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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.

Background: This phase 3 study evaluated the efficacy and safety of 6-month treatment with romosozumab in Korean postmeno pausal women with osteoporosis. Methods: Sixty-seven postmenopausal women with osteoporosis (bone mineral density [BMD] T-scores ≤-2.5 at the lumbar spine, total hip, or femoral neck) were randomized (1:1) to receive monthly subcutaneous injections of romosozumab (210 mg; n=34) or placebo (n=33) for 6 months. Results: At month 6, the difference in the least square (LS) mean percent change from baseline in lumbar spine BMD (primary effi cacy endpoint) between the romosozumab (9.5%) and placebo (-0.1%) groups was significant (9.6%; 95% confidence interval, 7.6 to 11.5; P

Background: We compared the efficacy of a fixed dose combination of raloxifene 60 mg/vitamin D 800 IU to raloxifene 60 mg alone on vitamin D status, as indicated by change in serum 25-hydroxy-vitamin D (25[OH]D) levels.Methods: In this 16-week, open-label, randomized, active controlled, multicenter clinical trial conducted in 4 university-affiliated hospitals in Korea, postmenopausal women aged 55 to 70 years with osteoporosis or osteopenia were randomly assigned in a 1:1 ratio to receive raloxifene 60 mg/cholecalciferol 800 IU combination therapy or raloxifene 60 mg monotherapy. Primary endpoint was change in serum 25(OH)D level from baseline to 16 weeks after the intervention.Results: A total of 96 participants were randomly assigned to raloxifene/vitamin D combination therapy (N=49) and raloxifene monotherapy (N=47) groups. At week 16, serum 25(OH)D level increased from baseline, only in the raloxifene/vitamin D combination therapy group. Change in serum 25(OH)D level from baseline to week 16 was higher in the raloxifene/vitamin D combination therapy group (2.7±6.5 ng/mL) than in the raloxifene monotherapy (-1.7±6.2 ng/mL; P=0.0034) group. Proportions and number of adverse events (AEs) categorized by the System-Organ Class were not different between the groups. There was only one severe AE case (spondylolisthesis; raloxifene/vitamin D group), unlikely to be related to trial intervention.Conclusions: Among postmenopausal women with osteoporosis or osteopenia, a fixed dose combination of raloxifene 60 mg/vitamin D 800 IU showed superior efficacy in elevating serum 25(OH)D levels compared with raloxifene 60 mg alone during 16 weeks of follow-up. The safety of raloxifene/vitamin D combination was comparable to raloxifene alone.

Thyrotropin (TSH) suppression therapy is a standard treatment after surgery for differentiated thyroid carcinoma (DTC). It may be associated with osteoporosis in postmenopausal women. However, there are no guidelines for bone mineral density (BMD) testing intervals to screen for osteoporosis in these patients. Therefore, we evaluated the timing of repeated BMD testing in DTC patients with TSH suppression according to baseline T-scores.We retrospectively evaluated 658 DTC patients who underwent BMD testing more than twice between January 2007 and January 2020. A 1:3 propensity score matching was conducted to compare the timing of repeated BMD tests between the DTC and non-DTC groups. We stratified the participants into four groups based on their baseline T-scores: normal (-1.00 or higher), mild osteopenia (-1.01 to -1.49), moderate osteopenia (-1.50 to -1.99), and severe osteopenia (-2.00 to -2.49). Additionally, the 10% of patients in each group that transitioned to osteoporosis were analysed.The estimated BMD testing interval for 10% of patients who developed osteoporosis was 85 months for patients with initially mild osteopenia, 65 months for those with moderate osteopenia, and 15 months for those with severe osteopenia in the DTC group. In the non-DTC group, the testing intervals for mild, moderate, and severe osteopenia were 98, 57, and 13 months, respectively. On multivariate analysis, baseline T-score (mild osteopenia: hazard ratio [HR] 5.91, p = .105; moderate osteopenia: HR, 25.27, p = .02; and severe osteopenia: HR, 134.82, p .001) and duration of TSH suppression (tertile 2: HR, 2.25, p = .005; Tertile 3: 1.78, p = .033) were independent risk factors for osteoporosis in the DTC group.This study provides guidance for the timing of repeated BMD tests in women over 50 years of age with TSH suppression. The rescreening interval for BMD testing can be modified based on the baseline T-score. The appropriate BMD testing intervals in female DTC patients were similar to those in non-DTC females.

Patient-reported outcomes (PROs) provide practical guides for treatment; however, studies that have evaluated PROs of women in Korea with postmenopausal osteoporosis (PMO) are lacking. This cross-sectional, multi-center (29 nationwide hospitals) study, performed from March 2013 to July 2014, aimed to assess PROs related to treatment satisfaction, medication adherence, and quality of life (QoL) in Korean PMO women using osteoporosis medication for prevention/treatment. Patient demographics, clinical characteristics, treatment patterns, PROs, and experience using medication were collected. The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) (score-range, 0-100; domains: effectiveness, side effects, convenience, global satisfaction), Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS) (score-range, 0-8), and EuroQol-5 dimensions questionnaire (index score range, - 0.22 to 1.0; EuroQol visual analog scale score range, 0-100) were used. To investigate factors associated with PROs, linear (treatment satisfaction/QoL) or logistic (medication adherence) regression analyses were conducted. A total of 1804 patients (age, 62 years) were investigated; 60.1% used bisphosphonate, with the majority (67.2%) using weekly medication, 27.8% used daily hormone replacement therapy, and 12.1% used daily selective estrogen receptor modulator. Several patients reported gastrointestinal (GI) events (31.6%) and dental visits due to problems (24.1%) while using medication. Factors associated with the highest OS-MMAS domain scores were convenience and global satisfaction. GI events were associated with non-adherence. TSQM scores for effectiveness, side effects, and GI risk factors were significantly associated with QoL. Our study elaborately assessed the factors associated with PROs of Korean PMO women. Based on our findings, appropriate treatment-related adjustments such as frequency/choice of medications and GI risk management may improve PROs.

Bone mass is controlled by a balance between bone resorption and formation by osteoclasts and osteoblasts, respectively. An imbalance between osteoblasts and osteoclasts increases the risk of osteoporosis and fractures. Although inhibition of osteoclasts is beneficial for preventing and treating osteoporosis, enhanced bone formation through activation of osteoblast differentiation can be a more promising therapeutic approach. In this study, we attempted to isolate small molecules that promote osteoblast differentiation and found that IBIP (3-(2,3-dimethoxyphenyl)-1-[9-methyl-2-phenyl-9H-imidazo[1,2-a]benzimidazol-3-yl]-2-propen-1-one) was a potent activator of osteoblast differentiation. Upon bone morphogenetic protein-2 (BMP2) stimulation, IBIP promoted osteoblast differentiation and increased the expression of osteoblast-specific gene markers, such as osterix and alkaline phosphatase, in a dose-dependent manner. The phosphorylation of SMADs and extracellular signal-regulated kinase (ERK) increased after IBIP treatment. While enhanced SMAD phosphorylation by IBIP was abolished by a BMP inhibitor, IBIP-induced ERK phosphorylation was sustained in the presence of this inhibitor, but was decreased by an ERK kinase inhibitor. Suppression of IBIP-induced SMAD and ERK phosphorylation diminished osteoblast differentiation. Most importantly, IBIP enhanced bone formation and calcification in a BMP2-independent manner in vitro and advanced the skeletal development of zebrafish larvae in vivo. Collectively, IBIP may have beneficial effects on bone loss through potentiation of bone formation.

