Clinical Outcomes of Repeated Radioactive Iodine Therapy for Graves’ Disease

Background@#Radioactive iodine (RAI) therapy is a successful therapeutic modality for Graves’ disease. However, RAI therapy can fail, and RAI therapy after antithyroid drugs (ATDs) has a lower remission rate. Therefore, many patients require repeated RAI therapy. This study investigated the clinical outcomes of repeated RAI therapy for Graves’ disease. @*Methods@#Patients who underwent RAI therapy as second-line therapy after failure of ATD treatment between 2001 and 2015 were reviewed. Remission was defined as hypothyroid or euthyroid status without ATD, and with or without levothyroxine at 12 months after RAI therapy. @*Results@#The 1-year remission rate after 2nd RAI therapy (66%, 152/230) is significantly higher than that after 1st RAI therapy (48%, 393/815) or long-term ATD treatment after 1st RAI therapy failure (42%). The clinical response to 2nd RAI therapy was more rapid. The median time intervals from the 2nd RAI therapy to ATD discontinuation (1.3 months) and to the start of levothyroxine replacement (2.5 months) were significantly shorter than those for the 1st RAI therapy. A smaller goiter size, a longer time interval between the 1st and 2nd RAI therapies, and a longer ATD discontinuation period predicted remission after the 2nd RAI therapy. Finally, in 78 patients who failed the 2nd RAI therapy, the mean ATD dosage significantly reduced 5.1 mg over 12 months. @*Conclusion@#Repeated RAI therapy can be a good therapeutic option, especially in patients with smaller goiters and those who are more responsive to the 1st RAI therapy.

Comparison of Korean vs. American Thyroid Imaging Reporting and Data System in Malignancy Risk Assessment of Indeterminate Thyroid Nodules

Background@#The management of cytologically indeterminate thyroid nodules is challenging for clinicians. This study aimed to compare the diagnostic performance of the Korean Thyroid Imaging Reporting and Data Systems (K-TIRADS) with that of the American College of Radiology (ACR)-TIRADS for predicting the malignancy risk of indeterminate thyroid nodules. @*Methods@#Thyroid nodules diagnosed by fine-needle aspiration (FNA) followed by surgery or core needle biopsy at a single referral hospital were enrolled. @*Results@#Among 200 thyroid nodules, 78 (39.0%) nodules were classified as indeterminate by FNA (Bethesda category III, IV, and V), and 114 (57.0%) nodules were finally diagnosed as malignancy by surgery or core needle biopsy. The area under the curve (AUC) was higher for FNA than for either TIRADS system in all nodules, while all three methods showed similar AUCs for indeterminate nodules. However, for Bethesda category III nodules, applying K-TIRADS 5 significantly increased the risk of malignancy compared to a cytological examination alone (50.0% vs. 26.5%, P=0.028), whereas applying ACR-TIRADS did not lead to a change. @*Conclusion@#K-TIRADS and ACR-TIRADS showed similar diagnostic performance in assessing indeterminate thyroid nodules, and K-TIRADS had beneficial effects for malignancy prediction in Bethesda category III nodules.

Clinical Value of Serum Mitochondria-Inhibiting Substances in Assessing Renal Hazards: A Community-Based Prospective Study in Korea

Background@#Mitochondrial dysfunction is strongly associated with several kidney diseases. However, no studies have evaluated the potential renal hazards of serum mitochondria-inhibiting substance (MIS) and aryl hydrocarbon receptor ligand (AhRL) levels. @*Methods@#We used serum level of MIS and AhRL and clinical renal outcomes from 1,511 participants of a prospective community-based cohort in Ansung. MIS was evaluated based on intracellular adenosine triphosphate (MIS-ATP) or reactive oxygen species (MIS-ROS) generation measured using cell-based assays. @*Results@#During a mean 6.9-year follow-up, 84 participants (5.6%) developed a rapid decline in kidney function. In the lowest quartile group of MIS-ATP, patients were older and had metabolically deleterious parameters. In multivariate logistic regression analysis, higher MIS-ATP was associated with decreased odds for rapid decline: the odds ratio (OR) of 1% increase was 0.977 (95% confidence interval [CI], 0.957 to 0.998; P=0.031), while higher MIS-ROS was marginally associated with increased odds for rapid decline (OR, 1.014; 95% CI, 0.999 to 1.028; P=0.055). However, serum AhRL was not associated with the rapid decline in kidney function. In subgroup analysis, the renal hazard of MIS was particularly evident in people with hypertension and low baseline kidney function. @*Conclusion@#Serum MIS was independently associated with a rapid decline in kidney function, while serum AhRL was not. The clinical implication of renal hazard on serum MIS requires further evaluation in future studies.

