Association between iodine intake and metabolic syndrome in euthyroid adult in an iodine-replete area: a nationwide population-based study.

Metabolic syndrome (MetS) is considered very important because of the increased risk for cardiovascular diseases. Identifying modifiable factors may help prevent MetS. We aimed to investigate the relationship between iodine intake as a dietary factor and MetS in euthyroid adult in an iodine-replete area. A total of 4,277 adult aged ≥19 years from the Korea National Health and Nutrition Examination Survey VI (2013-2015) with urinary iodine concentration (UIC) results and normal thyroid function were included. Participants were grouped according to their iodine nutrition status based on the WHO recommendations and modifications: insufficient (<100 µg/L), adequate (100-299 µg/L), and excessive (≥300 µg/L) iodine intake. We estimated the odds ratios (ORs) for MetS according to the UIC groups using logistic regression models. Of the study participants, 27.2% men and 23.9% women had MetS. Men with excessive iodine intake had a significantly lower risk of elevated triglycerides [OR 0.733, 95% confidence interval (CI) 0.603-0.890, p = 0.010], as compared to those with adequate iodine intake. Women with insufficient iodine intake had a significantly greater risk of elevated blood glucose (OR 1.519, 95% CI 1.011-2.282, p = 0.044), as compared to those with adequate iodine intake. In women, insufficient iodine intake was a significant risk factor for MetS compared to adequate iodine intake, even after adjusting for confounding variables including age, smoking, alcohol consumption, walking activity, serum thyroid-stimulating hormone, free thyroxine, and anti-thyroid peroxidase antibody (OR 1.544, 95% CI 1.031-2.311, p = 0.035). There was no association between iodine intake and risk of MetS in men. In conclusion, insufficient iodine intake was associated with an increased risk of MetS only in euthyroid adult women. Our data support that sex differences may influence the relationship between iodine intake as a dietary pattern and MetS.

Subclinical thyroid dysfunction and chronic kidney disease: a nationwide population-based study.

BACKGROUND: Chronic kidney disease (CKD) has a significant impact on global health. Studies have shown that subclinical thyroid dysfunction may be related to CKD, but the association between subclinical thyroid dysfunction and CKD in the general population is unclear. We aimed to evaluate the risk of CKD according to thyroid function status in a large cohort. METHODS: We analyzed data from a nationwide, population-based, cross-sectional survey (KNHANES VI). A total of 3,257 participants aged ≥ 19 years who underwent thyroid and kidney function assessments were included in this study. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 and/or urine albumin-creatinine ratio ≥ 30 mg/g. The risk of CKD according to thyroid function status was assessed using logistic regression, adjusted for potential confounders. RESULTS: Overall, 6.7% of the participants had CKD. There were no significant differences in thyroid-stimulating hormone and free thyroxine levels between the groups with and without CKD. The proportion of participants with CKD was significantly different among the thyroid function status groups (p = 0.012) and tended to increase significantly in the following order: subclinical hyperthyroidism (1.5%), euthyroidism (6.6%), and subclinical hypothyroidism (12.6%) (p for trend < 0.001). Subclinical hypothyroidism was a significant risk factor for CKD, even after adjusting for sex, age, household income, education, smoking, alcohol consumption, walking activity, abdominal obesity, hypertension, low high-density lipoprotein cholesterol, elevated triglycerides, hyperglycemia, free thyroxine, and thyroid-peroxidase anibody (odds ratio 2.161, 95% confidence interval 1.032-4.527, p = 0.041). CONCLUSION: Subclinical hypothyroidism is an independent predictor of CKD in the general population.

Association of thyroid autoimmunity with nonalcoholic fatty liver disease in euthyroid middle-aged subjects: A population-based study.