Background: Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. Methods: The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between −2·5 and −4·0 if no previous radiographic vertebral fracture, or between −1·5 and −4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than −4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). Findings: Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43–40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45–60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40–0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39–0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68–0·87; all p

The inflammatory biomarkers that fully characterize the metabolically unhealthy (MU) state-which is a risk factor for cardiovascular disease (CVD)-remain unclear. Recent studies suggest follistatin-like protein 1 (FSTL1) could be used as a biomarker for inflammation and CVD, however there is little information on FSTL1 levels in the MU state. We aimed to evaluate the associations between FSTL1, the presence of MU state and subclinical coronary atherosclerosis. In a cross-sectional study, we evaluated FSTL1 levels and their relationship with the presence of MU state and coronary artery plaques in 230 Korean patients. Significant increase in FSTL1 levels was observed in subjects with MU state (p = 0.020), but not those with obesity state according to body mass index criteria (p = 0.790). After adjusting for confounders, the odd ratio (OR) for the MU state among patients in the highest FSTL1 tertile (T3) was higher in comparison with the lowest tertile (T1) (OR = 3.60, 95% confidence interval [95% CI] = 1.20-10.83). In a subgroup (n = 66), FSTL1 levels were also marginally higher in patients with plaques (p = 0.098). The OR for plaque presence in patients with T3 was significantly higher in comparison with T1 after adjusting for confounders (OR = 12.51, 95% CI = 1.15-135.73). Plasma FSTL1 may be a useful biomarker for the risk of MU state and CVD.

A novel role of leucine-rich repeat-containing 17 (LRRc17), an LRR protein secreted by osteoblasts, as a negative regulator of receptor activator of NF-κB ligand–induced osteoclast differentiation was found. However, the clinical association between LRRc17 and osteoporotic fracture (OF) has not yet been investigated. We hypothesized that low circulating plasma level of LRRc17 might serve as an independent and additive risk factor for OF, including vertebral fractures (VF) and non-vertebral fractures (non-VF). In this case-control study, 102 OF cases and 102 age- and body mass index–matched controls (mean age, 63.2 years) were analyzed among 532 postmenopausal women. VF (n = 49) and non-VF (n = 60) participants were identified using lateral thoracolumbar radiographs and an interviewer-assisted questionnaire, respectively. Median LRRc17 levels were significantly lower in participants with any OF (117.5 versus 197.3 pg/mL, p

Although sclerostin (SOST) and Dickkopf-related protein 1 (DKK1) are major regulators in bone metabolism, their associations with osteoporotic fracture (OF) in Asians are inconclusive. Furthermore, there have been no clinical studies separately considering non-vertebral and vertebral fractures in terms of the blood levels of SOST and DKK1. Among 513 consecutive postmenopausal Korean women, we identified 103 cases defined as subjects with OF (i.e., non-vertebral and/or vertebral fractures). The controls were randomly selected from the remaining 410 subjects and matched 1:1 to cases according to both age and body mass index. Non-vertebral and morphological vertebral fractures were identified by an interviewer-assisted questionnaire and lateral thoracolumbar radiographs, respectively. Bone mineral density (BMD) and plasma levels of SOST and DKK1 were measured. Plasma SOST levels were lower in subjects with OF than in the control group. Each standard deviation decrement of plasma SOST concentration was associated with a multivariable-adjusted odds ratio of 1.77 for any prevalent OF type. The odds for OF was 2.97-fold higher in subjects in the lowest SOST tertile compared with subjects in the highest SOST tertile. These associations remained significant when the non-vertebral and vertebral fractures were analyzed separately. However, prevalent OF was not associated with plasma DKK1 levels, regardless of the type of fracture and the adjustment model employed. Consistently, plasma SOST levels were positively related with BMD values at all measured skeletal sites, although this was not observed for DKK1. Circulating SOST but not DKK1 may be a potential biomarker for predicting bone health in Asians.

Background Recent studies have shown an association between thyroid hormone levels and metabolic syndrome (MetS) among euthyroid individuals; however, there have been some inconsistencies between studies. Here, we evaluated the relationship between thyroid hormone levels and MetS in euthyroid middle-aged subjects in a large cohort. Methods A retrospective analysis of 13,496 euthyroid middle-aged subjects who participated in comprehensive health examinations was performed. Subjects were grouped according to thyroid stimulating hormone, total triiodothyronine (T3), total thyroxine (T4), and T3-to-T4 ratio quartile categories. We estimated the odds ratios (ORs) for MetS according to thyroid hormone quartiles using logistic regression models, adjusted for potential confounders. Results Of the study patients, 12% (n=1,664) had MetS. A higher T3 level and T3-to-T4 ratio were associated with unfavourable metabolic profiles, such as higher body mass index, systolic and diastolic blood pressure, triglycerides, fasting glucose and glycated hemoglobin, and lower high density lipoprotein cholesterol levels. The proportion of participants with MetS increased across the T3 quartile categories (P for trend

The relationship between iodine intake and development of thyroid diseases shows a U-shaped curve with an increase of risk in both deficient and excessive iodine intakes. Our aim was to investigate the relationship between iodine intake and thyroid cancer in patients with thyroid nodules in an iodine-replete area. Retrospective analysis of 1170 patients with thyroid nodules was performed. Urinary iodine concentration (UIC) was measured by inductively-coupled plasma mass spectrometry. Predictive factors for thyroid cancer were evaluated using multivariate logistic regression models. The median UIC in all patients with thyroid nodules was 360 μg/L (range from 4 to 9631 μg/L). More than half of the patients (650/1170, 56 %) belonged to the category of excessive iodine intake (UIC ≥ 300 μg/L) according to WHO iodine recommendations. Patients with thyroid cancer were more likely to be distributed in UIC

The aim of this study was to determine the diagnostic efficacy of free metanephrines in plasma samples drawn in the seated position compared with 24-h urinary metanephrines in detecting pheochromocytomas in Asian patients. This prospective study was conducted at Samsung Medical Center between May 2010 and July 2011. The study contained 245 subjects, including 28 patients with histologically-proven pheochromocytoma, 44 with histologically-proven non-pheochromocytoma, 112 controls suspected of having tumors but with negative investigations during two or more years of follow-up, and 45 healthy normotensive volunteers. Plasma-free metanephrines were measured by LC-MS/MS. The cut-off values with optimal sensitivity and specificity for plasma metanephrine and plasma normetanephrine were 0.33 nmol/L and 0.61 nmol/L, respectively. Both the plasma metanephrines measurement and urinary metanephrines measurement had a sensitivity of 96.4% (p = 1.00). However, the urinary metanephrines measurement was significantly more specific than the plasma metanephrines measurement (94.2% vs. 75.6%; p < 0.001). When we applied cut-off values based on BMI, specificity improved from 75.6% to 87.2%, with a comparable gain in sensitivity. From a diagnostic perspective, measurement of free metanephrines in plasma drawn in the seated position is highly sensitive but insufficiently specific when compared with measurement of 24-h urinary fractionated metanephrines. The specificity may be improved by applying cut-off values based on BMI. We suggest that free metanephrines in plasma drawn from seated position can also be used as an initial screening test to ensure that pheochromocytomas are not missed in Asian patients.

