Search

Brain-derived neurotrophic factor (BDNF), an exercise-induced neurotrophin, is an important factor in memory consolidation and cognitive function. This study evaluates the association between plasma BDNF levels and frailty in community-dwelling older adults. Plasma BDNF levels were analyzed in a total of 302 individuals aged 70–84 years from the Korean Frailty and Aging Cohort Study. There were 30 (9.9%) participants with frailty. They were older and had a higher prevalence of dementia and depression than those without frailty. There were no differences in the proportion of male sex between the frail and non-frail groups. Plasma BDNF levels were significantly lower in participants with frailty than in those without frailty. The presence of frailty was significantly associated with plasma BDNF levels (odds ratio 0.508, 95% confidence interval 0.304–0.849) as well as age, hemoglobin, and the presence of dementia, and depression. After adjustment for confounding factors, the significant association between plasma BDNF and frailty was maintained (0.495, 0.281–0.874). This association remained consistent after exclusion of individuals with dementia, depression, stroke, diabetes, and osteoporosis. Plasma BDNF levels were significantly associated with frailty in community-dwelling older adults. Our study may suggest the possible role of BDNF as a novel biomarker of frailty.

Background: Recently, a few studies have reported different results regarding the relationship between metabolic health and obesity phenotype and several cancers. We examined the effects of metabolic health and obesity phenotype on pancreatic cancer using a nationwide population-based cohort database. Methods: Using the Korean National Health Insurance Service–Health Screening Cohort, we enrolled 347,434 Korean adults who underwent a health examination between 2009 and 2010 and were followed until 2015. This population was divided into four groups based on metabolically healthy status and body mass index (BMI): metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Results: Over a median follow-up of 6.1 (5.5–6.5) years, 886 individuals were diagnosed with pancreatic cancer. The adjusted HRs for incident pancreatic cancer were 1.52 [95% confidence interval (CI) 1.27–1.81] and 1.34 (95% CI, 1.12–1.61) for the MUNW and MUO phenotypes (compared with the MHNW phenotype) after adjusting for various confounding factors. However, compared with the MHNW phenotype, the MHO phenotype did not show an elevated risk of pancreatic cancer. Moreover, the HR for pancreatic cancer gradually increased with an increase in number of metabolically unhealthy components, even after adjusting for BMI (Ptrend < 0.001). Conclusions: Regardless of BMI, metabolically unhealthy phenotype demonstrated significantly increased risk of pancreatic cancer, whereas obese individuals with metabolically healthy phenotype did not. Impact: These findings suggest that metabolically unhealthy phenotype might represent a potential risk factor for pancreatic cancer occurrence independent of obesity.

Background: Advanced thyroid cancers, including differentiated thyroid carcinoma (DTC) with distant metastasis, and anaplastic thyroid carcinoma (ATC), are associated with poor clinical outcomes an...

Background: The clinical outcomes of delayed radioiodine remnant ablation (RRA) therapy in patients with low-risk papillary thyroid carcinoma (PTC) are unclear. We aimed to evaluate the clinical impact of the interval between total thyroidectomy (TT) and RRA therapy in patients with low-risk PTC.Methods: We included 526 patients who underwent TT and RRA for low-risk PTC with a primary tumor size of >1 cm between 2000 and 2012. Patients were divided into the early (3 months after TT considering other prognostic factors.

Major clinical challenges exist with differentiated thyroid cancers with distant metastases or rare but aggressive types, such as poorly differentiated thyroid carcinomas and anaplastic thyroid carcinomas. The precise characterization of the mutational profile in these advanced thyroid cancers is crucial. Samples were collected from primary tumors and distant metastases of 64 patients with distant metastases from differentiated thyroid cancer, poorly differentiated thyroid carcinoma, or anaplastic thyroid carcinoma. Targeted next-generation sequencing was performed with 50 known thyroid-cancer-related genes. Of the 82 tissues, 63 were from primary tumors and 19 from distant metastases. The most prevalent mutation observed from the primary tumors was TERT promoter mutation (56%), followed by BRAF (41%) and RAS (24%) mutations. TP3 was altered by 11%. Mutations in histone methyltransferases, SWI/SNF subunit–related genes, and PI3K/AKT/mTOR pathway-related genes were present in 42%, 12%, and 22%, respectively. When the mutational status was analyzed in 15 matched pairs of thyroid tumors and their matched distant metastases and one pair of distant metastases with two distinct sites, the concordance was high. A similar frequency of mutations in TERT promoter (58%) and BRAF (42%) as well as histone methyltransferases (37%), SWI/SNF subunits (10%), and PI3K/AKT/mTOR pathway (26%) were noted. The same main, early and late mutations were practically always present in individual primary tumor–metastasis pairs. Enrichment of TERT promoter, BRAF, and RAS mutations were detected in highly advanced thyroid cancers with distant metastasis. The genetic profiles of primary thyroid tumors and their corresponding distant metastases showed a high concordance.

