ABSTRACT
Postoperative pathological diagnosis of differentiated thyroid cancer (DTC) is important to confirm the diagnosis and predict the risk of recurrence and death. Further treatment plans, such as completion thyroidectomy, radioiodine remnant ablation, or external beam radiation therapy, are then opted for to reduce the predicted risk of recurrence or death. The World Health Organization has classified thyroid cancers into seven distinct categories based on the molecular profile and tumor cell origin. Our recommendation is applicable to differentiated follicular cell-derived carcinoma, the most common form of thyroid cancer, and cribriform morular thyroid carcinoma. Postoperative clinical and pathological staging is recommended for all patients with DTC to determine their prognosis and subsequent treatment decisions. In particular, the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system is recommended for staging DTCs for disease mortality prediction and national cancer registries. The information in the pathology report, including histologic features of the tumor that are necessary for AJCC/UICC staging and recurrence prediction, can help assess the patient’s risk.
ABSTRACT
The prevalence of thyroid cancer in pregnant women is unknown; however, given that thyroid cancer commonly develops in women, especially young women of childbearing age, new cases are often diagnosed during pregnancy. This recommendation summarizes the follow-up and treatment when thyroid cancer is diagnosed during pregnancy and when a woman with thyroid cancer becomes pregnant. If diagnosed in the first trimester, surgery should be postponed until after delivery, and the patient should be monitored with ultrasound. If follow-up before 24–26 weeks of gestation shows that thyroid cancer has progressed, surgery should be considered. If it has not progressed at 24–26 weeks of gestation or if papillary thyroid cancer is diagnosed after 20 weeks of pregnancy, surgery should be considered after delivery.
ABSTRACT
The American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging classification of thyroid cancer can predict death but cannot determine the type and frequency of follow-up testing. Risk stratification is a concept proposed by the American Thyroid Association that uses additional prognostic factors that are not included in the AJCC/UICC classification, such as number or size of metastatic lymph nodes, genetic mutations, and vascular invasion in follicular cancer, to further refine the prognosis of thyroid cancer. The risk of recurrence was categorized as low, intermediate, and high risk, and the need for total thyroidectomy, radioiodine therapy, or thyroid-stimulating hormone suppression was determined depending on each risk level. This approach has been accepted worldwide, and the previous recommendations of the Korean Thyroid Association followed a similar line of thinking but these have been modified in the revised 2024 guidelines.For the revised initial risk stratification, after careful review of the results of the recent meta-analyses and large observational studies and after a multidisciplinary meeting, four major changes were made: 1) thyroid cancer was reclassified according to the World Health Organization (WHO) 2022 tumor classification system; 2) recurrence risk was stratified by combining encapsulated follicular variant papillary thyroid cancer, follicular thyroid cancer, and oncocytic thyroid cancer, which have similar recurrence risk and associated factors, into follicular-patterned tumor; 3) low-risk groups were defined as those with a known recurrence rate of ≤5%, high-risk groups were upgraded to those with a known recurrence rate of ≥30%, and intermediate-risk groups were those with a recurrence risk of 5–30%; and 4) the intermediate risk group had the recurrence rate presented according to various clinicopathological factors, mainly based on reports from Korea. Thus, it is recommended to evaluate the initial risk group by predicting the recurrence rate by combining each clinical factor in individual patients, rather than applying the recurrence rate caused by single risk factor.
ABSTRACT
The selected treatment for a nodule that is diagnosed as thyroid cancer is surgery. Imaging and blood tests are performed prior to surgery to determine the extent of the surgery. An Ultrasound (US) of the thyroid and neck should be performed to evaluate the size of the cancer, whether it is multifocal and has invaded surrounding tissues, and the status of the cervical lymph nodes (LNs). In addition to US, contrast-enhanced computed tomography may help detect cervical LN metastasis and evaluate patients suspected with invasive thyroid cancer.Generally, routine preoperative measurement of serum thyroglobulin and thyroglobulin antibody concentrations is not recommended. Integrated 18F-fluorodeoxyglucose positron-emission/computed tomography may be helpful either in patients with suspected lateral cervical LNs or distant metastasis or in patients with aggressive histology.
