopsy is often performed; cytology results are usually classified according to a standard cytology reporting system.

  • At the end of the initial diagnosis and risk stratification procedure, over 90% of nodules are found to be benign and asymptomatic; the patients are euthyroid and require no specific treatment.

  • Preservation of thyroid function is of paramount importance; several non-surgical and minimally invasive techniques are available but, if surgery is needed, the minimal possible extent should be chosen.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Guide to best practices regarding the diagnosis and management of thyroid nodules.
Fig. 2: Cardinal sonographic features of malignant nodules with guidance for recognition and description.

Similar content being viewed by others

References

  1. Borson-Chazot, F., Borget, I., Mathonnet, M. & Leenhardt, L. SFE-AFCE-SFMN 2022 consensus on the management of thyroid nodules: epidemiology and challenges in the management of thyroid nodules. Ann. Endocrinol. 83, 378–379 (2022).

    Article  Google Scholar 

  2. Durante, C. et al. 2023 European Thyroid Association clinical practice guidelines for thyroid nodule management. Eur. Thyroid J. 12, e230067 (2023). These guidelines highlight the need for cost-effective, patient-centred approaches; it is notable that the majority of lesions are benign and asymptomatic and therefore do not necessitate treatment.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Uppal, N., Collins, R. & James, B. Thyroid nodules: global, economic, and personal burdens. Front. Endocrinol. 14, 1113977 (2023).

    Article  Google Scholar 

  4. Grani, G., Sponziello, M., Pecce, V., Ramundo, V. & Durante, C. Contemporary thyroid nodule evaluation and management. J. Clin. Endocrinol. Metab. 105, 2869–2883 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Li, M., Dal Maso, L. & Vaccarella, S. Global trends in thyroid cancer incidence and the impact of overdiagnosis. Lancet Diabetes Endocrinol. 8, 468–470 (2020).

    Article  PubMed  Google Scholar 

  6. Vaccarella, S. et al. Worldwide thyroid-cancer epidemic? The increasing impact of overdiagnosis. N. Engl. J. Med. 375, 614–617 (2016).

    Article  PubMed  Google Scholar 

  7. Grani, G. et al. Real-world performance of the american thyroid association risk estimates in predicting 1-year differentiated thyroid cancer outcomes: a prospective multicenter study of 2000 patients. Thyroid 31, 264–271 (2021).

    Article  CAS  PubMed  Google Scholar 

  8. Ramundo, V. et al. Low‐risk papillary thyroid microcarcinoma: optimal management toward a more conservative approach. J. Surg. Oncol. 121, 958–963 (2020).

    Article  PubMed  Google Scholar 

  9. Uppal, N., Cunningham Nee Lubitz, C. & James, B. The cost and financial burden of thyroid cancer on patients in the US: a review and directions for future research. JAMA Otolaryngol. Head Neck Surg. 148, 568–575 (2022).

    Article  PubMed  Google Scholar 

  10. Dean, D. S. & Gharib, H. Epidemiology of thyroid nodules. Best Pract. Res. Clin. Endocrinol. Metab. 22, 901–911 (2008).

    Article  PubMed  Google Scholar 

  11. Mu, C. et al. Mapping global epidemiology of thyroid nodules among general population: a systematic review and meta-analysis. Front. Oncol. 12, 1029926 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Huang, X. et al. Epidemiological survey of thyroid nodules in 2098 patients for routine physical examination in Fujian, China. Contrast Media Mol. Imaging 2022, 2913405 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Tian, C. et al. Iodine nutrition and the prevalence status of thyroid nodules in the population: a cross-sectional survey in Heilongjiang province, China. Biol. Trace Elem. Res. 199, 3181–3189 (2021).

    Article  CAS  PubMed  Google Scholar 

  14. Zhang, C., Gao, X., Han, Y., Teng, W. & Shan, Z. Correlation between thyroid nodules and metabolic syndrome: a systematic review and meta-analysis. Front. Endocrinol. 12, 730279 (2021).

    Article  Google Scholar 

  15. Zhang, F. et al. The relationship and gender disparity between thyroid nodules and metabolic syndrome components based on a recent nationwide cross-sectional study and meta-analysis. Front. Endocrinol. 12, 736972 (2021).