Background: Lenvatinib, an oral multikinase inhibitor, is the latest addition to the treatment options for radioactive iodine (RAI)-refractory progressive differentiated thyroid carcinoma (DTC). Th...

OBJECTIVE Evidence for American Thyroid Association (ATA) risk stratification stems largely from studies involving patients undergoing total thyroidectomy. We aimed to assess the risk of recurrence according to the present ATA risk stratification system in patients who underwent lobectomy. DESIGN Retrospective cohort study. PATIENTS Patients who underwent thyroid lobectomy for 1-4 cm-sized papillary thyroid carcinoma (n = 571). MEASUREMENTS Disease-free survival (DFS) was compared according to the ATA risk stratification, and specific lymph node (LN) characteristics were evaluated to modify the ATA criteria with a higher predictability for recurrence. RESULTS Based on the ATA risk stratification, 439 patients (61.1%) were classified into intermediate- or high-risk group, and consideration for completion thyroidectomy is suggested by ATA guidelines for these patients. However, no significant differences were found in DFS among the low-, intermediate- and high-risk groups (P = .9). In contrast, when patients were stratified according solely to the LN criteria from the ATA risk stratification, only 127 patients (22.2%) had intermediate risk (intermediate-N1a) and exhibited significantly poorer DFS than those with N0 disease (P = .035). Modifying the intermediate-N1a criteria by adding the extranodal extension (ENE) status and omitting the clinical nodal disease enabled the subclassification of 19 patients (3%) with a high risk for recurrence. CONCLUSIONS The present study suggests that risk stratification based solely on LN metastases is more reasonable for predicting structural persistence/recurrence following lobectomy than that based on the overall ATA criteria. Considering the ENE status can assist in selecting patients with a high risk of recurrence to minimize further treatments.

Self-monitoring of capillary blood glucose is important for controlling diabetes. Recently, a laser lancing device (LMT-1000) that can collect capillary blood without skin puncture was developed. We enrolled 150 patients with type 1 or 2 diabetes mellitus. Blood sampling was performed on the same finger on each hand using the LMT-1000 or a conventional lancet. The primary outcome was correlation between glucose values using the LMT-1000 and that using a lancet. And we compared the pain and satisfaction of the procedures. The capillary blood sampling success rates with the LMT-1000 and lancet were 99.3% and 100%, respectively. There was a positive correlation (r=0.974, P

BackgroundOptimal treatment for persistent Graves’ disease following 12–18 months of treatment with anti-thyroid drugs (ATDs) is unclear. Given the increased risk of cardiovascular morbidity and mortality with hyperthyroidism, assessing the risk of cardiovascular events associated with different treatment modalities after the conventional ATD course would be valuable in determining the appropriate next-line therapy.MethodsThis retrospective cohort study included data from the Korean National Health Insurance database of 16,882 patients with newly diagnosed hyperthyroidism who received primary ATD treatment for 24 months. Patients were categorized based on the treatment they received after receiving ATD for 24 months: continued ATD for at least 12 more months (ATD group), radioiodine ablation (RIA) with remission (RIA group 1), and RIA without remission (RIA group 2). The incidence and risk of heart failure (HF), the leading cause of cardiovascular mortality in hyperthyroidism, were compared between patients and age-and sex-matched controls.ResultsThere were 16,516 (97.8%) patients in the ATD group, 230 (1.4%) in RIA group 1, and 136 (0.8%) in RIA group 2. Compared to that of controls, a significant difference in the cumulative incidence of HF was observed according to second-line treatment modality after adjusting for covariates; the risk was highest in patients in RIA group 2, with a hazard ratio (HR) of 2.54 (95% confidence interval (CI) 1.60–4.03), followed by those in the ATD group, with an HR of 1.23 (95% CI 1.20–1.36). Patients in RIA group 1 were not at an increased risk of HF compared to their matched controls (HR 0.77; 95% CI 0.38–1.54). When patients in the ATD group were further classified by the duration of ATD treatment at one-year intervals, the risk of HF was higher in patients with longer ATD use (p for linear trend < 0.001).ConclusionsIn patients with long-standing hyperthyroidism treated with conventional duration of ATD therapy, the risk of HF was attenuated by RIA with remission of hyperthyroidism and increased as ATD was required for longer duration. To reduce the risk of HF, resolution of hyperthyroidism with RIA should be considered in patients with long-standing Graves’ disease.

