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Obesity and Metabolism
2014 Clinical Practice Guidelines for Overweight and Obesity in Korea
Mee Kyoung Kim, Won-Young Lee, Jae-Heon Kang, Jee-Hyun Kang, Bom Taeck Kim, Seon Mee Kim, Eun Mi Kim, Sang-Hoon Suh, Hye Jung Shin, Kyu Rae Lee, Ki Young Lee, Sang Yeoup Lee, Seon Yeong Lee, Seong-Kyu Lee, Chang Beom Lee, Sochung Chung, In Kyung Jeong, Kyung Yul Hur, Sung Soo Kim, Jeong-taek Woo
Endocrinol Metab. 2014;29(4):405-409.   Published online December 29, 2014
DOI: https://doi.org/10.3803/EnM.2014.29.4.405
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AbstractAbstract PDFPubReader   

The dramatic increase in the prevalence of obesity and its accompanying comorbidities are major health concerns in Korea. Obesity is defined as a body mass index ≥25 kg/m2 in Korea. Current estimates are that 32.8% of adults are obese: 36.1% of men and 29.7% of women. The prevalence of being overweight and obese in national surveys is increasing steadily. Early detection and the proper management of obesity are urgently needed. Weight loss of 5% to 10% is the standard goal. In obese patients, control of cardiovascular risk factors deserves the same emphasis as weight-loss therapy. Since obesity is multifactorial, proper care of obesity requires a coordinated multidisciplinary treatment team, as a single intervention is unlikely to modify the incidence or natural history of obesity.

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Close layer
Bone Metabolism
NF-κB-Mediated Regulation of Osteoclastogenesis
Brendan F. Boyce, Yan Xiu, Jinbo Li, Lianping Xing, Zhenqiang Yao
Endocrinol Metab. 2015;30(1):35-44.   Published online March 27, 2015
DOI: https://doi.org/10.3803/EnM.2015.30.1.35
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AbstractAbstract PDFPubReader   

Osteoclasts are multinucleated cells formed mainly on bone surfaces in response to cytokines by fusion of bone marrow-derived myeloid lineage precursors that circulate in the blood. Major advances in understanding of the molecular mechanisms regulating osteoclast formation and functions have been made in the past 20 years since the discovery that their formation requires nuclear factor-kappa B (NF-κB) signaling and that this is activated in response to the essential osteoclastogenic cytokine, receptor activator of NF-κB ligand (RANKL), which also controls osteoclast activation to resorb (degrade) bone. These studies have revealed that RANKL and some pro-inflammatory cytokines, including tumor necrosis factor, activate NF-κB and downstream signaling, including c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), and inhibition of repressors of NFATc1 signaling, to positively regulate osteoclast formation and functions. However, these cytokines also activate NF-κB signaling that can limit osteoclast formation through the NF-κB signaling proteins, TRAF3 and p100, and the suppressors of c-Fos/NFATc1 signaling, IRF8, and RBP-J. This paper reviews current understanding of how NF-κB signaling is involved in the positive and negative regulation of cytokine-mediated osteoclast formation and activation.

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Close layer
Original Article
Adrenal gland
Effects of Chronic Restraint Stress on Body Weight, Food Intake, and Hypothalamic Gene Expressions in Mice
Joo Yeon Jeong, Dong Hoon Lee, Sang Soo Kang
Endocrinol Metab. 2013;28(4):288-296.   Published online December 12, 2013
DOI: https://doi.org/10.3803/EnM.2013.28.4.288
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AbstractAbstract PDFPubReader   
Background

Stress affects body weight and food intake, but the underlying mechanisms are not well understood.

Methods

We evaluated the changes in body weight and food intake of ICR male mice subjected to daily 2 hours restraint stress for 15 days. Hypothalamic gene expression profiling was analyzed by cDNA microarray.