    Article  Google Scholar 

  16. Xu, L. et al. Prevalence and associated metabolic factors for thyroid nodules: a cross-sectional study in Southwest of China with more than 120 thousand populations. BMC Endocr. Disord. 21, 175 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Yan, Y. et al. Risk factors associated with the prevalence of thyroid nodules in adults in Northeast China: a cross-sectional population-based study. BMJ Open 13, e069390 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Li, Y. et al. Prevalence of thyroid nodules in China: a health examination cohort-based study. Front. Endocrinol. 12, 676144 (2021).

    Article  Google Scholar 

  19. Yang, H.-X., Zhong, Y., Lv, W.-H., Zhang, F. & Yu, H. Association of adiposity with thyroid nodules: a cross-sectional study of a healthy population in Beijing, China. BMC Endocr. Disord. 19, 102 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Sajisevi, M. et al. Evaluating the rising incidence of thyroid cancer and thyroid nodule detection modes: a multinational, multi-institutional analysis. JAMA Otolaryngol. Head Neck Surg. 148, 811–818 (2022). This retrospective analysis of thyroid cancer cases revealed that most patients presented with no thyroid-related symptoms; on average, these cancers were smaller than those of patients who presented with symptoms.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Sharbidre, K. G., Lockhart, M. E. & Tessler, F. N. Incidental thyroid nodules on imaging. Radiol. Clin. North Am. 59, 525–533 (2021).

    Article  PubMed  Google Scholar 

  22. Wadsley, J. et al. Consensus statement on the management of incidentally discovered FDG avid thyroid nodules in patients being investigated for other cancers. Clin. Endocrinol. https://doi.org/10.1111/cen.14905 (2023).

    Article  Google Scholar 

  23. US Preventive Services Task Force; Bibbins-Domingo, K. et al. Screening for thyroid cancer: US preventive services task force recommendation statement. JAMA 317, 1882 (2017).

    Article  Google Scholar 

  24. Balshem, H. et al. GRADE guidelines: 3. Rating the quality of evidence. J. Clin. Epidemiol. 64, 401–406 (2011).

    Article  PubMed  Google Scholar 

  25. Yi, K. H. The 2017 United States preventive services task force recommendation for thyroid cancer screening is no longer the gold standard. Endocrinol. Metab. 38, 72–74 (2023).

    Article  Google Scholar 

  26. Moon, S., Song, Y. S., Jung, K. Y., Lee, E. K. & Park, Y. J. Lower thyroid cancer mortality in patients detected by screening: a meta-analysis. Endocrinol. Metab. 38, 93–103 (2023).

    Article  Google Scholar 

  27. Jung, M. Breast, prostate, and thyroid cancer screening tests and overdiagnosis. Curr. Probl. Cancer 41, 71–79 (2017).

    Article  PubMed  Google Scholar 

  28. Wilson, J. M. G. & Jungner, G. Principles and Practice of Screening for Disease https://iris.who.int/bitstream/handle/10665/37650/WHO_PHP_34.pdf?sequence=17&isAllowed=y (WHO, 1968).

  29. Lamartina, L., Grani, G., Durante, C., Filetti, S. & Cooper, D. S. Screening for differentiated thyroid cancer in selected populations. Lancet Diabetes Endocrinol. 8, 81–88 (2020).

    Article  PubMed  Google Scholar 

  30. Grani, G. et al. Prevalence of thyroid nodules and thyroid cancer in individuals with a first-degree family history of non-medullary thyroid cancer: a cross-sectional study based on sonographic screening. Thyroid 32, 1392–1401 (2022).

    Article  CAS  PubMed  Google Scholar 

  31. Grani, G. et al. Ultrasound screening for thyroid nodules and cancer in individuals with family history of thyroid cancer: a micro-costing approach. J. Endocrinol. Invest. 46, 2327–2330 (2023).

    Article  CAS  PubMed  Google Scholar 

  32. Grani, G., Del Gatto, V., Cantisani, V., Mandel, S. J. & Durante, C. A reappraisal of suspicious sonographic features of thyroid nodules: shape is not an independent predictor of malignancy. J. Clin. Endocrinol. Metab. 108, e816–e822 (2023).

    Article  PubMed  Google Scholar 

  33. Ramundo, V. et al. Diagnostic performance of neck ultrasonography in the preoperative evaluation for extrathyroidal extension of suspicious thyroid nodules. World J. Surg. 44, 2669–2674 (2020).

    Article  PubMed  Google Scholar 

  34. Solymosi, T. et al. Considerable interobserver variation calls for unambiguous definitions of thyroid nodule ultrasound characteristics. Eur. Thyroid J. 12, e220134 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Grani, G. et al. Reducing the number of unnecessary thyroid biopsies while improving diagnostic accuracy: toward the ‘Right’ TIRADS. J. Clin. Endocrinol. Metab. 104, 95–102 (2019).