Iodine is a vital trace element for systemic metabolic control as well as thyroid hormone synthesis. Though iodine has significant antioxidant and anti-inflammatory effects, reports on its effects on metabolic disorders are limited and inconsistent.Impact of urinary iodine concentrations (UICs) on fasting blood glucose (FBG) levels and blood pressure (BP) in the general Korean population was evaluated adjusting for covariates including thyrotropin level and presence of thyroid diseases.The median UIC was 302.3 μg/L in all participants and was significantly lower in those with dysglycemia (303.6 μg/L in normal participants, 285.1 μg/L in participants with FBG levels of 100-125 mg/dL, and 261.8 μg/L in participants with FBG levels ≥ 126 mg/dL; p = 0.002). Similarly, the UIC was lower in participants with higher BP (311.6 μg/L in normal participants, 288.7 μg/L in prehypertensive participants, and 265.8 μg/L in hypertensive participants; p 0.001). The multiple linear regression model showed a negative correlation between the UIC and FBG levels (p = 0.002), and the UIC and systolic BP (p 0.001). One standard deviation increase in the UIC showed odds ratios of 0.84 (95% confidence interval [CI] = 0.73-0.98) for elevated FBG levels (≥ 100 mg/dL) and 0.94 (95% CI = 0.88-0.99) for elevated SBP (≥ 120 mm Hg) after full adjustment.Higher UICs were associated with lower FBG and BP levels, independent of thyroid function and other confounding factors in Korea, an iodine-replete country.

Possible links between periodontitis and various cardiometabolic and autoimmune diseases have been advocated on the basis of chronic inflammation or oxidative stress. However, the association between periodontitis and thyroid dysfunction is under-researched. Participants without previous thyroid disease or ongoing thyroid-related medication were included from a nationwide population-level survey. Participants were categorized into tertiles of thyroid stimulating hormone (TSH) levels (first tertile 2.83 mIU/L), and periodontal condition was assessed using the Community Periodontal Index. Of the total of 5468 participants, 1423 had periodontitis (26%). A significant difference in the weighted prevalence of periodontitis according to TSH tertiles was observed, with the highest prevalence in the first tertile (26.5%) and the lowest prevalence in the third tertile (20.9%, p = 0.003). Subjects in the first TSH tertile had higher odds for periodontitis than those in the third tertile (OR 1.36, 95% CI 1.10–1.68; p for trend = 0.005) after adjusting for covariates. This association was consistent across subgroups and within sensitivity analyses among subjects without specific factors affecting thyroid function or diseases reported to be related to periodontitis. The present study demonstrated that low TSH levels were associated with significantly higher odds for periodontitis.

BackgroundThe global incidence of NAFLD is rising sharply due to various risk factors. As previous studies reported adverse health impact of long working hours on metabolic diseases, such as diabetes mellitus and obesity, it is plausible that NAFLD is also associated with working excessive hours. However, data regarding this issue is limited.MethodsIn this cross-sectional study based on Korea National Health and Nutrition Examination Survey VII, 5,661 working adults without previous liver disease or heavy alcohol drinking habits were included. The subjects were categorized into three groups according to working hours: 36–42, 43–52, and 53–83 hours/week. NAFLD was defined using the hepatic steatosis index (HSI), which is a validated prediction model for determining NAFLD.ResultsThe prevalence of NAFLD (HSI ≥36) increased with longer working hours: 23.0%, 25.6%, and 30.6% in the 36–42, 43–52, and 53–83 hours/week group, respectively (p vs. shift workers) or occupation type (office vs. manual workers). In particular, the relationship between long working hours and NAFLD was pronounced in workers aged ConclusionsLong working hours was significantly associated with NAFLD. Further prospective studies are required to validate this finding with causal relationship.

Background: The lymphocyte-to-monocyte ratio (LMR), which reflects the tumor-infiltrating immune cell status and host immunity, has been reported as a prognostic marker in various cancers. The aim ...

