Ultrasonographic characteristics of Hürthle cell neoplasms: prediction of malignancy

Purpose@#This study investigated the ultrasound (US) features of malignancy in patients with Hürthle cell neoplasms (HCNs) of the thyroid gland. @*Methods@#The present study included 139 HCNs that had undergone surgical excision at a single institution from 1996 to 2020 and had preoperative US images. The sonographic characteristics of HCNs were correlated with their pathological results. The US findings associated with malignancy were explored using logistic regression analysis, and the diagnostic performance and cutoff were assessed using receiver operating characteristic analysis. @*Results@#The most common US findings of HCNs were a solid content (76.3%), oval to round shape (100%), hypoechogenicity (70.5%), a smooth margin (95.0%), the halo sign (90.6%), and no calcifications (93.5%). HCNs were commonly smaller in pathologic measurements than in US measurements (smaller, same, and greater than US measurements in 60.4%, 21.6%, and 18.0% of HCNs, respectively; P3.35 cm might be used as a criterion to suggest malignancy. The size of HCNs often showed discrepancies between US and pathologic measurements.

Identification of Mutations in the Thyroxine-Binding Globulin (TBG) Gene in Patients with TBG Deficiency in Korea

Background@#Thyroxine-binding globulin (TBG) is a major transporter protein for thyroid hormones. The serpin family A member 7 (SERPINA7) gene codes for TBG, and mutations of the SERPINA7 gene result in TBG deficiency. Although more than 40 mutations have been reported in several countries, only a few studies of TBG deficiency and SERPINA7 gene mutation have been performed in Korea. The aim of this study is to review the clinical presentations and laboratory findings of patients with TBG deficiency and to investigate the types of SERPINA7 gene mutation. @*Methods@#Five unrelated Korean adults with TBG deficiency attending endocrinology clinic underwent SERPINA7 gene sequencing. Four patients harbored a SERPINA7 gene mutation. Serum thyroid hormones, anti-microsomal antibodies, and TBG were measured. Genomic DNA was extracted from whole blood. All exons and intron-exon boundaries of the TBG gene were amplified and sequencing was performed. @*Results@#Two patients were heterozygous females, and the other two were hemizygous males. One heterozygous female had coexisting hypothyroidism. The other heterozygous female was erroneously prescribed levothyroxine at a local clinic. One hemizygous male harbored a novel mutation, p.Phe269Cysfs*18, which caused TBG partial deficiency. Three patients had the p.Leu372Phefs*23 mutation, which is known as TBG-complete deficiency Japan (TBG-CDJ) and was also presented in previous mutation analyses in Korea. @*Conclusion@#This study presents four patients diagnosed with TBG deficiency and provides the results of SERPINA7 gene sequencing. One novel mutation, p.Phe269Cysfs*18, causing TBD-partial deficiency and three cases of TBG-CDJ were demonstrated. It is necessary to identify TBG deficiency to prevent improper treatment. Also, sequencing of the SERPINA7 gene would provide valuable information about the TBG variants in Korea.

What is the difference between the tall cell variant and the classic type of papillary thyroid carcinoma on ultrasonography?

Purpose@#The prevalence of the tall cell variant of papillary thyroid carcinoma (TCVPTC), which has a poor prognosis, has increased as its definition has been modified. We sought to investigate whether TCVPTC is different from the classic type on ultrasonography (US). @*Methods@#This study included 46 consecutive TCVPTC patients and 92 classic papillary thyroid carcinoma (PTC) patients who were confirmed surgically at the authors’ institution. The US findings and pathologic reports of these patients were retrospectively reviewed. US features based on the Korean Thyroid Imaging Reporting and Data System, preoperative US suspicion for lymph node metastasis, and the presence of capsular location were evaluated. @*Results@#Univariable and multivariable analyses identified that TCVPTC showed more frequent irregular tumor margin (odds ratio [OR], 6.62; 95% confidence interval [CI], 1.46 to 30.09; P=0.014) and capsular location (OR, 4.63; 95% CI, 1.49 to 14.41; P=0.008) than classic PTC. Capsular location was an independent predictor of TCVPTC for tumors less than or equal to 1.5 cm in size (OR, 4.23; 95% CI, 1.12 to 15.92; P=0.033). Irregular margin was an independent predictor of TCVPTC for tumors larger than 1.5 cm (OR, 10.46; 95% CI, 1.16 to 94.48; P=0.037). Extrathyroidal extension was not significantly different between the two groups. @*Conclusion@#The two key features of TCVPTC on US are frequent capsular location for tumors less than or equal to 1.5 cm in size and the higher likelihood of an irregular margin for tumors larger than 1.5 cm.