An adequate supply of vitamin D is considered necessary for osteoporosis management and fracture prevention. Intermittent high-dose vitamin D supplementation is an effective and convenient way to achieve and maintain sufficient vitamin D status. However, the long-term effectiveness of supplementation for preventing falls and fractures is unclear, and some deleterious effects of such treatments have been reported. Concerning these issues, the Korean Society for Bone and Mineral Research task force team reviewed previous clinical trials and provided the following perspectives based on current evidence: 1) An adequate supply of vitamin D is necessary for preventing falls and fractures in postmenopausal women and men older than 50 years. An oral intake of 800 to 1,000 IU/day of vitamin D is generally recommended. 2) Care should be taken concerning the routine use of intermittent high-dose vitamin D, as large-scale clinical trials showed increased risk of falls or fractures after high-dose vitamin D administration. Intermittent high-dose vitamin D supplementation is recommendable only in cases of malabsorption or when oral administration is not suitable. 3) Monitoring of the serum level of 25-hydroxy-vitamin D (25[OH]D) is advisable, especially when intermittent high-dose vitamin D is used for supplementation. The task force team suggests that a serum 25(OH)D level of >20 ng/mL is generally appropriate for the prevention of osteoporosis, and that a serum 25(OH)D level of >30 ng/mL is probably helpful both for the management of osteoporosis and the prevention of fractures and falls. However, serum 25(OH)D level >50 ng/mL (this value can vary depending on the measurement method used) is unnecessary and may be undesirable. These perspectives are relevant for the management of osteoporosis, falls, or fractures. Other metabolic bone diseases or non-skeletal disorders are not within the scope of these perspectives.

Metabolically healthy obese is the designation for a subgroup of obese individuals with normal metabolic features. However, metabolically healthy obese individuals are prone to developing metabolic syndrome. Serum triiodothyronine (T3) levels are associated with various metabolic risk factors including obesity. Therefore, this longitudinal study aimed to explore the possible correlation between serum T3 concentration and the onset of MetS in metabolically healthy obese persons. A retrospective analysis of 992 euthyroid metabolically healthy obese subjects who underwent yearly health checkups over 6 years was performed. The risk of developing MetS was analyzed according to baseline T3 concentration, as both tertiles and continuous values, using Cox regression analysis. Serum T3 concentration at the end of the study was further analyzed according to the final metabolic phenotype. The incidence of MetS was 464 cases (46.8%) during a median 3.3 years of follow-up (3168.2 person-years). The hazard ratio for incident MetS enhanced with increasing T3 concentration in both the crude and adjusted models. Higher baseline serum T3 levels were associated with unfavorable metabolic parameters. However, over the course of the study, serum T3 concentration significantly increased in subjects who sustained metabolically healthy phenotypes compared to baseline value, while it significantly decreased in the subjects who developed MetS. Serum T3 concentrations exhibit distinct associations with development of metabolic syndrome in euthyroid metabolically healthy obese persons, but its increment during follow-up maintained metabolically healthy state. These findings suggest that serum T3 modulation might be an adaptive process to protect against metabolic deterioration.

Background The effect of subclinical thyroid dysfunction on vascular atherosclerosis remains uncertain. The objective of this study was to elucidate the association between sustained subclinical thyroid dysfunction and carotid plaques, which are an early surrogate marker of systemic atherosclerosis. Methods The study included 21,342 adults with consistent thyroid hormonal status on serial thyroid function tests (TFTs) and carotid artery duplex ultrasonography at a health screening center between 2007 and 2014. The effect of subclinical thyroid dysfunction on baseline carotid plaques and newly developed carotid plaques during 5-year follow-up was determined by logistic regression analyses and GEE (Generalized Estimating Equations), respectively. Results Carotid plaques were more common in the subclinical hypothyroidism (55.6%) than the euthyroidism (47.8%) at baseline. However, in multivariable analysis, thyroid status was not a significant risk for the carotid plaques at baseline. Instead, traditional cardiovascular risk factors, such as age (P

Background: The aim of this study was to assess the clinical differences between acromegalic patients with microadenoma and pa- tients with macroadenoma, and to evaluate the predictive value of growth hormone (GH) levels for early detection of macroadenoma. Methods: We performed a retrospective analysis of 215 patients diagnosed with a GH-secreting pituitary adenoma. The patients were divided into two groups: the microadenoma group and the macroadenoma group, and the clinical parameters were compared between these two groups. The most sensitive and specific GH values for predicting macroadenoma were selected using receiver operating characteristic (ROC) curves. Results: Compared with the microadenoma group, the macroadenoma group had a significantly younger age, higher body mass in- dex, higher prevalence of hyperprolactinemia and hypogonadism, and a lower proportion of positive suppression to octreotide. How- ever, there were no significant differences in the gender or in the prevalence of diabetes between the two groups. The tumor diameter was positively correlated with all GH values during the oral glucose tolerance test (OGTT). All GH values were significantly higher in the macroadenoma group than the microadenoma group. Cut-off values for GH levels at 0, 30, 60, 90, and 120 minutes for optimal discrimination between macroadenoma and microadenoma were 5.6, 5.7, 6.3, 6.0, and 5.8 ng/mL, respectively. ROC curve analysis revealed that the GH value at 30 minutes had the highest area under the curve. Conclusion: The GH level of 5.7 ng/mL or higher at 30 minutes during OGTT could provide sufficient information to detect mac- roadenoma at the time of diagnosis.

Background The ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1) has been reported to be associated with metabolic syndrome (MetS) and insulin resistance (IR). Non-HDL-C is regarded as a surrogate marker for apoB in routine clinical practice. However, it is unclear whether the ratio of non-HDL-C to HDL-C is an equal or a better predictor than the apoB/apoA1 ratio for the identification of MetS and IR. Methods We performed a retrospective study of 41,821 Korean adults who participated in a routine health screening examination. Anthropometry, fasting glucose, fasting insulin, HOMA-IR, CRP, lipid profiles, apoB, and apoA1 were measured. Results To compare the predictive value for MetS between different lipid ratios, we analyzed the ROC curves of apoB/apoA1 and non-HDL-C/HDL-C ratios. ROC analysis showed that the AUCs of non-HDL-C/HDL-C (0.75 [95% CI=0.74–0.76] in men and 0.84 [95% CI=0.83–0.85] in women) were significantly higher than those of apoB/apoA1 (0.66 [95% CI=0.65–0.67] in men and 0.77 [95% CI=0.76–0.78] in women). The non-HDL-C/HDL-C ratio also showed a significantly stronger association with HOMA-IR than the apoB/apoA1 ratio. The optimal cutoff value of the non-HDL-C/HDL-C ratio for detection of MetS in men was 3.39, with a sensitivity of 66.7% and a specificity of 71.8%, whereas the optimal ratio cutoff value in women was 2.89, with a sensitivity of 75.7% and a specificity of 78.1%. Conclusions Our findings indicate that the non-HDL-C/HDL-C ratio is a better marker than the apoB/apoA1 ratio for identifying IR and MetS in Koreans.