Persistence of thyroglobulin antibody (TgAb) in patients with papillary thyroid carcinoma (PTC) years after total thyroidectomy (TT) followed by ablation occurs even without any evidence of structural disease. Few studies have studied the natural course of TgAb positivity and factors that may influence this course. The present study evaluated the time trends of TgAb in ablated PTC patients and aimed to identify the predictive factors for the rate of negative conversion of TgAb.Overall, 1279 patients who underwent TT and subsequent ablation for PTC, with available data on thyroid peroxidase Ab (TPOAb) and TgAb prior to surgery (preop-) and ablation (abl-) were enrolled. Patients with initial distant metastasis or recurrence during follow-up were excluded.Preop-TgAb was positive in 24.9% of patients (n = 319), whereas abl-TgAb positivity decreased to 12.8% (n = 164). In 164 patients positive for abl-TgAb, TgAb in patients with higher abl-TgAb levels decreased more gradually than those observed in patients with lower abl-TgAb levels (p 0.001). Furthermore, in patients within the same range of abl-TgAb levels, patients positive for abl-TPOAb had a higher rate of negative conversion of TgAb compared with negative patients for abl-TPOAb (log rank p 0.001). TPOAb significantly increased the rate of negative conversion in multivariate analysis adjusted for abl-TgAb (odds ratio 1.59, 95% confidence interval 1.11-2.28, p = 0.011). This study clearly showed that abl-TgAb titers and abl-TPOAb status can predict the rate of negative conversion. These findings can guide the optimal timing for additional examination in patients positive for TgAb during follow-up.

The concept of a dynamic risk-stratification scheme has been suggested for individualized management of patients with papillary thyroid carcinoma (PTC). However, there is no specified follow-up strategy for patients with an indeterminate response.This study evaluated 403 PTC patients who had an indeterminate response during the first 12-24 months after initial therapy. All patients underwent total thyroidectomy with radioactive iodine remnant ablation. Patients were further classified into three groups based on risk of structural persistence/recurrence: a Tg+ group (detectable thyroglobulin [Tg], regardless of antithyroglobulin antibody [TgAb] or imaging findings; 196 patients), a TgAb+ group (positive results for TgAb with undetectable Tg, regardless of imaging findings; 46 patients), and an Image+ group (nonspecific findings on neck ultrasonography or faint uptake in the thyroid bed on whole-body scan, with undetectable Tg and negative results for TgAb; 161 patients).With a median of 9.6 years (interquartile range 7.7-11.2 years) of follow-up, 56 (14%) PTC patients had structural persistent/recurrent disease: 50 (89%) at locoregional sites and six (11%) at distant sites. The recurrence rate in Tg+, TgAb+, and Image + groups were 26.5%, 8.7%, and 0%, respectively. The median time to detection of structural persistent/recurrent disease from the initial thyroid surgery was 3.7 years (interquartile range 2.5-6.3 years). The optimal cutoff stimulated Tg level to predict structural persistent/recurrent disease was 3.1 ng/mL in the Tg+ group. This classification system revealed higher predictability of structural persistent/recurrent disease than the tumor-node-metastasis staging system and American Thyroid Association risk stratification (proportion of variation explained: 15.7% vs. 2.4% and 0.9%, respectively). Six (3%) patients with distant metastatic disease were all classified in the Tg+ group, and all had lung metastasis.The findings suggest a more individualized follow-up strategy for patients with an indeterminate response. More careful evaluation, including early evaluation of distant metastasis, is necessary in patients with elevated Tg levels. However, for patients testing positive for TgAb or those with only nonspecific imaging findings, regular follow-ups of Tg and TgAb levels and neck ultrasonography are sufficient.

The recently published eighth edition of the American Joint Committee on Cancer (AJCC) staging system has emphasized the importance of gross extrathyroidal extension (gETE) while classifying the tumor (T) stage in differentiated thyroid carcinoma (DTC). However, the clinical impact of gETE invading only the strap muscles or the recurrent laryngeal nerve (RLN) remains unclear due to scarce and conflicting data.A retrospective cohort study was carried out in patients with DTC who underwent thyroid surgery from 1996 to 2005. In total, 3104 patients were included, and disease-specific survival (DSS) was compared according to the degree of gETE, with a median follow-up duration of 10 years.Patients with gETE invading only the strap muscles and with a tumor size ≤4 cm (T3b [≤4 cm]) showed no difference in DSS compared to patients with T2 stage disease (hazard ratio [HR] = 0.81 [confidence interval (CI) 0.24-2.77]; p = 0.737) but rather showed a better DSS than patients with T3a disease (HR = 0.19 [CI 0.05-0.72]; p = 0.014). Conversely, patients with gETE invading to the posterior direction showed significantly poorer DSS than patients with T3 stage disease, even when only the RLN was invaded (HR = 7.78 [CI 3.41-17.75]; p 0.001). However, there was no difference in DSS between gETE invading only the RLN and that invading other posterior organs beyond the RLN (p = 0.563). A modified T classification was suggested to downgrade patients with T3b (≤4 cm) disease to the T2 stage, which revealed higher predictability of survival than the T classification according to the eighth edition of the American Joint Committee on Cancer tumor-node-metastasis staging system (proportion of variation explained: 3.6% vs. 2.65%).gETE invading only the strap muscles did not significantly affect DSS, while that invading the posterior organs significantly affected DSS, even when only the RLN was invaded. The data support the applicability of downgrading patients with T3b (≤4 cm) disease to the T2 stage for a better predictability of survival.