Bone Mineral Density Screening Interval and Transition to Osteoporosis in Asian Women

Background@#Bone mineral density (BMD) testing is indicated for women aged 65 years, but screening strategies for osteoporosis are controversial. Currently, there is no study focusing on the BMD testing interval in Asian populations. The current study aimed to evaluate the estimated time interval for screening osteoporosis. @*Methods@#We conducted a study of 6,385 subjects aged 50 years and older who underwent dual-energy X-ray absorptiometry screening more than twice at Samsung Medical Center as participants in a routine health checkup. Subjects were divided based on baseline T-score into mild osteopenia (T-score, –1.5), moderate osteopenia (T-score, ≤–1.5 to >–2.0), and severe osteopenia (T-score, ≤–2.0 to >–2.5). Information about personal medical and social history was collected by a structured questionnaire. @*Results@#The adjusted estimated BMD testing interval for 10% of the subjects to develop osteoporosis was 13.2 years in mild osteopenia, 5.0 years in moderate osteopenia, and 1.5 years in severe osteopenia. @*Conclusion@#Our study provides extended information about BMD screening intervals in Asian female population. Baseline T-score was important for predicting BMD screening interval, and repeat BMD testing within 5 years might not be necessary in mild osteopenia subjects.

Graves’ Disease and the Risk of End-Stage Renal Disease: A Korean Population-Based Study

Background@#Hyperthyroidism is associated with an increased glomerular filtration rate (GFR) in the hyperdynamic state, which is reversible after restoring euthyroidism. However, long-term follow-up of renal dysfunction in patients with hyperthyroidism has not been performed. @*Methods@#This was a retrospective cohort study using the Korean National Health Insurance database and biannual health checkup data. We included 41,778 Graves’ disease (GD) patients and 41,778 healthy controls, matched by age and sex. The incidences of end-stage renal disease (ESRD) were calculated in GD patients and controls. The cumulative dose and duration of antithyroid drugs (ATDs) were calculated for each patient and categorized into the highest, middle, and lowest tertiles. @*Results@#Among 41,778 GD patients, 55 ESRD cases occurred during 268,552 person-years of follow-up. Relative to the controls, regardless of smoking, drinking, or comorbidities, including chronic kidney disease, GD patients had a 47% lower risk of developing ESRD (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37 to 0.76). In particular, GD patients with a higher baseline GFR (≥90 mL/min/1.73 m2; HR, 0.33; 95% CI, 0.11 to 0.99), longer treatment duration (>33 months; HR, 0.31; 95% CI, 0.17 to 0.58) or higher cumulative dose (>16,463 mg; HR, 0.29; 95% CI, 0.15 to 0.57) of ATDs had a significantly reduced risk of ESRD. @*Conclusion@#This was the first epidemiological study on the effect of GD on ESRD, and we demonstrated that GD population had a reduced risk for developing ESRD.