Results

Daily body weight and food intake measurements revealed that both parameters decreased rapidly after initiating daily restraint stress. Body weights of stressed mice then remained significantly lower than the control body weights, even though food intake slowly recovered to 90% of the control intake at the end of the experiment. cDNA microarray analysis revealed that chronic restraint stress affects the expression of hypothalamic genes possibly related to body weight control. Since decreases of daily food intake and body weight were remarkable in days 1 to 4 of restraint, we examined the expression of food intake-related genes in the hypothalamus. During these periods, the expressions of ghrelin and pro-opiomelanocortin mRNA were significantly changed in mice undergoing restraint stress. Moreover, daily serum corticosterone levels gradually increased, while leptin levels significantly decreased.

Conclusion

The present study demonstrates that restraint stress affects body weight and food intake by initially modifying canonical food intake-related genes and then later modifying other genes involved in energy metabolism. These genetic changes appear to be mediated, at least in part, by corticosterone.

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Close layer
Review Articles
Glucocorticoid-Induced Diabetes Mellitus: An Important but Overlooked Problem
Sunghwan Suh, Mi Kyoung Park
Endocrinol Metab. 2017;32(2):180-189.   Published online May 29, 2017
DOI: https://doi.org/10.3803/EnM.2017.32.2.180
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AbstractAbstract PDFPubReader   ePub   

Glucocorticoids are widely used as potent anti-inflammatory and immunosuppressive drugs to treat a wide range of diseases. However, they are also associated with a number of side effects, including new-onset hyperglycemia in patients without a history of diabetes mellitus (DM) or severely uncontrolled hyperglycemia in patients with known DM. Glucocorticoid-induced diabetes mellitus (GIDM) is a common and potentially harmful problem in clinical practice, affecting almost all medical specialties, but is often difficult to detect in clinical settings. However, scientific evidence is lacking regarding the effects of GIDM, as well as strategies for prevention and treatment. Similarly to nonsteroid-related DM, the principles of early detection and risk factor modification apply. Screening for GIDM should be considered in all patients treated with medium to high doses of glucocorticoids. Challenges in the management of GIDM stem from wide fluctuations in postprandial hyperglycemia and the lack of clearly defined treatment protocols. Together with lifestyle measures, hypoglycemic drugs with insulin-sensitizing effects are indicated. However, insulin therapy is often unavoidable, to the point that insulin can be considered the drug of choice. The treatment of GIDM should take into account the degree and pattern of hyperglycemia, as well as the type, dose, and schedule of glucocorticoid used. Moreover, it is essential to instruct the patient and/or the patient's family about how to perform the necessary adjustments. Prospective studies are needed to answer the remaining questions regarding GIDM.

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Close layer
Obesity and Metabolism
Diabetes in Asians
Eun-Jung Rhee
Endocrinol Metab. 2015;30(3):263-269.   Published online September 22, 2015
DOI: https://doi.org/10.3803/EnM.2015.30.3.263
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AbstractAbstract PDFPubReader   

The prevalence of diabetes is increasing globally, particularly in Asia. According to the 2013 Diabetes Atlas, an estimated 366 million people are affected by diabetes worldwide; 36% of those affected live in the Western Pacific region, with a significant proportion in East Asia. The reasons for this marked increase in the prevalence of diabetes can be extrapolated from several distinct features of the Asian region. First, the two most populated countries, China and India, are located in Asia. Second, Asians have experienced extremely rapid economic growth, including rapid changes in dietary patterns, during the past decades. As a result, Asians tend to have more visceral fat within the same body mass index range compared with Westerners. In addition, increased insulin resistance relative to reduced insulin secretory function is another important feature of Asian individuals with diabetes. Young age of disease onset is also a distinctive characteristic of these patients. Moreover, changing dietary patterns, such as increased consumption of white rice and processed red meat, contributes to the deteriorated lifestyle of this region. Recent studies suggest a distinctive responsiveness to novel anti-diabetic agents in Asia; however, further research and efforts to reverse the increasing prevalence of diabetes are needed worldwide.