The diagnosis of encapsulated follicular-patterned thyroid carcinoma (EFPTC) is challenging, and the detection of capsular invasion and/or vascular invasion is essential in distinguishing benign lesions from malignant lesions. In this study, we present a modified transverse-vertical gross examination method with additional vertical cuts at the upper and lower ends of thyroid nodules. In addition, we compared the clinicopathological characteristics of patients with EFPTC between conventional and modified methods. The diagnostic rate of follicular thyroid carcinoma and invasive encapsulated follicular variant of papillary thyroid carcinoma was higher with the modified method (p = 0.003 and p = 0.028, respectively). Furthermore, the paraffin block number and the number of capsular invasion per centimeter were significantly higher with the modified method (p

Background Although body weight change (BWC) is a common manifestation of thyroid dysfunction, solid evidence for whether to perform or on whom to perform thyroid function test in subjects complaining of BWC is lacking. Objective To evaluate the association between thyroid dysfunction and BWC using a nationwide survey. Method Data was obtained from the Korea National Health and Nutrition Examination Survey VI 2013-2015 and 5,456 subjects without previous thyroid disease were included. Serum thyroid-stimulating hormone (TSH), free T4, and self-reported BWC during the previous year were used for the evaluation. Weight loss or gain was defined as weight change of at least 3 kg. Results In total, 1,017 men (37.3%) and 1,175 women (43.0%) reported BWCs during the previous year. The overall weighted prevalence of thyroid dysfunction was not significantly associated with the extent of BWC in men (p = 0.705) or women (p = 0.094). However, when the impact of TSH levels on weight change was separately evaluated for weight gain and loss after adjusting for age and body mass index in each sex, weight loss in women was significantly associated with TSH levels (hazard ratio 0.64, 95% CI 0.47-0.85, p = 0.03). No association of thyroid dysfunction was observed for weight gain in women (p = 0.23) or any changes in men (p = 0.875 in weight gain, p = 0.923 in weight loss). Conclusions This study highlights the necessity of performing thyroid function testing in women who complain of weight loss, but such testing may be less vital in women with weight gain or men with any changes in weight.

Simple Summary Aggressive variants of papillary thyroid carcinoma (PTC) are associated with unfavorable clinical outcomes. However, limited data exist on the genetic profile of these variants of PTC. We performed targeted next-generation sequencing in 36 tissue samples from patients with aggressive variants of PTC. Aggressive variants of PTC had a higher prevalence of the BRAF mutation and a lower prevalence of RAS mutation than other types of thyroid cancer. The prevalence of mutations in the TERT promoter, TP53, and genes encoding histone methyl transferases (HMTs), switch/sucrose non-fermenting (SWI/SNF) chromatin remodeling complex, and the phosphoinositide 3-kinase/protein kinase B (PKB/AKT)/mammalian target of the rapamycin (PI3K/AKT/mTOR) pathway was between the range of PTCs and poorly differentiated/anaplastic carcinoma from The Cancer Genome Atlas (TCGA) and the Memorial Sloan Kettering Cancer Center (MSKCC) data. Abstract Aggressive variants of papillary thyroid carcinoma (PTC) have been described with increasing frequency and are associated with unfavorable clinical outcomes. However, limited data exist on the comprehensive genetic profile of these variants. We performed targeted next-generation sequencing in 36 patients with aggressive variants of PTC and compared it to PTC from The Cancer Genome Atlas (TCGA) project and poorly differentiated thyroid cancers (PDTCs)/anaplastic thyroid cancers (ATCs) from the Memorial Sloan Kettering Cancer Center (MSKCC). BRAF mutation was the most prevalent (89%) in aggressive variants of PTC compared to that in other thyroid cancers. RAS mutation was identified in one patient (3%), which was less frequent than in others. TERT promoter mutation (17%) ranged between that of PTCs (9%) and PDTCs (40%). Tumor suppressor genes, ZFHX3, TP53, and CHEK2, were mutated in 14%, 3%, and 6% of aggressive variants of PTC, respectively. The mutation rate of TP53 (3%) was significantly higher than that of PTCs (0.7%) and lower than that of ATCs (73%). Mutations in three functional groups, histone methyl transferases, SWI/SNF chromatin remodeling complex, and the PI3K/AKT/mTOR pathway, were present in 11%, 14%, and 11% of samples, respectively. In conclusion, aggressive variants of PTC had higher BRAF and lower NRAS mutation prevalence than other thyroid cancers. The prevalence of mutations in the TERT promoter, TP53, and genes encoding three functional groups ranged between that of PTCs and PDTCs/ATCs.

