Active surveillance (AS) is recommended for low-risk papillary thyroid microcarcinoma (PTMC) in many guidelines. However, while its clinical application requires incorporation of patient values, implementing shared decision-making (SDM) in practice remains challenging. To generate reliable evidence, facilitate the integration of SDM into routine PTMC managements and improve patient satisfaction, this study developed a PTMC-specific SDM model (SM group) and aims to evaluate whether it improves patient-reported outcomes (PROs) compared to usual care (UC group) in patients with low-risk PTMC. This multicenter, parallel-group, cluster-randomized controlled trial will enroll 310 patients with low-risk PTMC across seven academic hospitals in Korea. Participants will be assigned to either the SM group (model) or the UC group (control) through cluster randomization of 26 clinicians, stratified by specialty and AS experience. The SM group will receive structured counseling using a newly developed PTMC-specific SDM model, supported by decision aids such as educational videos, web-based card news, and illustrated leaflets regarding disease-information and patients' values. The UC group will receive standard counseling. The primary outcome is the Decisional Conflict Scale score. Secondary outcomes include satisfaction with decision-making process, decision regret, anxiety, and thyroid-specific quality of life. Data will be collected via the iCReaT v2.0 electronic Case Report Form, supplemented by electronic and paper-based PRO surveys. Assessments will be conducted at baseline, 1-4 weeks, and 6 months after the treatment decision. Trial Registration: ClinicalTrials.gov Identifier: NCT06730893.

BACKGROUND:Transoral robotic thyroidectomy (TORT) has traditionally used a four-port technique. The original three-port approach, which eliminates the axillary port, makes TORT truly scarless. This study compares outcomes between these techniques. METHODS:A retrospective review was conducted on consecutive patients who underwent TORT lobectomy for thyroid cancer between August 2021 and January 2025. The four-port technique was used until January 2024, after which only the three-port technique was performed. RESULTS:Thirty (M:F 6:24) and 59 (M:F 8:51) patients were included in the four-port and three-port groups, respectively. The three-port group had a significantly shorter operation time (107.1 vs. 141.0 min, p < 0.001). Transient recurrent laryngeal nerve injury occurred in one four-port case, while the three-port group had one seroma and one wound inflammation. No cases of conversion to open surgery were observed. CONCLUSIONS:Truly scarless three-port TORT is a feasible and efficient alternative and may replace four-port TORT for selected thyroidectomy patients.

Purpose:The BRAFV600E mutation is a common genetic alteration in papillary thyroid carcinoma (PTC) and is associated with poor prognostic factors. Accurate detection is crucial for risk stratification. This study compares the performance of direct Sanger sequencing (SS), immunohistochemistry (IHC), and droplet digital PCR (ddPCR) in detecting the BRAFV600E mutation in PTC. Methods:Tumor samples from patients undergoing thyroidectomy were analyzed for BRAFV600E using SS, IHC, and ddPCR. A mutant allele fraction >1% was considered ddPCR positive. Sensitivity and concordance rates were evaluated. Results:A total of 48 PTC and 9 benign samples were tested. All benign samples were negative for BRAFV600E by both SS and ddPCR. Among PTC cases, the mutation was detected in 72.9% by SS, 89.6% by IHC, and 83.3% by ddPCR. Both IHC and ddPCR were significantly more sensitive than SS (P = 0.001 and P < 0.001, respectively). Concordant results across all 3 methods were seen in 83.3% of PTC cases. Among the 8 discordant samples (all SS-negative), 5 were positive by both IHC and ddPCR, and 3 were IHC-positive only. Of these, 6 showed adenine peaks on SS chromatograms, with a mean ddPCR mutant allele fraction of 14.5%, compared to 0.36% in the 2 without adenine peaks. Conclusion:IHC and ddPCR demonstrated superior sensitivity compared to SS for detecting BRAFV600E mutations in PTC. These findings support the use of IHC and ddPCR as more reliable alternatives to SS in clinical practice.

