Publications by authors named "Seong Hee Ahn"

51 Publications

Incidence and Risk of Venous Thromboembolism in Bisphosphonates and Selective Estrogen Receptor Modulators Treatment in Korea.

J Korean Med Sci 2021 Jul 12;36(27):e186. Epub 2021 Jul 12.

Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea.

Background: Selective estrogen receptor modulators (SERMs) were associated with an increased risk of venous thromboembolism (VTE) due to the estrogen effect. In this study, we investigated the effect of SERMs on VTE compared to bisphosphonates (BPs) using the Korean National Health Insurance claims database.

Methods: This was a retrospective cohort study. Women over 50 years old who were first prescribed BPs or SERMs for osteoporosis treatment in 2012 were included. The difference in VTE incidence between the SERMs and BP groups was compared. Both groups were followed up for VTE or PE occurrence, death, or until December 2016. The study population was analyzed by 3:1 matching according to age using a multivariate Cox model.

Results: The hazard ratio (HR) for VTE was 0.72 (95% confidence interval [CI], 0.40-1.28) in the SERMs group compared to BP group. Older age (60-69 vs. 50-59 years: HR, 3.77; 95% CI, 2.07-6.86 and 70-79 vs. 50-59 years: HR, 5.88; 95% CI, 3.14-11.02), major osteoporotic fracture (HR, 1.77; 95% CI, 1.16- 2.70), atrial fibrillation (HR, 3.31; 95% CI, 1.35-8.11), and estrogen replacement (HR, 3.40; 95% CI, 2.01-5.73) all increased VTE risk. In subgroup analysis of the SERMs group, past hospitalization (HR, 2.24; 95% CI, 1.02-4.92), estrogen replacement (HR, 5.75; 95% CI, 2.29-14.39), and glucocorticoid replacement (HR, 2.71; 95% CI, 1.05-7.0) increased VTE risk.

Conclusion: SERMs did not increase the risk of VTE compared to BPs in Koreans with osteoporosis. However, old age and estrogen replacement both increased VTE risk.
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http://dx.doi.org/10.3346/jkms.2021.36.e186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275462PMC
July 2021

Use of statin for the primary prevention of cardiovascular outcomes in elderly patients: A propensity-matched cohort study.

Atherosclerosis 2021 07 5;328:92-99. Epub 2021 Jun 5.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University College of Medicine, Incheon, South Korea. Electronic address:

Background And Aims: Herein, we investigate whether statin treatment as primary prevention reduces cardiovascular outcomes in elderly Asian patients.

Methods: Data were obtained from the Korean National Health Insurance Service-Senior Cohort database (n = 558,147). A total of 81,729 elderly patients (≥75 years) without clinically recognized atherosclerotic cardiovascular disease (CVD) were included. The patients who did not have a history of statin use in year 2003 were followed from January 2004 to the end of 2012. New statin users (n = 3670) were matched on the basis of the propensity score in a 1:2 ratio with non-users. Incidences of myocardial infarction, ischemic stroke, and death from CVD were compared using the Cox proportional hazards model.

Results: The risk of cardiovascular death was significantly reduced in the statin treatment group compared with the non-user group (hazard ratio [HR] 0.34, 95% confidence interval [CI] 0.29 to 0.40; p < 0.001). This effect was observed in both patient groups with and without diabetes. In patients with diabetes, the HR for statin use was 0.85 (95% CI 0.55 to 1.33) for myocardial infarction and 0.75 (95% CI 0.60 to 0.93) for ischemic stroke. In participants without diabetes, the HR of statin use was 0.95 (95% CI 0.73 to 1.24) for myocardial infarction and 1.13 (95% CI 1.01 to 1.26) for ischemic stroke. The presence of hypertension was also a significant factor in the prevention of ischemic stroke by statin treatment.

Conclusions: In elderly patients without clinically recognized atherosclerotic CVD, the risk of cardiovascular mortality was significantly reduced with statin treatment than with non-users. In participants with type 2 diabetes, statin treatment was associated with a reduction in ischemic stroke.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.05.022DOI Listing
July 2021

Osteoporosis and Osteoporotic Fracture Fact Sheet in Korea.

J Bone Metab 2020 Nov 30;27(4):281-290. Epub 2020 Nov 30.

Division of Endocrinology, Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea.

Background: The socioeconomic burdens of osteoporosis and related fractures have increased in parallel with population aging. The Korea Society of Bone and Mineral Research published fact sheets on these topics in 2017, 2018, and 2019. This study provides complied epidemiological data based on these fact sheets for understanding current status of osteoporosis in Korea.

Methods: Data from the Korea National Health and Nutrition Examination Survey (2008-2011) performed by the Korea Centers for Disease Control and Prevention and from National Health Information database (2008-2016) by National Health Insurance Service of Korea was used for analyzing the prevalence and incidence of osteoporosis and related fractures, respectively, fatality rates after fractures, and prescription status of anti-osteoporotic medications (AOMs).

Results: Among Korean adults aged ≥50 years, 22.4% and 47.9% had osteopenia or osteoporosis, respectively. Incidences of osteoporotic hip, vertebral, humerus, and distal radius fractures plateaued in 2013. The cumulative incidence of subsequent fractures gradually increased over 4 years of follow-up once an osteoporotic fracture occurred. Crude fatality rates in the first 12 months after hip fracture were 14.0% for women and 21.0% for men. Only 33.5% of patients with osteoporosis took AOMs, and even after an osteoporotic fracture, only 41.9% of patients took AOMs within the following 12 months. Despite a steady increase in AOM prescriptions of ~6% per annum, only 33.2% of patients were medication compliant (medication possession ratio ≥80%) at 12 months after treatment initiation.

Conclusions: Continuous efforts are required to diagnose patients at high risk of fracture and ensure proper management in Korea.
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http://dx.doi.org/10.11005/jbm.2020.27.4.281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746478PMC
November 2020

Serum Levels of Adipocyte Fatty Acid-Binding Protein Are Associated with Rapid Renal Function Decline in Patients with Type 2 Diabetes Mellitus and Preserved Renal Function.

Diabetes Metab J 2020 12 10;44(6):875-886. Epub 2020 Jul 10.

Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea.

Background: Recent studies have demonstrated that the levels of adipocyte fatty acid-binding protein (A-FABP) are closely associated with diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). This study aimed to examine the association between serum A-FABP level and rapid renal function decline in patients with T2DM and preserved renal function.