Context Although long-term glucose variability has been reported to be a risk factor associated with osteoporosis, there have been no previous studies between the relationship of glucose variability and fractures in people without diabetes. Objective We assessed visit-to-visit variations in fasting plasma glucose (FPG) as a prognostic factor in predicting osteoporotic fractures in individuals without diabetes. Methods Using a nationwide cohort database, we examined the impact of FPG on the development of osteoporotic fractures in men and women (aged ≥50 years). The primary outcomes were the number of total fractures and vertebral fractures. FPG variability was measured using standard deviation (FPG-SD), coefficient of variation (FPG-CV), and variability independent of the mean (FPG-VIM). Results Of the 92 929 participants, 5262 (5.7%) developed osteoporotic fractures during the mean follow-up of 8.4 years. Individuals in the highest quartile of FPG-SD showed an 11% and 16% increase in risk of total and vertebral fractures, respectively, compared with those in the lowest quartile after adjustment for mean FPG and other risk factors. Analyses using FPG-CV and FPG-VIM demonstrated similar results. Subgroup analyses and sensitivity analyses to explore potential heterogeneity showed consistent results. Conclusion FPG variability may be a novel risk factor for osteoporotic fractures independent of risk factors in the general population without diabetes.

Background: Serum calcitonin measurement contains various clinical and methodological aspects. Its reference level is wide and unclear despite sensitive calcitonin kits are available. This study aimed to identify the specific reference range in the healthy Korean adults.Methods: Subjects were ≥20 years with available calcitonin (measured by a two-site immunoradiometric assay) data by a routine health checkup. Three groups were defined as all eligible subjects (group 1, n=10,566); subjects without self or family history of thyroid disease (group 2, n=5,152); and subjects without chronic kidney disease, autoimmune thyroid disease, medication of proton pump inhibitor/H2 blocker/steroid, or other malignancies (group 3, n=4,638).Results: This study included 6,341 male and 4,225 female subjects. Males had higher mean calcitonin than females (2.3 pg/mL vs. 1.9 pg/mL, P

Background: Recently, the role of radioactive iodine (RAI) ablation in the treatment of low risk differentiated thyroid carcinoma (DTC), especially for papillary thyroid microcarcinoma (PTMC), is controversial. This study aims to compare quality of life (QoL) parameters in patients with PTMC underwent total thyroidectomy (TT) versus TT with RAI ablation. Methods: In this cross-sectional study, patients with PTMC who underwent TT with/without RAI remnant ablation were prospectively enrolled between June 2016 and October 2017. All patients completed three questionnaires: 12-item short-form health survey (SF-12), thyroid cancer specific quality of life (THYCA-QOL), and fear of progression (FoP). Results: The TT and TT with RAI groups comprised 107 and 183 patients, respectively. The TT with RAI group had significantly lower serum TSH level than TT group. However, after matching of TSH level between the groups (TT with RAI = 100, TT = 100), there was no significant difference in baseline characteristics. According to the SF-12, the score for general health showed significantly lower in TT with RAI group than TT group (p = 0.047). The THYCA-QOL also showed statistically significant difference in felt chilly score between the groups (p = 0.023). No significant differences in FoP scores were seen between the groups. Conclusion: Patients with PTMC underwent TT with RAI ablation experienced more health-related problems than those managed by TT alone. These findings support RAI ablation should be carefully determined in patients with low-risk DTCs.

Objective Evidence for unfavorable outcomes of each type of aggressive variant papillary thyroid carcinoma (AV-PTC) is not clear because most previous studies are focused on tall cell variant (TCV) and did not control for other major confounding factors contributing to clinical outcomes. Design Retrospective cohort study. Methods This study included 763 patients with classical PTC (cPTC) and 144 with AV-PTC, including TCV, columnar cell variant (CCV) and hobnail variants. Disease-free survival (DFS) and dynamic risk stratification (DRS) were compared after two-to-one propensity score matching by age, sex, tumor size, lymph node metastasis and extrathyroidal extension. Results The AV-PTC group had significantly lower DFS rates than its matched cPTC group (HR = 2.16, 95% CI: 1.12–4.16, P = 0.018). When TCV and CCV were evaluated separately, there was no significant differences in DFS and DRS between patients with TCV (n = 121) and matched cPTC. However, CCV group (n = 18) had significantly poorer DFS than matched cPTC group (HR = 12.19, 95% CI: 2.11–70.33, P = 0.005). In DRS, there were significantly more patients with structural incomplete responses in CCV group compared by matched cPTC group (P = 0.047). CCV was an independent risk factor for structural persistent/recurrent disease in multivariate analysis (HR = 4.28; 95% CI: 1.66–11.00, P = 0.001). Conclusions When other clinicopathological factors were similar, patients with TCV did not exhibit unfavorable clinical outcome, whereas those with CCV had significantly poorer clinical outcome. Individualized therapeutic approach might be necessary for each type of AV-PTCs.