BACKGROUND:Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. METHODS:This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. CONCLUSION:This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Purpose: Shared decision-making (SDM) is a collaborative process in which patients and healthcare providers exchange medical information regarding treatment options and reach an optimal decision that reflects the patient’s values and preferences. In managing low-risk thyroid cancer, both surgery and active surveillance are valid treatment options, making SDM essential.Current Concepts: Although both surgery and active surveillance for low-risk thyroid cancer yield excellent long-term outcomes, each option has distinct advantages and disadvantages. The optimal treatment choice depends on the patient’s unique values, preferences, and clinical circumstances. Effective SDM in this setting requires active engagement from both patients and healthcare providers, interactive information exchange regarding treatment options and patient preferences, integration of patient values into the decision-making process, and, ultimately, agreement on a mutually acceptable treatment plan. To facilitate this process in practice, we applied a six-step SDM model and developed decision aids specifically tailored for patients with low-risk thyroid cancer.Discussion and Conclusion: SDM is expected to improve patient satisfaction with both the decision-making process and treatment outcomes, while reducing unnecessary interventions and decisional regret, thereby advancing truly patient-centered care.

Young Joo Park, Eun Kyung Lee, Young Shin Song, Bon Seok Koo, Hyungju Kwon, Keunyoung Kim, Mijin Kim, Bo Hyun Kim, Won Gu Kim, Won Bae Kim, Won Woong Kim, Jung-Han Kim, Hee Kyung Kim, Hee Young Na, Shin Je Moon, Jung-Eun Moon, Sohyun Park, Jun-Ook Park, Ji-In Bang, Kyorim Back, Youngduk Seo, Dong Yeob Shin, Su-Jin Shin, Hwa Young Ahn, So Won Oh, Seung Hoon Woo, Ho-Ryun Won, Chang Hwan Ryu, Jee Hee Yoon, Ka Hee Yi, Min Kyoung Lee, Sang-Woo Lee, Seung Eun Lee, Sihoon Lee, Young Ah Lee, Joon-Hyop Lee, Ji Ye Lee, Jieun Lee, Cho Rok Lee, Dong-Jun Lim, Jae-Yol Lim, Yun Kyung Jeon, Kyong Yeun Jung, Ari Chong, Yun Jae Chung, Chan Kwon Jung, Kwanhoon Jo, Yoon Young Cho, A Ram Hong, Chae Moon Hong, Ho-Cheol Kang, Sun Wook Kim, Woong Youn Chung, Do Joon Park, Dong Gyu Na, Korean Thyroid Association Guideline Committee on the Managements of Thyroid Nodule and Cancer. Int J Thyroidol 2024;17:1-20. https://doi.org/10.11106/ijt.2024.17.1.1

Background: Telomere length is associated with cancer risk and cancer aggressiveness. Radioactive iodine (RAI) therapy for thyroid cancer has raised concerns for second primary malignancy (SPM) in patients with high cumulative doses. The association between RAI dose and peripheral blood leukocyte telomere length was examined. Methods: A total of 425 patients were included who underwent total thyroidectomy and were followed up for at least 1 year with or without RAI treatment. The relative telomere length (RTL) of the patients was assessed via a quantitative polymerase chain reaction amplification method. RAI doses were divided into five groups on the basis of cumulative dose, and a comparison was made among these groups. Results: The number of patients with RAI treatment was 287 (67.5%), and the cumulative RAI dose was 3.33 GBq (range, 1.11-131.35 GBq). The mean RTL was significantly shorter in the highest RAI group (>22.2 GBq) compared to both the no-RAI and lower dose groups. The association between RAI dose and RTL was positive in the lower RAI group (1.1-3.7 GBq) and negative in the highest RAI group in both univariate and multivariate analyses. We observed 59 (13.9%) SPMs and 20 (4.7%) mortalities, and RTL did not show a significant risk effect for all-cause, thyroid cancer-specific, or SPM-specific mortality. Conclusions: In patients with thyroid cancer who underwent total thyroidectomy, peripheral blood leukocyte telomere length exhibited a significant association with cumulative RAI dose higher than 22.2 GBq. These results suggest the possibility of telomere length shortening in patients who undergo high-dose RAI treatment.