Aims/Introduction The goal of the present study was to evaluate predictive factors for good efficacy and durability to sitagliptin with ongoing metformin or metformin plus glimepiride therapy in a real practice situation. The present observational study was carried out over a 60-week period and involved Korean patients with type 2 diabetes mellitus. Materials and Methods A total of 100 mg of sitagliptin were added once daily to the two most popular therapy regimens (group 1: metformin, group 2: metformin plus glimepiride). Before adding sitagliptin, mean initial glycated hemoglobin (HbA1c) levels were 7.8% (62 mmol/mol) and mean diabetes duration was 8.3 years. Results After 60 weeks, the mean change in HbA1c from baseline was −0.9% (−10 mmol/mol) in group 1 and −1.0% (−11 mmol/mol) in group 2. Decreased HbA1c levels were significantly associated with higher initial HbA1c and lower log-transformed C-peptide levels in a multivariate regression analysis. Logistic regression analysis showed that a sustained reduction in HbA1c levels after 12 weeks was significantly associated with older age (≥60 years), higher baseline HbA1c (group 1 ≥ 7.0% [53 mmol/mol], group 2 ≥ 7.5% [58 mmol/mol]) and slower reduction of HbA1c (ΔHbA1c

SummaryObjective Although papillary thyroid microcarcinoma (PTMC) has a favourable long-term prognosis, disease recurrence after initial treatment remains a problem and controversy exists regarding the role of radioactive iodine (RAI) ablation in PTMC. We performed this study to evaluate the effect of RAI ablation on disease recurrence in patients with PTMC. Patients and Methods Between 1994 and 2004, 2579 patients underwent thyroid surgery for thyroid cancer at Samsung Medical Center. Among these patients, 704 patients with PTMC presumed disease-free after initial treatment were followed up for disease recurrence (median, 64 months; range, 1–185 months). Patients with PTMC with microscopic extrathyroidal extension, cervical lymph node metastases or multifocality were considered to be in the intermediate-risk group for recurrence. Results Disease recurrence was found in six patients at a median of 29 months (range, 10–70 months) after initial treatment; all six patients with recurrent tumours had received RAI treatment after total thyroidectomy. Disease-related mortality was not observed, even after recurrence. Based on a Cox regression model considering the standardized inverse probability of treatment weight (IPTW) within each propensity score stratum of patients with a similar likelihood of having received RAI ablation, the likelihood ratio for recurrence did not differ between the RAI ablation group and no RAI group (P = 0·17). When we performed a subgroup analysis considering only patients with PTMC at intermediate-risk for recurrence, RAI ablation again did not have a significant effect on recurrence (P = 0·79). Conclusions Radioactive iodine ablation after total thyroidectomy in low- and intermediate-risk patients with PTMC did not prevent recurrent tumours. Future randomized, controlled, multicenter prospective trials involving a larger sample of patients followed-up for a longer duration are warranted to confirm our findings.

BackgroundSeveral cross-sectional studies have reported that thyroid hormone levels are associated with cardiovascular risk markers and metabolic syndrome (MetS) even in euthyroid subjects. However, the prognostic role of serum thyroid hormone levels in the risk of incident MetS has not been elucidated.AimWe aimed to investigate the associations of baseline serum thyroid hormone levels with the development of MetS in healthy subjects.MethodsThis 6-year, cross-sectional, longitudinal and follow-up study was conducted in 12 037 euthyroid middle-aged subjects without MetS subjected to comprehensive health examinations. Subjects were grouped according to total triiodothyronine (T3) quartiles. The hazard ratio (HR) for the development of MetS according to T3 quartiles was estimated using Cox proportional hazards model.ResultsDuring the 6-year period, 3544 incident cases of MetS (29%) were identified. The proportion of subjects with incident MetS increased across the T3 quartiles (Pfor trend P ConclusionIn euthyroid middle-aged subjects, serum T3 levels are associated with increased risk for future development of MetS.

Both deficient and excessive iodine intake leads to thyroid disease, which shows U-shaped curves. Our previous study showed that a relatively low [urinary iodine concentration (UIC)

This study sought to determine the minimal serum 25-hydroxyvitamin D [25(OH)D] concentration required to maintain bone health in postmenopausal women with low bone mass. A serum 25(OH)D concentration of 20 ng/mL rather than 30 ng/mL was appropriate for bone health. There is no consensus on the minimal serum 25-hydroxyvitamin D [25(OH)D] concentration required to maintain bone health. The aim of this study was to investigate the relationship between 25(OH)D measured via liquid chromatography-mass spectrometry (LC–MS/MS), which is the current gold standard, and biochemical markers of bone turnover, PTH, and bone mineral densitometry (BMD). The medical records of 750 postmenopausal women newly diagnosed with osteoporosis or osteopenia at Samsung Medical Center from 2009 to 2014 were investigated. Subjects were divided into four groups according to serum 25(OH)D concentration

Inadequate calcium and vitamin D intake is a possible risk factor of osteoporosis. Our purposes were to estimate calcium and vitamin D intake in Korean women, and to determine associated risk factors for low calcium and vitamin D intake. This is a multicenter, hospital-based, and cross-sectional study on osteoporosis. In this study, 1516 women of 50 years or older were involved. Dietary calcium and vitamin D intake were evaluated using the self-reporting KCAT questionnaire. Average daily calcium intake was 662.8 ± 473.8 mg, and vitamin D intake 9.5 ± 10.7 μg. In multivariate analysis, older age (OR 1.02, 95 % CI 1.00–1.04, p = 0.001), and rural residence (OR 2.43, 95 % CI 1.34–4.43, p = 0.004) were significant risk factors for lower calcium intake, and older age (OR 1.03, 95 % CI 1.02–1.04, p < 0.001), and rural residence (OR 1.85, 95 % CI 1.10–3.11, p < 0.001) were significant risk factors for lower vitamin D intake. About 70 % of women aged 50 years or older had calcium and vitamin D intake below the recommended dietary intake. Older age and rural residence were significant risk factors for lower calcium and vitamin D intake in Korean women.