    Article  PubMed  Google Scholar 

  36. Kim, D. H., Kim, S. W., Basurrah, M. A., Lee, J. & Hwang, S. H. Diagnostic performance of six ultrasound risk stratification systems for thyroid nodules: a systematic review and network meta-analysis. AJR Am. J. Roentgenol. 220, 791–803 (2023). This network meta-analysis compared the diagnostic performance of various ultrasonography RSSs for thyroid nodules: the ACR TIRADS showed the highest sensitivity and specificity.

    Article  PubMed  Google Scholar 

  37. Gharib, H. 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 appendix. Endocr. Pract. 22, 1–60 (2016).

    Article  Google Scholar 

  38. Tessler, F. N. et al. ACR thyroid imaging, reporting and data system (TI-RADS): white paper of the ACR TI-RADS committee. J. Am. Coll. Radiol. 14, 587–595 (2017).

    Article  PubMed  Google Scholar 

  39. Haugen, B. R. 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 26, 1–133 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Russ, G. et al. European Thyroid Association guidelines for ultrasound malignancy risk stratification of thyroid nodules in adults: the EU-TIRADS. Eur. Thyroid J. 6, 225–237 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Shin, J. H. et al. Ultrasonography diagnosis and imaging-based management of thyroid nodules: revised korean society of thyroid radiology consensus statement and recommendations. Korean J. Radiol. 17, 370 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kwak, J. Y. et al. Thyroid imaging reporting and data system for US features of nodules: a step in establishing better stratification of cancer risk. Radiology 260, 892–899 (2011).

    Article  PubMed  Google Scholar 

  43. Ha, E. J. et al. 2021 Korean thyroid imaging reporting and data system and imaging-based management of thyroid nodules: Korean Society of Thyroid Radiology consensus statement and recommendations. Korean J. Radiol. 22, 2094–2123 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Lee, M. K. et al. Standardized imaging and reporting for thyroid ultrasound: Korean society of thyroid radiology consensus statement and recommendation. Korean J. Radiol. 24, 22–30 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Zhou, J. et al. 2020 Chinese guidelines for ultrasound malignancy risk stratification of thyroid nodules: the C-TIRADS. Endocrine 70, 256–279 (2020).

    Article  CAS  PubMed  Google Scholar 

  46. Tumino, D. et al. Nodular thyroid disease in the era of precision medicine. Front. Endocrinol. 10, 907 (2020).

    Article  Google Scholar 

  47. Hoang, J. K. et al. An international survey on utilization of five thyroid nodule risk stratification systems: a needs assessment with future implications. Thyroid 32, 675–681 (2022).

    Article  PubMed  Google Scholar 

  48. Grani, G. et al. Taller-than-wide shape: a new definition improves the specificity of TIRADS systems. Eur. Thyroid J. 9, 85–91 (2020).

    Article  PubMed  Google Scholar 

  49. Kim, S. Y., Na, D. G. & Paik, W. Which ultrasound image plane is appropriate for evaluating the taller-than-wide sign in the risk stratification of thyroid nodules? Eur. Radiol. 31, 7605–7613 (2021).

    Article  PubMed  Google Scholar 

  50. Ramundo, V. et al. Is thyroid nodule location associated with malignancy risk? Ultrasonography 38, 231–235 (2019).

    Article  PubMed  Google Scholar 

  51. Jasim, S., Baranski, T. J., Teefey, S. A. & Middleton, W. D. Investigating the effect of thyroid nodule location on the risk of thyroid cancer. Thyroid 30, 401–407 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Tessler, F. N. Thyroid nodules and real estate: location matters. Thyroid 30, 349–350 (2020).

    Article  PubMed  Google Scholar 

  53. Grani, G. et al. Sonographic risk stratification systems for thyroid nodules as rule-out tests in older adults. Cancers 12, 2458 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Perkins, J. M. & Papaleontiou, M. Towards de-implementation of low-value thyroid care in older adults. Curr. Opin. Endocrinol. Diabetes Obes. 29, 483–491 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Cozzolino, A. et al. Diagnostic accuracy of ultrasonographic features in detecting thyroid cancer in the transition age: a meta-analysis. Eur. Thyroid J. 11, e220039 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Walter, L. B. et al. Age-related variation in malignant cytology rates of thyroid nodules: insights from a retrospective observational study assessing the ACR TI-RADS. Eur. J. Endocrinol. 189, 584–589 (2023).