Background: Hypothyroidism, a prevalent endocrine disorder, results from insufficient thyroid hormone production or release, affecting metabolism. However, disparities in comorbidities and treatment trajectories may exist between endogenous and exogenous hypothyroidism.Methods: Data from the Korean National Health Insurance Service from 2004 to 2018. Endogenous hypothyroidism was defined as cases with two or more diagnostic codes for hypothyroidism coupled with a history of thyroid hormone intake exceeding 60 days. To eliminate iatrogenic hypothyroidism, individuals with diagnosis codes for thyroid cancer, treatment codes for thyroid surgery, or radiotherapy were excluded. Hypothyroidism-related comorbidities were defined as new occurrences of the corresponding diagnosis code after the diagnosis of hypothyroidism during the entire study period.Results: The age-standardized incidence of endogenous hypothyroidism among men was 0.2 per 1,000 person-years in 2004, increasing to 0.8 in 2018. Among women, the incidence increased from 1.6 per 1,000 person-years in 2004 to 3.7 in 2018. When comparing age groups of 20s–50s and 60s–90s, both sexes in the 60s–90s demonstrated a more rapid increase in incidence than those in the 20s–50s age range. Patients with endogenous hypothyroidism demonstrated a higher incidence of mood disorders across all age groups and cerebrovascular disease in individuals ≥60 years old, regardless of sex.Conclusion: In Republic of Korea, endogenous hypothyroidism incidence has been increased in recent years. The incidence of endogenous hypothyroidism is increasing more rapidly in men than in women, especially in the elderly. Patients with endogenous hypothyroidism seem to have a heightened risk for cerebrovascular disease and mood disorders.

Young Joo Park, Eun Kyung Lee, Young Shin Song, Su Hwan Kang, Bon Seok Koo, Sun Wook Kim, Dong Gyu Na, Seung-Kuk Baek, So Won Oh, Min Kyoung Lee, Sang-Woo Lee, Young Ah Lee, Yong Sang Lee, Ji Ye Lee, Dong-Jun Lim, Leehi Joo, Yuh-Seog Jung, Chan Kwon Jung, Yoon Young Cho, Yun Jae Chung, Won Bae Kim, Ka Hee Yi, Ho-Cheol Kang and Do Joon Park. Int J Thyroidol 2024;17:208-44. https://doi.org/10.11106/ijt.2024.17.1.208

Objective: To investigate surgical, and clinical outcomes in patients with low-risk papillary thyroid microcarcinoma (PTMC) according to treatment options [immediate operation (IOP) vs delayed operation after active surveillance (AS) (DOP)]. Background: AS has been adopted as an alternative to immediate surgery in patients with low-risk PTMC. Although some patients undergo surgery during AS, there is little information on surgical, and clinical outcomes after delayed operation after AS. Methods: A multicenter prospective cohort study including 1177 patients was conducted at 3 tertiary hospitals in Korea from June 2016 to January 2020. Patients with low-risk PTMC were enrolled. The participants were self-assigned into AS or IOP, and during AS, the patients underwent surgery if there were signs of disease progression or if the patient’s choice changed. Results: A total of 516 patients underwent operation; 384 (74.4%) in the IOP group and 132 (25.6%) in the DOP group. Compared with the IOP group, the DOP group was significantly associated with a larger tumor size (P=0.002), higher rates of lymphatic invasion (P=0.002), and multifocality (P=0.008). However, the rates of total thyroidectomy, postoperative hypoparathyroidism and vocal cord palsy did not differ significantly between the groups (P= 0.283, P=0.184, and P=0.284, respectively). Of the 132 patients in the DOP group, disease progression was present in 39 (29.5%) patients. The DOP group with disease progression had a significantly higher rate of lymph node metastasis (P=0.021) and radioiodine therapy (P=0.025) than the DOP group without disease progression. Conclusions: These results suggest that AS might be considered an alternative treatment option for patients with low-risk PTMC regarding the extent of thyroidectomy and postoperative complications in the DOP group. To assess oncologic outcomes, long-term follow-up will be needed. Trial registration: ClinicalTrials.gov Identifier: NCT02938702.