Methods: This was a prospective observational study of 452 patients with T2DM and preserved renal function who had serial measurements of estimated glomerular filtration rate (eGFR). Rapid renal function decline was defined as an eGFR decline of >4% per year. The association between baseline serum A-FABP level and rapid renal function decline was investigated.

Results: Over a median follow-up of 7 years, 82 participants (18.1%) experienced rapid renal function decline. Median A-FABP levels were significantly higher in patients with rapid renal function decline, compared to non-decliners (20.2 ng/mL vs. 17.2 ng/mL, P=0.005). A higher baseline level of A-FABP was associated with a greater risk of developing rapid renal function decline, independent of age, sex, duration of diabetes, body mass index, systolic blood pressure, history of cardiovascular disease, baseline eGFR, urine albumin creatinine ratio, total cholesterol, glycosylated hemoglobin, high-sensitivity C-reactive protein and use of thiazolidinedione, insulin, angiotensin-converting-enzyme inhibitors and angiotensin II-receptor blockers and statin (odds ratio, 3.10; 95% confidence interval, 1.53 to 6.29; P=0.002).

Conclusion: A high level of serum A-FABP is associated with an increased risk of rapid renal function decline in patients with T2DM and preserved renal function. This suggests that A-FABP could play a role in the progression of DKD in the early stages.
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http://dx.doi.org/10.4093/dmj.2019.0221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801760PMC
December 2020

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

Endocrinol Metab (Seoul) 2020 06 24;35(2):272-287. Epub 2020 Jun 24.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea.

Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.
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http://dx.doi.org/10.3803/EnM.2020.35.2.272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386113PMC
June 2020

Low muscle mass is associated with carotid atherosclerosis in patients with type 2 diabetes.

Atherosclerosis 2020 07 16;305:19-25. Epub 2020 Jun 16.

Department of Endocrinology and Metabolism, Inha University School of Medicine, Incheon, Republic of Korea. Electronic address:

Background And Aims: Sarcopenia leads to metabolic and vascular abnormalities. However, little is known regarding the independent relationship between skeletal muscle mass and atherosclerosis in patients with type 2 diabetes mellitus (T2DM). This study aimed to evaluate the association between skeletal muscle mass and carotid atherosclerosis in men and women with T2DM.

Methods: In this cross-sectional study, a total of 8202 patients with T2DM were recruited from the Seoul Metabolic Syndrome cohort. Skeletal muscle mass was estimated using bioimpedance analysis, while skeletal muscle mass index (SMI, %) was defined as total skeletal muscle mass (kg)/body weight (kg) × 100. Both carotid arteries were examined by B-mode ultrasound. Carotid atherosclerosis was defined by having a carotid plaque or mean carotid intima-media thickness (IMT) ≥1.1 mm.

Results: Among the entire population, 4299 (52.4%) subjects had carotid atherosclerosis. The prevalence of carotid atherosclerosis increased with decreasing SMI quartiles for both sexes. The odds ratios for carotid atherosclerosis were 2.33 (95% confidence interval [CI], 1.17-4.63) and 2.24 (95% CI, 1.06-4.741) in the lowest versus highest SMI quartile in men and women, respectively, after the adjustment for clinical risk factors. In men, the risk of atherosclerosis increased linearly with decreasing SMI quartiles (p for trend = 0.036).

Conclusions: Low skeletal muscle mass was independently associated with the presence of carotid atherosclerosis in men and women with T2DM.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.05.021DOI Listing
July 2020

Different Relationships Between Thyrotropin and Muscle Strength According to Sex and Age in Euthyroid Koreans (The 6th Korea National Health and Nutritional Examination Survey 2014-2015).

Thyroid 2020 12 29;30(12):1710-1717. Epub 2020 Jun 29.

Department of Endocrinology and Metabolism, Inha University Hospital, Inha University School of Medicine, Incheon, Republic of Korea.

Changes in muscle mass and strength can be caused by multiple endocrine factors, including thyroid dysfunction. However, the relationship between thyroid function and muscle strength in euthyroid individuals is not clear. In the present study, we investigated the relationship between thyroid function and handgrip strength (HGS) in euthyroid Koreans, especially according to sex and age. This was a population-based, cross-sectional study from the 6th Korea National Health and Nutrition Examination Survey including 2894 Koreans (1487 men and 1407 women) aged ≥19 years. Serum thyrotropin (TSH) and free thyroxine (fT4) levels were measured. HGS was measured using a digital grip strength dynamometer. Serum TSH level, but not serum fT4 level, was significantly associated with HGS in men, but neither TSH nor fT4 level was associated with HGS in women. Serum TSH showed a negative association with HGS in men aged <65 years ( = 1376;  = -0.566,  = 0.008), but a positive association in men aged ≥65 years ( = 111;  = 1.158,  = 0.010) after adjusting for confounders. HGS decreased as TSH tertile increased in men aged <65 years ( for trend = 0.010), but increased with TSH tertile in men aged ≥65 years ( for trend = 0.009) after adjusting for confounders. Odds ratios (ORs) for the lowest quartile of HGS increased in the highest tertile of TSH among men aged <65 years (OR = 1.657 [95% confidence interval {CI} 1.099-2.500],  = 0.006) and decreased in the highest tertile of TSH among men aged ≥65 years (OR = 0.176 [CI 0.032-0.966],  = 0.034) after adjusting for confounders. In euthyroid Koreans, serum TSH levels were significantly associated with HGS only in men and this relationship was found to depend significantly on age. These findings suggest that age has a distinct influence on the effect of even subtle change of thyroid function on muscle strength in men.
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http://dx.doi.org/10.1089/thy.2019.0601DOI Listing
December 2020

Use of Bone Turnover Markers in Clinical Practice for the Management of Osteoporosis in Korea: From the Survey on the Prescription Pattern of Bone Turnover Markers.

J Bone Metab 2019 Nov 30;26(4):271-277. Epub 2019 Nov 30.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea.

Background: There has been interest in the clinical potential of bone turnover markers (BTMs) as tools both for assessing fracture risk and for monitoring treatment. However, the practical use of BTMs has been limited by their biological variability and difficulties in the interpretation of results. We investigated the current situation of application of BTMs by clinicians in Korea for the management of osteoporosis through a survey asking the patterns of BTMs prescription in clinical practice.