Serum Carcinoembryonic Antigen as a Biomarker for Medullary Thyroid Cancer

Background and Objectives@#The lack of known elevated biomarkers in cancer surveillance is a challenge for diagnostics. However, few studies have assessed the proportion of patients with medullary thyroid cancer (MTC) that presented with elevated serum carcinoembryonic antigen (CEA) level. @*Materials and Methods@#This was a retrospective study of 115 patients treated for MTC at Samsung Medical Center between 1995 and 2017. Serum calcitonin and CEA levels that were available at one of the following time points were included: (a) within 3 months before the initial surgery, (b) when a structural recurrence was confined to the neck, or (c) when a distant metastasis was identified during follow-up. Considering the high false-positive rate of serum CEA testing, 5 ng/mL was selected as the cut-off threshold. @*Results@#The sensitivity of CEA at the time of diagnosis was 54%, but it significantly increased with anatomical stage, from 20% in stage I to 88% in stage IV (p for trend ＜0.001). At the time of diagnosis, larger tumor size, more frequent gross extra-thyroidal extension, more frequent N1b, and a higher number of metastatic lymph nodes were significantly observed in CEA-positive patients compared with CEA-negative patients (p＜0.05). The sensitivity of CEA at the time of recurrence was 56% for local recurrence and 80% for distant recurrence. @*Conclusion@#The CEA value was associated with anatomical stage as a biomarker for MTC and could be used to predict poor prognosis. However, serum CEA testing plays a limited role in diagnosis and follow-up of MTC because it can show normal values even in advanced disease.

Clinicopathological Features of Patients Diagnosed with Both Primary Thyroid Cancer and Primary Renal Cell Cancer and Its Comparison with Patients with Thyroid Cancer or Renal Cell Cancer Alone

Background and Objectives@#Thyroid cancer (TC) and renal cell carcinoma (RCC) display more frequent co-occurrence than would be expected by chance. We investigated clinicopathological features of patients with both primary TC and primary RCC (TC/RCC) group to facilitate a greater understanding of the relationship between two cancers. @*Materials and Methods@#A total of 53 patients who diagnosed with TC/RCC were enrolled. 13,663 TC-alone and 3279 RCC-alone patients who had undergone surgery at Samsung Medical Center between 1994 and 2014 were included as control groups. The clinicopathological characteristics of these patients were retrospectively reviewed. @*Results@#The median age at the time of TC or RCC diagnosis was 54 years in TC/RCC group and the RCC-alone group, while the patients in TC-alone group were significantly younger (47 years). The TC/RCC group showed a nearly equal sex prevalence (49% male), significantly different than the results of the TC-alone group (80% female) and RCC-alone group (71% male). A higher grade of pathologic stage (56.6% in stage 3) and greater number of patients with multifocality of thyroid tumors (45 vs. 32%), and more family history of cancer (32 vs. 0.4%) were revealed in TC/RCC group than in TC-alone group. In addition, 15.1% of patients in TC/RCC group presented with additional primary cancers such as prostate, colon, stomach, breast, and lung cancers. Conclusion: Patients in the TC/RCC group have a high rate of cancer family history, multifocality of thyroid tumors, and additional cancers. To understand this unique subset group, additional studies for environmental and genetic factors would be helpful for earlier diagnosis of combined cancers.

Clinicopathological Features of Patients Diagnosed with Both Primary Thyroid Cancer and Primary Renal Cell Cancer and Its Comparison with Patients with Thyroid Cancer or Renal Cell Cancer Alone

Background and Objectives@#Thyroid cancer (TC) and renal cell carcinoma (RCC) display more frequent co-occurrence than would be expected by chance. We investigated clinicopathological features of patients with both primary TC and primary RCC (TC/RCC) group to facilitate a greater understanding of the relationship between two cancers. @*Materials and Methods@#A total of 53 patients who diagnosed with TC/RCC were enrolled. 13,663 TC-alone and 3279 RCC-alone patients who had undergone surgery at Samsung Medical Center between 1994 and 2014 were included as control groups. The clinicopathological characteristics of these patients were retrospectively reviewed. @*Results@#The median age at the time of TC or RCC diagnosis was 54 years in TC/RCC group and the RCC-alone group, while the patients in TC-alone group were significantly younger (47 years). The TC/RCC group showed a nearly equal sex prevalence (49% male), significantly different than the results of the TC-alone group (80% female) and RCC-alone group (71% male). A higher grade of pathologic stage (56.6% in stage 3) and greater number of patients with multifocality of thyroid tumors (45 vs. 32%), and more family history of cancer (32 vs. 0.4%) were revealed in TC/RCC group than in TC-alone group. In addition, 15.1% of patients in TC/RCC group presented with additional primary cancers such as prostate, colon, stomach, breast, and lung cancers. Conclusion: Patients in the TC/RCC group have a high rate of cancer family history, multifocality of thyroid tumors, and additional cancers. To understand this unique subset group, additional studies for environmental and genetic factors would be helpful for earlier diagnosis of combined cancers.