Congenital adrenal hyperplasia (CAH) is characterized by decreased adrenal hormone production due to enzymatic defects and subsequent rise of adrenocorticotrophic hormone that stimulates the adrenal cortex to become hyperplastic, and sometimes tumorous. As the pathophysiology is basically a defect in the biosynthesis of cortisol, one may not consider CAH in patients with hypercortisolism. We report a case of a 41-yr-old man with a 4 cm-sized left adrenal tumorous lesion mimicking Cushing's syndrome who was diagnosed with CAH. He had central obesity and acanthosis nigricans involving the axillae together with elevated 24-hr urine cortisol level, supporting the diagnosis of Cushing's syndrome. However, the 24-hr urine cortisol was suppressed by 95% with the low dose dexamethasone suppression test. CAH was suspected based on the history of precocious puberty, short stature and a profound suppression of cortisol production by dexamethasone. CAH was confirmed by a remarkably increased level of serum 17-hydroxyprogesterone level. Gene mutation analysis revealed a compound heterozygote mutation of CYP21A2 (I173N and R357W).

Osteomalacia is a metabolic bone disease that leads to softening of the bones and can be caused by hypophosphatemia. Large clinical studies of low-dose adefovir dipivoxil (adefovir) have found no evidence of renal tubular dysfunction leading to hypophosphatemia after 48 weeks of treatment. We report two cases of low-dose adefovir-induced hypophosphatemic osteomalacia that initially presented with diffuse musculoskeletal pain. The first patient was a 62-year-old man with a 2-year history of bone pain involving the dorsal mid-thorax, lower anterior chest wall, right sacroiliac joint area, and both knees. The patient had been receiving adefovir for 5 years before confirmation of hypophosphatemia and urinary phosphate wasting. Bone scintigraphy revealed multifocal lesions including multiple ribs, costochondral junctions, costovertebral junctions, sacrum, both posterior iliac bones, both proximal tibia, right calcaneus, and the left second metatarsophalangeal joint area, which were suggestive of metabolic bone disorder. Bone pain was significantly reduced within 3 months after supplementation with phosphate and calcitriol. The second patient was a 54-year-old male who presented with an 18-month history of severe bone pain of the right medial knee and low back. The patient had been taking adefovir for approximately 40 months before the development of bone pain. Laboratory data revealed hypophosphatemia and vitamin D deficiency. Bone scintigraphy showed increased uptake in bilateral ribs, sternum, both scapulae, both costovertebral junctions, both pelvic bones, medial cortex of the right proximal femur, right proximal tibia, and the left lateral tarsal bone. The symptoms improved by changing the antiviral agent from adefovir to entecavir. Because osteomalacia often presents with diffuse bone pain, non-specific radiologic findings and non-characteristic routine serum biochemical changes, the disease can be confused with various musculoskeletal diseases and a high index of suspicion is necessary for an early diagnosis in patients receiving adefovir therapy.

The aim of this study was to assess the prevalence of diabetes and to study the effects of excess growth hormone (GH) on insulin sensitivity and β-cell function in Korean acromegalic patients. One hundred and eighty-four acromegalic patients were analyzed to assess the prevalence of diabetes, and 52 naive acromegalic patients were enrolled in order to analyze insulin sensitivity and insulin secretion. Patients underwent a 75 g oral glucose tolerance test with measurements of GH, glucose, insulin, and C-peptide levels. The insulin sensitivity index and β-cell function index were calculated and compared according to glucose status. Changes in the insulin sensitivity index and β-cell function index were evaluated one to two months after surgery. Of the 184 patients, 17.4% were in the normal glucose tolerance (NGT) group, 45.1% were in the pre-diabetic group and 37.5% were in the diabetic group. The insulin sensitivity index (ISI(0,120)) was significantly higher and the HOMA-IR was lower in the NGT compared to the diabetic group (P = 0.001 and P = 0.037, respectively). The ISI(0,120) and disposition index were significantly improved after tumor resection. Our findings suggest that both insulin sensitivity and β-cell function are improved by tumor resection in acromegalic patients.

The diagnosis of pheochromocytoma depends on the documentation of catecholamine overproduction. The use of urinary fractionated metanephrines has recently become common for the diagnosis of pheochromocytoma. In order to avoid false positive and false negative results, optimal cut-off levels are necessary; however, there have been few published reports on whether different cut-off levels are needed to diagnose pheochromocytoma according to sex. We reviewed the medical records of 815 subjects (including 103 pheochromocytoma patients) whose of 24-h urinary fractionated metanephrine was measured using high-performance liquid chromatography methods and adrenal imaging at Samsung Medical Center. Receiver operating characteristic (ROC) curves were used to determine cut-off values according to sex. The upper limit values of fractionated metanephrine in healthy volunteers and the control group were significantly higher in male subjects compared with females. When we applied cut-off values according to sex, the diagnostic efficacies (defining a positive test as either metanephrine or normetanephrine levels above the cut-off value) were a sensitivity of 96% in male subjects and 98.1% in female subjects and a specificity of 88.6% in male subjects and 94.1% in female subjects. However, when we applied cut-off values without considering sex, the specificity decreased from 88.6% to 77.8% in male subjects. In this study, urinary fractionated metanephrines had a high level of sensitivity and specificity for the diagnosis of pheochromocytoma. However, diagnostic cut-off values were higher in male subjects than in female subjects. Therefore, different cut-off values may be needed according to sex to diagnose pheochromocytoma in Koreans.

We investigated the in vitro and in vivo osteogenic activity of licochalcone A. At low concentrations, licochalcone A stimulated the differentiation of mouse pre-osteoblastic MC3T3-E1 subclone 4 (MC4) cells and enhanced the bone morphogenetic protein (BMP)-2-induced stimulation of mouse bi-potential mesenchymal precursor C2C12 cells to commit to the osteoblast differentiation pathway. This osteogenic activity of licochalcone A was accompanied by the activation of extracellular-signal regulated kinase (ERK). The involvement of ERK was confirmed in a pharmacologic inhibition study. Additionally, noggin (a BMP antagonist) inhibited the osteogenic activity of licochalcone A in C2C12 cells. Licochalcone A also enhanced the BMP-2-stimulated expression of various BMP mRNAs. This suggested that the osteogenic action of licochalcone A in C2C12 cells could be dependent on BMP signaling and/or expression. We then tested the in vivo osteogenic activity of licochalcone A in two independent animal models. Licochalcone A accelerated the rate of skeletal development in zebrafish and enhanced woven bone formation over the periosteum of mouse calvarial bones. In summary, licochalcone A induced osteoblast differentiation with ERK activation in both MC4 and C2C12 cells and it exhibited in vivo osteogenic activity in zebrafish skeletal development and mouse calvarial bone formation. The dual action of licochalcone A in stimulating bone formation and inhibiting bone resorption, as described in a previous study, might be beneficial in treating bone-related disorders.