High Serum-Induced AhRL Is Associated with Prevalent Metabolic Syndrome and Future Impairment of Glucose Tolerance in the Elderly

Background@#High circulating levels of dioxins and dioxin-like chemicals, acting via the aryl hydrocarbon receptor (AhR), have previously been linked to diabetes. We now investigated whether the serum AhR ligands (AhRL) were higher in subjects with metabolic syndrome (MetS) and in subjects who had developed a worsened glucose tolerance over time. @*Methods@#Serum AhRL at baseline was measured by a cell-based AhRL activity assay in 70-year-old subjects (n=911) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The main outcome measures were prevalent MetS and worsening of glucose tolerance over 5 years of follow-up. @*Results@#AhRL was significantly elevated in subjects with prevalent MetS as compared to those without MetS, following adjustment for sex, smoking, exercise habits, alcohol intake and educational level (P=0.009). AhRL at baseline was higher in subjects who developed impaired fasting glucose or diabetes at age 75 years than in those who remained normoglycemic (P=0.0081). The odds ratio (OR) of AhRL for worsening glucose tolerance over 5 years was 1.43 (95% confidence interval [CI], 1.13 to 1.81; P=0.003, continuous variables) and 2.81 (95% CI, 1.31 to 6.02; P=0.008, in the highest quartile) adjusted for sex, life style factors, body mass index, and glucose. @*Conclusion@#These findings support a large body of epidemiologic evidence that exposure to AhR transactivating substances, such as dioxins and dioxin-like chemicals, might be involved in the pathogenesis of MetS and diabetes development. Measurement of serum AhRL in humans can be a useful tool in predicting the onset of metabolic disorders.

High Serum-Induced AhRL Is Associated with Prevalent Metabolic Syndrome and Future Impairment of Glucose Tolerance in the Elderly

Background@#High circulating levels of dioxins and dioxin-like chemicals, acting via the aryl hydrocarbon receptor (AhR), have previously been linked to diabetes. We now investigated whether the serum AhR ligands (AhRL) were higher in subjects with metabolic syndrome (MetS) and in subjects who had developed a worsened glucose tolerance over time. @*Methods@#Serum AhRL at baseline was measured by a cell-based AhRL activity assay in 70-year-old subjects (n=911) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The main outcome measures were prevalent MetS and worsening of glucose tolerance over 5 years of follow-up. @*Results@#AhRL was significantly elevated in subjects with prevalent MetS as compared to those without MetS, following adjustment for sex, smoking, exercise habits, alcohol intake and educational level (P=0.009). AhRL at baseline was higher in subjects who developed impaired fasting glucose or diabetes at age 75 years than in those who remained normoglycemic (P=0.0081). The odds ratio (OR) of AhRL for worsening glucose tolerance over 5 years was 1.43 (95% confidence interval [CI], 1.13 to 1.81; P=0.003, continuous variables) and 2.81 (95% CI, 1.31 to 6.02; P=0.008, in the highest quartile) adjusted for sex, life style factors, body mass index, and glucose. @*Conclusion@#These findings support a large body of epidemiologic evidence that exposure to AhR transactivating substances, such as dioxins and dioxin-like chemicals, might be involved in the pathogenesis of MetS and diabetes development. Measurement of serum AhRL in humans can be a useful tool in predicting the onset of metabolic disorders.

Association of Vitamin D Deficiency with Diabetic Nephropathy

Background@#Low 25-hydroxyvitamin D (25OHD) levels are associated with the incidence of type 2 diabetes mellitus (T2DM). However, the association between 25OHD and metabolic health status or diabetic complications is inconclusive. We evaluated this relationship between vitamin D status and metabolic parameters and complications of T2DM. @*Methods@#This study included 1,392 patients with T2DM who visited Eulji and Ewha Diabetes Center between January 2011 and August 2016. Anthropometric parameters and laboratory tests including glycated hemoglobin (HbA1c), lipid profile, liver and kidney function, and urinary albumin-to-creatinine ratio (UACR) were evaluated. Diabetic macro- and microvascular complications were determined through a medical record review. Serum 25OHD concentrations were measured by chemiluminescent immunoassay. @*Results@#The mean 25OHD level was 16.8±9.6 ng/mL. Vitamin D deficiency (<20 ng/mL) and severe deficiency (<10 ng/mL) were observed in 990 (71.1%) and 351 (25.2%) participants, respectively. 25OHD level was positively correlated with age and highdensity lipoprotein cholesterol (HDL-C) level and negatively correlated with HbA1c, triglyceride level, and UACR. HDL-C and UACR were significantly associated with 25OHD after adjusting for other variables. Vitamin D deficiency was independently related to nephropathy after adjusting for confounding variables. @*Conclusion@#Vitamin D deficiency was common among Korean T2DM patients; it was independently associated with microalbuminuria and HDL level, and positively related to diabetic nephropathy.