ABSTRACT
Surgical resection is typically the primary treatment for differentiated thyroid cancer (DTC), followed by radioactive iodine (RAI) and thyroid-stimulating hormone suppression therapies based on the cancer stage and risk of recurrence. Nevertheless, further treatment may be necessary for patients exhibiting persistent disease following RAI therapy, residual disease refractory to RAI, or unresectable locoregional lesions. This guideline discusses the role of external beam radiotherapy and chemotherapy following surgical resection in patients with DTC. External beam radiotherapy is ineffective if DTC has been entirely excised (Grade 2). Adjuvant external beam radiotherapy may be optionally performed in patients with incomplete surgical resection or frequently recurrent disease (Grade 2). In patients at high risk of recurrence following surgery and RAI therapy, adjuvant external beam radiotherapy may be optionally considered (Grade 3). However, external beam radiotherapy may increase the risk of serious adverse events after tyrosine kinase inhibitor therapy. Therefore, careful consideration is needed when prescribing external beam radiotherapy for patients planning to undergo tyrosine kinase inhibitor therapy. There is no evidence supporting the benefits of the routine use of adjuvant chemotherapy for DTC treatment (Grade 2).
ABSTRACT
Only a small percentage of patients (2-5%) with differentiated thyroid cancer (DTC) exhibit distant metastasis at the initial diagnosis or during the disease course. The most common metastatic sites of DTC are the lungs, followed by the bones. Radioactive iodine (RAI) therapy is considered the primary treatment for RAI-avid distant metastatic DTC. Depending on the characteristics of metastatic lesions, local treatment such as surgical resection, radiofrequency ablation, and external beam radiation therapy may be considered for some patients with metastatic DTC. Slowly growing and asymptomatic metastases can be monitored with follow-up while receiving thyroid-stimulating hormone (TSH) suppression therapy. In patients with a limited number of lung metastases and good performance status, surgical removal of the metastatic lesions may be considered. Systemic therapy should be considered for patients with progressive RAI refractory DTC. In this clinical guideline, we aim to outline the treatment principles for patients with lung, bone, and brain metastases of DTC.
ABSTRACT
These guidelines aim to establish the standard practice for diagnosing and treating patients with differentiated thyroid cancer (DTC). Based on the Korean Thyroid Association (KTA) Guidelines on DTC management, the “Treatment of Advanced DTC” section was revised in 2024 and has been provided through this chapter. Especially, this chapter covers surgical and nonsurgical treatments for the local (previous surgery site) or regional (cervical lymph node metastasis) recurrences. After drafting the guidelines, it was finalized by collecting opinions from KTA members and related societies. Surgical resection is the preferred treatment for local or regional recurrence of advanced DTC. If surgical resection is not possible, nonsurgical resection treatment under ultrasonography guidance may be considered as an alternative treatment for local or regional recurrence of DTC. Furthermore, if residual lesions are suspected even after surgical resection or respiratory-digestive organ invasion, additional radioactive iodine and external radiation treatments are considered.
ABSTRACT
Thyroid surgery complications include voice change, vocal fold paralysis, and hypoparathyroidism. The voice status should be evaluated pre- and post-surgery. In patients with voice change, laryngeal visualization is needed.Intraoperative neuromonitoring helps reduce recurrent laryngeal nerve injury. The measurement of serum calcium, parathyroid hormone, and 25-hydroxyvitamin D levels is recommended to evaluate perioperative parathyroid function and prescribe supplementation preoperatively if necessary. For postoperative hypoparathyroidism, vitamin D and oral calcium supplementation are indicated based on serum parathyroid hormone and calcium levels and the severity of symptoms or signs of hypocalcemia. If long-term treatment is required, the appropriateness of treatment should be evaluated based on the disease itself and the consideration of potential benefits and harms from long-term replacement.