The amount of amyloid detectable in islets varies, and is not always correlated with degree of β-cell loss. It has been hypothesized that islet amyloid polypeptide (IAPP) aggregation causes β-cell dysfunction. In this study, we investigated the relationship between IAPP expression and glucose homeostasis in pancreatectomized patients. Human pancreatic head tissues were collected from 46 pancreatic tumor patients. We divided the diabetic cases into two groups, patients with higher IAPP–expressing islets (DM-H) and patients with lower IAPP–expressing islets (DM-L), and compared both groups to patients with normal glucose tolerance (NGT). Interestingly, oral glucose tolerance test analyses showed that DM-L patients had significantly higher glucose levels and lower C-peptide levels than DM-H patients. Furthermore, the DM-H group showed a relative β-cell volume similar to that of the NGT group, as well as a significantly higher relative β-cell volume than the DM-L group. The DM-L group was significantly higher than the DM-H group, not only in the rates of replication and apoptosis, but also in the nuclear C/EBP homologous protein and the ratio of oligomer to IAPP. Thus, IAPP expression may not be an indicator of cell death induction. IAPP, including oligomer, may be an important determinant in the fate of islet β-cells. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. (J Histochem Cytochem 58:731–740, 2010)

Patient preferences, convenience, and bone turnover markers were evaluated for the monthly ibandronate over the weekly risedronate regimen in Korean postmenopausal osteoporotic women. This was a 6-month, prospective, randomized, open-label, multicenter study with a two-period and two-sequence crossover treatment design. After a 30-day screening period, eligible participants with postmenopausal osteoporosis were randomized to receive either monthly oral ibandronate 150 mg for 3 months followed by weekly oral risedronate 35 mg for 12 weeks (sequence A) or the same regimen in reverse order (sequence B). Patient preference and convenience were evaluated by questionnaire. The changes in serum C-telopeptide after 3 months of treatment were analyzed. A total of 365 patients were enrolled in this study (sequence A 182, sequence B 183). Of patients expressing a preference (83.4%), 74.8% preferred the monthly ibandronate regimen over the weekly regimen (25.2%). More women stated that the monthly ibandronate regimen was more convenient (84.2%) than the weekly regimen (15.8%). There was no significant difference in the change in bone turnover marker between the two treatments. The two regimens were similarly tolerable. There were fewer adverse events in the monthly ibandronate group compared to the weekly risedronate group in terms of gastrointestinal side effects (nausea and abdominal distension). This study revealed a strong preference and convenience for monthly ibandronate over weekly risedronate in Korean postmenopausal osteoporotic women. There was no significant difference in change of bone turnover marker and safety profile between the two regimens.

The receptor activator of nuclear factor-kappaB ligand (RANKL) plays a critical role in the differentiation and bone resorptive activity of osteoclasts. Recently, the development of anti-resorptive agents from natural substances has become a subject of interest. Therefore, we evaluated the effects of 222 natural compounds on the RANKL-induced tartrate-resistance acid phosphatase (TRAP; a marker for osteoclast differentiation) activity and multinucleated osteoclast formation in RAW264.7 murine macrophage cells. We found that saurolactam was one of the compounds inhibiting the RANKL-induced osteoclastogenesis; it significantly inhibited the RANKL-induced TRAP activity and formation of multinucleated osteoclasts without any cytotoxicity. Interestingly, saurolactam prevented RANKL-induced activation of MAP kinases and NF-kappaB, and mRNA expression of osteoclast-related genes and transcription factors (c-Fos, Fra-2, and NFATc1). We also observed the inhibitory effect of saurolactam on the differentiation of mouse bone marrow-derived macrophages into osteoclasts. Furthermore, saurolactam inhibited the bone resorptive activity of mature osteoclasts with the induction of apoptotic signaling cascade and the inhibition of survival signaling pathways such as c-Src/PI3K/Akt, Ras/ERK, and JNK/c-Jun. In conclusion, although further studies are needed to determine the precise mechanism and biological efficacy of saurolactam in osteoclast-mediated bone disorders, our results demonstrate that saurolactam potentially inhibits osteoclast differentiation by preventing the activation of MAP kinases and transcription factors that consequently affect the regulation of genes required for osteoclastogenesis, and the bone resorptive activity of mature osteoclasts by inhibiting osteoclast survival-related signaling pathways and triggering the apoptotic signaling cascade.

In bone remodeling, an imbalance caused by increased bone resorption over bone formation leads to adult skeletal diseases such as osteoporosis. Therefore, the development of anti-resorptive agents has still gained more interest. In this study, using cell-based assay systems in RAW264.7 murine macrophage cells, we found that baicalein significantly inhibited the receptor activator of NF-kappaB ligand (RANKL)-induced tartrate-resistance acid phosphatase (TRAP) activity and the formation of multinucleated osteoclasts in a dose-dependent manner. Interestingly, baicalein inhibited RANKL-induced activation of signaling molecules (Akt, ERK/MAP kinase and NF-kappaB) and mRNA expression of osteoclast-associated genes (TRAP, matrix metalloproteinase 9 and c-Src) and another transcription factors (c-Fos, Fra-2 and NFATc1). In addition, baicalein inhibited the bone resorptive activity of mature osteoclasts by inducing apoptosis. The inhibitory effects of baicalein on the formation of mouse bone marrow macrophage-derived osteoclasts and their bone resorptive activity were also observed. In conclusion, although further studies are needed to determine its biological efficacy and precise mechanism in bone, the present results demonstrated that baicalein has a potential to inhibit osteoclast differentiation and induce mature osteoclast apoptosis.

Licochalcone A on the formation and bone resorptive activity of osteoclasts up to 5muM significantly inhibited the receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL)-induced activity of tartrate-resistant acid phosphatase (TRAP) activity and formation of osteoclasts without any effect on cell viability. Interestingly, licochalcone A was shown to inhibit the RANKL-induced activation of extracellular signal-regulated kinase, translocation of NF-kappaB into nucleus and mRNA expression of Fra-2. Licochalcone A also inhibited the bone resorptive activity of mature osteoclasts and the expression of bone resorption-related genes. Inhibitory effects of licochalcone A on the formation and bone resorptive activity of mouse bone marrow macrophage-derived osteoclasts were also observed. In conclusion, licochalcone A has the potential to inhibit the formation of osteoclasts as well as the bone resorptive activity of mature osteoclasts.

Although many studies have reported an association between total white blood cell count and metabolic syndrome, relatively few reports are available on the association between differential white blood cell counts and metabolic syndrome. The medical records of 15,654 subjects (age, median 46, range 14-90 yr; 8,380 men and 7,274 women) who visited the Center for Health Promotion were investigated. It was found that as total white blood cell (WBC) and differential WBC counts increased the frequencies of diabetes, hypertension, obesity, dyslipidemia, and metabolic syndrome also increased. Moreover, these significant relationships persisted after adjusting for age, gender, smoking, alcohol intake, educational background, and household income. The odds ratios (95% CI) for metabolic syndrome was 2.64 (2.30- 3.04) in the highest quartile of total WBC count, with corresponding figures of 2.14 (1.88-2.44) for neutrophils, 2.32 (2.03-2.64) for lymphocytes, 1.56 (1.37-1.78) for monocytes, 1.36 (1.20-1.54) for basophils, and 1.82 (1.59-2.08) for eosinophils versus the lowest quartiles of the appropriate total and differential counts, respectively, after adjusting for the variables mentioned above. These independent associations were also observed by subgroup analyses according to the smoking status. Our data suggest that even within normal ranges, total WBC count and the differential WBC counts are associated with the presence of metabolic syndrome.

