Publications by authors named "Sung Hye Kong"

34 Publications

The Impact of COVID-19 on the Optimal Management of Osteoporosis.

J Bone Metab 2021 May 31;28(2):115-122. Epub 2021 May 31.

Department of Orthopedic Surgery, Ewha Womans University, College of Medicine, Mokdong Hospital, Seoul, Korea.

Osteoporosis does not take a break while Coronavirus disease 2019 (COVID-19) stunned and overtook everyone's lives. Medical resources were immediately shifted, self-isolation and telemedicine were expanded, ambulatory care services such as bone densitometry and osteoporosis-centered clinics came to a near halt. Progress with fracture prevention has been challenged because osteoporotic fracture with low energy injury is more prevalent even though restriction of people's movement. Thus we must re-engage with chronic bone health concerns and fracture prevention. This review discusses challenges in management of osteoporosis during the COVID-19 pandemic and reinforces the need to implementing recommendations concerning the importance of bone fragility care with at least those patients who are already treated with antiosteoporotic drugs maintaining their adherence to treatments.
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http://dx.doi.org/10.11005/jbm.2021.28.2.115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206610PMC
May 2021

Application of the Trabecular Bone Score in Clinical Practice.

J Bone Metab 2021 May 31;28(2):101-113. Epub 2021 May 31.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

The trabecular bone score (TBS) was introduced as an indirect index of trabecular microarchitecture, complementary to bone mineral density (BMD), and is derived using the same dual energy X-ray absorptiometry images. Recently, it has been approved for clinical use in Korea. Therefore, we conducted a comprehensive review to optimize the use of TBS in clinical practice. The TBS is an independent predictor of osteoporotic fractures in postmenopausal women and men aged >50 years. The TBS is potentially useful in monitoring the skeletal effects of anabolic agents but not of antiresorptive agents. In postmenopausal women with type 2 diabetes mellitus, the TBS assesses osteoporotic fracture risk not captured by BMD. However, high body mass index and soft tissue thickness can cause underestimation of the TBS; however, this limitation has been improved in recent versions of the TBS software. However, a high precision error and low reproducibility limit the use of TBS. This review may provide information on the application of the TBS in clinical practice based on reliable evidence.
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http://dx.doi.org/10.11005/jbm.2021.28.2.101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206609PMC
May 2021

Measurements of Bone Health after Thyroid-Stimulating Suppression Therapy in Postmenopausal Women with Differentiated Thyroid Carcinoma: Bone Mineral Density versus the Trabecular Bone Score.

J Clin Med 2021 May 3;10(9). Epub 2021 May 3.

Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea.

Background: Thyroid-stimulating hormone (TSH) suppression therapy is an important treatment modality for differentiated thyroid carcinoma (DTC), but it increases fracture risk. The aim of this study was to evaluate changes in bone mineral density (BMD) and trabecular bone score (TBS) in postmenopausal DTC patients receiving TSH suppression therapy.

Methods: A total of 410 postmenopausal DTC patients who underwent thyroidectomy and had at least two dual-energy X-ray absorptiometry measurements, including a preoperative measurement, were included. Patients who had osteoporosis medication for more than 1 year were classified as 'patients with osteoporosis'.

Results: In patients without osteoporosis, the change in %BMD was similar between TSH suppression (-) and (+) groups, while the decrease in %TBS was significantly greater in the TSH suppression (+) group than that of the TSH suppression (-) group. The relative risk of vertebral fracture was decreased by TBS changes but not by BMD changes. In patients with osteoporosis, both BMD and TBS showed significant increases in the TSH suppression (-) group but not in TSH suppression (+) group. At year 4, TBS was significantly lower in the TSH suppression (+) group than that in the TSH suppression (-) group, while BMD showed no difference between groups.

Conclusions: TBS may better reflect bone health than BMD in postmenopausal DTC patients with TSH suppression therapy.
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http://dx.doi.org/10.3390/jcm10091964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125563PMC
May 2021

Long-term Outcome of Microscopic Transsphenoidal Surgery for Prolactinomas as an Alternative to Dopamine Agonists.

J Korean Med Sci 2021 Apr 19;36(15):e97. Epub 2021 Apr 19.

Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea.

Background: Although long-term dopamine agonist (DA) therapy is recommended as a first-line treatment for prolactinoma, some patients may prefer surgical treatment because of the potential adverse effects of long-term medication, or the desire to become pregnant. This study aimed to determine whether surgical treatment of prolactinomas could be an alternative to DA therapy.

Methods: In this retrospective study, 96 consecutive patients (74 female, 22 male) underwent primary pituitary surgery without long-term DA treatment for prolactinomas at a single institution from 1990 to 2010. All patients underwent primary surgical treatment in the microscopic transsphenoidal approach (TSA).

Results: The median age and median follow-up period were 31 (16-73) years and 139.1 (12.2-319.6) months, respectively. An initial overall remission was accomplished in 47.9% (46 of 96 patients, 33 macroadenomas, and 13 microadenomas) of patients. DA dose reduction was achieved in all patients after TSA. A better remission rate was independently predicted by lower diagnostic prolactin levels and by a greater extent of surgical resection. Overall remission at the last follow-up was 33.3%, and the overall recurrence rate was 30.4%. The permanent complication rate was 3.1%, and there was no mortality.

Conclusion: TSA can be considered a safe and potentially curative treatment for selective microprolactinomas as an alternative to treatment with a long-term DA.
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http://dx.doi.org/10.3346/jkms.2021.36.e97DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055511PMC
April 2021

Radioactive Parathyroid Adenomas on Sestamibi Scans: Low Parathyroid Hormone Secretory Potential and Large Volume.

Endocrinol Metab (Seoul) 2021 Apr 6;36(2):351-358. Epub 2021 Apr 6.

Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Background: We investigated the clinical characteristics of parathyroid adenomas according to radioactivity on 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) in primary hyperparathyroidism (PHPT) patients.

Methods: The study included 217 patients diagnosed with PHPT from 2000 to 2019 at Seoul National University Hospital who underwent 99mTc-MIBI SPECT/CT scans. On SPECT/CT, the radioactivity of parathyroid adenomas was measured as the ratio of the mean radioactivity count of the parathyroid adenoma to that of the contralateral thyroid.