Effect of the Orally Active Growth Hormone Secretagogue MK-677 on Somatic Growth in Rats

PURPOSE: Growth hormone secretagogues (GHSs) possess the ability to release growth hormone (GH) in the body. This study aimed to investigate the effects of MK-677, an orally active GHS, on somatic growth in rats. MATERIALS AND METHODS: The serum levels of GH were measured after oral administration of MK-677 to confirm GH stimulatory effects. Body weight, body length, tibia length, epiphyseal plate width, and serum levels of insulin-like growth factor (IGF)-I were measured after oral administration of 4 mg/kg of MK-677 for 6 weeks to investigate growth-promoting effects. RESULTS: Oral administration of MK-677 at 4 mg/kg increased peak GH concentrations by 1.8-fold, compared to baseline. However, oral administration of MK-677 for 6 weeks did not increase body growth or serum levels of IGF-I. At 6 weeks after treatment, the GH response to MK-677 was abolished. Pituitary GH mRNA and hypothalamic GH-releasing hormone mRNA, and GH secretagogue receptor (GHSR) mRNA expression in the pituitary and hypothalamus did not differ between the control and treatment group. Somatostatin (SST) mRNA expression in the hypothalamus was markedly increased in the treatment group, whereas SST receptor (SSTR)-2 mRNA expression in the pituitary gland was decreased. Protein expression of hypothalamic GHSR, SST, and pituitary SSTR-2 showed patterns similar to those for mRNA expression. CONCLUSION: Our results suggest that prolonged administration of MK-677 in rats does not promote growth despite the GH stimulatory effect of MK-677, which may be related to increased expression of SST in the hypothalamus. Further studies are needed to overcome the observed desensitization to GHS.

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.

Prognosis of Differentiated Thyroid Carcinoma with Initial Distant Metastasis: A Multicenter Study in Korea

BACKGROUND: Most patients with differentiated thyroid cancer (DTC) have a favorable prognosis. However, patients with DTC and initial distant metastasis have not been commonly found, and their clinical characteristics have seldom been reported. In this study, we analyzed the clinical features and prognosis of patients with DTC and initial distant metastasis in Korea. METHODS: We retrospectively reviewed the clinical data of 242 patients with DTC and initial distant metastasis treated from 1994 to 2013, collected from five tertiary hospitals in Korea. RESULTS: The patients' median age was 51 years, and 65% were women. They were followed for a median of 7 years. Lung was the most common site of distant metastasis: only lung 149 patients (62%), only bone 49 (20%), other single site one (pleura), and combined sites 43 (40 were lung and bone, two were bone and other site, and one was lung and other site). At the time of diagnosis, 50 patients (21%) had non-radioactive iodine (RAI) avidity. Five-year disease-specific survival (DSS) was 85% and 10-year DSS was 68%, which were better than those in previous studies. After multivariate analysis, old age, male sex, metastatic site, and histologic type (follicular type) were significant factors for poor prognosis. However, negative RAI avidity status was not a significant prognostic factor after adjusting for other variables. CONCLUSION: The prognosis of Korean patients with DTC and initial distant metastasis was better than in previous studies. Old age, male sex, metastasis site, and histologic type were significant prognostic factors.