A 42-year old woman presented with headache, palpitation and facial flushing. Ultrasonograms and computed tomograms revealed tumors in both of the adrenal glands, anterior aspect of the inferior vena cava, and the right lobe of the thyroid gland. Fine needle aspiration biopsy of the thyroid nodule revealed papillary thyroid carcinoma. Serum calcitonin, CEA, intact PTH and calcium levels were within normal limits. Markedly elevated levels of urinary normetanephrine and vanillylmandelic acid, and the result of 131I-metaiodobenzylguanidine (131I-MIBG) scintigraphy indicated that both adrenal masses were pheochromocytoma. Bilateral adrenalectomy, paracaval mass removal and total thyroidectomy together with central lymph node dissection were performed. The final pathological diagnosis was bilateral adrenal pheochromocytoma, paraganglioma, papillary thyroid carcinoma and either parathyroid adenoma or hyperplasia. Analysis of the RET proto-oncogene mutation, von Hippel Lindau mutation, succinate dehydrogenase subunit B mutation, and succinate dehydrogenase subunit D mutation yielded negative results. The relationship of these lesions could not be determined. This is the first report of a combination of bilateral pheochromocytoma, abdominal paraganglioma, papillary thyroid carcinoma and either parathyroid adenoma or hyperplasia without hyperparathyroidism.

Upstream stimulatory factor (USF) has a negative effect on the cell proliferation in some cell types. However, its effect on thyrocytes is not clear. Therefore, we investigated the effects of USF on the proliferation and function of thyroid follicular cells. Complementary DNAs of the USF-1 and USF-2 were synthesized using RT-PCR from FRTL-5 cells, and each was transfected to FRTL-5 cells and papillary thyroid carcinoma cell lines. Cyclic AMP (cAMP) production and [methyl-3H] thymidine uptake after thyroid stimulating hormone (TSH) treatment were measured in FRTL-5 cells. In the carcinoma cell lines, 5-bromo-2'-deoxyuridine (BrdU) uptake was assayed to evaluate cell proliferation. Apoptosis was tested by Hoechst staining and cell cycle analysis was done using a fluorescence activated cell sorting. Expression of cell cycle regulating genes was evaluated by Northern and Western blotting. Overexpression of USF-1 and USF-2 significantly suppressed TSH-stimulated [methyl-3H] thymidine uptake (p

Background The independent skeletal effect of thyrotropin (thyroid stimulating hormone, TSH) has been suggested in animal studies. However, clinical data on the association between bone loss and variations in TSH levels is inconsistent. This study aimed to investigate the relationship between TSH levels and bone mineral density (BMD). Methods We conducted a cross-sectional study with 37,431 subjects (33,052 cases with euthyroidism and 4,379 cases with subclinical thyroid dysfunction) aged over 35 years. We performed thyroid function tests and measured BMD at the lumbar spine, femur neck, and total hip. Results Levels of TSH and T3 were positively correlated in women (r = 0.076, P = 0.001) and uncorrelated in men. In both men and women, TSH levels correlated positively and T3 levels correlated negatively with BMD at all skeletal sites in age and body mass index adjusted analyses. BMD increased steadily with TSH levels from the subclinical hyperthyroid to subclinical hypothyroid range in subjects with T3 levels in the highest tertile (119.5–200.0 ng/dL), but was no longer significant in subjects with lower plasma T3 levels. Conclusions The variations in TSH levels within the euthyroid and subclinical range were positively correlated with BMD in healthy men and women. The negative effect of T3 on BMD appears to be compensated for by increased TSH in subjects with plasma T3 levels in the upper normal range.

The cause of continued suppression of serum thyroid-stimulating hormone (TSH) levels during antithyroid drug therapy in some Graves' patients is unclear. Recently, there has been a notable explanation involving the direct inhibition of TSH receptor antibody (TRAb) on TSH secretion in the pituitary gland. The purpose of this study is to verify the relation between TRAb or other clinical parameters and the continued suppression of serum TSH level during antithyroid drug therapy in patients with Graves' disease. We reviewed the medical records of patients with Graves' disease between 1995 and 2002 at Samsung Medical Center. We selected 167 Graves' patients who had been euthyroid for at least 12 months after recovery of serum T3 and T4 levels during the antithyroid drug therapy. We analyzed the correlation of the interval until recovery of serum TSH with the pretreatment clinical parameters. We compared the recovery rates of suppressed TSH levels between pretreatment thyrotrophin-binding inhibitory immunoglobulin (TBII)-positive (>15%) and TBII-negative patients. We also compared the clinical parameters between two groups at the time of diagnosis and after recovery of thyroid hormone. Pretreatment serum T3 level, (131)I uptake, TBII activity, and the time to recovery of T3 or T4/free T4 level showed significant positive correlations with the interval until recovery of serum TSH level ( p < 0.05). Recovery rates of serum TSH levels at 3 months after recovery of thyroid hormone were significantly lower in pretreatment TBII-positive patients than those in TBII-negative patients ( p < 0.01). Serum TSH levels were significantly lower in TBII-positive patients at 3 months after recovery of thyroid hormone ( p < 0.05). TBII activities inversely correlated only with serum TSH levels at 3months after recovery of thyroid hormone ( p < 0.001). In conclusion, continued suppression of serum TSH level may be attributed to TRAb activity as well as the pretreatment severity of thyrotoxicosis and the time to recovery of thyroid hormone in patients with Graves' disease during antithyroid drug therapy.

To investigate the pathogenesis of distal pancreatectomy (d-Px)-induced diabetes in Korean patients, we investigated insulin secretory and sensitivity indexes obtained by oral glucose tolerance testing in 20 patients that had received d-Px (10 with d-Px-induced diabetes and 10 with normal glucose tolerance with d-Px [NGT d-Px]) and in 164 control subjects (77 with type 2 diabetes mellitus and 87 with NGT) that did not receive d-Px. The pancreatectomized subjects had lower fasting serum insulin, homeostasis model assessment of pancreatic beta-cell function (HOMA-beta) levels, and insulinogenic indices than the NGT controls. The HOMA-beta values of nonobese NGT d-Px- and d-Px-induced diabetic subjects were 73.7% and 38.7% of those for nonobese NGT controls, respectively, and HOMA-beta was significantly lower only for d-Px-induced diabetic subjects (P.01). In obese subjects, the HOMA-beta values of obese d-Px-induced diabetic subjects were significantly lower than those of obese NGT controls (P.05). The insulin sensitivity was significantly lower in nonobese type 2 diabetes mellitus controls than in nonobese NGT d-Px or in nonobese d-Px-induced diabetic subjects (P.001 and .05, respectively). These results show that a reduced insulin secretory function is a typical feature of glucose homeostasis in distal pancreatectomized patients and that insulin secretory defect plays a major role in the development of diabetes in these patients. In addition, the study suggests that pancreatic resections of 60% or less and body mass index are not the main causes of diabetes onset after d-Px in this study.