ABSTRACT
The primary treatment for differentiated thyroid cancer (DTC) with distant metastasis is high-dose radioactive iodine (RAI) therapy, which can have various effects depending on the iodine uptake of thyroid cancer cells. The iodine uptake of metastatic lesions decreases over time, and approximately 40-70% of patients eventually develop RAI refractory disease. Although the prognosis of patients with RAI refractory DTC is very poor, clinical outcomes vary depending on the location and progression of metastatic lesions. Therefore, it is crucial to determine which patients should receive active systemic therapy with tyrosine kinase inhibitor (TKI) and how to apply local treatment before or during systemic therapy. This guideline covers the definition, treatment principles, systemic anticancer agents, and complications of progressive RAI-refractory DTC. RAI refractory DTC is defined as (1) the absence of RAI uptake on whole body scan, (2) presence of RAI uptake in some lesions but not in others, or (3) disease progression despite RAI uptake. Treatment options for RAI refractory DTC include surgery, external beam radiation therapy, locoregional therapies such as high-intensity focused ultrasound ablation, and systemic anticancer therapy.In patients with minimal symptoms and progression, active surveillance without specific treatment may be considered. Systemic treatment should be considered for patients with multiple progressive lesions by RECIST criteria. Furthermore, testing for cancer gene mutations, including BRAF, NTRK, and RET genes, is recommended for personalized therapy. Systemic therapy should be decided based on shared decision-making between the patient and specialist, considering anticipated benefits and risks. Regular assessment of treatment responses and evaluation of adverse events is essential, with dose adjustment based on these assessments. The optimal time of use, clinical approaches for the prevention and control of adverse events, and individualized treatment approaches based on patient characteristics will be of great help in the treatment of patients with RAI-refractory DTC.
ABSTRACT
The initial treatment for differentiated thyroid cancer includes appropriate surgery and radioactive iodine (RAI) therapy, followed by thyroid-stimulating hormone (TSH) suppression therapy as long-term management to prevent recurrence. RAI therapy following thyroidectomy has the three main purposes: remnant ablation, adjuvant therapy, and therapy for known disease. To optimize the goals and targets of RAI therapy, postoperative disease assessment, determination of recurrence risk, and consideration of various individual factors are necessary. The objectives of RAI therapy are determined based on the individual’s recurrence risk, and the administered activity of RAI is then determined according to these treatment objectives. Adequate stimulation of serum TSH is necessary before RAI therapy, and recombinant human TSH is widely used because of its advantage in reducing the risk of exacerbation of comorbidities associated with levothyroxine discontinuation and improving patients’ quality of life. Additionally, reducing iodine intake through appropriate low-iodine diet is necessary. Whole-body scans are conducted to assess the disease status after RAI therapy. If planar whole-body scans are inconclusive, additional single-photon emission computed tomography (SPECT)/CT imaging is recommended. Over the past decade, prospective randomized or retrospective clinical studies on the selection of candidates for RAI therapy, administered activity, methods of TSH stimulation, and advantages of SPECT/CT have been published. Based on these latest clinical research findings and recommendations from relevant overseas medical societies, this clinical practice guideline presents the indications and methods for administering RAI therapy after thyroidectomy.
ABSTRACT
Based on the clinical, histopathological, and perioperative data of a patient with differentiated thyroid cancer (DTC), risk stratification based on their initial recurrence risk is a crucial follow-up (FU) strategy during the first 1–2 years after initial therapy. However, restratifiying the recurrence risk on the basis of current clinical data that becomes available after considering the response to treatment (ongoing risk stratification, ORS) provides a more accurate prediction of the status at the final FU and a more tailored management approach. Since the 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and DTC, the latest guidelines that include the National Comprehensive Cancer Network clinical practice and European Association for Medical Oncology guidelines have been updated to reflect several recent evidence in ORS and thyroid-stimulating hormone (TSH) suppression of DTC. The current clinical practice guideline was developed by extracting FU surveillance after the initial treatment section from the previous version of guidelines and updating it to reflect recent evidence. The current revised guideline includes recommendations for recent ORS, TSH target level based on risk stratification, FU tools for detection of recurrence and assessment of disease status, and long-term FU strategy for consideration of the disease status. These evidence-based recommendations are expected to avoid overtreatment and intensive FU of the majority of patients who will have a very good prognosis after the initial treatment of DTC patients, thereby ensuring that patients receive the most appropriate and effective treatment and FU options.