Reference intervals of thyroid hormones during pregnancy in Korea, an iodine-replete area

BACKGROUND/AIMS: Maternal thyroid dysfunction has been associated with adverse pregnancy outcomes. The purpose of our study was to establish trimester-specific reference intervals for thyroid hormones in pregnant women in Korea, where iodine intake is more than adequate and to examine pregnancy and perinatal outcomes in their offspring. METHODS: Among 459 healthy pregnant women who were screened, we enrolled 417 subjects who had negative results for thyroid autoantibodies. Serum thyroid stimulating hormone (TSH) and free thyroxine were measured using an immunoradiometric assay. Urine iodine concentration was measured using inductively coupled plasma-mass spectrometry in 275 women. Reference ranges of thyroid hormones were determined according to the guidelines of the National Academy of Clinical Biochemistry. Pregnancy and perinatal outcomes were compared according to maternal thyroid function. RESULTS: The reference ranges of serum TSH were 0.03 to 4.24 mIU/L in the first trimester, 0.13 to 4.84 mIU/L in the second trimester, and 0.30 to 5.57 mIU/L in the third trimester. Pregnancy and perinatal outcomes did not vary in mothers with subtle changes in thyroid function. CONCLUSIONS: Trimester-specific thyroid hormone reference intervals in Korean pregnant women differ from those of other countries with different iodine nutrition status and ethnicity. The establishment of population-based, reliable trimester-specific reference intervals is critical for the interpretation of thyroid function in pregnant women to avoid unnecessary tests and treatments.

Disease-Specific Mortality of Differentiated Thyroid Cancer Patients in Korea: A Multicenter Cohort Study

BACKGROUND: Little is known regarding disease-specific mortality of differentiated thyroid cancer (DTC) patients and its risk factors in Korea. METHODS: We retrospectively reviewed a large multi-center cohort of thyroid cancer from six Korean hospitals and included 8,058 DTC patients who underwent initial surgery between 1996 and 2005. RESULTS: Mean age of patients at diagnosis was 46.2±12.3 years; 87% were females. Most patients had papillary thyroid cancer (PTC; 97%) and underwent total thyroidectomy (85%). Mean size of the primary tumor was 1.6±1.0 cm. Approximately 40% of patients had cervical lymph node (LN) metastases and 1.3% had synchronous distant metastases. During 11.3 years of follow-up, 150 disease-specific mortalities (1.9%) occurred; the 10-year disease-specific survival (DSS) rate was 98%. According to the year of diagnosis, the number of disease-specific mortality was not different. However, the rate of disease-specific mortality decreased during the study period (from 7.7% to 0.7%). Older age (≥45 years) at diagnosis, male, follicular thyroid cancer (FTC) versus PTC, larger tumor size (>2 cm), presence of extrathyroidal extension (ETE), lateral cervical LN metastasis, distant metastasis and tumor node metastasis (TNM) stage were independent risk factors of disease-specific mortality of DTC patients. CONCLUSION: The rate of disease-specific mortality of Korean DTC patients was 1.9%; the 10-year DSS rate was 98% during 1996 to 2005. Older age at diagnosis, male, FTC, larger tumor size, presence of ETE, lateral cervical LN metastasis, distant metastasis, and TNM stages were significant risk factors of disease-specific mortality of Korean DTC patients.

First Report of Familial Dysalbuminemic Hyperthyroxinemia With an ALB Variant

Familial dysalbuminemic hyperthyroxinemia (FDH) is an inherited disease characterized by increased circulating total thyroxine (T4) levels and normal physiological thyroid function. Heterozygous albumin gene (ALB) variants have been reported to be the underlying cause of FDH. To our knowledge, there have been no confirmed FDH cases in Korea. We recently observed a female patient with mild T4 elevation (1.2 to 1.4-fold) and variable levels of free T4 according to different assay methods. Upon Sanger sequencing of her ALB, a heterozygous c.725G>A (p.Arg242His) variant was identified. The patient's father and eldest son had similar thyroid function test results and were confirmed to have the same variant. Although the prevalence of FDH might be very low in the Korean population, clinical suspicion is important to avoid unnecessary evaluation and treatment.