Methods: The survey was conducted online using the "google survey" by the BTM committee authorized by the Korean Society for Bone and Mineral Research.

Results: Total 108 clinicians responded the survey. Most of the respondents prescribed BTMs (80.6%) when they prescribed anti-osteoporotic medications (AOMs). The most frequently prescribed bone resorption and formation markers were serum C-terminal telopeptide of type I collagen (90.7%) and osteocalcin (65.1%), respectively. BTMs were mostly prescribed before starting AOMs (90.8%) and used for the purpose of evaluating treatment response (74.4%). Treatment response and compliance to AOMs were evaluated according to the change of absolute value of BTMs (55.1%). The respondents complained difficulties in the interpretation of BTMs (33.3%), the choice of proper BTMs (17.2%), and the proper sample preparation and handling (13.8%).

Conclusions: In Korea, most of clinicians recognized the benefit of BTMs in the management of osteoporosis. However, there are limitations in the broad use of these markers in clinical practice. Therefore, a clear recommendation for BTM in Korea enhances their use in clinical practice.
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http://dx.doi.org/10.11005/jbm.2019.26.4.271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901689PMC
November 2019

Position Statement on the Use of Bone Turnover Markers for Osteoporosis Treatment.

J Bone Metab 2019 Nov 30;26(4):213-224. Epub 2019 Nov 30.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea.

Current evidences continue to support the clinical application of bone turnover markers (BTMs) in the management of postmenopausal osteoporosis. The limitations of bone mineral density measured by dual energy X-ray absorptiomet especially emphasize the beneficial roles of BTMs, such as serum C-terminal telopeptide of type I collagen and serum procollagen type I N-propeptide, as monitoring tools to assess the responses to treatment. Therefore, the proper application and assessment of BTM in clinical practice is very important. However, their use in Korea is still insufficient. Therefore, the BTM committee has set up by the Korean Society for Bone and Mineral Research have been constituted and provided a position statement which will suggest on the clinical application of BTM for the management of postmenopausal osteoporosis in Korea.
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http://dx.doi.org/10.11005/jbm.2019.26.4.213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901690PMC
November 2019

Incidence and mortality of subsequent vertebral fractures: analysis of claims data of the Korea National Health Insurance Service from 2007 to 2016.

Spine J 2020 02 4;20(2):225-233. Epub 2019 Oct 4.

Department of Endocrinology and Metabolism, Kyung Hee University, School of Medicine, Seoul 05278, Republic of Korea. Electronic address:

Background Context: Vertebral fracture is related to an increased risk for subsequent and recurrent osteoporotic fracture as well as increased mortality. However, no study has investigated the exact incidence and mortality of subsequent vertebral fractures.

Objective: The purpose of our study was to determine trends in the incidence and mortality of subsequent vertebral fractures after first-time vertebral fracture in Koreans older than 50 years using the national claims database.

Study Design: Retrospective cohort study.

Patient Sample: Data from the Korea National Health Insurance Service database from 2007 to 2016.

Outcome Measures: The incidence of subsequent vertebral fracture during a 4-year follow-up period. The mortality and standardized mortality ratio (SMR) after subsequent vertebral fractures during the 1-year period after fracture were also determined. Analysis was restricted to patients older than 50 years.

Methods: The national claims data set was analyzed to find all new visits and revisits after 6 months from the last claim to a hospital or clinic for vertebral fractures and revisits in men and women aged 50 years or older between 2007 and 2016. The number of first-time vertebral fractures in 2012 was investigated to determine subsequent vertebral fractures. The incidence, mortality rates, and SMR of subsequent vertebral fractures were calculated. There were no sources of funding and no conflicts of interest associated with this study.

Results: During the 4-year follow-up period, the overall cumulative incidence of subsequent vertebral fractures were 27.53%. According to sex, the cumulative incidence of subsequent vertebral fractures was 20.09% in men and 29.98% in women. The cumulative mortality rate over the first year after subsequent vertebral fractures was 5%. The mortality rates over 1 year were 10.04% for men and 3.81% for women. The overall SMR at the 1-year follow-up after subsequent vertebral fractures was 10.58 (95% confidence interval: 9.29-12.05) in men and 3.88 (95% confidence interval: 3.5-4.3) in women.

Conclusions: Our study showed that subsequent vertebral fractures were more common in women, with an incidence rate of 29.98% over 4 years. However, the mortality rate was higher in men, reaching 10.04% in 1 year. Subsequent vertebral fractures occurred in large numbers, and the mortality rates were relatively high. Thus, first vertebral fracture may be considered as an early warning of high risk for future subsequent vertebral fractures, especially in women.
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http://dx.doi.org/10.1016/j.spinee.2019.09.025DOI Listing
February 2020

Lower hand grip strength in older adults with non-alcoholic fatty liver disease: a nationwide population-based study.

Aging (Albany NY) 2019 07;11(13):4547-4560

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Although both liver and muscle are metabolically active endocrine organs, and non-alcoholic fatty liver disease (NAFLD) and sarcopenia may share common pathogenic determinants, there have been few clinical studies of the relationship between NAFLD and muscle strength, especially in the elderly. We conducted a nationally representative population-based, cross-sectional study using data from the Korea National Health and Nutrition Examination Survey, which involved 1,897 men aged ≥50 years and 2,206 postmenopausal women. NAFLD was defined using the hepatic steatosis index (HSI) and low muscle strength was defined using the Korea-specific cut-off point of hand grip strength (HGS). Men and women with NAFLD had 7.3% and 7.9% lower HGS than controls, respectively. The odds ratios for low muscle strength in the presence of NAFLD were 2.51 in men and 2.34 in women. HSI inversely correlated with HGS in both men and women. Consistently, compared with men and women in the lowest HSI quartile, those in the highest quartile had 7.6% and 12.4% lower HGS, respectively, and were 5.63- and 3.58-times more likely to have low muscle strength, respectively. These results provide the first clinical evidence that NAFLD can be associated with muscular impairment in older adults, as demonstrated by lower muscle strength.
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http://dx.doi.org/10.18632/aging.102068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660042PMC
July 2019

Clinical Application of Bone Turnover Markers in Osteoporosis in Korea.

J Bone Metab 2019 Feb 28;26(1):19-24. Epub 2019 Feb 28.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea.