BACKGROUND AND AIM: The association between thyroid autoimmunity and nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, we aimed to investigate the relationship between thyroid autoimmunity and NAFLD in a large cohort of euthyroid subjects. METHODS: We analyzed clinical and biochemical data from a nationwide, population-based, cross-sectional survey (KNHANES VI). A total of 1589 middle-aged participants aged 45-65 years, with normal thyroid function, were included in this study. NAFLD was defined as a hepatic steatosis index of > 36. We estimated the odds ratios (ORs) for NAFLD according to anti-thyroid peroxidase antibody (TPOAb) positivity by using logistic regression models, and adjusted for potential confounders. RESULTS: Overall, 24% (n = 378) of the subjects had NAFLD. Subjects with NAFLD showed a higher positivity for TPOAb (11% vs 7%, P = 0.014) compared with those without NAFLD. TPOAb positivity was a significant risk factor for NAFLD [OR 1.668, 95% confidence interval (CI) 1.019-2.730, P = 0.042] even after adjusting for confounding variables, including age, sex, household income, education, smoking, alcohol consumption, walking activity, abdominal obesity, elevated blood pressure, dyslipidemia and hyperglycemia. In addition, TPOAb positivity predicted the risk of advanced liver fibrosis (OR 3.112, 95% CI 1.256-7.713, P = 0.014) in subjects with NAFLD, independent of the confounding variables. CONCLUSION: In euthyroid subjects, thyroid autoimmunity is associated with NAFLD and advanced liver fibrosis, independent of known metabolic risk factors. Large longitudinal studies in the future will help clarify the causality.

Shear wave elasticity by tracing total nodule showed high reproducibility and concordance with fibrosis in thyroid cancer.

BACKGROUND: Although shear wave elastography (SWE) is reported to be useful in detecting malignant thyroid nodules, it shows a wide range of cut-off values of elasticity index (EI) in detecting malignant nodules. The cause of discrepancy remains unclear. Fibrosis of the tumors is known to increase the EI in SWE, and matching of SWE and surgical histopathology has not been fully illustrated in thyroid cancer. We aimed to evaluate the reproducibility of the new total nodular region of interest (ROI) method excluding the subjective features of focal circular ROI placement and to determine the lesion that causes the elevation of EI on SWE and on histopathology. METHODS: A total of 29 thyroid cancers from 28 patients were included. We evaluated the reproducibility of EI in the new total nodular ROI using Q-Box Trace program and compared the EI in focal nodular ROI using a 3-mm circular area. We analyzed the correlation between fibrosis and EI. RESULT: The coefficient of variation (CV) of the intrarater assay was significantly lower in total nodular ROI than in focal nodular ROI within the image in rater 1 (1.7% vs. 13.4%, p < 0.001) and in rater 2 (1.4% vs. 16.9%, p < 0.001) and in different images in rater 1 (7.6% vs. 12.3%, p = 0.040) and in rater 2 (7.5% vs. 19.8%, p = 0.004). Moreover, CV of the interrater assay showed similar results (14.9% vs. 19%, p = 0.030). Interrater intraclass correlation coefficient showed better agreement in total nodular ROI than in focal nodular ROI (0.863 vs. 0.783). The degree of fibrosis on histopathology showed significant correlations with EI (EMean, p < 0.001; EMax, p = 0.027), and the location of fibrosis was concordant with the high EI area on SWE. CONCLUSION: Our study revealed that the new total nodular ROI method showed higher reproducibility and better agreement in intra- and interrater assay than the focal nodular ROI method, suggesting a valuable and standardized method in clinical practice. Moreover, our results showed that fibrosis in the histopathology increased EI on SWE and might lead to the discrepancy of the cut-off values in detecting thyroid cancer.

The circulating exosomal microRNAs related to albuminuria in patients with diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is associated with high risk of cardiovascular disease and mortality. Exosomal microRNAs (miRNAs) regulate gene expression in a variety of tissues and play important roles in the pathology of various diseases. We hypothesized that the exosomal miRNA profile would differ between DN patients and patients without nephropathy. METHODS: We prospectively enrolled 74 participants, including healthy volunteers (HVs), diabetic patients without nephropathy, and those with DN. The serum exosomal miRNA profiles of participants were examined using RNA sequencing. RESULTS: The expression levels of 107 miRNAs differed between HVs and patients without DN, whereas the expression levels of 95 miRNAs differed between HVs and patients with DN. Among these miRNAs, we found 7 miRNAs (miR-1246, miR-642a-3p, let-7c-5p, miR-1255b-5p, let-7i-3p, miR-5010-5p, miR-150-3p) that were uniquely up-regulated in DN patients compared to HVs, and miR-4449 that was highly expressed in DN patients compared to patients without DN. A pathway analysis revealed that these eight miRNAs are likely involved in MAPK signaling, integrin function in angiogenesis, and regulation of the AP-1 transcription factor. Moreover, they were all significantly correlated with the degree of albuminuria. CONCLUSIONS: Patients with DN have a different serum exosomal miRNA profile compared to HVs. These miRNAs may be promising candidates for the diagnosis and treatment of DN and cardiovascular disease.