Thyroid hormone plays a critical role in fetal growth and development, and thyroid dysfunction during pregnancy is associated with several adverse outcomes, such as miscarriage and preterm birth. In this review, we introduce and explain three major changes in the revised Korean Thyroid Association (KTA) guidelines for the diagnosis and management of thyroid disease during pregnancy: first, the normal range of thyroid-stimulating hormone (TSH) during pregnancy; second, the treatment of subclinical hypothyroidism; and third, the management of euthyroid pregnant women with positive thyroid autoantibodies. The revised KTA guidelines adopt 4.0 mIU/L as the upper limit of TSH in the first trimester. A TSH level between 4.0 and 10.0 mIU/L, combined with free thyroxine (T4) within the normal range, is defined as subclinical hypothyroidism, and a TSH level over 10 mIU/L is defined as overt hypothyroidism regardless of the free T4 level. Levothyroxine treatment is recommended when the TSH level is higher than 4 mIU/L in subclinical hypothyroidism, regardless of thyroid peroxidase antibody positivity. However, thyroid hormone therapy to prevent miscarriage is not recommended in thyroid autoantibody-positive women with normal thyroid function.

Background: This study aimed to investigate the changes of incidence and treatment of choice for hyperthyroidism from 2003 to 2018 and explore the treatment-related complications and concomitant comorbidities in South Korea using data from the National Health Insurance Service.Methods: This is a retrospective observational study. Hyperthyroidism was defined as a case having two or more diagnostic codes of thyrotoxicosis, with antithyroid drug intake for more than 6 months.Results: The average age-standardized incidence of hyperthyroidism from 2003 to 2018 was 42.23 and 105.13 per 100,000 men and women, respectively. In 2003 to 2004, hyperthyroidism was most often diagnosed in patients in their 50s, but in 2017 to 2018, people were most often diagnosed in their 60s. During the entire period, about 93.7% of hyperthyroidism patients were prescribed with antithyroid drugs, and meanwhile, the annual rates of ablation therapy decrease from 7.68% in 2008 to 4.56% in 2018. Antithyroid drug-related adverse events, mainly agranulocytosis and acute hepatitis, as well as complications of hyperthyroidism such as atrial fibrillation or flutter, osteoporosis, and fractures, occurred more often in younger patients.Conclusion: In Korea, hyperthyroidism occurred about 2.5 times more in women than in men, and antithyroid drugs were most preferred as the first-line treatment. Compared to the general population, hyperthyroid patients may have a higher risk of atrial fibrillation or flutter, osteoporosis, and fractures at a younger age.

This meta-analysis investigated whether thyroidectomy or radioactive iodine treatment (RAIT) in patients with differentiated thyroid cancer (DTC) was associated with an increase in adverse pregnancy outcomes, such as miscarriage, preterm delivery, and congenital malformations. A total of 22 articles (5 case-control and 17 case series studies) from 1262 studies identified through a literature search in the PubMed and EMBASE databases from inception up to 13 September 2021 were included. In patients with DTC who underwent thyroidectomy, the event rates for miscarriage, preterm labor, and congenital anomalies were 0.07 (95% confidence interval [CI], 0.05–0.11; 17 studies), 0.07 (95% CI, 0.05–0.09; 14 studies), and 0.03 (95% CI, 0.02–0.06; 17 studies), respectively. These results are similar to those previously reported in the general population. The risk of miscarriage or abortion was increased in patients with DTC when compared with controls without DTC (odds ratio [OR], 1.80; 95% CI, 1.28–2.53; I2 = 33%; 3 studies), while the OR values for preterm labor and the presence of congenital anomalies were 1.22 (95% CI, 0.90–1.66; I2 = 62%; five studies) and 0.73 (95% CI, 0.39–1.38; I2 = 0%; two studies) respectively, which showed no statistical significance. A subgroup analysis of patients with DTC according to RAIT revealed that the risk of miscarriage, preterm labor, or congenital anomalies was not increased in the RAIT group when compared with patients without RAIT. The results of this meta-analysis suggest that thyroid cancer treatment, including RAIT, is not associated with an increased risk of adverse pregnancy outcomes, including miscarriage, preterm labor, and congenital anomalies.