Bone turnover markers (BTMs) have important role in the management of osteoporosis. Recently the clinical application of BTMs has achieved significant progress and measurement of BTMs give us better understanding of pathogenesis of osteoporosis. However, the use of BTMs is still insufficient in Korea. We summarized the available methods and standard interval of the BTMs in Korea. Also we reviewed published literatures on pre-analytical variability in the measurement of BTMs and provided recommendations for standardized sample handling and patient preparation for reducing those pre-analytical variabilities. The clinical application of BTMs in patients with chronic kidney disease who have a higher fracture risk than the general population is summarized.
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http://dx.doi.org/10.11005/jbm.2019.26.1.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416153PMC
February 2019

Presence of Carotid Plaque Is Associated with Rapid Renal Function Decline in Patients with Type 2 Diabetes Mellitus and Normal Renal Function.

Diabetes Metab J 2019 12 12;43(6):840-853. Epub 2019 Mar 12.

Department of Endocrinology and Metabolism, Inha University School of Medicine, Incheon, Korea.

Background: Recent evidences indicate that early rapid renal function decline is closely associated with the development and progression of diabetic kidney disease. We have investigated the association between carotid atherosclerosis and rapid renal function decline in patients with type 2 diabetes mellitus and preserved renal function.

Methods: In a prospective, multicenter cohort, a total of 967 patients with type 2 diabetes mellitus and preserved renal function were followed for 6 years with serial estimated glomerular filtration rate (eGFR) measurements. Common carotid intima-media thickness (CIMT) and presence of carotid plaque were assessed at baseline. Rapid renal function decline was defined as an eGFR decline >3.3% per year.

Results: Over a median follow-up of 6 years, 158 participants (16.3%) developed rapid renal function decline. While there was no difference in CIMT, the presence of carotid plaque in rapid decliners was significantly higher than in non-decliners (23.2% vs. 12.2%, <0.001). In multivariable logistic regression analysis, presence of carotid plaque was an independent predictor of rapid renal function decline (odds ratio, 2.33; 95% confidence interval, 1.48 to 3.68; <0.0001) after adjustment for established risk factors. The model including the carotid plaque had better performance for discrimination of rapid renal function decline than the model without carotid plaque (area under the receiver operating characteristic curve 0.772 vs. 0.744, =0.016).

Conclusion: Close monitoring of renal function and early intensive management may be beneficial in patients with type 2 diabetes mellitus and carotid plaques.
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http://dx.doi.org/10.4093/dmj.2018.0186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943261PMC
December 2019

High circulating follistatin-like protein 1 as a biomarker of a metabolically unhealthy state.

Endocr J 2019 Mar 8;66(3):241-251. Epub 2019 Feb 8.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul 06591, Korea.

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.
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http://dx.doi.org/10.1507/endocrj.EJ18-0352DOI Listing
March 2019

Change of skeletal muscle mass in patients with pheochromocytoma.

J Bone Miner Metab 2019 Jul 20;37(4):694-702. Epub 2018 Sep 20.

Division of Endocrinology and Metabolism, Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.

The effects of catecholamine excess due to pheochromocytoma on body composition, including skeletal muscle mass, are unknown. Here, we investigated the effects of catecholamine metabolites on body composition in subjects with pheochromocytoma. After body compositions using bioelectrical impedance analysis, urinary metanephrine (UM), and urinary normetanephrine (UNM) were measured in 16 patients with pheochromocytoma and 224 patients with nonfunctioning adrenal incidentaloma (NFAI), we compared skeletal muscle mass and fat mass (FM) between the two groups. After adjustments for confounders, UM (β = - 0.171, P = 0.006) and UNM (β = - 0.249, P < 0.001) levels were correlated inversely with skeletal muscle mass index (SMI), but not FM or percentage FM (pFM), in all subjects. Patients with pheochromocytoma had lower ASM by 7.7% (P = 0.022) and SMI by 6.6% (P = 0.001) than patients with NFAI. Conversely, FM and pFM were not statistically different between the two groups. The odds ratio for low skeletal muscle mass in the presence of pheochromocytoma was 10.33 (95% confidence interval, 2.65-40.22). Our results indicate that patients with pheochromocytoma have a reduced skeletal muscle mass and suggest that catecholamine excess has adverse effects on skeletal muscle metabolism.
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http://dx.doi.org/10.1007/s00774-018-0959-3DOI Listing
July 2019

Impact of Socioeconomic Status on Health Behaviors, Metabolic Control, and Chronic Complications in Type 2 Diabetes Mellitus.

Diabetes Metab J 2018 Oct 29;42(5):380-393. Epub 2018 Jun 29.

Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Korea.

Background: The aim of the study was to assess the impact of socioeconomic status (SES) on health behaviors, metabolic control, and chronic complications in people with type 2 diabetes mellitus (T2DM) from South Korea, a country with universal health insurance coverage and that has experienced rapid economic and social transition.

Methods: A total of 3,294 Korean men and women with T2DM aged 30 to 65 years, participating in the Korean National Diabetes Program (KNDP) cohort who reported their SES and had baseline clinical evaluation were included in the current cross-sectional analysis. SES included the level of education and monthly household income.

Results: Lower education level and lower income level were closely related, and both were associated with older age in men and women. Women and men with lower income and education level had higher carbohydrate and lower fat intake. After adjustment for possible confounding factors, higher education in men significantly lowered the odds of having uncontrolled hyperglycemia (glycosylated hemoglobin ≥7.5%) (odds ratio [OR], 0.63; 95% confidence interval [CI], 0.43 to 0.91 for highest education; (trend)=0.048), while higher household income in men significantly lowered the odds of having diabetic retinopathy (OR, 0.59; 95% CI, 0.37 to 0.95 for highest income level; (trend)=0.048). In women, lower income was associated with a higher stress level.

Conclusion: Men with lower SES had higher odds of having diabetic retinopathy and uncontrolled hyperglycemia, showing the need to improve care targeted to this population.
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http://dx.doi.org/10.4093/dmj.2017.0102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202566PMC
October 2018

A clinical prediction model to estimate the metastatic potential of pheochromocytoma/paraganglioma: ASES score.