Bisphosphonates Use and Risk of Subtrochanteric and Diaphyseal Femur Fractures in Korea: Results from the National Claim Registry.

Although Asian with bisphosphonate has been considered to have higher risk of subtrochanteric and diaphyseal femur (ST/DF) fractures, the occurrence of those fractures has been still unclear in Asia. The purpose of this study was to investigate the incidence rate of ST/DF fractures among bisphosphonate users from nationwide database in South Korea. Using national health insurance claim database, we only included the bisphosphonate users who took bisphosphonate for the first time in 2008 and evaluated the incidence rate of ST/DF fracture from 2008 to 2013. Non-user controls were matched to bisphosphonate users by propensity score matching with age and gender. Cox regression models were used to calculate hazard ratios of ST/DF fracture with and without adjustment for comorbidity. A total of 682 ST/DF fractures were observed among 348,311 bisphosphonate users. The incidence rate of ST/DF fracture among bisphosphonate users (37.75/100,000 person years, 95% CI 35.02-40.70) was higher compared with non-users (24.41/100,000 person years, 95% CI 22.31-26.71). The risk of ST/DF fracture was greater in bisphosphonate users compared with non-users (hazard ratio 1.541, 1.370-1.734; p < 0.001). The incidence rate of ST/DF fracture after bisphosphonate use could be determined in Korean patients, which can provide basal information for further studies on risk and benefit of continuing bisphosphonate.

Assessment of patient-reported outcomes (PROs): treatment satisfaction, medication adherence, and quality of life (QoL) and the associated factors in postmenopausal osteoporosis (PMO) patients in Korea.

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.

Iodine intake as a risk factor for BRAF mutations in papillary thyroid cancer patients from an iodine-replete area.

PURPOSE: 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) <300 µg/L] and extremely excessive (UIC ≥ 2500 µg/L) iodine intake were associated with thyroid cancer in Korea, an iodine-replete area. Papillary thyroid cancer (PTC) accounts for more than 97 % of thyroid cancer and 80% or more PTC cases harbor the BRAF mutation in Korea. We aimed to investigate the relationship between iodine intake and the prevalence of the BRAF mutation in PTC in Korea. METHODS: UIC was measured by inductively coupled plasma mass spectrometry. The BRAF mutation was detected using both allele-specific polymerase chain reaction and mutant enrichment with 3'-modified oligonucleotide sequencing. Risk factors for the occurrence of BRAF mutations in PTC were evaluated using multivariate logistic regression models. RESULTS: The median UIC in all patients with PTC was 287 µg/L (range from 7 to 7, 426 µg/L). Nearly half of the patients (102/215, 47%) belonged to the excessive iodine intake category (UIC ≥ 300 µg/L) according to the WHO iodine recommendations. The frequency of BRAF mutations was lowest in the 300-499 µg/L UIC group; it was significantly different compared to the relatively low (UIC < 300 µg/L) and more than excessive (UIC ≥ 500 µg/L) iodine intake groups. UIC was an independent predictor for BRAF mutations in PTC. The multivariate-adjusted odds ratios (95% confidence intervals) in the relatively low and more than excessive iodine intake groups for the BRAF mutation were 4.761 (1.764-12.850) and 6.240 (2.080-18.726), respectively, compared to the 300-499 µg/L UIC group. CONCLUSION: Relatively low iodine intake and more than excessive iodine intake seem to be significant risk factors for the occurrence of BRAF mutations in the thyroid and, therefore, may be risk factors for the development of PTC in an iodine-replete area.

Low calcium and vitamin D intake in Korean women over 50 years of age.

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.

Strong association of relatively low and extremely excessive iodine intakes with thyroid cancer in an iodine-replete area.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 300 µg/L and in UIC ≥ 2500 µg/L than those with benign thyroid nodules. Male gender (OR 1.528, p = 0.028) and UIC were independent predictors for thyroid cancer. The multivariate-adjusted OR (95 % CI) in the relatively low (UIC < 300 µg/L) and extremely excessive (UIC ≥ 2500 µg/L) iodine intake groups for thyroid cancer were 1.519 (1.099-2.098) and 1.874 (1.094-3.208), respectively, compared to the other iodine intake group (300-2499 µg/L). CONCLUSION: Male gender and UIC were independent predictors of thyroid cancer in patients with thyroid nodules. This study suggests that relatively low and extremely excessive iodine intakes are associated with thyroid cancer in an iodine-replete area.