Background Although smoking is generally carcinogenic, its effect on thyroid cancers is still subject to controversy. The purpose of this study was to summarize the role of smoking in relation to thyroid cancer occurrence. Methods We performed a meta-analysis of 24 eligible studies: 21 case-control studies and three prospective cohort studies. The summary odds ratio (OR) and 95% confidence interval (CI) of all studies were acquired based on random effect model. Further subgroup analyses were conducted according to gender, histological type of thyroid cancer, and smoking status of patients for the case-control studies. Results The summary effect size indicated a negative association of smoking for thyroid cancer (OR, 0.798; 95% CI, 0.681 to 0.935). From the subgroup analyses for the case-control studies, reduced risk of thyroid cancer was observed in both men (OR, 0.734; 95% CI, 0.553 to 0.974) and women (OR, 0.792; 95% CI, 0.700 to 0.897). The protective effect of smoking was observed in studies in which thyroid cancer was limited to differentiated thyroid cancers (DTCs) (OR, 0.798; 95% CI, 0.706 to 0.902). Conclusion Our results suggests that smoking may have a protective effect on thyroid cancer, especially on DTCs. Further studies with larger sample sizes should be conducted in elucidating the dose and time dependent effect of smoking on thyroid cancer with specific focus on the types of thyroid cancers.

Introduction Bone loss caused by primary hyperparathyroidism (PHPT) is an indication for parathyroidectomy (PTX). However, whether adding bisphosphonates would be superior to PTX alone to increase bone mass remains unclear. We thus aimed to compare the skeletal effects of the combination treatment of bisphosphonates and PTX with PTX alone. Materials and methods In this retrospective analysis, bone mineral density (BMD) changes after 1 year of combination treatment and PTX alone were compared. We also analyzed the correlation between changes in serum biochemical parameters and BMD after 1 year of treatment in both groups. Results The baseline characteristics of patients treated with PTX alone ( n = 24) and combination treatment ( n = 26) were comparable. BMD significantly increased after 1 year of treatment in both groups (all p < 0.001), and the increase in BMD at the femur neck was higher in the PTX alone group than in the combination group ( p = 0.011). There was a decreasing trend in serum alkaline phosphatase (ALP) levels in PTX alone compared to the combination treatment group ( p = 0.053). In the study cohort, lower BMD and higher ALP levels at baseline were associated with higher 1-year BMD changes at all sites. Interestingly, a significant association was found between changes in ALP and BMD at the femur neck in the PTX alone group ( p = 0.003), but abolished in the combination group ( p = 0.946). Conclusions There is no additional benefit of BMD in combination treatment with bisphosphonates and PTX over PTX alone in osteoporotic patients with PHPT. Combined bisphosphonate treatment might interfere with the increase in bone mass caused by PTX.