Results: Tumors were localized by MIBI scans in 190 patients (MIBI [+] group) and by ultrasound or parathyroid four-dimensional CT in 27 patients (MIBI [-] group). The mean age was 55 years, and mean body mass index was 23.4 kg/m2. Patients in the MIBI (+) group had higher parathyroid hormone (iPTH) and lower 25-hydroxy vitamin D levels than those in the MIBI (-) group (168.0 pg/mL [interquartile range, IQR, 111.0 to 250.7] vs. 134.7 pg/mL [IQR, 98.2 to 191.2], P=0.049; 15.4 ng/mL [IQR, 11.1 to 20.8] vs. 21.2 ng/mL [IQR, 13.9 to 24.8], P=0.012, respectively). Patients in the MIBI (+) group had larger tumor volumes, but lower iPTH/volume ratios than those in the MIBI (-) group (1,216.66 [IQR, 513.40 to 2,663.02], 499.82 mm3 [IQR, 167.77 to 1,229.80], P=0.002; 0.18 [IQR, 0.08 to 0.46], 0.40 pg/mL/mm3 [IQR, 0.16 to 1.29], P=0.016, respectively). Adenoma radioactivity was positively correlated with calcium, iPTH, and volume (r=0.180, P=0.020; r=0.208, P=0.006; r=0.288, P<0.001, respectively), but not with iPTH/volume.

Conclusion: Parathyroid adenomas with positive MIBI scans had larger volumes and higher iPTH than adenomas with negative scans, but lower iPTH per unit volume.
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http://dx.doi.org/10.3803/EnM.2020.823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090467PMC
April 2021

Epidemiology and prognosis of parathyroid carcinoma: real-world data using nationwide cohort.

J Cancer Res Clin Oncol 2021 Mar 18. Epub 2021 Mar 18.

Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.

Purpose: Parathyroid carcinoma (PC) is an exceedingly rare endocrine malignancy with a poor prognosis. Due to the rarity, the natural course and prognostic factors of the disease are yet unclear. Therefore, we aimed to identify the incidence, prognosis, and prognostic factors of PC in the nationwide cohort study.

Methods: The study is a nationwide study using the National Health Insurance Services database in Korea from 2002 to 2017. PC was defined as patients with ICD-10 code of PC and a procedural code for parathyroidectomy.

Results: From 2002 to 2017, 255 patients were diagnosed with PC whose mean age was 53.2 years, and 155 (60.2%) were women. The crude and age-standardized incidence were 10.2 and 6.6/10,000,000 person-year in 2016, rising from 4.1 and 3.8/10,000,000 person-year in 2003 (p < 0.001), respectively. The 5- and 10-year survival rates were 86.5 and 72.9%, respectively. In survival analysis, age over 50 years, thyroidectomy at the initial surgery, and reoperation had increased risk of mortality with HRs of 4.83 (95% CI 1.47-15.90), and 4.21 (95% CI 1.60-11.08), and 1.05 (95% CI 1.02-1.08) in multivariate analysis, respectively.

Conclusion: Incidence of PC has been rising over time, similar to the trends in Western countries. The prognostic factors for mortality were old age, parathyroidectomy alone, and recurrence, emphasizing the importance of preoperative suspicion of the disease. The study is clinically meaningful in the first Asian nationwide study to reveal the natural course of PC.
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http://dx.doi.org/10.1007/s00432-021-03576-9DOI Listing
March 2021

Metabolic changes in serum steroids for diagnosing and subtyping Cushing's syndrome.

J Steroid Biochem Mol Biol 2021 Jun 26;210:105856. Epub 2021 Feb 26.

Molecular Recognition Research Center, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea; Department of Chemistry, Korea University, Seoul 02841, Republic of Korea. Electronic address:

To evaluate the diagnostic value of serum levels of adrenal steroids for diagnosing and subtyping Cushing's syndrome. Patients diagnosed with endogenous Cushing's syndrome (34 and 19 patients with adrenal and pituitary Cushing's syndrome, respectively) and healthy controls (n = 34) were consecutively enrolled at Seoul National University from 2016 to 2020. Morning serum samples were collected before and 3 months after treatment. Serum steroids were profiled using liquid chromatography-mass spectrometry. The diagnostic value of each and the combination of steroids were assessed using the area under the curve of receiver operating characteristic (AUROC) and decision tree analysis. Tetrahydrocortisone and 6β-hydroxycortisol showed the highest AUROC (0.893 and 0.890, respectively) for the diagnosis of endogenous Cushing's syndrome. The decision tree composed of tetrahydrocortisone and 6β-hydroxycortisol correctly classified 79/87 (90.8 %) subjects. For subtyping into adrenal or pituitary Cushing's syndrome, dehydroepiandrosterone sulfate (DHEA-S) showed the highest AUROC (0.988), which was similar to that of plasma ACTH (0.994, P = 0.458). The decision tree composed of only DHEA-S correctly classified 51/53 (96.2 %) of the Cushing's syndrome subtype. DHEA-S showed a significant linear correlation with the plasma ACTH level, but not with the 24 -h urine free cortisol or dexamethasone suppression test results. All steroids, except allo-tetrahydrocortisol and tetrahydrocortisone, decreased significantly at 3 months post-treatment with similar patterns in both adrenal and pituitary Cushing's syndrome. Serum steroid profiling using a single morning serum sample provides valuable information for diagnosing and subtyping Cushing's syndrome.
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http://dx.doi.org/10.1016/j.jsbmb.2021.105856DOI Listing
June 2021

Identification of Novel Genetic Variants Related to Trabecular Bone Score in Community-Dwelling Older Adults.

Endocrinol Metab (Seoul) 2020 12 24;35(4):801-810. Epub 2020 Nov 24.

Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Background: As the genetic variants of trabecular bone microarchitecture are not well-understood, we performed a genome-wide association study to identify genetic determinants of bone microarchitecture analyzed by trabecular bone score (TBS).

Methods: TBS-associated genes were discovered in the Ansung cohort (discovery cohort), a community-based rural cohort in Korea, and then validated in the Gene-Environment Interaction and Phenotype (GENIE) cohort (validation cohort), consisting of subjects who underwent health check-up programs. In the discovery cohort, 2,451 participants were investigated for 1.42 million genotyped and imputed markers.