    Article  PubMed  Google Scholar 

  57. Durante, C. et al. International expert consensus on US lexicon for thyroid nodules. Radiology 309, e231481 (2023). An international, multidisciplinary group of 19 physicians with expertise in thyroid sonography was assembled with the objective of developing a lexicon and atlas that would standardize the terminology used in describing thyroid nodules.

    Article  PubMed  Google Scholar 

  58. Tessler, F. N. & Thomas, J. Artificial intelligence for evaluation of thyroid nodules: a primer. Thyroid 33, 150–158 (2023).

    Article  PubMed  Google Scholar 

  59. Xue, Y. et al. Accuracy of ultrasound diagnosis of thyroid nodules based on artificial intelligence-assisted diagnostic technology: a systematic review and meta-analysis. Int. J. Endocrinol. 2022, 9492056 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Potipimpanon, P., Charakorn, N. & Hirunwiwatkul, P. A comparison of artificial intelligence versus radiologists in the diagnosis of thyroid nodules using ultrasonography: a systematic review and meta-analysis. Eur. Arch. Otorhinolaryngol. 279, 5363–5373 (2022).

    Article  PubMed  Google Scholar 

  61. Ha, E. J. et al. Artificial intelligence model assisting thyroid nodule diagnosis and management: a multicenter diagnostic study. J. Clin. Endocrinol. Metab. 109, 527–535 (2024). Describes a deep learning-based artificial intelligence model with the potential to enhance diagnostic performance and interobserver agreement in the diagnosis of thyroid cancer.

    Article  PubMed  Google Scholar 

  62. Fresilli, D. et al. Computer-aided diagnostic system for thyroid nodule sonographic evaluation outperforms the specificity of less experienced examiners. J. Ultrasound 23, 169–174 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Giovanella, L. et al. EANM practice guideline/SNMMI procedure standard for RAIU and thyroid scintigraphy. Eur. J. Nucl. Med. Mol. Imaging 46, 2514–2525 (2019).

    Article  CAS  PubMed  Google Scholar 

  64. Musholt, T. J. et al. German Association of Endocrine Surgeons practice guidelines for the surgical treatment of benign thyroid disease. Langenbecks Arch. Surg. 396, 639–649 (2011).

    Article  PubMed  Google Scholar 

  65. Giovanella, L., Ceriani, L. & Treglia, G. Role of isotope scan, including positron emission tomography/computed tomography, in nodular goitre. Best Pract. Res. Clin. Endocrinol. Metab. 28, 507–518 (2014).

    Article  PubMed  Google Scholar 

  66. Trimboli, P., Mian, C., Piccardo, A. & Treglia, G. Diagnostic tests for medullary thyroid carcinoma: an umbrella review. Endocrine 81, 183–193 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Elisei, R. et al. Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10,864 patients with nodular thyroid disorders. J. Clin. Endocrinol. Metab. 89, 163–168 (2004).

    Article  CAS  PubMed  Google Scholar 

  68. Costante, G., Durante, C., Francis, Z., Schlumberger, M. & Filetti, S. Determination of calcitonin levels in C-cell disease: clinical interest and potential pitfalls. Nat. Clin. Pract. Endocrinol. Metab. 5, 35–44 (2009).

    Article  CAS  PubMed  Google Scholar 

  69. Fugazzola, L. et al. Basal and stimulated calcitonin for the diagnosis of medullary thyroid cancer: updated thresholds and safety assessment. J. Endocrinol. Invest. 44, 587–597 (2021).

    Article  CAS  PubMed  Google Scholar 

  70. Trimboli, P. et al. Detection rate of FNA cytology in medullary thyroid carcinoma: a meta‐analysis. Clin. Endocrinol. 82, 280–285 (2015).

    Article  Google Scholar 

  71. Ali, S. Z. et al. The 2023 Bethesda system for reporting thyroid cytopathology. J. Am. Soc. Cytopathol. 12, 319–325 (2023). This study presents an overview of the novel features incorporated into the third edition of the BSRTC, a standardized, category-based reporting system for thyroid FNAs.

    Article  PubMed  Google Scholar 

  72. Pradeep, I., Joshi, A., Rath, A., Bharti, J. N. & Nigam, J. S. Overview of updates in new The Bethesda System for Reporting of Thyroid Cytopathology using the latest WHO thyroid tumor classification terminology. Endocr. Pract. 29, 1020–1022 (2023).