Background Recently, there has been some controversy regarding the role of radioactive iodine (RAI) ablation in the treatment of low-risk differentiated thyroid carcinoma (DTC), especially papillary thyroid microcarcinoma (PTMC). This study aimed to compare quality of life (QoL) parameters between patients with PTMC who underwent total thyroidectomy (TT) alone and those who underwent TT with RAI ablation. Methods In this cross-sectional study, patients with PTMC who underwent TT with/without RAI remnant ablation were prospectively enrolled between June 2016 and October 2017. All patients completed three questionnaires: the 12-item short-form health survey (SF-12), thyroid cancer-specific quality of life (THYCA-QoL) questionnaire, and fear of progression (FoP) questionnaire. Results The TT and TT with RAI groups comprised 107 and 182 patients, respectively. The TT with RAI group had significantly lower serum thyrotropin (TSH) levels than the TT group. However, after matching for TSH levels between the groups (n=100 in both groups), there were no significant differences in baseline characteristics. According to the SF-12, the score for general health was significantly lower in the TT with RAI group than in the TT group (P=0.047). The THYCA-QoL also showed a significant difference in the "felt chilly" score between groups (P=0.023). No significant differences in FoP scores were observed between the groups. Conclusion Patients with PTMC who underwent TT with RAI ablation experienced more health-related problems than those managed with TT alone. These findings support the idea that RAI ablation should be carefully considered in patients with low-risk DTCs.

SummaryObjective Previous studies did not focus on the differences in the extent of cervical lymph node (LN) dissection according to coexistent Hashimoto's thyroiditis (HT) in patients with papillary thyroid carcinoma (PTC) and its clinical impact. We aimed to determine whether extensive cervical LN dissection is responsible for favourable clinical outcomes in PTC patients with HT and whether the coexistence of HT itself has an independent protective effect regardless of LN status. Design Retrospective cohort study. Patients 1369 patients with PTC who underwent total thyroidectomy with central compartment neck dissection. Measurements Metastatic LN ratio, defined as number of metastatic LNs divided by number of removed LNs, was used to evaluate the extent of LN dissection as well as the status of LN metastasis. Disease-free survival and dynamic risk stratification were compared for clinical outcomes. Results Presence of HT did not lower the risk of cervical LN metastasis (61.6% in patients with HT vs 65.1% in patients without HT, P = .292). Patients with HT had significantly larger numbers of removed LNs than patients without HT (11 vs 8, respectively, P

Objective: Thyrotoxic periodic paralysis (TPP) is characterized by acute onset paralysis and hypokalemia predominantly in male patients with thyrotoxicosis. Recent studies have emphasized the importance of potassium channels, which might explain the underlying mechanism of TPP. The KCNJ2 gene encodes the inward-rectifying potassium channel. In this study, we evaluated the role of KCNJ2 in the development of TPP. Design: Case-control analysis of KCNJ2 genetic association with TPP. Patients: 83 male patients with Graves’ disease (GD) were recruited for this study; 43 patients had TPP, whereas 40 patients had no history of TPP. Measurements: We analyzed the genotype and allelic frequency of a single-nucleotide polymorphism (SNP; rs312691) (C>T) adjacent to the KCNJ2 gene that is known to be related to TPP development. Results: The frequency of the CC genotype of the rs312691 SNP was 0.51 in TPP patients and 0.05 in controls (p-value=6.18×10−6). The C allele frequency of the SNP was 0.67 in the TPP group and 0.38 in the control group (odds ratio 3.24; 95% confidence interval 1.65–6.51; p-value, 3.1×10−4). The rs312691 SNP was significantly associated with TPP. Conclusions: We demonstrated that the rs312691 SNP was significantly associated with TPP. These findings suggest that KCNJ2 plays an important role in the pathophysiology of TPP in Korean GD patients with TPP.