Results: In the validation cohort, identified as significant variants were evaluated in 2,733 participants. An intronic variant in iroquois homeobox 3 (IRX3), rs1815994, was significantly associated with TBS in men (P=3.74E-05 in the discovery cohort, P=0.027 in the validation cohort). Another intronic variant in mitogen-activated protein kinase kinase 5 (MAP2K5), rs11630730, was significantly associated with TBS in women (P=3.05E-09 in the discovery cohort, P=0.041 in the validation cohort). Men with the rs1815994 variant and women with the rs11630730 variant had lower TBS and lumbar spine bone mineral density. The detrimental effects of the rs1815994 variant in men and rs11630730 variant in women were also identified in association analysis (β=-0.0281, β=-0.0465, respectively).

Conclusion: In this study, the rs1815994 near IRX3 in men and rs11630730 near MAP2K5 in women were associated with deterioration of the bone microarchitecture. It is the first study to determine the association of genetic variants with TBS. Further studies are needed to confirm our findings and identify additional variants contributing to the trabecular bone microarchitecture.
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http://dx.doi.org/10.3803/EnM.2020.735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803610PMC
December 2020

Characteristics of germline mutations in Korean patients with pheochromocytoma/paraganglioma.

J Med Genet 2020 Nov 20. Epub 2020 Nov 20.

Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea (the Republic of)

Background: Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing neuroendocrine tumours. PPGLs are a rare but important cause of secondary hypertension owing to their high morbidity and mortality. Patients with PPGL exhibit an increased prevalence of mutations in one of the PPGL susceptibility genes according to previous studies. We aimed to investigate the characteristics of germline mutations in the largest number of Korean patients with PPGL.

Methods: In this study, 161 patients with PPGL were evaluated. Phenotype data, including biochemical, pathological and anatomical imaging results, were collected. Germline mutations in 10 PPGL-related genes were tested by targeted next-generation sequencing (NGS), Sanger sequencing and multiplex ligation-dependent probe amplification.

Results: Approximately 21% of apparently sporadic PPGLs harboured germline mutations of the PPGL-related genes. The mutation carriers were younger at the first diagnosis and had more bilateral (28.6% vs 4.0%, p<0.001) and multifocal (11.4% vs 1.6%, p=0.027) PPGLs, but showed no metastatic risk (17.1% vs 11.1%, p=0.504), than non-mutation carriers. Missense mutation of p.V111I was found in this cohort of Asian patients, which was associated with unilateral pheochromocytoma with dominantly epinephrine production.

Conclusion: This study covered the largest number of Korean patients with PPGL. To our knowledge, it is the first to compare results of targeted NGS panel with those of conventional sequencing methods in Asia. We demonstrated that the variant type, as well as the mutated gene, may determine the phenotype and prognosis of PPGLs.
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http://dx.doi.org/10.1136/jmedgenet-2020-107102DOI Listing
November 2020

Serum Spermidine as a Novel Potential Predictor for Fragility Fractures.

J Clin Endocrinol Metab 2021 Jan;106(2):e582-e591

Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.

Context: Metabolomics is an emerging tool that provides insights into the dynamics of phenotypic changes. It is a potential method for the discovery of novel serum markers of fracture.

Objective: To identify metabolite parameters that can be used as a proxy for osteoporotic fracture risk.

Design: Prospective study based on the Ansung cohort in Korea.

Setting: The general community.

Participants: A total of 1504 participants with metabolomic analyses.

Interventions: None.

Main Outcome Measure: Fragility fractures.

Results: We measured 135 baseline metabolite profiles in fasting serum of the participants. The participants had a mean age of 60.2 years and were comprised of 585 (38.9%) men. During a mean 9-year follow-up, 112 osteoporotic fracture events occurred. Of all metabolites measured, only serum spermidine concentrations were positively associated with the risk of fracture (hazard ratio [HR] per 1 μM of spermidine 1.35, 95% confidence interval [CI] = 1.03-1.65, P = 0.020) after adjusting for age, sex, body mass index, diabetes, hypertension, smoking status, previous fracture history, and baseline tibial quantitative ultrasound. Participants with spermidine concentrations >1.57 μM had a 2.2-fold higher risk of fractures (95% CI 1.08-4.51, P = 0.030) compared with those with concentrations ≤1.57 μM after adjustment. In a subgroup analysis, women with baseline spermidine concentrations >1.57 μM also had a 2.4-fold higher risk of fracture than those with concentrations ≤1.57 μM (95% CI 1.02-5.48, P = 0.047).

Conclusions: Increased baseline spermidine concentrations were associated with a risk of osteoporotic fracture during a mean 9-year follow-up. The biological significance of the metabolites in the musculoskeletal system could be a subject for future studies.
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http://dx.doi.org/10.1210/clinem/dgaa745DOI Listing
January 2021

Contralateral adrenal thinning as a distinctive feature of mild autonomous cortisol excess of the adrenal tumors.

Eur J Endocrinol 2020 Sep;183(3):325-333

Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.

Objective: To identify radiologic features that correlate with mild autonomous cortisol excess using planar and volumetric analysis.

Design: Cross-sectional study.

Methods: In the study, 64 patients with overt Cushing syndrome (CS), 59 patients with mild autonomous cortisol excess (MACE), and 64 patients with nonfunctioning adrenal tumors (NFAT) with evaluable CT scans were included. Patients with NFAT and MACE were BMI-matched with those with overt CS. Planar and volumetric analyses of CT scans were performed in DICOM images using OsiriX software.

Results: The mean age was 56.6 ± 1.01 years, and 123 patients (65.1%) were female. In the order of NFAT, MACE, and overt CS, the diameters and volumes of the adenoma increased, while limb widths and volumes of the contralateral adrenal gland decreased. Patients with MACE or overt CS were more likely to have osteoporosis than those with NFAT (P = 0.006), and patients with overt CS were more likely to experience a fragility fracture than those with NFAT or MACE (P = 0.002). Among radiologic features, the limb width of the contralateral adrenal gland correlated with the cortisol level after overnight dexamethasone suppression test (r = -0.583, P < 0.001).

Conclusions: The study showed that the contralateral adrenal limb thinning was a distinctive radiologic feature of autonomous cortisol excess in the planar and volumetric analysis.
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http://dx.doi.org/10.1530/EJE-20-0301DOI Listing
September 2020

Subclinical Hypothyroidism Affects the Long-Term Outcomes of Patients Who Undergo Coronary Artery Bypass Grafting Surgery but Not Heart Valve Surgery.