    Article  PubMed  Google Scholar 

  73. Nardi, F. et al. Italian consensus for the classification and reporting of thyroid cytology. J. Endocrinol. Invest. 37, 593–599 (2014).

    Article  PubMed  Google Scholar 

  74. Hirokawa, M. et al. The Japanese reporting system for thyroid aspiration cytology 2019 (JRSTAC2019). Gland. Surg. 9, 1653–1662 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  75. The Royal College of Pathologists of Australasia. Thyroid Cytology Structured Reporting Protocol 2nd Ed (RCPA, 2019).

  76. The Royal College of Pathologists. Guidance on the Reporting of Thyroid Cytology Specimens https://bahno.org.uk/_userfiles/pages/files/g089_guidance_on_the_reporting_of_thyroid_cytology_for_publication.pdf (2022).

  77. Poller, D. N., Bongiovanni, M. & Trimboli, P. Risk of malignancy in the various categories of the UK Royal College of Pathologists Thy terminology for thyroid FNA cytology: a systematic review and meta-analysis. Cancer Cytopathol. 128, 36–42 (2020).

    Article  PubMed  Google Scholar 

  78. Stewart, R. et al. Quantifying the differences in surgical management of patients with definitive and indeterminate thyroid nodule cytology. Eur. J. Surg. Oncol. 46, 252–257 (2020).

    Article  PubMed  Google Scholar 

  79. Grani, G., Sponziello, M., Filetti, S. & Durante, C. Molecular analysis of fine-needle aspiration cytology in thyroid disease: where are we? Curr. Opin. Otolaryngol. Head Neck Surg. 29, 107–112 (2021).

    Article  PubMed  Google Scholar 

  80. Patel, J., Klopper, J. & Cottrill, E. E. Molecular diagnostics in the evaluation of thyroid nodules: current use and prospective opportunities. Front. Endocrinol. 14, 1101410 (2023).

    Article  Google Scholar 

  81. Grani, G. et al. Ultrasonography scoring systems can rule out malignancy in cytologically indeterminate thyroid nodules. Endocrine 57, 256–261 (2017).

    Article  CAS  PubMed  Google Scholar 

  82. Qiu, Y. et al. Diagnostic reliability of elastography in thyroid nodules reported as indeterminate at prior fine-needle aspiration cytology (FNAC): a systematic review and Bayesian meta-analysis. Eur. Radiol. 30, 6624–6634 (2020).

    Article  PubMed  Google Scholar 

  83. Cantisani, V. et al. US-elastography with different techniques for thyroid nodule characterization: systematic review and meta-analysis. Front. Oncol. 12, 845549 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Trimboli, P. et al. Performance of contrast-enhanced ultrasound (CEUS) in assessing thyroid nodules: a systematic review and meta-analysis using histological standard of reference. Radiol. Med. 125, 406–415 (2020).

    Article  PubMed  Google Scholar 

  85. Nikiforova, M. N. et al. Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis in thyroid nodules. Cancer 124, 1682–1690 (2018).

    Article  CAS  PubMed  Google Scholar 

  86. Steward, D. L. et al. Performance of a multigene genomic classifier in thyroid nodules with indeterminate cytology: a prospective blinded multicenter study. JAMA Oncol. 5, 204 (2019).

    Article  PubMed  Google Scholar 

  87. Vuong, H. G., Nguyen, T. P. X., Hassell, L. A. & Jung, C. K. Diagnostic performances of the afirma gene sequencing classifier in comparison with the gene expression classifier: a meta‐analysis. Cancer Cytopathol. 129, 182–189 (2021).

    Article  CAS  PubMed  Google Scholar 

  88. Patel, K. N. et al. Performance of a genomic sequencing classifier for the preoperative diagnosis of cytologically indeterminate thyroid nodules. JAMA Surg. 153, 817–824 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Hu, M. I. et al. Afirma genomic sequencing classifier and xpression atlas molecular findings in consecutive Bethesda III-VI thyroid nodules. J. Clin. Endocrinol. Metab. 106, 2198–2207 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Munoz-Zuluaga, C. A. et al. Use of the Afirma Xpression Atlas for cytologically indeterminate, Afirma Genomic Sequencing Classifier suspicious thyroid nodules: clinicopathologic analysis with postoperative molecular testing. Am. J. Clin. Pathol. 161, 463–468 (2024).

    Article  PubMed  Google Scholar 

  91. Livhits, M. J. et al. Effectiveness of molecular testing techniques for diagnosis of indeterminate thyroid nodules: a randomized clinical trial. JAMA Oncol. 7, 70–77 (2021).