Effect of Dialysis on Aryl Hydrocarbon Receptor Transactivating Activity in Patients with Chronic Kidney Disease

Changes of Nodular Size and Its Risk Factors in Iodine-Sufficient Area: a Retrospective Cohort Analysis of 7753 Thyroid Nodules

Background and Objectives@#Iodine is known to be an important factor in the occurrence of goiter, and South Korea is a region with sufficient iodine supplementation. In this regard, we checked the size change of thyroid nodules found by health check-up in Koreans and examined which risk factors influence the size change. @*Materials and Methods@#A total 7753 subjects who underwent thyroid sonography two or more times were included. We defined that there was a change in the size of the nodule when the difference in diameter identified in the last ultrasound was more than 3 mm. @*Results@#Thyroid nodules were decreased in 895 subjects (11.5%) and increased in 1041 subjects (13.5%). The rate of increased nodule was on an increasing trend according to the duration (annual percent change 2.6%, p＜0.001). In contrast, the rate of decreased nodule was unchanged. Predictive factors related to decrease of the nodule size were young age, male sex, larger initial nodule size and thyroiditis. Similarly, young age, larger initial nodule size and diffuse parenchymal abnormality were significant predictive factors for increased nodules. However, diffuse parenchymal abnormality was not a predictive factor when we analyzed only thyroid nodules larger than 1 cm. @*Conclusion@#In our study, 11.5-13.5% of benign thyroid nodules were increased or decreased during median 27 months of follow-up in iodine sufficient condition. Young age, larger initial size and diffuse parenchymal abnormality were common predictive factor affecting both the increase and decrease of thyroid nodules.

Repeated Dry Sauna Therapy Improves Quality of Life in Obese Korean People / 가정의학회지

Background@#Dry sauna treatments improve the quality of life for chronic pain, congestive heart failure, and type 2 diabetes patients. This study aimed to determine whether dry sauna therapy improved the quality of life of obese people. @*Methods@#A total of 38 consecutive participants aged over 20 years with a body mass index of ≥25 kg/m2 were recruited for the study. The participants were treated with a 90°C dry sauna for 15 minutes, twice daily for 4 consecutive days. To assess the quality of life, all participants completed the 5 level EQ-5D questionnaires and the EQ-Visual Analog Scale. Study parameters were measured on the same day prior to commencing the sauna sessions in a fasted state and 2 days after the last sauna session. @*Results@#The average age was 62.3±9.5 years; 84.2% of the participants were female. The mean body mass index was 28.5±2.4 kg/m2. Dry sauna significantly improved the mean 5 level EQ-5D index scores from 0.83±0.12 to 0.89±0.11 and increased the mean EQ-Visual Analog Scale from 79.0±15.2 to 91.1±9.7. However, there were no significant changes in body mass index, blood pressure, heart rate, or body composition before and after the 8-session sauna therapy. @*Conclusion@#Dry sauna improved the health-related quality of life of obese patients without adverse events. Further clinical studies in larger study populations are needed to verify these findings and provide concrete evidence for obesity treatment.

Diagnosis and Treatment of Growth Hormone Deficiency: A Position Statement from Korean Endocrine Society and Korean Society of Pediatric Endocrinology

Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.