Endocrinol Metab (Seoul) 2020 06 24;35(2):308-318. Epub 2020 Jun 24.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.

Background: The aim of this study was to determine the associations between subclinical hypothyroidism (SCH) and long-term cardiovascular outcomes after coronary artery bypass grafting (CABG) or heart valve surgery (HVS).

Methods: We retrospectively reviewed and compared all-cause mortality, cardiovascular mortality, and cardiovascular events in 461 patients who underwent CABG and 104 patients who underwent HVS.

Results: During a mean±standard deviation follow-up duration of 7.6±3.8 years, there were 187 all-cause deaths, 97 cardiovascular deaths, 127 major adverse cardiovascular events (MACE), 11 myocardial infarctions, one unstable angina, 70 strokes, 30 hospitalizations due to heart failure, 101 atrial fibrillation, and 33 coronary revascularizations. The incidence of all-cause mortality after CABG was significantly higher in patients with SCH (n=36, 55.4%) than in euthyroid patients (n=120, 30.3%), with a hazard ratio of 1.70 (95% confidence interval, 1.10 to 2.63; P=0.018) after adjustment for age, sex, current smoking status, body mass index, underlying diseases, left ventricular dysfunction, and emergency operation. Interestingly, low total triiodothyronine (T3) levels in euthyroid patients who underwent CABG were significantly associated with increased risks of all-cause mortality, cardiovascular mortality, and MACE, but those associations were not observed in HVS patients. Both free thyroxine and thyroid-stimulating hormone levels in euthyroid patients were not related with any cardiovascular outcomes in either the CABG or HVS group.

Conclusion: SCH or low total T3 might be associated with a poor prognosis after CABG, but not after HVS, implying that preoperative thyroid hormonal status may be important in ischemic heart disease patients.
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http://dx.doi.org/10.3803/EnM.2020.35.2.308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386124PMC
June 2020

Bone health in neuromyelitis optica: Bone mineral density and fractures.

Mult Scler Relat Disord 2020 Jul 28;42:102080. Epub 2020 Apr 28.

Department of Neurology, Seoul National University Bundang Hospital, Gyeonggi, Republic of Korea; Department of Neurology, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: The bone health in neuromyelitis optica spectrum disorder with aquaporin-4 immunoglobulin G antibodies (NMOSD-AQP4) have not been fully evaluated. To evaluate the prevalence of fractures and bone loss in patients with NMOSD-AQP4 compared to healthy controls and patients with multiple sclerosis (MS) and to identify the risk factors associated with fractures and low bone mineral density (BMD) in patients with NMOSD-AQP4.

Methods: Seventy-one patients with NMOSD-AQP4 were included. The two control groups consisted of 213 age-, sex-, menopause-, and body mass index (BMI)-matched healthy participants from the Korean National Health and Nutrition Examination Survey (healthy controls) and 41 patients with multiple sclerosis (disease controls). We collected demographic and clinical data related to bone health including BMD and FRAX score.

Results: Patients with NMOSD-AQP4 had a higher prevalence of fractures than the healthy control group (OR = 5.40, CI = 2.004-14.524, p = 0.001), with falling, but not steroid use, being associated with an increased risk of fractures after diagnosis with NMOSD-AQP4 (OR = 24.902, CI = 3.086-200.947, p = 0.003). They also had significantly lower BMD than controls (femur neck, p = 0.044; total hip, p < 0.001), which was more prominent in young participants. The BMD in the NMOSD-AQP4 group was associated with cumulative dose of oral steroids, age, sex, BMI, and partly with the prophylactic calcium supplements. Though the patients with NMOSD-AQP4 did not differ significantly from patients with MS in terms of fracture rate and BMD, they had higher risk of fractures as measured by the Fracture Risk Assessment Tool (for major osteoporotic fractures, (p = 0.001; for hip fractures, p = 0.018).

Conclusion: Patients with NMOSD-AQP4 had a significantly higher risk of fractures that could mostly be attributed to falling. Additionally, low BMD was observed in these patients; it was more prominent among young patients, associated with steroid use, and may partially prevented by the use of prophylactic calcium supplements.
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http://dx.doi.org/10.1016/j.msard.2020.102080DOI Listing
July 2020

Aromatase inhibitors attenuate the effect of alendronate in women with breast cancer.

J Bone Miner Metab 2020 Sep 13;38(5):730-736. Epub 2020 May 13.

Department of Internal Medicine, Seoul National University College of Medicine, 101 Dae-hak ro, Jongno gu, Seoul, 03080, Republic of Korea.

Introduction: Aromatase inhibitors are known to accelerate bone loss in patients with breast cancer. However, how much AIs affect the efficacy of antiresorptive agents has not been studied. The study aimed to compare the effect of alendronate on bone mineral density (BMD) between patients with and without AI treatment.

Materials And Methods: In this retrospective study, 90 postmenopausal women with early breast cancer who were being treated with both AI and alendronate 70 mg weekly (ALN + AI), and 90 age- and body mass index (BMI)-matched patients who were only taking alendronate (ALN-only) were analyzed. BMD and bone turnover markers (BTMs) were assessed at the baseline and 12 months.

Results: The mean age was 63 years. At baseline, the ALN-only group had lower lumbar spine (LS), femur neck (FN), and total hip (TH) BMD than ALN + AI group. After 1-year of alendronate treatment, the LS and FN BMD were improved more in the ALN-only group than those in the ALN + AI group after adjustments for age, BMI, baseline BMD, diabetes, hypertension, renal function, and previous fracture history [LS BMD: 6.2% (3.1%; 9.2%) in ALN-only, 3.5% (-0.5%; 6.5%) in ALN + AI, p = 0.001; FN BMD: 2.5% (0.3%; 5.7%) in ALN-only, 0.9% (- 1.8%; 3.6%) in ALD + AI, p = 0.032]. BTMs were significantly decreased in both groups, but the changes between groups were similar.

Conclusion: The effect of alendronate on the LS and FN BMD was attenuated in postmenopausal women who were taking AI compared to those who were not on AI.
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http://dx.doi.org/10.1007/s00774-020-01111-3DOI Listing
September 2020

Protein Expression of Cyclin B1, Transferrin Receptor, and Fibronectin Is Correlated with the Prognosis of Adrenal Cortical Carcinoma.