ABSTRACT
Radioactive iodine (RAI) therapy can effectively eliminate persistent or recurrent disease in patients with advanced differentiated thyroid cancer (DTC), potentially improving progression-free, disease-specific, and overall survival rates. Repeated administration of RAI along with thyroid-stimulating hormone (TSH) suppression is the mainstay of treatment for patients with distant metastases. Remarkably, one in three patients with distant metastases can be cured using RAI therapy and experience a near-normal life expectancy. Patients with elevated serum thyroglobulin and a negative post-RAI scan may be considered for empiric RAI therapy in the absence of structurally evident disease. However, in some patients, the iodine uptake capacity of advanced lesions decreases over time, potentially resulting in RAI-refractory disease. RAI-administered dose can be either empirically fixed high activities or dosimetry-based individualized activities for treatment of known diseases. The preparation method (levothyroxine withdrawal vs. recombinant human TSH administration) should be individualized for each patient.RAI therapy is a reasonable and safe treatment for patients with advanced DTC. Despite the risk of radiation exposure, administration of low-activity RAI has not been associated with an increased risk of a secondary primary cancer (SPM), leukemia, infertility, adverse pregnancy outcomes, etc. However, depending on the cumulative dose, there is a risk of acute or delayed-onset adverse effects including salivary gland damage, dental caries, nasolacrimal duct obstruction, and SPM. Therefore, as with any treatment, the expected benefit must justify the use of RAI in patients with advanced DTC.
ABSTRACT
Thyroid nodules represent a prevalent condition that is detectable via palpation or ultrasound. In recent years, there has been a paradigm shift toward enhanced diagnostic precision and less aggressive therapeutic approaches, highlighting the growing necessity for tailored clinical recommendations to optimize patient outcomes. The Korean Thyroid Association (KTA) has developed guidelines for managing patients with thyroid nodules, following a comprehensive review by task force members of the relevant literature identified via electronic database searches. The recommendations are provided with a level of recommendation for each section. The guidelines encompass thyroid cancer screening in high-risk groups, appropriate diagnostic methods for thyroid nodules, role of pathologic and molecular marker testing in making a diagnosis, long-term follow-up and treatment of benign thyroid nodules, and special considerations for pregnant women. The major revisions that were made in the 2023 guidelines were the definition of high-risk groups for thyroid cancer screening, application of the revised Korean Thyroid Imaging Reporting and Data System (K-TIRADS), addition of the role of core needle biopsy and molecular marker tests, application of active surveillance in patients with low-risk papillary thyroid microcarcinoma, and updated indications for nonsurgical treatment of benign thyroid nodules. In the 2024 revision of the KTA guidelines for thyroid cancer, the evidence for some recommendations has been updated to address the tumor size in the context of active surveillance in patients with low-risk thyroid cancer and the surgical size cutoff. These evidence-based recommendations serve to inform clinical decision-making in the management of thyroid nodules, thereby facilitating the delivery of optimal and efficacious treatments to patients.
ABSTRACT
Pediatric differentiated thyroid cancers (DTCs), mostly papillary thyroid cancer (PTC, 80-90%), are diagnosed at more advanced stages with larger tumor sizes and higher rates of locoregional and/or lung metastasis. Despite the higher recurrence rates of pediatric cancers than of adult thyroid cancers, pediatric patients demonstrate a lower mortality rate and more favorable prognosis. Considering the more advanced stage at diagnosis in pediatric patients, preoperative evaluation is crucial to determine the extent of surgery required. Furthermore, if hereditary tumor syndrome is suspected, genetic testing is required. Recommendations for pediatric DTCs focus on the surgical principles, radioiodine therapy according to the postoperative risk level, treatment and follow-up of recurrent or persistent diseases, and treatment of patients with radioiodine-refractory PTCs on the basis of genetic drivers that are unique to pediatric patients.