The Association between Pulmonary Functions and Incident Diabetes: Longitudinal Analysis from the Ansung Cohort in Korea

Background@#We sought to explore whether reduced pulmonary function is an independent risk factor for incident diabetes in Koreans. @*Methods@#We conducted a prospective cohort study of pulmonary function as a risk factor for incident diabetes using 10-year follow-up data from 3,864 middle-aged adults from the Ansung cohort study in Korea. The incidence of diabetes was assessed using both oral glucose tolerance tests and glycosylated hemoglobin levels. @*Results@#During 37,118 person-years of follow-up, 583 participants developed diabetes (incidence rate: 15.7 per 1,000 personyears). The mean follow-up period was 8.0±3.7 years. Forced vital capacity (FVC; % predicted) and forced expiratory volume in 1 second (FEV1; % predicted) were significantly correlated with incident diabetes in a graded manner after adjustment for sex, age, smoking, exercise, and metabolic parameters. The adjusted hazard ratio (HR) and confidence interval (CI) for diabetes were 1.408 (1.106 to 1.792) and 1.469 (1.137 to 1.897) in the first quartiles of FVC and FEV1, respectively, when compared with the highest quartile. Furthermore, the FVC of the lowest first and second quartiles showed a significantly higher 10-year panel homeostasis model assessment of insulin resistance index, with differences of 0.095 (95% CI, 0.010 to 0.018; P=0.028) and 0.127 (95% CI, 0.044 to 0.210; P=0.003), respectively, when compared to the highest quartiles. @*Conclusion@#FVC and FEV1 are independent risk factors for developing diabetes in Koreans. Pulmonary factors are possible risk factors for insulin resistance and diabetes.

Ultrasonographic Characteristics of the Hyperfunctioning Thyroid Nodule and Predictive Factors for Thyroid Stimulating Hormone Suppression

BACKGROUND AND OBJECTIVES: Thyroid scan is a good tool for diagnosis of hyperfunctioning thyroid nodules (HNs), however it has been limited in use in a primary clinical practice, because of its inconvenience and low accessibility. This study aimed to analyze ultrasonographic (US) characteristics of HNs and to predict HNs by US. MATERIALS AND METHODS: We included 114 patients who exhibited results of ‘hot’ nodule in the thyroid scan from 2008 to 2017. Analysis for US characteristics included 73 patients without unclear US images and other inevitable reasons. We compared US characteristics of HNs with cold nodules that showed “cold” in the thyroid scan. Additionally, we compared US characteristics of HNs between suppressed thyroid-stimulating hormone (TSH) (<0.25 uIU/mL) or normal TSH, and analysis receiver operating characteristics (ROC) curve for prediction of suppressed TSH among HNs. RESULTS: The HNs showed more partially cystic nodule, isoechoic echogenicity, hypervascularity and presence of halo in the US finding than the cold nodule. In subgroup analysis of nodules with TSH suppression among HNs, the TSH suppression nodules was lager in max size and volume than the normal TSH nodules. In ROC analyses for prediction of the TSH suppression among HNs, area under receiver operating characteristics curves was 0.736 in max size, 0.761 in volume. CONCLUSION: HNs showed more frequently partially cystic contents, isoechoic echogenicity, hypervascularity, and peripheral halo sign in US finding. Thyroid nodule size and volume were associated with suppressed TSH level of HNs, and optimal cutoff levels for prediction of TSH suppression among HNs were 2.6 cm and 1.13 cm3, respectively.

Postoperative Thyroid-Stimulating Hormone Levels Did Not Affect Recurrence after Thyroid Lobectomy in Patients with Papillary Thyroid Cancer

BACKGROUND: Thyroid-stimulating hormone (TSH) suppression is recommended for patients who undergo thyroidectomy for differentiated thyroid cancer (DTC). However, the impact of TSH suppression on clinical outcomes in low-risk DTC remains uncertain. Therefore, we investigated the effects of postoperative TSH levels on recurrence in patients with low-risk DTC after thyroid lobectomy. METHODS: Patients (n=1,528) who underwent thyroid lobectomy for papillary thyroid carcinoma between 2000 and 2012 were included in this study. According to the mean and dominant TSH values during the entire follow-up period or 5 years, patients were divided into four groups (<0.5, 0.5 to 1.9, 2.0 to 4.4, and ≥4.5 mIU/L). Recurrence-free survival was compared among the groups. RESULTS: During the 5.6 years of follow-up, 21 patients (1.4%) experienced recurrence. Mean TSH levels were within the recommended low-normal range (0.5 to 1.9 mIU/L) during the total follow-up period or 5 years in 38.1% or 36.0% of patients. The mean and dominant TSH values did not affect recurrence-free survival. Adjustment for other risk factors did not alter the results. CONCLUSION: Serum TSH levels did not affect short-term recurrence in patients with low-risk DTC after thyroid lobectomy. TSH suppression should be conducted more selectively.