Surgery 2018 09 19;164(3):511-517. Epub 2018 Jun 19.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Electronic address:

Background: Malignant pheochromocytoma and paraganglioma can be defined only after the development of metastases in nonchromaffin tissues. There is no single clinical parameter that is sufficiently reliable to predict metastatic potential, so our goal was to develop a prediction model based on multiple clinical parameters.

Methods: The baseline age, size, extra-adrenal location, secretory type score was calculated in a retrospective cohort study comprising 333 patients with pheochromocytoma and paraganglioma. In each patient, each variable for age ≤35 years, tumor size ≥ 6.0 cm, extra-adrenal, and norepinephrine-secretory type was coded as 1 point (otherwise 0 point); these points were summed to yield age, size, extra-adrenal location, secretory type score.

Results: Metastases occurred in 23 of 333 patients (6.9%). Metastatic pheochromocytoma and paraganglioma was associated with age ≤35 years (hazard ratio [HR] 2.74, 95% confidence interval [95% CI] 1.19-6.35), tumor size ≥6.0 cm (HR 2.43, 95% CI 1.06-5.56), extra-adrenal location (HR 2.73, 95% confidence interval 1.10-7.40), and tumor producing only norepinephrine (HR 2.96, 95% CI 1.30-6.76). The area under the curve of the age, size, extra-adrenal location, secretory type score was 0.735. There was a significant difference in metastasis-free survival between participants with age, size, extra-adrenal location, secretory type score ≥2 and score <2 (P < .0001 by the log rank test). The negative predictive value of this system was 96.5% for a cutoff point of 2.

Conclusion: We developed a new prediction model, the age, size, extra-adrenal location, secretory type score, based on multiple clinical parameters to assess the metastatic potential of pheochromocytoma and paraganglioma.
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http://dx.doi.org/10.1016/j.surg.2018.05.001DOI Listing
September 2018

Characteristics of Adrenal Incidentalomas in a Large, Prospective Computed Tomography-Based Multicenter Study: The COAR Study in Korea.

Yonsei Med J 2018 Jun;59(4):501-510

Division of Endocrinology and Metabolism, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

Purpose: Previous studies on adrenal incidentalomas (AIs) are limited by their retrospective design, small numbers of patients, Western populations, or use of an outdated imaging technique. We investigated the characteristics of AIs in Korean patients and compared them with those reported in the largest retrospective study in Italy to discover the effects of improved imaging techniques and ethnicity differences.

Materials And Methods: This was a prospective, multicenter, cross-sectional observational study including 1005 Korean patients. Levels of plasma adrenocorticotrophic hormone, 24-h urinary free cortisol (UFC), serum cortisol after a 1 mg-dexamethasone suppression test, 24-h urinary fractionated metanephrine, and plasma aldosterone and plasma renin activity were measured. All AIs were characterized using computed tomography (CT).

Results: Compared with the results of the Italian study, AIs in Korean patients were observed more frequently in men and predominantly on the left side. Korean patients with AIs were slightly younger, and fewer patients underwent surgery. Most AIs were nonfunctional in both studies, while fewer subclinical hypercortisolism and more primary aldosteronism (PA) cases were detected in Korean patients. In our study, high UFC levels showed very low sensitivity, compared to those in the Italian study. In pheochromocytoma or PA cases, there were no hormonal differences between the studies. AIs in Korean patients were smaller, such that a lower cutoff size for detecting adrenocortical carcinoma (ACC) could be warranted.

Conclusion: Recent advances in CT technology were leveraged to provide accurate characteristics of AIs and to detect smaller ACCs.
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http://dx.doi.org/10.3349/ymj.2018.59.4.501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949292PMC
June 2018

Alteration in skeletal muscle mass in women with subclinical hypercortisolism.

Endocrine 2018 07 1;61(1):134-143. Epub 2018 May 1.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.

Purpose: Despite the well-known deleterious effects of cortisol on skeletal muscle, whether subtle cortisol excess in subclinical hypercortisolism (SH) affects skeletal muscle mass is unknown. Our objective was to understand the effects of the cortisol level on skeletal muscle mass in patients with SH.

Methods: We compared skeletal muscle mass and fat mass (FM) between 21 patients with SH (12 women and 9 men) and 224 controls (67 women and 157 men) with nonfunctioning adrenal incidentaloma (NFAI). Medical records were reviewed, and we measured body composition parameters using bioelectrical impedance analysis and serum cortisol levels after the overnight 1-mg dexamethasone suppression test (DST).

Results: After adjusting for confounding factors, 1-mg DST levels were inversely correlated with appendicular skeletal muscle mass (ASM) (γ = -0.245, P = 0.040), lower limb ASM (γ = -0.244, P = 0.040), and appendicular skeletal muscle index (ASMI; height-adjusted ASM) (γ = -0.229, P = 0.048) in all women, but not men. ASM and ASMI were significantly lower by 6.2% (P = 0.033) and 5.9% (P = 0.046), respectively, in women with SH compared with those with NFAI, but not men. Conversely, FM and percent fat mass were similar between the two groups. Compared with women with NFAI, among those with SH, lower limb, but not upper limb, ASM was lower by 6.8% (P = 0.020).

Conclusions: This study showed that women with SH had lower skeletal muscle mass, especially of the lower limb, and suggested that subtle cortisol excess also has adverse effects on skeletal muscle metabolism.
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http://dx.doi.org/10.1007/s12020-018-1598-0DOI Listing
July 2018

Osteoclast-secreted SLIT3 coordinates bone resorption and formation.

J Clin Invest 2018 04 5;128(4):1429-1441. Epub 2018 Mar 5.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Coupling is the process that links bone resorption to bone formation in a temporally and spatially coordinated manner within the remodeling cycle. Several lines of evidence point to the critical roles of osteoclast-derived coupling factors in the regulation of osteoblast performance. Here, we used a fractionated secretomic approach and identified the axon-guidance molecule SLIT3 as a clastokine that stimulated osteoblast migration and proliferation by activating β-catenin. SLIT3 also inhibited bone resorption by suppressing osteoclast differentiation in an autocrine manner. Mice deficient in Slit3 or its receptor, Robo1, exhibited osteopenic phenotypes due to a decrease in bone formation and increase in bone resorption. Mice lacking Slit3 specifically in osteoclasts had low bone mass, whereas mice with either neuron-specific Slit3 deletion or osteoblast-specific Slit3 deletion had normal bone mass, thereby indicating the importance of SLIT3 as a local determinant of bone metabolism. In postmenopausal women, higher circulating SLIT3 levels were associated with increased bone mass. Notably, injection of a truncated recombinant SLIT3 markedly rescued bone loss after an ovariectomy. Thus, these results indicate that SLIT3 plays an osteoprotective role by synchronously stimulating bone formation and inhibiting bone resorption, making it a potential therapeutic target for metabolic bone diseases.
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http://dx.doi.org/10.1172/JCI91086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873876PMC
April 2018

Beneficial Effects of Aerobic Exercise Training Combined with Rosiglitazone on Glucose Metabolism in Otsuka Long Evans Tokushima Fatty Rats.