ABSTRACT
Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.
ABSTRACT
The primary objective of initial treatment for thyroid cancer is minimizing treatment-related side effects and unnecessary interventions while improving patients’ overall and disease-specific survival rates, reducing the risk of disease persistence or recurrence, and conducting accurate staging and recurrence risk analysis. Appropriate surgical treatment is the most important requirement for this purpose, and additional treatments including radioactive iodine therapy and thyroid-stimulating hormone suppression therapy are performed depending on the patients’ staging and recurrence risk. Diagnostic surgery may be considered when repeated pathologic tests yield nondiagnostic results (Bethesda category 1) or atypia of unknown significance (Bethesda category 3), depending on clinical risk factors, nodule size, ultrasound findings, and patient preference. If a follicular neoplasm (Bethesda category 4) is diagnosed pathologically, surgery is the preferred option. For suspicious papillary carcinoma (suspicious for malignancy, Bethesda category 5), surgery is considered similar to a diagnosis of malignancy (Bethesda category 6). As for the extent of surgery, if the cancer is ≤1 cm in size and clinically free of extrathyroidal extension (ETE) (cT1a), without evidence of cervical lymph node (LN) metastasis (cN0), and without obvious reason to resect the contralateral lobe, a lobectomy can be performed. If the cancer is 1-2 cm in size, clinically free of ETE (cT1b), and without evidence of cervical LN metastasis (cN0), lobectomy is the preferred option. For patients with clinically evident ETE to major organs (cT4) or with cervical LN metastasis (cN1) or distant metastasis (M1), regardless of the cancer size, total thyroidectomy and complete cancer removal should be performed at the time of initial surgery. Active surveillance may be considered for adult patients diagnosed with low-risk thyroid papillary microcarcinoma. Endoscopic and robotic thyroidectomy may be performed for low-risk differentiated thyroid cancer when indicated, based on patient preference.
ABSTRACT
Thyroid hormone plays an important role in the process of implantation of a fertilized egg in the endometrium, as well as in the division and development of the fertilized egg. In addition, maternal thyroid hormone is essential for the formation and development of the fetal brain, nervous system, and bones. Therefore, when maternal thyroid hormone is insufficient, complications such as miscarriage, stillbirth, low birth weight and preeclampsia increase. Guidelines for the diagnosis and treatment of thyroid dysfunction during pregnancy were established and published by the American Endocrine Society, the American Thyroid Association, and the European Thyroid Society. The Korean Thyroid Society also published recommendations for diagnosis and treatment of thyroid disease during pregnancy and postpartum in 2014. However, since the revised guidelines of the American Thyroid Association were published in 2017, many studies, including large-scale randomized controlled trials, have been published in relation to thyroid and pregnancy, and the need to revise the existing recommendations has emerged in Korea.The main revisions of this recommendation are changes in the normal range of TSH during pregnancy, detailed description of treatment policies according to pregnant women’s autoantibodies and thyroid function status. Also, a description of the effect of thyroid autoantibodies on assisted reproductive procedures has been added.