Background: Graves' disease is the most common cause of hyperthyroidism which is caused by stimulating autoantibodies against thyroid-stimulating hormone receptor. There is no etiology-specific treatment for Graves' disease. Current Concepts: Graves' disease can be treated with antithyroid drugs (ATDs), radioactive iodine, or thyroidectomy. ATDs are the most preferred first-line therapy, because they do not cause either permanent hypothyroidism or exacerbation of orbitopathy, despite low remission rate. ATDs have serious adverse reactions including agranulocytosis and fulminant hepatic necrosis requiring liver transplantation. Methimazole (MMI) is recommended in every patient starting ATD therapy, except during the first trimester of pregnancy and in cases of thyroid storm, because of relatively lower incidence and severity of serious adverse reactions compared with propylthiouracil. Treatment should be continued for 12 to 18 months, then discontinued if the levels of thyroid-stimulating hormone and thyroid-stimulating hormone receptor antibodies are normalized. In cases of relapse of hyperthyroidism, radioactive iodine or thyroidectomy can be recommended for definitive therapy; however, recent studies support longer-term maintenance of low dose MMI as a favorable alternative therapy. All ATDs may induce congenital anomalies when exposed during early pregnancy. Every female patient of reproductive age should be advised to postpone pregnancy until their thyroid function is maintained within normal range and to stop ATDs when pregnancy is confirmed to avoid the risk of congenital anomalies. Discussion and Conclusion: Longer-term low dose MMI therapy can be a good choice for Graves' hyperthyroidism with relapse. Before pregnancy, hyperthyroidism should be controlled to stop ATDs during pregnancy.

Post-thyroidectomy hypoparathyroidism may result in various transient or permanent symptoms, ranging from tingling sensation to severe breathing difficulties. Its incidence varies among surgeons and institutions, making it difficult to determine its actual incidence and associated factors. This study attempted to estimate the incidence of post-operative hypoparathyroidism in patients at two tertiary institutions that share a common data model, the Observational Health Data Sciences and Informatics. This study used the Common Data Model to extract explicitly specified encoding and relationships among concepts using standardized vocabularies. The EDI-codes of various thyroid disorders and thyroid operations were extracted from two separate tertiary hospitals between January 2013 and December 2018. Patients were grouped into no evidence of/transient/permanent hypoparathyroidism groups to analyze the likelihood of hypoparathyroidism occurrence related to operation types and diagnosis Of the 4848 eligible patients at the two institutions who underwent thyroidectomy, 1370 (28.26%) experienced transient hypoparathyroidism and 251 (5.18%) experienced persistent hypoparathyroidism. Univariate logistic regression analysis predicted that, relative to total bilateral thyroidectomy, radical tumor resection was associated with a 48% greater likelihood of transient hypoparathyroidism and a 102% greater likelihood of persistent hypoparathyroidism. Moreover, multivariate logistic analysis found that radical tumor resection was associated with a 50% greater likelihood of transient hypoparathyroidism and a 97% greater likelihood of persistent hypoparathyroidism than total bilateral thyroidectomy. These findings, by integrating and analyzing two databases, suggest that this analysis could be expanded to include other large databases that share the same Observational Health Data Sciences and Informatics protocol.

Background We aimed to evaluate the clinicopathological features and biological behaviors of Korean thyroid cancer patients with rare variants of papillary thyroid carcinoma (PTC) to address the ambiguity regarding the prognostic consequences of these variants. Methods We retrospectively reviewed the medical records of 5,496 patients who underwent thyroid surgery for PTC, between January and December 2012, in nine tertiary hospitals. Rare PTC variants included tall cell (TCV), columnar cell (CCV), diffuse sclerosing (DSV), cribriform-morular (CMV), solid (SV), hobnail, and Warthin-like variants. Recurrence-free survival (RFS) was defined as the time from the date of thyroidectomy until recurrence. Results Rare variants accounted for 1.1% (n=63) of the PTC patients; with 0.9% TCV, 0.02% CCV, 0.1% DSV, 0.1% CMV, and 0.1% SV. The mean age of patients and primary tumor size were 42.1±13.1 years and 1.3±0.9 cm, respectively. Extrathyroidal extension and cervical lymph node metastasis were observed in 38 (60.3%) and 37 (58.7%) patients, respectively. Ultrasonographic findings revealed typical malignant features in most cases. During a median follow-up of 7 years, 6.3% of patients experienced a locoregional recurrence. The 5-year RFS rates were 71.4% in patients with DSV or SV, 95.9% for TCV, or CCV, and 100% for other variants. DSV emerged an independent risk factor associated with shorter RFS. Conclusion In this multicenter Korean cohort, rare variants accounted for 1.1% of all PTC cases, with TCV being the most frequent subtype. DSV emerged as a significant prognostic factor for RFS.