Endocrinol Metab (Seoul) 2020 03;35(1):132-141

Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Background: Adrenal cortical carcinoma (ACC) is a rare cancer with a variable prognosis. Several prognostic factors of ACC have been previously reported, but a proteomic analysis has not yet been performed. This study aimed to investigate prognostic biomarkers for ACC using a proteomic approach.

Methods: We used reverse-phase protein array data from The Cancer Proteome Atlas, and identified differentially expressed proteins in metastatic ACCs. Multivariate Cox regression analysis adjusted by age and staging was used for survival analysis, and the C-index and category-free net reclassification improvement (cfNRI) were utilized to evaluate additive prognostic value.

Results: In 46 patients with ACC, cyclin B1, transferrin receptor (TfR1), and fibronectin were significantly overexpressed in patients with distant metastasis. In multivariate models, high expression of cyclin B1 and TfR1 was significantly associated with mortality (hazard ratio [HR], 6.13; 95% confidence interval [CI], 1.02 to 36.7; and HR, 6.59; 95% CI, 1.14 to 38.2; respectively), whereas high fibronectin expression was not (HR, 3.92; 95% CI, 0.75 to 20.4). Combinations of high cyclin B1/high TfR1, high cyclin B1/high fibronectin, and high TfR1/high fibronectin were strongly associated with mortality ([HR, 13.72; 95% CI, 1.89 to 99.66], [HR, 9.22; 95% CI, 1.34 to 63.55], and [HR, 18.59; 95% CI, 2.54 to 135.88], respectively). In reclassification analyses, cyclin B1, TfR1, fibronectin, and combinations thereof improved the prognostic performance (C-index, 0.78 to 0.82-0.86; cfNRI, all values <0.05).

Conclusion: In ACC patients, the overexpression of cyclin B1, TfR1, and fibronectin and combinations thereof were associated with poor prognosis.
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http://dx.doi.org/10.3803/EnM.2020.35.1.132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090291PMC
March 2020

A Novel Fracture Prediction Model Using Machine Learning in a Community-Based Cohort.

JBMR Plus 2020 Mar 10;4(3):e10337. Epub 2020 Feb 10.

Department of Internal Medicine Seoul National University College of Medicine Seoul Republic of Korea.

The prediction of fracture risk in osteoporotic patients has been a topic of interest for decades, and models have been developed for the accurate prediction of fracture, including the fracture risk assessment tool (FRAX). As machine-learning methodologies have recently emerged as a potential model for medical prediction tools, we aimed to develop a novel fracture prediction model using machine-learning methods in a prospective community-based cohort. In this study, 2227 participants (1257 females) with a baseline bone mineral density (BMD) and trabecular bone score were enrolled from the Ansung cohort. The primary endpoint was the fragility fractures reported by patients or confirmed by X-rays. We used 3 different models: CatBoost, support vector machine (SVM), and logistic regression. During a mean 7.5-year follow-up (range, 2.5 to 10 years), fragility fractures occurred in 537 (25.6%) of participants. In predicting total fragility fractures, the area under the curve (AUC) values of the CatBoost, SVM, and logistic regression models were 0.688, 0.500, and 0.614, respectively. The AUC value of CatBoost was significantly better than that of FRAX (0.663;  < 0.001), whereas the the SVM and logistic regression models were not. Compared with the conventional models such as SVM and logistic regression, the CatBoost model had the best performance in predicting total fragility fractures ( < 0.001). According to feature importance in the CatBoost model, the top predicting factors (listed in order) were total hip, lumbar spine, and femur neck BMD, subjective arthralgia score, serum creatinine, and homocysteine. The latter three factors were listed higher than conventional predictors such as age or previous fracture history. In summary, we hereby report the development of a prediction model for fragility fractures using a machine-learning method, CatBoost, which outperforms the FRAX model as well as two conventional machine-learning models. The model was also able to propose novel high-ranking predictors. © 2020 The Authors. published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbm4.10337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059838PMC
March 2020

Longitudinal Assessment of Quality of Life According to Treatment Options in Low-Risk Papillary Thyroid Microcarcinoma Patients: Active Surveillance or Immediate Surgery (Interim Analysis of MAeSTro).

Thyroid 2019 08 12;29(8):1089-1096. Epub 2019 Jul 12.

1Department of Internal Medicine, Seoul National University Hospital and College of Medicine, Seoul, Republic of Korea.

In this ongoing multicenter prospective cohort study on active surveillance (AS) in low-risk papillary thyroid microcarcinoma (PTMC), we aimed to compare the quality of life (QoL) of participants based on their choice of treatment, that is, AS or immediate surgery (OP). QoL of 203 participants who chose AS and 192 participants who underwent OP was evaluated using a thyroid-specific QoL questionnaire at diagnosis and during follow-up (median 8 months). The mean ages of the participants in the AS and OP groups were 47.3 ± 11.7 and 45.6 ± 10.5 years ( = 0.138), respectively, and the mean tumor sizes were 5.7 ± 1.6 and 6.5 ± 2.1 mm ( = 0.065), respectively. At baseline, significantly better psychological health (7.1 ± 1.3 vs. 6.8 ± 1.6,  = 0.023) and overall health (6.8 ± 1.2 vs. 6.5 ± 1.3,  = 0.018) were observed in the AS group than in the OP group. During follow-up, significantly better physical (7.9 ± 1.1 vs. 7.4 ± 1.2,  < 0.001), psychological (7.4 ± 1.3 vs. 6.9 ± 1.6,  = 0.004), and overall health (6.9 ± 1.0 vs. 6.5 ± 1.1,  = 0.002) were observed in the AS group than in the OP group, whereas spiritual health was comparable between the two groups. Compared with the AS group, the OP group experienced more fatigue, changes in voice and appearance, less satisfaction, and low fear of recurrence. The self-assessed financial burden was similar at baseline and follow-up in both groups. The QoL of PTMC patients is different according to the type of treatment. Better psychological health at baseline and physical and psychological health at follow-up were observed in the AS group than in the OP group. However, studies with longer follow-up periods are needed.
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http://dx.doi.org/10.1089/thy.2018.0624DOI Listing
August 2019

Dehydroepiandrosterone Sulfate and Free Testosterone but not Estradiol are Related to Muscle Strength and Bone Microarchitecture in Older Adults.