The aim of this study was to evaluate the long-term clinical outcomes of papillary thyroid carcinoma (PTC) patients exhibiting biochemical incomplete response (BIR) to initial therapy. We evaluated 102 patients with PTC showing a BIR during the first 12–24 months after total thyroidectomy and radioactive iodine therapy. Patients were divided into three groups according to changes in stimulated thyroglobulin (Tg) and anti-Tg antibody (TgAb) levels: the increasing TgAb group (n = 19, 18.6%), the decreasing Tg group (n = 58, 56.9%), and the increasing Tg group (n = 25, 24.5%). With a median follow-up of 12 years, 43 (42%) patients had structural persistent disease as follows: 36 (84%) at regional sites and 7 (16%) at distant sites. The rate of structural persistent disease was significantly different between groups, with 21%, 41%, and 60% in the increasing TgAb, decreasing Tg, and increasing Tg groups, respectively (P = 0.012). Among patients without structural persistent disease, only 19 (18.6%) showed no evidence of disease and 40 (39.2%) were of a biochemical persistent status at the time of final follow-up. Increasing Tg after initial therapy was a significant risk factor for structural persistent disease in patients with BIR (HR, 4.16; 95% confidence interval (CI): 1.38–12.54, P = 0.011). PTC patients with BIR showed a high rate of structural persistent disease and Tg change after initial therapy is the most important prognostic factor for determining clinical outcomes of these patients.

The use of antithyroid drug (ATD) therapy in patients with Graves' disease (GD) hyperthyroidism has been increasing, but ATD therapy is associated with a higher relapse rate. We aimed to evaluate clinical factors for predicting relapse of GD after ATD therapy.Patients (n = 149) with newly diagnosed GD who achieved remission of hyperthyroidism after ATD therapy (≥6 months) were followed up for18 months after ATD withdrawal. We evaluated the predictive factors of relapse during a median of 6.9 years of follow-up.Disease relapse occurred in 52 patients (34.9%). By multivariate analyses, a duration of the minimum maintenance dose therapy (MMDT) of 6 months was a significant factor in disease relapse (hazard ratio [HR], 2.58; 95% confidence interval [CI], 1.47-4.52; p 0.001), and a T3/free T4 (fT4) ratio 120 at ATD withdrawal was significantly more frequent in patients with relapse (HR 2.43; 95% CI, 1.36-4.34; p = 0.002). In the prediction-of-relapse model, the likelihood of relapse was greater in the high-risk group, which had a short MMDT duration and a T3/fT4 ratio ≥120 (HR, 5.81; 95% CI, 2.52-13.39; p 0.001) and the intermediate-risk group, which had a short MMDT duration or a T3/fT4 ratio 120 (HR, 2.77; 95% CI, 1.26-6.13; p 0.001), than in the low-risk group, which had a long MMDT duration and a T3/fT4 ratio 120.An MMDT longer than 6 months and a high T3/fT4 ratio at ATD withdrawal were independent predictors of relapse in patients who achieved initial remission after ATD for GD. These factors could be used to determine the optimal time to withdraw ATD during the treatment of GD hyperthyroidism.

Background: Tumor volume (TV) of papillary thyroid carcinoma (PTC) increases exponentially during active surveillance, and the growth rate differs for each patient. TV doubling time (TVDT) is consi...

Given the emerging evidence supporting the lack of prognostic significance of gross extrathyroidal extension invading only strap muscles (strap-gETE), this study investigated whether lobectomy is feasible for patients with strap-gETE. A retrospective cohort study was conducted with 636 patients who had 1- to 4-cm-sized papillary thyroid carcinoma (PTC) treated with thyroid lobectomy. Patients with gross invasion of perithyroidal organs other than strap muscles or synchronous distant metastasis were excluded from the study. Disease-free survival (DFS) was compared according to the presence of strap-gETE. Strap-gETE was present in 50 patients (7.9%), with the remaining 586 patients (92.1%) showing no evidence of gETE. During the median follow-up period of 7.4 years, 6% of the patients with strap-gETE and 5.1% of the patients without gETE experienced structural persistent/recurrent disease (p = 0.99). No differences in DFS were observed between the two groups (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.38–4.08; p = 0.720). After adjustment for five major risk factors (age, gender, tumor size, multifocality, and cervical lymph node metastasis status) in the multivariate analysis, the presence of strap-gETE did not exhibit an independent role in the development of structural persistent/recurrent disease (HR 1.05; 95% CI 0.24–4.53, p = 0.950). Strap-gETE did not increase the risk of structural persistent/recurrent disease for the patients who underwent lobectomy for 1- to 4-cm-sized PTC. The study data support the limited role of strap-gETE in clinical outcomes and may broaden the indications for lobectomy for patients with PTCs.