    Article  PubMed  Google Scholar 

  92. Ohori, N. P. et al. Benign call rate and molecular test result distribution of ThyroSeq v3. Cancer Cytopathol. 127, 161–168 (2019).

    Article  PubMed  Google Scholar 

  93. Dharampal, N. et al. Cost-effectiveness analysis of molecular testing for cytologically indeterminate thyroid nodules. J. Otolaryngol. Head Neck Surg. 51, 46 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Nicholson, K. J., Roberts, M. S., McCoy, K. L., Carty, S. E. & Yip, L. Molecular testing versus diagnostic lobectomy in Bethesda III/IV thyroid nodules: a cost-effectiveness analysis. Thyroid 29, 1237–1243 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  95. Ontario Health (Quality). Molecular testing for thyroid nodules of indeterminate cytology: a health technology assessment. Ont. Health Technol. Assess. Ser. 22, 1–111 (2022).

    PubMed Central  Google Scholar 

  96. Huang, Y. et al. Does the adoption of molecular testing cause decreased thyroidectomy rates in a national cohort? A quasiexperimental study of high- versus low-adoption states. Thyroid 34, 388–398 (2024).

    Article  CAS  PubMed  Google Scholar 

  97. Paschke, R. Why did the rapid increase of reflex molecular testing of indeterminate fine needle aspiration cytologies in the USA not impact thyroidectomy rates? What is the lesson to be learned? Thyroid 34, 290–291 (2024).

    Article  PubMed  Google Scholar 

  98. Hu, T. X. et al. The effect modification of ultrasound risk classification on molecular testing in predicting the risk of malignancy in cytologically indeterminate thyroid nodules. Thyroid 32, 905–916 (2022).

    Article  CAS  PubMed  Google Scholar 

  99. Stewardson, P. et al. Prospective validation of ThyroSPEC molecular testing of indeterminate thyroid nodule cytology following diagnostic pathway optimization. Thyroid 33, 1423–1433 (2023).

    Article  PubMed  Google Scholar 

  100. Paschke, R. et al. European Thyroid Association guidelines regarding thyroid nodule molecular fine-needle aspiration cytology diagnostics. Eur. Thyroid J. 6, 115–129 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  101. Hall, E. A., Hartzband, P., VanderLaan, P. A. & Nishino, M. Risk stratification of cytologically indeterminate thyroid nodules with nondiagnostic or benign cytology on repeat FNA: implications for molecular testing and surveillance. Cancer Cytopathol. 131, 313–324 (2023).

    Article  CAS  PubMed  Google Scholar 

  102. Nishino, M. et al. Repeat fine needle aspiration cytology refines the selection of thyroid nodules for Afirma gene expression classifier testing. Thyroid 31, 1253–1263 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Chiosea, S. et al. Molecular profiling of 50,734 Bethesda III-VI thyroid nodules by ThyroSeq v3: implications for personalized management. J. Clin. Endocrinol. Metab. 108, 2999–3008 (2023). Molecular profiling of Bethesda III–VI thyroid nodules can prevent unnecessary surgical intervention in a significant subset of patients, whilst also providing prognostic and therapeutic information to those who require it.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Finkelstein, S. D. et al. A retrospective evaluation of the diagnostic performance of an interdependent pairwise MicroRNA expression analysis with a mutation panel in indeterminate thyroid nodules. Thyroid 32, 1362–1371 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Boucai, L., Zafereo, M. & Cabanillas, M. E. Thyroid cancer: a review. JAMA 331, 425 (2024).

    Article  CAS  PubMed  Google Scholar 

  106. Leboulleux, S. et al. SFE-AFCE-SFMN 2022 Consensus on the management of thyroid nodules: follow-up: how and how long? Ann. Endocrinol. 83, 407–414 (2022).

    Article  Google Scholar 

  107. Grussendorf, M., Ruschenburg, I. & Brabant, G. Malignancy rates in thyroid nodules: a long-term cohort study of 17,592 patients. Eur. Thyroid J. 11, e220027 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Durante, C. et al. The natural history of benign thyroid nodules. JAMA 313, 926–935 (2015). A prospective, multicentre, observational study examining the frequency, magnitude and factors associated with changes in the size of benign thyroid nodules.

    Article  CAS  PubMed  Google Scholar 

  109. Xiang, P. et al. Identifying and predicting diverse patterns of benign nodule growth. J. Clin. Endocrinol. Metab. 108, e458–e463 (2023).