Dietary evaluation of a low-iodine diet in Korean thyroid cancer patients preparing for radioactive iodine therapy in an iodine-rich region

BACKGROUND/OBJECTIVES: Despite the importance of a low-iodine diet (LID) for thyroid cancer patients preparing for radioactive iodine (RAI) therapy, few studies have evaluated dietary intake during LID. This study evaluated the amount of dietary iodine intake and its major food sources during a typical diet and during LID periods for thyroid cancer patients preparing for RAI therapy, and examined how the type of nutrition education of LID affects iodine intake. SUBJECTS/METHODS: A total of 92 differentiated thyroid cancer patients with total thyroidectomy were enrolled from Seoul National University Hospital. All subjects completed three days of dietary records during usual and low-iodine diets before 131I administration. RESULTS: The median iodine intake was 290 µg/day on the usual diet and 63.2 µg/day on the LID. The major food groups during the usual diet were seaweed, salted vegetables, fish, milk, and dairy products and the consumption of these foods decreased significantly during LID. The mean energy intake on the LID was 1,325 kcal, which was 446 kcal lower than on the usual diet (1,771 kcal). By avoiding iodine, the intake of most other nutrients, including sodium, was significantly reduced during LID (P < 0.005). Regarding nutritional education, intensive education was more effective than a simple education at reducing iodine intake. CONCLUSION: Iodine intake for thyroid cancer patients was significantly reduced during LID and was within the recommended amount. However, the intake of most other nutrients and calories was also reduced. Future studies are needed to develop a practical dietary protocol for a LID in Korean patients.

Selenium Concentration in Korean Patients with Thyroid Disease: a Preliminary Report

BACKGROUND AND OBJECTIVES: Selenium is an important trace element for thyroid hormone metabolism, and its deficiency can cause hypothyroidism. Serum selenium concentration is the best biomarker to reflect selenium intake and reserve, although other markers can reflect. Therefore, we preliminarily assessed serum and urine selenium concentrations in patients with thyroid disease compared to those of a healthy population. We also investigated the correlation between serum and urine selenium concentration, thyroid hormone and urinary iodine concentration (UIC). MATERIALS AND METHODS: A total of 97 patients (32 men, 65 women, 52.4±14.7 years) with benign thyroid nodules or thyroid dysfunction who visited the Samsung Medical Center between 2008 and 2013 were included. Data for 175 healthy subjects provided by Lee et al. were used as the control. Serum T3, free T4, and thyroid stimulating hormone (TSH) were measured using commercialized RIA or IRMA kits. Serum/urine selenium and UIC were measured by inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: Median serum selenium concentration was 110 µg/L (95% CI, 73-156). Median urine selenium concentration was 66.3 µg/gCr (95% CI, 28.7-283.5). Compared to 175 healthy subjects (serum 84 µg/L [95% CI, 30-144], urine 34.5 µg/gCr [95% CI, 0.8-107.2]), serum and urine selenium concentrations of patients with thyroid disease were significantly higher than those of healthy subjects (p<0.001). Serum selenium concentration was significantly correlated with urine selenium concentration after log transformation (r=0.88, p=0.022), but was not significantly correlated with UIC, T3, free T4 and TSH. CONCLUSION: Selenium concentrations of patients with thyroid disease were significantly higher than those of healthy subjects. Serum selenium concentration was significantly correlated with urine selenium concentration.

Selenium Concentration in Korean Patients with Thyroid Disease: a Preliminary Report