ABSTRACT
Subclinical hypothyroidism (SCH), characterized by elevated serum thyroid-stimulating hormone (TSH) levels and normal free thyroxine levels, usually presents without symptoms, and is often discovered incidentally during routine blood test. The Task Force of the Korean Thyroid Association Committee of Clinical Practice Guidelines has established a guideline to evaluate and manage SCH; the guideline emphasizes the implementation of diagnostic criteria based on the TSH reference range for Koreans and focuses on the proven health benefits of levothyroxine (LT4) treatment. Based on the Korea National Health and Nutrition Examination Survey (2013-2015), serum TSH level of 6.8 mIU/L is considered the reference value for SCH. SCH can be categorized as mild (TSH 6.8-10.0 mIU/L) or severe (TSH ＞10.0 mIU/L), and patients are classified as adults (age ＜70 years) or elderly patients (age ≥70years) depending on the health effects of LT4 treatment. An initial increase in serum TSH levels should be reassessed with a subsequent measurement, along with the thyroid peroxidase antibody test, preferably 2-3 months after the initial evaluation. Usually, LT4 treatment is not recommended for mild SCH in adults; however, treatment is necessary for severe SCH in patients with underlying coronary artery disease or heart failure and can be considered for coexisting dyslipidemia. LT4 treatment is not recommended for mild or even severe SCH in elderly patients, in general. Patients with SCH who receive LT4 treatment, the LT4 dosage should be personalized, and serum TSH levels should be monitored to ensure optimal LT4 dosage (dosage that is neither excessive nor insufficient). Patients with SCH who do not receive LT4 treatment require periodic follow-up at appropriate testing intervals determined by disease severity. The guideline also provides several educational points applicable in clinical settings.
ABSTRACT
Thyroid nodules are a prevalent condition that can be detected through palpation or ultrasound. However, a small fraction of these nodules can be cancerous, and even benign nodules can cause symptoms if they grow and compress surrounding tissue. As such, it is important to monitor thyroid nodules and determine appropriate treatment options. In recent years, there has been a shift towards enhancing diagnostic accuracy and less aggressive treatment options. As a result, there is a growing need for the development of appropriate recommendations for their clinical application to ensure optimal patient outcomes. The present clinical practice guideline was developed by extracting the nodule section from the prior version of guidelines and updating it to fit the Korean circumstances. Task force members reviewed relevant studies selected after electronic database searching, and the recommendations are provided with a level of recommendation for each section. The revised guideline includes recommendations for thyroid cancer screening in high-risk groups, appropriate diagnostic methods for thyroid nodules, the role of pathological and molecular marker tests in diagnosis, long-term follow-up and treatment of benign thyroid nodules, and special considerations for pregnant women. The major changes in this revision are the definition of high-risk groups for thyroid cancer screening, the application of the revised Korean Thyroid Imaging Reporting and Data System (K-TIRADS), the addition of the role of core needle biopsy and molecular marker tests, the application of active surveillance in low-risk papillary thyroid microcarcinoma, and updated indications for non-surgical treatment of benign thyroid nodules. These evidence-based recommendations are expected to assist in clinical decision-making for thyroid nodule management, ensuring that patients receive the most appropriate and effective treatment options.
ABSTRACT
Background and Objectives@#Recent guidelines from the Korean Thyroid Association have proposed a threshold of 6.8 mIU/L for diagnosing subclinical hypothyroidism based on local research findings. However, due to the lack of standardization/harmonization, thyroid-stimulating hormone (TSH) testing yields varying results across different reagent manufacturers. Hence, the use of uniform reference intervals is challenging. We aimed to establish assay-specific Korean reference interval for TSH. @*Materials and Methods@#We performed duplicate measurements on 100 serum samples with varying TSH concentrations (0-23 mIU/L) using eight different TSH reagents including Alinity I TSH (Abbott), Access TSH (Beckman Coulter), Elecsys TSH (Roche), TSH3UL (Siemens),TSH IRMA (Beckman Coulter), TSH1 RIA (Brahms), TSH IRMA TUBE II (Riakey), Turbo TSH IRMA (Izotop).Correlation and simple linear regression analyses were conducted among 8 reagents with Roche as the reference. @*Results@#The correlation coefficient for each reagent was notably high at 0.99. Through regression analysis, TSH values equivalent to the 6.8 mIU/L (Roche) were determined for each reagent as follows: Abbott 5.2 mIU/L, Beckman 6.5 mIU/L, Siemens 6.9 mIU/L, Beckman-Radioimmunoassay 7.4 mIU/L, Brahms 5.7 mIU/L, Riakey 5.3 mIU/L, Izotop 6.0 mIU/L. Conclusion: Given the observed differences in TSH values associated with different reagents, it is imperative to consider these differences when interpreting results within various clinical contexts and adapting them to clinical practice.