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Close layer
Bone Metabolism
Effects of Resistance Exercise on Bone Health
A Ram Hong, Sang Wan Kim
Endocrinol Metab. 2018;33(4):435-444.   Published online November 30, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.4.435
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AbstractAbstract PDFPubReader   ePub   

The prevalence of chronic diseases including osteoporosis and sarcopenia increases as the population ages. Osteoporosis and sarcopenia are commonly associated with genetics, mechanical factors, and hormonal factors and primarily associated with aging. Many older populations, particularly those with frailty, are likely to have concurrent osteoporosis and sarcopenia, further increasing their risk of disease-related complications. Because bones and muscles are closely interconnected by anatomy, metabolic profile, and chemical components, a diagnosis should be considered for both sarcopenia and osteoporosis, which may be treated with optimal therapeutic interventions eliciting pleiotropic effects on both bones and muscles. Exercise training has been recommended as a promising therapeutic strategy to encounter the loss of bone and muscle mass due to osteosarcopenia. To stimulate the osteogenic effects for bone mass accretion, bone tissues must be exposed to mechanical load exceeding those experienced during daily living activities. Of the several exercise training programs, resistance exercise (RE) is known to be highly beneficial for the preservation of bone and muscle mass. This review summarizes the mechanisms of RE for the preservation of bone and muscle mass and supports the clinical evidences for the use of RE as a therapeutic option in osteosarcopenia.

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Obesity and Metabolism
Association of Adipokines with Development and Progression of Nonalcoholic Fatty Liver Disease
Chrysoula Boutari, Nikolaos Perakakis, Christos Socrates Mantzoros
Endocrinol Metab. 2018;33(1):33-43.   Published online March 21, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.1.33
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AbstractAbstract PDFPubReader   ePub   

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease affecting 30% of the general population and 40% to 70% of obese individuals. Adipose tissue plays a crucial role in its pathogenesis, as it produces and secretes pro- and anti-inflammatory cytokines called adipokines. Adiponectin and leptin have well-determined actions in terms of NAFLD pathophysiology. Adiponectin deficiency is associated with a pro-inflammatory condition, as it is observed in obesity and other metabolic disorders. On the other hand, increased leptin levels, above the normal levels, act as a pro-inflammatory stimulus. Regarding other adipokines (resistin, visfatin, chemerin, retinol-binding protein 4, irisin), data about their contribution to NAFLD pathogenesis and progression are inconclusive. In addition, pharmacological agents like thiazolidinediones (pioglitazone and rosiglitazone), that are used in the management of NAFLD exert favourable effects on adipokine levels, which in turn may contribute to the improvement of liver function. This review summarizes the current knowledge and developments in the association between adipokines and NAFLD and discusses possible therapeutic implications targeting the modulation of adipokine levels as a potential tool for the treatment of NAFLD.

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Close layer
Adrenal gland
How to Establish Clinical Prediction Models
Yong-ho Lee, Heejung Bang, Dae Jung Kim
Endocrinol Metab. 2016;31(1):38-44.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.38
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AbstractAbstract PDFPubReader   

A clinical prediction model can be applied to several challenging clinical scenarios: screening high-risk individuals for asymptomatic disease, predicting future events such as disease or death, and assisting medical decision-making and health education. Despite the impact of clinical prediction models on practice, prediction modeling is a complex process requiring careful statistical analyses and sound clinical judgement. Although there is no definite consensus on the best methodology for model development and validation, a few recommendations and checklists have been proposed. In this review, we summarize five steps for developing and validating a clinical prediction model: preparation for establishing clinical prediction models; dataset selection; handling variables; model generation; and model evaluation and validation. We also review several studies that detail methods for developing clinical prediction models with comparable examples from real practice. After model development and vigorous validation in relevant settings, possibly with evaluation of utility/usability and fine-tuning, good models can be ready for the use in practice. We anticipate that this framework will revitalize the use of predictive or prognostic research in endocrinology, leading to active applications in real clinical practice.