BACKGROUND AND OBJECTIVES: Selenium is an important trace element for thyroid hormone metabolism, and its deficiency can cause hypothyroidism. Serum selenium concentration is the best biomarker to reflect selenium intake and reserve, although other markers can reflect. Therefore, we preliminarily assessed serum and urine selenium concentrations in patients with thyroid disease compared to those of a healthy population. We also investigated the correlation between serum and urine selenium concentration, thyroid hormone and urinary iodine concentration (UIC). MATERIALS AND METHODS: A total of 97 patients (32 men, 65 women, 52.4±14.7 years) with benign thyroid nodules or thyroid dysfunction who visited the Samsung Medical Center between 2008 and 2013 were included. Data for 175 healthy subjects provided by Lee et al. were used as the control. Serum T3, free T4, and thyroid stimulating hormone (TSH) were measured using commercialized RIA or IRMA kits. Serum/urine selenium and UIC were measured by inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: Median serum selenium concentration was 110 µg/L (95% CI, 73-156). Median urine selenium concentration was 66.3 µg/gCr (95% CI, 28.7-283.5). Compared to 175 healthy subjects (serum 84 µg/L [95% CI, 30-144], urine 34.5 µg/gCr [95% CI, 0.8-107.2]), serum and urine selenium concentrations of patients with thyroid disease were significantly higher than those of healthy subjects (p<0.001). Serum selenium concentration was significantly correlated with urine selenium concentration after log transformation (r=0.88, p=0.022), but was not significantly correlated with UIC, T3, free T4 and TSH. CONCLUSION: Selenium concentrations of patients with thyroid disease were significantly higher than those of healthy subjects. Serum selenium concentration was significantly correlated with urine selenium concentration.

Seasonal Variation in Hemoglobin A1c in Korean Patients with Type 2 Diabetes Mellitus

A seasonal variation of glucose homeostasis in humans has been reported in various geographic regions. In this study, we examined seasonal variations in hemoglobin A1c (HbA1c) in patients with type 2 diabetes living in Korea. We analyzed 57,970 HbA1c values from 4,191 patients and the association of these values with ambient temperature for 3.5 yr. Overall, HbA1c exhibited its highest values from February to March and its lowest values from September to October (coefficient for cos t = -0.0743, P = 0.058) and the difference between the peak and nadir in a year was 0.16%-0.25%. A statistically significant seasonal variation was observed in the patients who were taking oral anti-diabetic drugs (OADs) without insulin treatment (coefficient for cos t = -0.0949, P < 0.05). The Spearman correlation coefficient between daily HbA1c values and the corresponding 3-month moving average ambient temperature was -0.2154 (95% confidence interval [CI]: -0.2711, -0.1580; P < 0.05). In conclusion, HbA1c values exhibited a seasonal variation in Korean patients with type 2 diabetes, with the highest values during the cold season, particularly in those who were treated with OADs, which should be taken into account in clinical practice for stable glucose control during the cold season.

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.

Follicular and Hurthle cell carcinoma of the thyroid in iodine-sufficient area: retrospective analysis of Korean multicenter data

BACKGROUND/AIMS: Follicular thyroid carcinoma (FTC) and Hurthle cell carcinoma (HCC) of the thyroid are relatively uncommon thyroid malignancies in iodine-sufficient areas. In this study we evaluated the clinical behavior, prognostic factors and treatment outcomes of FTC and HCC in Korea. METHODS: This multicenter study included 483 patients with FTC and 80 patients with HCC who underwent an initial surgery between 1995 and 2006 in one of the four tertiary referral hospitals in Korea. We evaluated clinicopathological factors associated with distant metastases and recurrence during a median of 6 years of follow-up. RESULTS: HCC patients were significantly older (49 years vs. 43 years; p < 0.001) and had more lymphovascular invasions (22% vs. 14%; p = 0.03) compared with FTC patients. Distant metastases were confirmed in 40 patients (8%) in the FTC group and in two patients (3%) in the HCC group (p = 0.07). Distant metastases were significantly associated with older age, widely invasive cancer and extrathyroidal invasion. Only 14 patients (3%) had recurrent disease and there was no significant difference between FTC and HCC groups (p = 0.38). Recurrence was associated with larger tumor size and cervical lymph node metastasis. CONCLUSIONS: HCC patients were older and had more lymphovascular invasions than FTC patients. However, FTC and HCC patients had similar initial clinicopathological features. Older age, wide invasiveness and extrathyroidal invasion were independent risk factors for predicting distant metastases in FTC and HCC patients.