Calcif Tissue Int 2019 Sep 4;105(3):285-293. Epub 2019 Jun 4.

Department of Preventive Medicine, Ajou University School of Medicine, #5 Wonchon-Dong, Youngtong-Gu, Suwon, 443-721, South Korea.

The study aimed to elucidate the relationship between sex steroids and muscle mass, muscle strength, and trabecular bone score (TBS) in a community-dwelling aged population. We analyzed 922 men > 60 years of age and 1244 postmenopausal women. Weak muscle strength was defined as hand grip strength < 26 kg for men and < 18 kg for women, whereas degraded bone microarchitecture was defined as a TBS ≤ 1.2. The mean age was 70.2 ± 6.8 years for men and 71.2 ± 6.7 years for women. Participants within higher dehydroepiandrosterone sulfate (DHEAS) and free testosterone (FT) tertiles were likely to be younger, have greater muscle mass, and have stronger hand grip strength. Based on logistic regression models, men within the lowest FT tertile had weaker muscle strength compared to those in the highest tertile (adjusted odds ratio [OR] 2.28; 95% confidence interval [CI] 1.33-3.91). Women within the lowest DHEAS and FT tertile had weaker muscle strength compared to those in the highest tertile (adjusted OR for DHEAS 1.42; 95% CI 1.02-1.99; adjusted OR for FT 1.77, 95% CI 1.26-2.48). Moreover, men within the lowest FT tertile exhibited degraded bone microarchitecture compared to those in the highest tertile (adjusted OR 2.57, 95% CI 1.46-4.51). However, estradiol was not related to muscle strength or bone microarchitecture in both sexes. In conclusion, in aged men, serum FT was closely associated with muscle strength and bone microarchitecture and in postmenopausal women, serum DHEAS and FT were related to muscle strength.
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http://dx.doi.org/10.1007/s00223-019-00566-5DOI Listing
September 2019

Effects of Dapagliflozin on Endothelial Function, Renal Injury Markers, and Glycemic Control in Drug-Naïve Patients with Type 2 Diabetes Mellitus.

Diabetes Metab J 2019 Oct 20;43(5):711-717. Epub 2019 Mar 20.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Background: The study aimed to evaluate the effects of dapagliflozin and metformin on vascular endothelial function and renal injury markers.

Methods: This prospective, randomized, open-label, crossover study included drug-naïve patients with type 2 diabetes mellitus, who were randomized to receive 8 weeks of initial treatment using metformin or dapagliflozin and crossed over for another 8 weeks of treatment after a 1-week washout period. Systemic endothelial function was evaluated via the reactive hyperemic index (RHI).

Results: The 22 participants included 10 males (45.5%) and had a median age of 58 years. The RHI values were not significantly changed during both 8-week treatment periods and there was no significant difference between the treatments. Relative to the metformin group, 8 weeks of dapagliflozin treatment produced significantly higher median -acetyl-beta-D-glucosaminidase levels (10.0 ng/mL [interquartile range (IQR), 6.8 to 12.1 ng/mL] vs. 5.6 ng/mL [IQR, 3.8 to 8.0 ng/mL], =0.013). Only the dapagliflozin group exhibited improved homeostatic model assessment of insulin resistance and body weight, while serum ketone and β-hydroxybutyrate levels increased.

Conclusion: Dapagliflozin treatment did not affect systemic endothelial function or renal injury markers except -acetyl-beta-D-glucosaminidase.
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http://dx.doi.org/10.4093/dmj.2018.0208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834840PMC
October 2019

Subclinical Hypothyroidism and Coronary Revascularization After Coronary Artery Bypass Grafting.

Am J Cardiol 2018 12 7;122(11):1862-1870. Epub 2018 Sep 7.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. Electronic address:

We aimed to investigate long-term cardiovascular sequelae after coronary artery bypass grafting (CABG) in patients with subclinical hypothyroidism (SCH). All-cause and cardiovascular-related mortality, and cardiovascular events were retrospectively reviewed in 222 euthyroid and 36 SCH patients who underwent CABG. During a mean follow-up period of 8.2 ± 4.1 years, there were 90 incidents of all-cause deaths, 20 cardiovascular-related deaths, 70 major cardiovascular adverse events, 6 myocardial infarctions, 12 unstable anginas, 31 strokes, 23 hospitalizations due to heart failure, 15 atrial fibrillation (AF) events, and 27 coronary revascularizations. The incidence rate of coronary revascularization was significantly higher in patients with SCH (n = 6, 16.6%) than in euthyroid patients (n = 20, 9.0%), with a hazard ratio (HR) of 3.179 (95% confidence interval [CI] 1.174, 8.605; p = 0.023) after adjustment. In subgroup analysis, SCH patients who experienced postoperative AF within 3 months after CABG surgery had a significantly higher risk of coronary revascularization (n = 4, 25.0%) than euthyroid patients without AF (n = 14, 8.9%) after adjustment (HR 11.759, 95% CI 2.747, 50.343, p = 0.001). The frequency of fatal or nonfatal unstable angina was also higher in patients with SCH (n = 2, 12.5%) than in euthyroid patients (n = 4, 2.5%) (HR 16.999, 95% CI 2.242, 128.860, p = 0.006). In conclusion, preoperative SCH is associated with less favorable cardiovascular outcomes, especially coronary revascularization after CABG. Moreover, SCH patients who develop postoperative AF exhibit significantly increased risks of unstable angina and coronary revascularization. Preoperative evaluation of thyroid function may be helpful for predicting long-term outcomes after CABG.
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http://dx.doi.org/10.1016/j.amjcard.2018.08.029DOI Listing
December 2018

Relation of Subclinical Hypothyroidism is Associated With Cardiovascular Events and All-Cause Mortality in Adults With High Cardiovascular Risk.