Diabetes Metab J 2017 Dec 15;41(6):474-485. Epub 2017 Nov 15.

Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea.

Background: Regular aerobic exercise is essential for the prevention and management of type 2 diabetes mellitus and may be particularly beneficial for those treated with thiazolidinediones, since it may prevent associated weight gain. This study aimed to evaluate the effect of combined exercise and rosiglitazone treatment on body composition and glucose metabolism in obese diabetes-prone animals.

Methods: We analyzed metabolic parameters, body composition, and islet profiles in Otsuka Long Evans Tokushima Fatty rats after 28 weeks of aerobic exercise, rosiglitazone treatment, and combined exercise and rosiglitazone treatment.

Results: Combined exercise with rosiglitazone showed significantly less increase in weight and epididymal fat compared to rosiglitazone treatment. Aerobic exercise alone and combined rosiglitazone and exercise treatment led to similar retention of lean body mass. All experimental groups showed a decrease in fasting glucose. However, the combined exercise and rosiglitazone therapy group showed prominent improvement in glucose tolerance compared to the other groups. Rescue of islet destruction was observed in all experimental groups, but was most prominent in the combined therapy group.

Conclusion: Regular aerobic exercise combined with rosiglitazone treatment can compensate for the adverse effect of rosiglitazone treatment and has benefit for islet preservation.
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http://dx.doi.org/10.4093/dmj.2017.41.6.474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741557PMC
December 2017

Lower Trabecular Bone Score in Patients With Primary Aldosteronism: Human Skeletal Deterioration by Aldosterone Excess.

J Clin Endocrinol Metab 2018 02;103(2):615-621

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Context: Despite the potential detrimental effects of aldosterone excess on bone metabolism, discrepancies exist between fracture risk and bone mass in patients with and without primary aldosteronism (PA).

Objective: To clarify the possibility that aldosterone excess might mainly affect bone properties not explained by the bone mineral density (BMD).

Design, Setting, And Patients: Among 625 consecutive patients with newly diagnosed adrenal incidentaloma (AI), 72 with biochemically confirmed PA and 335 with nonfunctional AI were defined as cases and controls, respectively.

Results: In women, although no statistically significant differences in lumbar spine BMD were found between groups, the lumbar spine trabecular bone score (TBS) was significantly lower in patients with PA than in controls after adjustment for confounders (P = 0.007). Consistently, the plasma aldosterone concentration (PAC) correlated inversely with the lumbar spine TBS (P = 0.028) but not with bone mass in women. Compared with women in the lowest PAC quartile, those in the highest PAC quartile had significantly lower lumbar spine TBSs (P = 0.004). Importantly, all these observations in women remained statistically significant after additional adjustment for the lumbar spine BMD in the multivariable model. However, BMD and TBS at the lumbar spine did not differ according to the presence of PA and the level of PAC in men.

Conclusion: These findings provide clinical evidence that aldosterone excess in PA might contribute to deteriorated bone quality through weak microarchitecture, regardless of bone mass, especially in women.
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http://dx.doi.org/10.1210/jc.2017-02043DOI Listing
February 2018

Validation of pathological grading systems for predicting metastatic potential in pheochromocytoma and paraganglioma.

PLoS One 2017 8;12(11):e0187398. Epub 2017 Nov 8.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: The Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP) was proposed for predicting the metastatic potential of pheochromocytoma and paraganglioma to overcome the limitations of the Pheochromocytoma of the Adrenal Scaled Score (PASS). However, to date, no study validating the GAPP has been conducted, and previous studies did not include mutations in the succinate dehydrogenase type B (SDHB) gene in the score calculation. In this retrospective cohort study, we validated the prediction ability of GAPP and assessed whether it would be improved by inclusion of the loss of SDHB immunohistochemical staining.

Methods: We divided the tumors into non-metastatic and metastatic groups based on the presence of synchronous or metachronous metastases. The GAPP score and PASS at the initial operation were measured. Moreover, we combined some GAPP parameters with the immunohistochemical staining of SDHB to obtain a modified GAPP (M-GAPP) score.

Results: Metastasis occurred in 15/72 (20.8%) patients, with a mean follow-up of 43.5 months. Loss of SDHB staining was more frequent (P = 0.044) in the metastatic group. The GAPP score (P = 0.006), PASS (P = 0.003), and M-GAPP score (P<0.001) were all higher in the metastatic group. Twelve of 40 (30.0%) moderately or poorly differentiated tumors, as defined by the GAPP score, and 12/34 (35.3%) tumors with a PASS ≥4 were metastatic. Conversely, 10/19 (52.6%) tumors with an M-GAPP score ≥3 were metastatic. The area under the curve of the M-GAPP score (0.822) was significantly higher than that of the GAPP (0.728) (P = 0.012), but similar to that of the PASS (0.753) (P = 0.411). The GAPP (P = 0.032) and M-GAPP scores (P = 0.040), but not PASS (P = 0.200), negatively correlated with metastasis-free survival.

Conclusion: The GAPP was validated, and M-GAPP, a combination of some GAPP parameters and loss of SDHB staining, might be useful for the prediction of the metastatic potential of pheochromocytoma and paraganglioma.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187398PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678867PMC
November 2017

Free Fatty Acid Receptor 4 Mediates the Beneficial Effects of n-3 Fatty Acids on Body Composition in Mice.

Calcif Tissue Int 2017 12 12;101(6):654-662. Epub 2017 Sep 12.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.