Objective: To investigate the heterogeneity of early-onset and ketosis-resistant diabetes and to define a not-arbitrary cut-off age for early-onset diabetes based on its clinical and metabolic characteristics, and diabetes complications. Methods: We classified 1015 early-onset diabetes subjects aged 21–40 into four groups (group I, age at diagnosis 21–25 years; group II, 26–30; group III, 31–35; group IV, 36–40). Familial and diabetic history, statue of insulin secretion, metabolic parameters, and diabetes complications were analyzed. Results: No significant difference in family history or the rate of diabetic complication was found in the four groups. Subjects with a 21 to a 25-year-old diabetes onset had the lowest serum C-peptide levels, with 50% of the cumulative 24-h urine C-peptide levels of the other three groups ( p < 0.0001). This group also had the lowest prevalence of hyperlipidemia and arterial hypertension ( p < 0.01 and

Functional role of peripheral benzodiazepine receptor on mitochondrial membrane in apoptosis and insulin secretion from insulinoma cells was studied. A prototypic peripheral benzodiazepine receptor agonist PK11195 induced insulinoma cell apoptosis, while a central benzodiazepine receptor agonist did not. Death of insulinoma cells by PK11195 was inhibited by cyclosporin A, a blocker of mitochondrial permeability transition pore. Caspase inhibitors further inhibited MIN6N8 cell death. PK11195 induced dissipation of mitochondrial potential and cytochrome c translocation to cytoplasm. PK11195 induced an increase in cytoplasmic [Ca(2+)], which was reversed by cyclosporin A. Rhod-2 staining showed decreased mitochondrial [Ca(2+)] after PK11195 treatment. PK11195 potentiated glucose-induced insulin secretion probably due to the increased cytoplasmic [Ca(2+)]. Calpain was activated following Ca(2+) release, and calpain inhibitors attenuated death of insulinoma cells by PK11195. These results suggest that PK11195 induces mitochondrial potential loss, cytochrome c translocation, increased insulin secretion in conjunction with an increase in cytoplasmic [Ca(2+)] and calpain activation, which collectively leads to apoptosis of insulinoma cells.

High-resolution ultrasonography (US) has made possible the detection of asymptomatic small thyroid nodules. Thyroid incidentalomas have created a clinical dilemma as to how to properly manage such incidental findings. We investigated the prevalence, the clinical and US characteristics, and optimal diagnostic approach to incidentally detected benign and malignant thyroid nodules1.5 cm. Retrospective review was done on 1475 patients who had visited Samsung Medical Center, Soul Korea from January 1999 to December 2000. The prevalence of thyroid incidentalomas was 13.4%. The malignancy rate within thyroid incidentalomas was 28.8%. There were no significant differences in age, nodule size and number, thyroid function test, and Tc99m thyroid scan between benign and malignant incidentalomas. US characteristics of solid echostructure, irregular margin, and calcification showed meaningful diagnostic value in detecting malignancy in thyroid incidentalomas (p0.05). Most malignant incidentalomas were low stage. In conclusion, occult thyroid cancers are a fairly common finding. There were no significant differences in clinical and laboratory parameters between benign and malignant thyroid nodules1.5 cm; however, US findings can be used in the decision of optimal management strategies.

Mutations in the CYP17 gene impair steroid biosynthesis in the adrenals and gonads and often cause 17α-hydroxylase/17,20-lyase deficiency, leading to amenorrhea, sexual infantilism, and hypokalemic low aldosterone hypertension. Several CYP17 mutations resulting in 17α-hydroxylase/17,20-lyase deficiency have been reported previously. In the present study, we found a novel CYP17 mutation from the molecular analysis of a Korean patient with primary amenorrhea with a 46,XX karyotype, and hypokalemic hypertension. We sequenced all 8 exons of the CYP17 gene that were amplified from patient's genomic DNA using polymerase chain reaction (PCR) and found a compound heterozygous mutation in the CYP17 structural gene; a 1-base deletion and a 1-base transversion (TAC→AA) at codon 329, leading to the production of a truncated protein (1-417 amino acids), and a 3-base deletion (TCC, either 350-351 or 351-352 codon) in the other allele. Restriction enzyme digestion analysis of patient's and parental DNA showed that the 1-base deletion and the 3-base deletion are inherited from mother and father, respectively. Here we conclude that these novel compound heterozygous mutations might account for the patient's clinical manifestations of 17α-hydroxylase/17,20-lyase deficiency. Copyright 2003 Elsevier, Inc. All rights reserved.

Catecholamines play a central role in the regulation of energy expenditure, in part stimulating lipid mobilization through lipolysis in fat cells. The [beta ] 2 -adrenergic receptor (ADRB2) is a major lipolytic receptor in human fat cells, and a recent study has shown that common polymorphisms occurring in codons 16 and 27 of the ADRB2 gene are significantly associated with obesity and lipolytic ADRB2 function in adipose tissue. We investigated whether previously described human ADRB2 gene polymorphisms are associated with obesity and diabetes in Korean subjects. According to the World Health Organization (WHO) criteria for oral glucose tolerance testing, 57 subjects had normal glucose tolerance (NGT), 32 had impaired glucose tolerance (IGT), and 106 had diabetes mellitus. The nondiabetic group (including NGT and IGT) consisted of 46 obese (defined as those with body mass index [BMI] of [ge ] 27 kg/m 2 ) and 43 nonobese subjects (BMI [lt ] 27 kg/m 2 ). The subjects with diabetes consisted of 62 obese and 44 nonobese subjects. There was no significant difference between nonobese and obese subjects in the allele frequency of ADRB2 gene polymorphisms at codons 16 and 27. There were no significant differences in BMI, percentage body fat, waist[ndash ]to-hip ratio (WHR), systolic blood pressure, diastolic blood pressure and concentrations of fasting plasma glucose, fasting serum insulin, serum low-density lipoprotein (LDL)-cholesterol, serum high-density lipoprotein (HDL)-cholesterol, serum triglyceride, and serum free fatty acids, according to ADRB2 gene polymorphisms at codons 16 and 27. The frequency of the Glu27 homozygote was 1.1%. These findings suggest that genetic variability in the ADRB2 gene may not be a major determinant for the development of obesity and diabetes in Koreans.

Over the past 20 years, allo-transplantation of islet or whole pancreas for reaching and sustaining near-normoglycemia, as close as possible to the physiological model, have been undertaken. As previously known, even though islet transplantation is possible as a safe re-transplant, it is not well known whether re-transplantation of islets is suitable for patients who have lost the grafted islet function. We have performed a human islet allo-transplantation and re-transplantation on an IDDM patient for the first time in Asia and Korea. The recipient was a 32-year-old male and his insulin requirement was 75–85 U per day. After islet transplantation, the basal C-peptide increased from 0.6 to 2.1 ng/ml and insulin requirement decreased from 80 to 36 U per day, indicating that the grafted islets were functional. However, the grafted islets lost function 70 days after the transplantation. So, we performed re-transplantation of the islets. After the re-transplantation, the glucose profile became more stable and frequent episodes of severe hypoglycemia completely disappeared. His severe neuropathic pain improved dramatically and he could engage his ordinary daily life without any antineuropathic drugs. The success of this re-transplantation is one step closer to becoming a viable alternative for the millions of individuals who are suffering from diabetes.