Prevalence of thyroid nodules and their associated clinical parameters: a large-scale, multicenter-based health checkup study

BACKGROUND/AIMS: We evaluated the prevalence and characteristics of thyroid nodules detected by thyroid ultrasound (US) at health checkups and the associated clinical parameters. METHODS: A total of 72,319 subjects who underwent thyroid US at three health checkup centers in Korea from January 2004 to December 2010 were included in this study. The correlations between the presence of thyroid nodules and other clinical parameters were analyzed. RESULTS: The prevalence of thyroid nodules and cysts was 34.2% (n = 24,757). Thyroid nodules were more prevalent in women and older age groups. Among the subjects with thyroid nodules with size information (n = 24,686), 18,833 (76.3%) had nodules measuring ≤ 1.0 cm. Women and older age groups showed higher proportion of larger nodules. Percentage of women, age, body mass index (BMI), waist circumference, body fat composition, blood pressure, and the level of fasting glucose, total cholesterol, and low density lipoprotein cholesterol were higher in the subjects with thyroid nodules compared to those without nodules. The prevalence of metabolic syndrome and overt/subclinical thyrotoxic state was higher in the subjects with thyroid nodules. In the multivariable logistic regression analysis, women, age, BMI, metabolic syndrome, and thyrotoxicosis were independently associated with the presence of thyroid nodules. CONCLUSIONS: The high prevalence of thyroid nodules in people who underwent thyroid US at a health checkup suggests that increased detection of thyroid nodules resulted in an increased prevalence in the general population. However, metabolic disturbances may also have contributed to the increase in thyroid nodule prevalence in Korea.

Association between Serum Fibroblast Growth Factor 21 Levels and Bone Mineral Density in Postmenopausal Women

BACKGROUND: Despite the beneficial effect of fibroblast growth factor 21 (FGF21) on metabolic disease, there are concerns about adverse effects on bone metabolism, supported by animal studies. However, a recent human study showed the positive association between serum FGF21 level and bone mineral density (BMD) in healthy premenopausal women. We undertook this study to examine the association between FGF21 level and BMD in healthy postmenopausal Korean women who are susceptible to osteoporosis. METHODS: We used data of 115 participants from a cohort of healthy postmenopausal women (>50 years old) to examine the association between serum FGF21 level and BMD. The clinical characteristics were obtained from the participants, and blood testing and serum FGF21 testing were undertaken. BMD of the lumbar spine, femoral neck and total hip area, and bone markers were used in the analyses. RESULTS: The mean age of the participants was 60.2±7.2 years. Serum FGF21 levels showed negative correlation with BMD and T-scores in all three areas, but there were no statistically significant differences. Multivariate analyses with adjustment for age and body mass index also did not show significant association between serum FGF21 level and BMD. In addition, serum FGF21 level also showed no correlation with osteocalcin and C-telopeptide levels. CONCLUSION: In our study, serum FGF21 level showed no significant correlation with BMD and T-scores.

Corrigendum: Association between Serum Fibroblast Growth Factor 21 Levels and Bone Mineral Density in Postmenopausal Women

No abstract available.

Free Thyroxine, Anti-Thyroid Stimulating Hormone Receptor Antibody Titers, and Absence of Goiter Were Associated with Responsiveness to Methimazole in Patients with New Onset Graves' Disease

BACKGROUND: Anti-thyroid drug therapy is considered a treatment of choice for Graves' disease; however, treatment response varies among individuals. Although several studies have reported risk factors for relapse after initial treatment, few have assessed responsiveness during the early treatment period. Our study aimed to identify the clinical characteristics for responsiveness to methimazole. METHODS: We included 99 patients diagnosed with Graves' disease for the first time. Drug responsiveness was defined as the correlation coefficients between decreasing rates of free thyroxine level per month and methimazole exposure dose. According to their responsiveness to treatment, the patients were classified into rapid or slow responder groups, and age, sex, free thyroxine level, and thyrotropin binding inhibiting immunoglobulin (TBII) titers were compared between groups. RESULTS: The mean patient age was 44.0±13.5 years and 40 patients were male (40%). The mean TBII titer was 36.6±74.4 IU/L, and the mean free thyroxine concentration was 48.9±21.9 pmol/L. The rapid responder group showed higher TBII titer and free thyroxine level at diagnosis, while age, sex, smoking, and presence of goiter did not differ between the two groups. Logistic regression analyses revealed that high level of serum thyroxine, high titer of TBII, and absence of goiter were significantly associated with a rapid response, while age, sex, and smoking were not significant factors for the prediction of responsiveness. CONCLUSION: In patients with new onset Graves' disease, high level of free thyroxine, high titer of TBII, and absence of goiter were associated with rapid responsiveness to methimazole treatment.