As populations continue to age worldwide, sarcopenic obesity has heightened interest due to its medical importance. Although much evidence now indicates that n-3 fatty acids (FAs) may have beneficial effects on body composition including fat and muscle, their exact mechanisms have not yet been elucidated. Because free FA receptor 4 (FFA4) has been reported to be a receptor for n-3 FAs, we hypothesized that the protective role of n-3 FAs on body composition could be mediated by FFA4. To test this possibility, we generated mice overexpressing n-3 FAs but lacking FFA4 by crossing fat-1 transgenic (fat-1 ) and FFA4 knockout (Ffar4 ) mice. Because fat-1 mice, in which n-6 is endogenously converted into n-3 FAs, contain high n-3 FA levels, they could be a good animal model for studying the effects of n-3 FAs in vivo. Male and female littermates were included in high-fat-diet- (HFD) and ovariectomy-induced models, respectively. In the HFD model, male fat-1 mice had a lower percentage of fat mass and a higher percentage of lean mass than their wild-type littermates only when they had the Ffar4 not the Ffar4 background. Female fat-1 mice showed less increase of fat mass percentage and less decrease of lean mass percentage after ovariectomy than wild-type littermates. However, these effects on body composition were attenuated in the Ffar4 background. Taken together, our results indicate that the beneficial effects of n-3 FAs on body composition were mediated by FFA4 and thus suggest that FFA4 may be a potential therapeutic target for modulating sarcopenic obesity.
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http://dx.doi.org/10.1007/s00223-017-0323-yDOI Listing
December 2017

The Relationship between Subclinical Thyroid Disease and Cardiovascular Disease Risk Score in Koreans.

J Korean Med Sci 2017 Oct;32(10):1626-1632

Department of Biomedical Sciences, Inha University College of Medicine, Incheon, Korea.

Subclinical hyperthyroidism and subclinical hypothyroidism are characterized by abnormal thyroid stimulating hormone (TSH) with normal free thyroxine. Subclinical thyroid diseases, to date, have received less attention compared with other thyroid diseases since they are asymptomatic. This study aimed to verify the association between subclinical thyroid diseases and cardiovascular diseases (CVDs) risk score in the Korean population. This was a population-based cohort study using data collected from 3,722 subjects (aged ≥ 30 years) during the 6th Korea National Health and Nutrition Examination Survey (KNHANES VI; 2013-2015). Gender-specific Framingham risk scores were calculated to identify the association between subclinical thyroid diseases and 10-year CVD risk score. Complex survey, with consideration of sampling weight, was analyzed using generalized linear models after stratification by gender. The TSH reference range was between 0.61 and 6.91 mIU/L in this study. TSH showed a positive association with the 10-year CVD risk score only in the female population (P = 0.001). There were significant differences in the least squares means of 10-year CVD risk score by the effect of subclinical hypothyroidism compared with euthyroidism (normal group) in females, after adjusting for body mass index, white blood cell, and urine iodine (P = 0.006 and Bonferroni corrected P = 0.012). In conclusion, subclinical hypothyroidism is associated with increased 10-year CVD risk score in the female Korean population aged 30 years or more. Therefore, we recommend to clinically checkup major CVD risk factors in female patients with subclinical hypothyroidism aged 30 years or more.
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http://dx.doi.org/10.3346/jkms.2017.32.10.1626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5592176PMC
October 2017

Lower Bone Mass and Higher Bone Resorption in Pheochromocytoma: Importance of Sympathetic Activity on Human Bone.

J Clin Endocrinol Metab 2017 08;102(8):2711-2718

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Context: Despite the apparent biological importance of sympathetic activity on bone metabolism in rodents, its role in humans remains questionable.

Objective: To clarify the link between the sympathetic nervous system and the skeleton in humans.

Design, Setting, And Patients: Among 620 consecutive subjects with newly diagnosed adrenal incidentaloma, 31 patients with histologically confirmed pheochromocytoma (a catecholamine-secreting neuroendocrine tumor) and 280 patients with nonfunctional adrenal incidentaloma were defined as cases and controls, respectively.

Results: After adjustment for confounders, subjects with pheochromocytoma had 7.2% lower bone mass at the lumbar spine and 33.5% higher serum C-terminal telopeptide of type 1 collagen (CTX) than those without pheochromocytoma (P = 0.016 and 0.001, respectively), whereas there were no statistical differences between groups in bone mineral density (BMD) at the femur neck and total hip and in serum bone-specific alkaline phosphatase (BSALP) level. The odds ratio (OR) for lower BMD at the lumbar spine in the presence of pheochromocytoma was 3.31 (95% confidence interval, 1.23 to 8.56). However, the ORs for lower BMD at the femur neck and total hip did not differ according to the presence of pheochromocytoma. Serum CTX level decreased by 35.2% after adrenalectomy in patients with pheochromocytoma, whereas serum BSALP level did not change significantly.

Conclusions: This study provides clinical evidence showing that sympathetic overstimulation in pheochromocytoma can contribute to adverse effects on human bone through the increase of bone loss (especially in trabecular bone), as well as bone resorption.
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http://dx.doi.org/10.1210/jc.2017-00169DOI Listing
August 2017

Replication of Caucasian Loci Associated with Osteoporosis-related Traits in East Asians.

J Bone Metab 2016 Nov 30;23(4):233-242. Epub 2016 Nov 30.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Most reported genome-wide association studies (GWAS) seeking to identify the loci of osteoporosis-related traits have involved Caucasian populations. We aimed to identify the single nucleotide polymorphisms (SNPs) of osteoporosis-related traits among East Asian populations from the bone mineral density (BMD)-related loci of an earlier GWAS meta-analysis.

Methods: A total of 95 SNPs, identified at the discovery stage of the largest GWAS meta-analysis of BMD, were tested to determine associations with osteoporosis-related traits (BMD, osteoporosis, or fracture) in Korean subjects (n=1,269). The identified SNPs of osteoporosis-related traits in Korean subjects were included in the replication analysis using Chinese (n=2,327) and Japanese (n=768) cohorts.

Results: A total of 17 SNPs were associated with low BMD in Korean subjects. Specifically, 9, 6, 9, and 5 SNPs were associated with the presence of osteoporosis, non-vertebral fractures, vertebral fractures, and any fracture, respectively. Collectively, 35 of the 95 SNPs (36.8%) were associated with one or more osteoporosis-related trait in Korean subjects. Of the 35 SNPs, 19 SNPs (54.3%) were also associated with one or more osteoporosis-related traits in East Asian populations. Twelve SNPs were associated with low BMD in the Chinese and Japanese cohorts. Specifically, 3, 4, and 2 SNPs were associated with the presence of hip fractures, vertebral fractures, and any fracture, respectively.