Am J Cardiol 2018 08 16;122(4):571-577. Epub 2018 May 16.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

The aim of this study was to determine the association between subclinical hypothyroidism and cardiovascular (CVD) events, and mortality using the atherosclerotic CVD risk score. We carried out an observational study in a prospective cohort that was followed up for 12 years. The study included 3,021 participants aged ≥ 40 years at baseline from the Ansung cohort, part of the Korean Genome and Epidemiology Study. Cox regression models were constructed to evaluate the hazards ratio (HR) and 95% confidence interval (CI) for all-cause mortality and CVD events in groups classified according to thyroid status. Subgroup analysis was performed with a cut-off age of 65 years or 7.5% of the 10-year atherosclerotic CVD risk score. The subclinical hypothyroidism group in the highest quartile of thyroid-stimulating hormone (>6.57 mIU/L) had a significantly increased risk of all-cause mortality (HR 2.12, 95% CI 1.27 to 3.56) and CVD events (HR 1.92, 95% CI 1.21 to 3.04) compared with euthyroid participants. Subgroup analysis by CVD risk revealed that participants with high CVD risk only had a high risk of all-cause mortality (HR 2.18, 95% CI 1.22 to 3.87) and CVD events (HR 2.42, 95% CI 1.35 to 4.33). Further analysis showed that participants aged <65 years with high CVD risk had the highest risk of all-cause mortality (HR 3.50, 95% CI 1.50 to 8.16) and CVD events (HR 3.37, 95% CI 1.46 to 9.57). Our results demonstrated that high thyroid-stimulating hormone levels were associated with a greater risk of mortality and new CVD risks, particularly among subjects with high CVD risk.
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http://dx.doi.org/10.1016/j.amjcard.2018.03.371DOI Listing
August 2018

Study Protocol of Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro).

Endocrinol Metab (Seoul) 2018 Jun;33(2):278-286

Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Background: The ongoing Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) aims to observe the natural course of papillary thyroid microcarcinoma (PTMC), develop a protocol for active surveillance (AS), and compare the long-term prognosis, quality of life, and medical costs between the AS and immediate surgery groups.

Methods: This multicenter prospective cohort study of PTMC started in June 2016. The inclusion criteria were suspicious of malignancy or malignancy based on fine needle aspiration or core needle biopsy, age of ≥18 years, and a maximum diameter of ≤1 cm. If there was no major organ involvement, no lymph node/distant metastasis, and no variants with poor prognosis, the patients were explained of the pros and cons of immediate surgery and AS before selecting AS or immediate surgery. Follow-up visits (physical examination, ultrasonography, thyroid function, and questionnaires) are scheduled every 6 months during the first 2 years, and then every 1 year thereafter. Progression was defined as a maximum diameter increase of ≥3, ≥2 mm in two dimensions, suspected organ involvement, or lymph node/distant metastasis.

Results: Among 439 enrolled patients, 290 patients (66.1%) chose AS and 149 patients (33.9%) chose immediate surgery. The median follow-up was 6.7 months (range, 0.2 to 11.9). The immediate surgery group had a larger maximum tumor diameter, compared to the AS group (7.1±1.9 mm vs. 6.6±2.0 mm, respectively; P=0.014).

Conclusion: The results will be useful for developing an appropriate PTMC treatment policy based on its natural course and risk factors for progression.
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http://dx.doi.org/10.3803/EnM.2018.33.2.278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021306PMC
June 2018

Thyroid Cancer Treatment Choice: A Pilot Study of a Tool to Facilitate Conversations with Patients with Papillary Microcarcinomas Considering Treatment Options.

Thyroid 2018 10 25;28(10):1325-1331. Epub 2018 Jul 25.

4 Department of Endocrinology Service, Memorial Sloan-Kettering Cancer Center , New York, New York Memorial Sloan Kettering Cancer Center, New York, New York.

Background: The 2015 American Thyroid Association guidelines recognize active surveillance as an alternative to immediate surgery in patients with papillary microcarcinomas (PMCs). As a way to incorporate active surveillance as one of the management options for patients with PMCs, we developed and tested a tool to support conversations between clinicians and patients with PMCs considering treatment options.

Methods: Thyroid Cancer Treatment Choice was developed using an iterative process based on the principles of interaction, design, and participatory action research. To evaluate the impact of the tool on treatment choice, a prospective study was conducted in two thyroid cancer clinics in Seongnam-si and Seoul, South Korea. Both clinics had the expertise to offer active surveillance as well as immediate surgery. One clinic was trained in the use of the conversation aid, while the other clinic continued to care for patients without access to the conversation aid.

Results: Between May 2016 and April 2017, 278 patients, mostly women (n = 220, 79%), were included in the study; 152 (53%) received care at the clinic using the conversation aid. Age, sex, and mean (±SD) tumor size (6.6 ± 1.6 mm and 6.5 ± 1.9 mm) distributions were similar across clinics. Overall, 233 (84%) patients opted for active surveillance and 53 (16%) for thyroid surgery. Patients in the conversation aid group were more likely to choose active surveillance than the patients seen in the usual care clinic (relative risk = 1.16 [confidence interval 1.04-1.29]). Of all patients opting for active surveillance, more patients in the conversation aid group had thyroid cancer nodules >5 mm than in the usual care group (81% vs. 67%; p = 0.013).

Conclusions: Thyroid Cancer Treatment Choice is an evidence-based tool that supports the presentation of treatment options for PMCs. Pilot testing suggests that this conversation tool increases acceptance of active surveillance, suggesting that this option is an acceptable and preferable alternative for informed patients. Further studies are warranted to confirm this finding.
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http://dx.doi.org/10.1089/thy.2018.0105DOI Listing
October 2018

Star-Shaped Intense Uptake of ¹³¹I on Whole Body Scans Can Reflect Good Therapeutic Effects of Low-Dose Radioactive Iodine Treatment of 1.1 GBq.

Endocrinol Metab (Seoul) 2018 Jun 4;33(2):228-235. Epub 2018 May 4.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Background: After initial radioactive iodine (RAI) treatment in differentiated thyroid cancer patients, we sometimes observe a star-shaped region of intense uptake of ¹³¹I on whole body scans (WBSs), called a 'star artifact.' We evaluated the clinical implications of star artifacts on the success rate of remnant ablation and long-term prognosis.

Methods: Total 636 patients who received ¹³¹I dose of 1.1 GBq for the initial RAI therapy and who did not show distant metastasis at the time of diagnosis were retrospectively evaluated. A negative second WBS was used for evaluating the ablation efficacy of the RAI therapy. Among them, 235 patients (36.9%) showed a star artifact on their first WBS.