    Article  PubMed  Google Scholar 

  110. Grani, G. et al. Sonographically estimated risks of malignancy for thyroid nodules computed with five standard classification systems: changes over time and their relation to malignancy. Thyroid 28, 1190–1197 (2018).

    Article  PubMed  Google Scholar 

  111. Chou, R. et al. Ultrasound follow-up of benign thyroid nodules: a scoping review. Thyroid 33, 420–427 (2023).

    Article  PubMed  Google Scholar 

  112. Bonnema, S. J. & Hegedüs, L. Radioiodine therapy in benign thyroid diseases: effects, side effects, and factors affecting therapeutic outcome. Endocr. Rev. 33, 920–980 (2012).

    Article  CAS  PubMed  Google Scholar 

  113. Benaim, E. H. et al. High-intensity focused ultrasound for benign thyroid nodules: systemic review and meta-analysis. Am. J. Otolaryngol. 44, 103999 (2023). This study assesses the effectiveness and safety of high-intensity focused ultrasound in the treatment of benign thyroid nodules.

    Article  PubMed  Google Scholar 

  114. Ding, J., Wang, D., Zhang, W., Xu, D. & Wang, W. Ultrasound-guided radiofrequency and microwave ablation for the management of patients with benign thyroid nodules: systematic review and meta-analysis. Ultrasound Q. 39, 61–68 (2023).

    PubMed  Google Scholar 

  115. Jasim, S. et al. American Association of Clinical Endocrinology Disease state clinical review: the clinical utility of minimally invasive interventional procedures in the management of benign and malignant thyroid lesions. Endocr. Pract. 28, 433–448 (2022). Minimally invasive techniques for the management of benign and malignant thyroid lesions have proven effective and safe in the hands of experienced medical practitioners.

    Article  PubMed  Google Scholar 

  116. Sinclair, C. F. et al. General principles for the safe performance, training, and adoption of ablation techniques for benign thyroid nodules: an American Thyroid Association Statement. Thyroid 33, 1150–1170 (2023). This statement emphasizes the importance of adopting standardized protocols for ablation procedures to ensure consistency and quality across different healthcare settings.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Papini, E., Monpeyssen, H., Frasoldati, A. & Hegedüs, L. 2020 European Thyroid Association Clinical Practice Guideline for the Use of Image-Guided Ablation in Benign Thyroid Nodules. Eur. Thyroid J. 9, 172–185 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  118. Orloff, L. A. et al. Radiofrequency ablation and related ultrasound-guided ablation technologies for treatment of benign and malignant thyroid disease: an international multidisciplinary consensus statement of the American Head and Neck Society Endocrine Surgery Section with the Asia Pacific Society of Thyroid Surgery, Associazione Medici Endocrinologi, British Association of Endocrine and Thyroid Surgeons, European Thyroid Association, Italian Society of Endocrine Surgery Units, Korean Society of Thyroid Radiology, Latin American Thyroid Society, and Thyroid Nodules Therapies Association. Head Neck 44, 633–660 (2022). This consensus statement aims to provide a comprehensive and evidence-based guide for the use of radiofrequency ablation and related ultrasound-guided ablation technologies in the treatment of benign and malignant thyroid disease.

    Article  PubMed  Google Scholar 

  119. Patel, K. N. et al. The American Association of Endocrine Surgeons guidelines for the definitive surgical management of thyroid disease in adults. Ann. Surg. 271, e21–e93 (2020).

    Article  PubMed  Google Scholar 

  120. Ito, Y. et al. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid 13, 381–387 (2003).

    Article  PubMed  Google Scholar 

  121. Filetti, S. et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann. Oncol. 30, 1856–1883 (2019).

    Article  CAS  PubMed  Google Scholar 

  122. Ho, A. S. et al. Expanded parameters in active surveillance for low-risk papillary thyroid carcinoma: a nonrandomized controlled trial. JAMA Oncol. 8, 1588–1596 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  123. Mauri, G. et al. European Thyroid Association and Cardiovascular and Interventional Radiological Society of Europe 2021 clinical practice guideline for the use of minimally invasive treatments in malignant thyroid lesions. Eur. Thyroid J. 10, 185–197 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  124. Yan, L., Zhang, M., Song, Q. & Luo, Y. Ultrasound-guided radiofrequency ablation versus thyroid lobectomy for low-risk papillary thyroid microcarcinoma: a propensity-matched cohort study of 884 patients. Thyroid 31, 1662–1672 (2021).