Conclusions: Our results identified the common SNPs of osteoporosis-related traits in both Caucasian and East Asian populations. These SNPs should be further investigated to assess whether they are true genetic markers of osteoporosis.
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http://dx.doi.org/10.11005/jbm.2016.23.4.233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5153380PMC
November 2016

Symptom-dependent cut-offs of urine metanephrines improve diagnostic accuracy for detecting pheochromocytomas in two separate cohorts, compared to symptom-independent cut-offs.

Endocrine 2016 Oct 2;54(1):206-216. Epub 2016 Aug 2.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

The development of advanced imaging techniques has increased the detection of subclinical pheochromocytomas. Because of the substantial proportions of subclinical pheochromocytomas, measurement of urine metanephrine concentrations is crucial due to detect or exclude pheochromocytoma. Although urine metanephrines are elevated in symptomatic subjects, diagnostic cut-offs according to the presence of adrenergic symptoms have not been studied. Pheochromocytomas patients who underwent adrenalectomy at Samsung Medical Center and a control group were compared to determine cut-off concentrations of urine metanephrines. An independent population was analyzed for urine metanephrines with different kits to validate the improvement in diagnostic accuracy using adjusted cut-offs. Symptom-dependent cut-offs of urine metanephrines were higher for symptomatic patients (307 μg/day in males, 235 μg/day in females for urine metanephrine, and 1,045 μg/day in males and 457 μg/day in females for urine normetanephrine) than for asymptomatic patients (206 μg/day in males, 199 μg/day in females for urine metanephrine, and 489 μg/day in males and 442 μg/day in females for urine normetanephrine). Symptom-dependent cut-offs of urine metanephrines improved a specificity from 92.7 % to 96.3 % and a high sensitivity of 97.8 % was maintained. Using the Symptom-dependent cut-offs raised diagnostic accuracy by 5.5 % (p <0.001). Similar trend was also observed in an independent population using different hormone kits. Using symptom-dependent cut-offs of urine metanephrines in symptomatic patients for pheochromocytomas resulted in a significant improvement in diagnostic accuracy in two separate cohorts.
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http://dx.doi.org/10.1007/s12020-016-1049-8DOI Listing
October 2016

The Association of Higher Plasma Macrophage Migration Inhibitory Factor Levels with Lower Bone Mineral Density and Higher Bone Turnover Rate in Postmenopausal Women.

Endocrinol Metab (Seoul) 2016 Sep 26;31(3):454-461. Epub 2016 Jul 26.

Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Despite evidence from animal and clinical studies showing the detrimental effects of macrophage migration inhibitory factor (MIF) on bone metabolism, there are no clinical studies relating circulating MIF levels to osteoporosis-related phenotypes. This cross-sectional study investigated the association of plasma MIF with bone mineral density (BMD), bone turnover markers (BTMs), and prevalence of osteoporosis in postmenopausal Korean women.

Methods: A total of 246 women not taking any medications or diagnosed with any diseases that could affect bone metabolism were enrolled. BMD values at the lumbar spine, femoral neck, and total femur, and blood levels of MIF and BTMs were measured in all subjects. Osteoporosis was defined by World Health Organization criteria.

Results: Before and after adjustment for confounding variables, higher MIF levels were significantly associated with lower BMD values at all measured sites and higher levels of all BTMs. All BMD values and BTMs significantly changed in a dose-dependent fashion across increasing MIF quartile. When participants were divided into two groups according to osteoporosis status, postmenopausal women with osteoporosis demonstrated 24.2% higher plasma MIF levels than those without osteoporosis (P=0.041). The odds ratio per each standard deviation increment of MIF levels for prevalent osteoporosis was 1.32 (95% confidence interval, 1.01 to 1.73).

Conclusion: This study provides the first epidemiological evidence that higher plasma MIF may be associated with higher risk of osteoporosis resulting from lower bone mass and higher bone turnover rate, and thus it could be a potential biomarker of poor bone health outcomes in postmenopausal women.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053059PMC
http://dx.doi.org/10.3803/EnM.2016.31.3.454DOI Listing
September 2016

New diagnostic criteria for subclinical hypercortisolism using postsurgical hypocortisolism: the Co-work of Adrenal Research study.

Clin Endocrinol (Oxf) 2017 Jan 29;86(1):10-18. Epub 2016 Jul 29.

Division of Endocrinology and Metabolism, Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Objective: There is no consensus on the biochemical diagnostic criteria for subclinical hypercortisolism (SH). Using parameters related to the hypothalamic-pituitary-adrenal axis, we aimed to develop a diagnostic model of SH for predicting postsurgical hypocortisolism and metabolic complications.

Design: Prospective and cross-sectional, observational, multicentre study in Korea.

Methods: After exclusion of overt Cushing's syndrome, adrenal incidentaloma (AI) patients who underwent unilateral adrenalectomy (n = 99) and AI patients (n = 843) were included. Primary outcome was defined as the presence of postsurgical hypocortisolism; secondary outcome was the presence of ≥4 complications (components of the metabolic syndrome and low bone mass). Postsurgical hypocortisolism was determined on the fifth postsurgery day using the ACTH stimulation test.

Results: Thirty-three of the 99 patients developed postsurgical hypocortisolism. Analysis of the presurgery overnight 1-mg dexamethasone suppression test (1-mg DST) showed that all patients with cortisol levels of >138 nmol/l experienced postsurgical hypocortisolism, whereas those with levels of ≤61 nmol/l did not. The models of (i) 1-mg DST >138 nmol/l or (ii) >61 nmol/l with the presence of one among low levels of ACTH and dehydroepiandrosterone-sulphate had the highest accuracy (89·9%, P < 0·001) and odds ratio [OR 111·62, 95% confidence interval (CI) 21·98-566·74, P < 0·001] for predicting postsurgical hypocortisolism. Finally, patients with the same criteria in the 843 AI patients showed the highest risk for having ≥4 complications (OR 3·51, 95% CI 1·84-6·69, P < 0·001), regardless of gender, age, body mass index and bilaterality.

Conclusions: Our proposed model is able to accurately predict subtle cortisol excess and its chronic manifestations in AI patients.
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http://dx.doi.org/10.1111/cen.13145DOI Listing
January 2017
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