Results: In patients with first stimulated thyroglobulin (sTg) levels ≤2 ng/mL, patients with star artifacts had a higher rate of negative second WBS compared with those without star artifacts (77.8% vs. 63.9%, P=0.044), and showed significantly higher recurrence-free survival (P=0.043) during the median 8.0 years (range, 1.0 to 10.0) of follow-up. The 5- and 10-year recurrence rates (5YRR, 10YRR) were also significantly lower in patients with star artifacts compared with those without (0% vs. 4.9%, respectively, P=0.006 for 5YRR; 0% vs. 6.4%, respectively, P=0.005 for 10YRR). However, ablation success rate or recurrence-free survival was not different among patients whose first sTg levels >2 ng/mL regardless of star artifacts.

Conclusion: Therefore, star artifacts at initial RAI therapy imply a good ablation efficacy or a favorable long-term prognosis in patients with sTg levels ≤2 ng/mL.
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http://dx.doi.org/10.3803/EnM.2018.33.2.228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021303PMC
June 2018

Insulin Resistance is Associated with Cognitive Decline Among Older Koreans with Normal Baseline Cognitive Function: A Prospective Community-Based Cohort Study.

Sci Rep 2018 01 12;8(1):650. Epub 2018 Jan 12.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

We evaluated whether metabolic factors were associated with cognitive decline, compared to baseline cognitive function, among geriatric population. The present study evaluated data from an ongoing prospective community-based Korean cohort study. Among 1,387 participants who were >65 years old, 422 participants were evaluated using the Korean mini-mental status examination (K-MMSE) at the baseline and follow-up examinations. The mean age at the baseline was 69.3 ± 2.9 years, and 222 participants (52.6%) were men. The mean duration of education was 7.1 ± 3.6 years. During a mean follow-up of 5.9 ± 0.1 years, the K-MMSE score significantly decreased (-1.1 ± 2.7 scores), although no significant change was observed in the homeostasis model assessment of insulin resistance (HOMA-IR) value. Participants with more decreased percent changes in K-MMSE scores had a shorter duration of education (p = 0.001), older age (p = 0.022), higher baseline K-MMSE score (p < 0.001), and increased insulin resistance (∆HOMA-IR, p = 0.002). The correlation between the percent changes in K-MMSE and ∆HOMA-IR values remained significant after multivariable adjustment (B = -0.201, p = 0.002). During a 6-year follow-up of older Koreans with normal baseline cognitive function, increased insulin resistance was significantly correlated with decreased cognitive function.
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http://dx.doi.org/10.1038/s41598-017-18998-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766537PMC
January 2018

Optimal follow-up strategies for adrenal incidentalomas: reappraisal of the 2016 ESE-ENSAT guidelines in real clinical practice.

Eur J Endocrinol 2017 Dec 4;177(6):475-483. Epub 2017 Sep 4.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.

Objective: Recently, the European Society of Endocrinology (ESE), in collaboration with the European Network for the Study of Adrenal Tumors (ENSAT), asserted that adrenal incidentalomas (AIs) <4 cm and ≤10 Hounsfield units (HU) do not require further follow-up imaging. To validate the clinical application of the follow-up strategies suggested by the 2016 ESE-ENSAT guidelines, we explored the clinical characteristics and natural course of AIs in a single center over 13 years.

Design And Methods: This retrospective cohort study included a total of 1149 patients diagnosed with AIs between 2000 and 2013 in a single tertiary center. Hormonal examination and radiological evaluations were performed at the initial diagnosis of AI and during the follow-up according to the appropriate guidelines.

Results: The mean age at diagnosis was 54.2 years, and the majority of AIs (68.0%) were nonfunctional lesions. Receiver operating curve analysis was used to discriminate malignant from benign lesions; the optimal cut-off value for mass size was 3.4 cm (sensitivity: 100%; specificity: 95.0%), and that for the pre-contrast HU was 19.9 (sensitivity: 100%; specificity: 67.4%). The majority of nonfunctional lesions did not change in size during the 4-year follow-up period. Applying a cut-off value of 1.8 μg/dL after a 1-mg overnight dexamethasone suppression test, 28.0% of all nonfunctional AIs progressed to autonomous cortisol secretion during the follow-up period. However, we observed no development of overt Cushing's syndrome in the study.

Conclusions: We advocate that no follow-up imaging is required if the detected adrenal mass is <4 cm and has clear benign features. However, prospective studies with longer follow-up are needed to confirm the appropriate follow-up strategies.
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http://dx.doi.org/10.1530/EJE-17-0372DOI Listing
December 2017

Association of angiotensin-II levels with albuminuria in subjects with normal glucose metabolism, prediabetes, and type 2 diabetes mellitus.

J Diabetes Complications 2017 Oct 6;31(10):1499-1505. Epub 2017 Jul 6.

Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, South Korea. Electronic address:

Objectives: The relationship between the renin-angiotensin system (RAS) and diabetes has been studied for many years. However, studies that assessed RAS components comprehensively were limited. We hypothesized that serum RAS components, especially the effector peptide angiotensin-II, might be closely associated with glucose metabolism status and diabetic complications.

Methods: We investigated the association of individual RAS component with albuminuria in 407 subjects with normal glucose metabolism (NGM), prediabetes, or type 2 diabetes mellitus (T2DM). Anthropometric and biochemical parameters, including glucose homeostasis, albuminuria, and RAS-related parameters such as plasma renin activity (PRA), aldosterone, angiotensin-converting enzyme (ACE), and angiotensin-II levels, were measured.

Results: The mean±standard deviation (SD) age and body mass index were 57.1±11.1years and 24.7±3.3kg/m, respectively. There were 54 subjects with NGM, 102 with prediabetes, and 251 with T2DM. The mean±SD angiotensin-II levels in these groups were 9.32±6.89, 12.89±10.39, and 17.00±15.28pg/mL, and the respective urinary albumin-to-creatinine ratios (ACRs) were 8.1±5.3, 13.3±17.3, and 30.7±51.9mg/g, which were significantly different among the groups. The serum angiotensin-II levels were correlated with levels of PRA, insulin resistance, C-reactive protein, and urinary ACR. Among RAS-related parameters, only the angiotensin-II level was significantly associated with urinary ACR after adjusting for relevant risk factors.

Conclusions: Angiotensin-II may play an important role in the development of albuminuria, particularly in subjects with impaired glucose metabolism.
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http://dx.doi.org/10.1016/j.jdiacomp.2017.07.002DOI Listing
October 2017
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