Preoperative serum thyroglobulin and changes in serum thyroglobulin during TSH suppression independently predict follicular thyroid carcinoma in thyroid nodules with a cytological diagnosis of follicular lesion.

BACKGROUND: Fine-needle aspiration biopsy (FNAB) cannot distinguish a follicular thyroid carcinoma (FTC) from a follicular adenoma in follicular lesions. We designed this study to determine whether the preoperative thyroglobulin (Tg) and change in serum Tg during thyroid-stimulating hormone (TSH) suppression can predict FTC in thyroid nodules with a cytological diagnosis of follicular lesion. METHODS: Among 854 patients who underwent thyroid surgery, the 198 patients who presented with thyroid nodules with a cytological diagnosis of follicular lesion were analyzed. Predictive factors for malignancy were evaluated using multivariate logistic regression models. Subgroup analyses of patients with TSH suppression therapy by levothyroxine were also conducted. RESULTS: Thirty-two patients (16%) had FTC, and 166 patients had confirmed benign nodules. The median preoperative serum Tg levels were significantly higher in patients with FTC compared to those with benign pathology (449 vs. 34 ng/mL, p < 0.001). The serum Tg (odds ratios (OR) 10.311, p < 0.001) and tumor volume (OR 4.500, p = 0.035) were found to be independent predictors for FTC in all patients with a cytological diagnosis of follicular lesion. Forty-eight patients received TSH suppression therapy. When we performed subgroup analyses on the patients with TSH suppression therapy, decrease less than 15% in serum Tg during TSH suppression was found to be an independent predictor of FTC (OR 13.918, p = 0.018). CONCLUSION: Preoperative serum Tg and changes in serum Tg during TSH suppression independently predict FTC in thyroid nodules with a cytological diagnosis of follicular lesion.

Patient Perception on Osteoporosis in Korean Female Patients with Osteoporosis.

BACKGROUND: Patient perception is a key element in improving compliance with medications for osteoporosis. This study evaluated the awareness, perception, sources of information, and knowledge of osteoporosis among Korean women with osteoporosis. METHODS: A questionnaire survey was conducted from July 22, 2021 to 13 August 2021. Patients who were followed up in endocrinology (Endo), orthopedic surgery (OS), and gynecology (GY) were recruited (N=40, 40, and 20 in each group). Patients were allocated according to their age, as follows: 15, 15, and 10 patients in their 60s, 70s, and 80s for Endo and OS, and 10 and 10 patients in their 60s and 70s for GY. The questionnaire was composed of the following topics: patient journey to the hospital, drug-related issues, communication with medical doctors, patient knowledge, and sources of information about osteoporosis. RESULTS: The results of medical check-ups were the most common reason for patient visits to the hospital for an initial diagnosis of osteoporosis (61%). A knowledge gap regarding mortality, refracture, and drug-induced osteoporosis was observed. Doctors were the most preferred and trustful source of information, while health-related TV shows were the second most common source of information. Patients with OS reported lower perceived severity and higher drug discontinuation, along with a higher proportion of fractures, as the initial reasons for hospital visits for osteoporosis. CONCLUSIONS: Variations in perceptions according to the issue and group were identified. These should be considered during patient consultations to improve compliance with osteoporosis treatment.

Effects of Bazedoxifene/Vitamin D Combination Therapy on Serum Vitamin D Levels and Bone Turnover Markers in Postmenopausal Women with Osteopenia: A Randomized Controlled Trial.

BACKGROUND: This study aimed to evaluate the effectiveness of bazedoxifene/vitamin D combination therapy in preventing osteoporosis in postmenopausal women with osteopenia. METHODS: This was an open-label, multicenter randomized-controlled, phase 4 clinical trial. Women between ages of 55 and 70 years in 9 medical tertiary centers in Korea were enrolled and assigned into 2 groups: an experiment group and a control group. The experimental group received bazedoxifene 20 mg/vitamin D 800 IU tablets for 6 months, and the control group received calcium 100 mg/vitamin D 1,000 IU tablets for 6 months. RESULTS: A total of 142 patients (70 in the experimental group and 72 in the control group) were included. The least-square mean±standard error of change in propeptide of type I collagen after 3 months was -6.87±2.56% in the experimental group and 1.22±2.54% in the control group. After 6 months, it was -21.07±2.75% in the experimental group and 1.26±2.71% in the control group. The difference between the 2 groups was -22.33% (p<0.01). The change of C-terminal telopeptide was -12.55±4.05% in the experimental group and 11.02±4.03% in the control group after 3 months. It was -22.0±3.95% and 10.20±3.89, respectively, after 6 months. The difference between the 2 groups was -32.21% (p<0.01) after 6 months. There was no significant difference in adverse events between the 2 groups. CONCLUSIONS: The osteoporosis preventive effect and safety of administering bazedoxifene/vitamin D combination pill were confirmed in postmenopausal women who needed osteoporosis prevention.