Identification of Maturity-Onset Diabetes of the Young Caused by Glucokinase Mutations Detected Using Whole-Exome Sequencing

Glucokinase maturity-onset diabetes of the young (GCK-MODY) represents a distinct subgroup of MODY that does not require hyperglycemia-lowering treatment and has very few diabetes-related complications. Three patients from two families who presented with clinical signs of GCK-MODY were evaluated. Whole-exome sequencing was performed and the effects of the identified mutations were assessed using bioinformatics tools, such as PolyPhen-2, SIFT, and in silico modeling. We identified two mutations: p.Leu30Pro and p.Ser383Leu. In silico analyses predicted that these mutations result in structural conformational changes, protein destabilization, and thermal instability. Our findings may inform future GCK-MODY diagnosis; furthermore, the two mutations detected in two Korean families with GCK-MODY improve our understanding of the genetic basis of the disease.

Serum Preadipocyte Factor 1 Levels Are Not Associated with Bone Mineral Density among Healthy Postmenopausal Korean Women

BACKGROUND: Multipotent mesenchymal stem cells can differentiate into adipocytes or osteoblasts through closely regulated lineage-control processes. However, adipocyte precursor cells release preadipocyte factor 1 (Pref-1), which inhibits the differentiation of mesenchymal stem cells into mature adipocytes and osteoblasts. Previous studies have also reported an inverse association between Pref-1 levels and bone mineral density (BMD) among patients with anorexia nervosa. METHODS: In this retrospective study, we examined the correlations between Pref-1 levels and BMD among 124 healthy postmenopausal women (>50 years old). The patients had provided information regarding their clinical characteristics, and underwent blood testing and serum Pref-1 testing. RESULTS: The subjects' mean age was 59.9±7.1 years and the median time since menopause onset was 9.1 years. A history of osteoporotic fracture was identified in 23 subjects (19%). Serum Pref-1 levels were not significantly correlated with BMD values at the lumbar spine (R²=0.038, P=0.109), femur neck (R²=0.017, P=0.869), and total hip (R²=0.041, P=0.09), and multivariate analyses with adjustment for age and body mass index also did not detect any significant correlations. Subgroup analyses according to a history of fracture also did not detect significant associations between Pref-1 levels and BMD values. CONCLUSION: In our study population, it does not appear that serum Pref-1 levels are significantly associated with BMD values and osteoporosis.

The Frequency and Clinical Implications of the BRAF(V600E) Mutation in Papillary Thyroid Cancer Patients in Korea Over the Past Two Decades

BACKGROUND: Over the past several decades, there has been a rapid worldwide increase in the prevalence of papillary thyroid cancer (PTC) as well as a number of changes in the clinicopathological characteristics of this disease. BRAF(V600E), which is a mutation of the proto-oncogene BRAF, has become the most frequent genetic mutation associated with PTC, particularly in Korea. Thus, the present study investigated whether the prevalence of the BRAF(V600E) mutation has increased over the past two decades in the Korean population and whether various PTC-related clinicopathological characteristics have changed. METHODS: The present study included 2,624 patients who underwent a thyroidectomy for PTC during two preselected periods; 1995 to 2003 and 2009 to 2012. The BRAF(V600E) mutation status of each patient was confirmed using the polymerase chain reaction-restriction fragment length polymorphism method or by the direct sequencing of DNA. RESULTS: The prevalence of the BRAF(V600E) mutation in Korean PTC patients increased from 62.2% to 73.7% (P=0.001) over the last two decades. Additionally, there was a greater degree of extrathyroidal extension (ETE) and lymph node metastasis in 2009 to 2012 patients with the BRAF(V600E) mutation and a higher frequency of thyroiditis and follicular variant-PTC in 2009 to 2012 patients with wild-type BRAF. However, only the frequency of ETE was significantly higher in 1995 to 2003 patients with the BRAF(V600E) mutation (P=0.047). Long-term recurrence rates during a 10-year median follow-up did not differ based on BRAF(V600E) mutation status. CONCLUSION: The BRAF(V600E) mutation rate in Korean PTC patients has been persistently high (approximately 70%) over the past two decades and continues to increase. The present findings demonstrate that BRAF(V600E)-positive PTC was associated with more aggressive clinicopathological features, especially in patients who were recently diagnosed, suggesting that BRAF(V600E) mutation status may be a useful prognostic factor for PTC in patients recently diagnosed with this disease.