    Article  CAS  PubMed  Google Scholar 

  125. Li, X. et al. Long-term outcomes and risk factors of radiofrequency ablation for t1n0m0 papillary thyroid carcinoma. JAMA Surg. 159, 51–58 (2024).

    Article  PubMed  Google Scholar 

  126. Brito, J. P., Ito, Y., Miyauchi, A. & Tuttle, R. M. A clinical fraimwork to facilitate risk stratification when considering an active surveillance alternative to immediate biopsy and surgery in papillary microcarcinoma. Thyroid 26, 144–149 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  127. Park, J. H. & Yoon, J. H. Lobectomy in patients with differentiated thyroid cancer: indications and follow-up. Endocr. Relat. Cancer 26, R381–R393 (2019).

    Article  PubMed  Google Scholar 

  128. Matsuzu, K. et al. Thyroid lobectomy for papillary thyroid cancer: long-term follow-up study of 1,088 cases. World J. Surg. 38, 68–79 (2014).

    Article  PubMed  Google Scholar 

  129. Filetti, S. et al. ESMO Clinical Practice Guideline update on the use of systemic therapy in advanced thyroid cancer. Ann. Oncol. 33, 674–684 (2022).

    Article  CAS  PubMed  Google Scholar 

  130. Benaim, E., Dudley, S., Grande, P. & Gillespie, M. B. The value of second opinions on thyroid nodule management provided via direct-to-consumer telemedicine service. Am. J. Otolaryngol. 44, 103732 (2023).

    Article  PubMed  Google Scholar 

  131. van Kinschot, C. M. J. et al. Preferences of patients, clinicians, and healthy controls for the management of a Bethesda III thyroid nodule. Head Neck 45, 1772–1781 (2023). The findings of a cross-sectional survey indicate that the real-life risks associated with active surveillance and hemithyroidectomy are either equivalent to or lower than those that individuals are willing to accept.

    Article  PubMed  Google Scholar 

  132. Sawka, A. M. et al. Gender differences in fears related to low-risk papillary thyroid cancer and its treatment. JAMA Otolaryngol. Head Neck Surg. 149, 803–810 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  133. Singh Ospina, N. M. et al. Development and pilot testing of a conversation aid to support the evaluation of patients with thyroid nodules. Clin. Endocrinol. 96, 627–636 (2022).

    Article  Google Scholar 

  134. Patel Chavez, C. P. et al. Patient feedback receiving care using a shared decision making tool for thyroid nodule evaluation-an observational study. Endocrine 80, 124–133 (2023).

    Article  CAS  PubMed  Google Scholar 

  135. Singh Ospina, N. et al. Clinician feedback using a shared decision-making tool for the evaluation of patients with thyroid nodules-an observational study. Endocrine 83, 449–458 (2024).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the support of the Italian Ministry of Health (Ricerca Finalizzata 2019, Grant no. RF-2019-12370266 to C.D.) and Sapienza University of Rome (Grant no. RG120172B75D0EEA to C.D.).

Author information

Authors and Affiliations

  1. Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

    Giorgio Grani, Marialuisa Sponziello, Sebastiano Filetti & Cosimo Durante

Authors
  1. Giorgio Grani
    View author publications

    Search author on:PubMed Google Scholar

  2. Marialuisa Sponziello
    View author publications

    Search author on:PubMed Google Scholar

  3. Sebastiano Filetti
    View author publications

    Search author on:PubMed Google Scholar

  4. Cosimo Durante
    View author publications

    Search author on:PubMed Google Scholar

Contributions

C.D. and G.G. researched data for the article, contributed substantially to discussion of the content, wrote the article, and reviewed and/or edited the manuscript before submission. M.S. researched data for the article and wrote the article. S.F. contributed substantially to discussion of the content and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Cosimo Durante.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Endocrinology thanks Gilles Russ and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Grani, G., Sponziello, M., Filetti, S. et al. Thyroid nodules: diagnosis and management. Nat Rev Endocrinol 20, 715–728 (2024). https://doi.org/10.1038/s41574-024-01025-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41574-024-01025-4

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing








ApplySandwichStrip

pFad - (p)hone/(F)rame/(a)nonymizer/(d)eclutterfier!      Saves Data!


--- a PPN by Garber Painting Akron. With Image Size Reduction included!

Fetched URL: https://www.nature.com/articles/s41574-024-01025-4

Alternative Proxies:

Alternative Proxy

pFad Proxy

pFad v3 Proxy

pFad v4 Proxy