Positive correlation between erythrocyte levels of n-3 polyunsaturated fatty acids and bone mass in postmenopausal Korean women with osteoporosis.

BACKGROUND: Osteoporosis, a major health problem among postmenopausal women, is influenced by dietary factors. The purpose of the present study was to evaluate the hypothesis that erythrocyte levels of n-3 polyunsaturated fatty acid (PUFA) and the dietary intake of fish are associated with risk of osteoporosis and correlate with bone mass in postmenopausal Korean women with the disease. METHODS: Fifty cases and 100 controls were recruited. Osteoporosis was defined according to the International Society for Clinical Densitometry guideline as a score lower than -2.5 SD below the T-score for lumbar vertebrae L1-L4, femoral neck or femoral total. RESULTS: The T-score of the femoral neck was positively correlated with erythrocyte levels of n-3 PUFA, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and the intake of fish, and was negatively correlated with the ratio of n-6/n-3 PUFA after adjusting for age, years after menopause and height. In addition, the risk of osteoporosis was positively associated with erythrocyte levels of saturated fatty acids but negatively associated with EPA + DHA. CONCLUSIONS: Erythrocyte levels of n-3 PUFA and the intake of fish were positively correlated with bone mass. In particular, erythrocyte levels of EPA + DHA reduced the risk of osteoporosis in postmenopausal Korean women.

Raloxifene/Vitamin D Combination Therapy vs. Raloxifene Monotherapy on Serum 25-Hydroxy-Vitamin D Level among Postmenopausal Women with Osteoporosis or Osteopenia: A Randomized Controlled Trial.

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.

Association of free thyroxine with obstructive lung pattern in euthyroid middle-aged subjects: A population-based study.

BACKGROUND: The association between thyroid hormone levels and pulmonary function in euthyroid population is still unclear. We aimed to examine the relationship between thyroid function and lung function in a large cohort study of euthyroid subjects. METHODS: We analyzed biochemical and spirometry data from a nationwide, population-based, cross-sectional survey (KNHANES VI). A total of 1,261 middle-aged participants aged 45-65 years with spirometry tests and normal thyroid function were included in this study. The subjects were grouped according to free thyroxine (fT4) (ng/dL) quartiles (Q1, 0.89-1.09; Q2, 1.10-1.19; Q3, 1.20-1.30; Q4, 1.31-1.76). Obstructive lung pattern was defined as forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) <0.7. The probability of obstructive lung patterns according to fT4 quartiles was assessed using logistic regression models, adjusted for potential confounders. RESULTS: Overall, 10.9% of the subjects had an obstructive lung pattern. The mean fT4 levels were significantly higher in those with obstructive lung pattern than in those with normal lung function (1.26 vs. 1.20 ng/dL, p<0.001). The proportion of participants with obstructive lung pattern increased across the fT4 quartile categories (p<0.001). With the Q1 group as reference, the multivariate-adjusted odds ratios (95% confidence intervals) for obstructive lung pattern in the Q3 and Q4 groups were 2.875 (1.265-6.535) and 2.970 (1.287-6.854), respectively, even after adjusting for confounding variables. CONCLUSION: High fT4 levels are an independent predictor of obstructive lung pattern in euthyroid middle-aged subjects. Further prospective studies are needed to confirm these findings.

Risk of carotid plaques according to triglyceride-glucose index stratified by thyroid function: A cross-sectional study.

BACKGROUND: Recent studies have indicated that the triglyceride-glucose (TyG) index or subclinical thyroid dysfunction is associated with carotid plaques, a predictor of cardiovascular disease risk. However, evidence for this association is limited and inconsistent. This study aimed to evaluate the risk of carotid plaques according to TyG index and thyroid function status in the general population. METHODS: A total of 2,931 individuals who underwent carotid ultrasound as part of a comprehensive health examination at the Health Promotion Center of Soonchunhyang University Hospital were retrospectively reviewed. Based on the TyG index and thyroid function status, the participants were divided into six groups: LoTyG-SHyper (low TyG index with subclinical hyperthyroidism), LoTyG-Eu (low TyG index with euthyroidism), LoTyG-SHypo (low TyG index with subclinical hypothyroidism), HiTyG-SHyper (high TyG index with subclinical hyperthyroidism), HiTyG-Eu (high TyG index with euthyroidism), and HiTyG-SHypo (high TyG index with subclinical hypothyroidism). A multivariate logistic regression analysis was conducted to determine the risk of carotid plaques. RESULTS: The proportion of participants with significant carotid plaques was significantly different among the six groups (p<0.001, p for trend<0.001). The odds ratio (OR) and 95% confidence interval (CI) for significant carotid plaques were significantly higher in the HiTyG-SHypo group than in the LoTyG-Eu group, even after adjusting for confounding variables including sex, age, smoking, obesity, hypertension and diabetes mellitus (OR 1.506, 95% CI 1.045-2.170, p = 0.028). The OR of significant carotid plaques was higher in the HiTyG-Eu group than in the LoTyG-Eu group; however no associations were observed after additional adjustment for confounding variables. CONCLUSION: The TyG index and thyroid function status are important predictors of the risk of carotid plaques in healthy individuals. Early evaluation of carotid plaques may be necessary for subjects with high insulin resistance and subclinical hypothyroidism.

Empagliflozin suppresses urinary mitochondrial DNA copy numbers and interleukin-1ß in type 2 diabetes patients.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular and renal outcomes in type 2 diabetes mellitus (T2DM) patients. However, the mechanisms by which SGLT2 inhibitors improve the clinical outcomes remain elusive. We evaluated whether empagliflozin, an SGLT2 inhibitor, ameliorates mitochondrial dysfunction and inflammatory milieu of the kidneys in T2DM patients. We prospectively measured copy numbers of urinary and serum mitochondrial DNA (mtDNA) nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) and urinary interleukin-1ß (IL-1ß) in healthy volunteers (n = 22), in SGLT2 inhibitor-naïve T2DM patients (n = 21) at baseline, and in T2DM patients after 3 months of treatment with empagliflozin (10 mg, n = 17 or 25 mg, n = 4). Both urinary mtDNA copy numbers and IL-1ß levels were higher in the T2DM group than in healthy volunteers. Baseline copy numbers of serum mtCOX-3 in the T2DM group were lower than those in healthy volunteers. Empagliflozin induced marked reduction in both urinary and serum mtND-1 and mtCOX-3 copy numbers, as well as in urinary IL-1ß. Empagliflozin could attenuate mitochondrial damage and inhibit inflammatory response in T2DM patients. This would explain the beneficial effects of SGLT2 inhibitors on cardiovascular and renal outcomes.

Efficacy of Differential Diagnosis of Thyroid Nodules by Shear Wave Elastography-the Stiffness Map.

BACKGROUND: Fine needle aspiration is the gold standard for differential diagnosis of thyroid nodules; however, the malignancy rate for indeterminate cytology is 20% to 50%. OBJECTIVE: We evaluated the efficacy of shear wave elastography added to ultrasonography for differential diagnosis of thyroid nodules. METHODS: We retrospectively reviewed the medical records of 258 consecutive patients. Thyroid nodules were divided into 4 categories according to maximum elasticity (EMax) and nodule depth/width (D/W) ratio: Category 1 (EMax ≥ 42.6 kPa; D/W < 0.9); Category 2 (EMax < 42.6 kPa; D/W < 0.9); Category 3 (EMax ≥ 42.6 kPa; D/W ≥ 0.9); and Category 4 (EMax < 42.6 kPa; D/W ≥ 0.9). The EMax cutoff value was set using receiver operating characteristic (ROC) curve analysis to predict nodular hyperplasia (NH) vs follicular neoplasm (FN). Cutoff value for nodule D/W ratio was set using ROC curve analysis for malignancy. RESULTS: NH was the most prevalent pathology group in Category 1, FN in Category 2, and papillary thyroid carcinoma in Category 3. Category 3 demonstrated the highest rate of malignancy (81.8%) and had 55.4% sensitivity and 90% specificity for predicting malignancy. When assessing the benign pathology of NH in follicular patterned lesion, Category 1 demonstrated the highest NH prevalence of 88.9% (34/37) and had 73.9% sensitivity and 85.0% specificity. CONCLUSION: The performance for malignancy was highest in Category 3 and predictive ability for benign pathology of NH in follicular lesion was highest in Category 1. The information of EMax and nodule D/W ratio was useful to predict the pathology of thyroid nodules.