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Close layer
Update on Modern Management of Pheochromocytoma and Paraganglioma
Jacques W. M. Lenders, Graeme Eisenhofer
Endocrinol Metab. 2017;32(2):152-161.   Published online June 23, 2017
DOI: https://doi.org/10.3803/EnM.2017.32.2.152
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AbstractAbstract PDFPubReader   ePub   

Despite all technical progress in modern diagnostic methods and treatment modalities of pheochromocytoma/paraganglioma, early consideration of the presence of these tumors remains the pivotal link towards the best possible outcome for patients. A timely diagnosis and proper treatment can prevent the wide variety of potentially catastrophic cardiovascular complications. Modern biochemical testing should include tests that offer the best available diagnostic performance, measurements of metanephrines and 3-methoxytyramine in plasma or urine. To minimize false-positive test results particular attention should be paid to pre-analytical sampling conditions. In addition to anatomical imaging by computed tomography (CT) or magnetic resonance imaging, new promising functional imaging modalities of photon emission tomography/CT using with somatostatin analogues such as 68Ga-DOTATATE (68Ga-labeled DOTA(0)-Tyr(3)-octreotide) will probably replace 123I-MIBG (iodine-123-metaiodobenzylguanidine) in the near future. As nearly half of all pheochromocytoma patients harbor a mutation in one of the 14 tumor susceptibility genes, genetic testing and counseling should at least be considered in all patients with a proven tumor. Post-surgical annual follow-up of patients by measurements of plasma or urinary metanephrines should last for at least 10 years for timely detection of recurrent or metastatic disease. Patients with a high risk for recurrence or metastatic disease (paraganglioma, young age, multiple or large tumors, genetic background) should be followed up lifelong.

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Close layer
Comprehensive Review on Kisspeptin and Its Role in Reproductive Disorders
Holly Clarke, Waljit S. Dhillo, Channa N. Jayasena
Endocrinol Metab. 2015;30(2):124-141.   Published online June 30, 2015
DOI: https://doi.org/10.3803/EnM.2015.30.2.124
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AbstractAbstract PDFPubReader   

Kisspeptin has recently emerged as a key regulator of the mammalian reproductive axis. It is known that kisspeptin, acting centrally via the kisspeptin receptor, stimulates secretion of gonadotrophin releasing hormone (GnRH). Loss of kisspeptin signaling causes hypogonadotrophic hypogonadism in humans and other mammals. Kisspeptin interacts with other neuropeptides such as neurokinin B and dynorphin, to regulate GnRH pulse generation. In addition, a growing body of evidence suggests that kisspeptin signaling be regulated by nutritional status and stress. Kisspeptin may also represent a novel potential therapeutic target in the treatment of fertility disorders. Early human studies suggest that peripheral exogenous kisspeptin administration stimulates gonadotrophin release in healthy adults and in patients with certain forms of infertility. This review aims to concisely summarize what is known about kisspeptin as a regulator of reproductive function, and provide an update on recent advances within this field.

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Close layer
Thyroid
Clinical Relevance of Environmental Factors in the Pathogenesis of Autoimmune Thyroid Disease
Wilmar M. Wiersinga
Endocrinol Metab. 2016;31(2):213-222.   Published online May 13, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.2.213
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AbstractAbstract PDFPubReader   

Genetic factors contribute for about 70% to 80% and environmental factors for about 20% to 30% to the pathogenesis of autoimmune thyroid disease (AITD). Relatives of AITD patients carry a risk to contract AITD themselves. The 5-year risk can be quantified by the so-called Thyroid Events Amsterdam-score, based on serum thyroid-stimulating hormone, thyroid peroxidase (TPO)-antibodies and family history. Subjects at risk may ask what they can do to prevent development of AITD. This review summarizes what is known about modulation of exposure to environmental factors in terms of AITD prevention. To stop smoking decreases the risk on Graves disease but increases the risk on Hashimoto disease. Moderate alcohol intake provides some protection against both Graves and Hashimoto disease. Low selenium intake is associated with a higher prevalence of thyroid autoimmunity, but evidence that selenium supplementation may lower TPO antibodies and prevent subclinical hypothyroidism remains inconclusive. Low serum vitamin D levels are associated with a higher prevalence of TPO antibodies, but intervention studies with extra vitamin D have not been done yet. Stress may provoke Graves hyperthyroidism but not Hashimoto thyroiditis. Estrogen use have been linked to a lower prevalence of Graves disease. The postpartum period is associated with an increased risk of AITD. Taking together, preventive interventions to diminish the risk of AITD are few, not always feasible, and probably of limited efficacy.

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Miscellaneous
Sarcopenia and Muscle Aging: A Brief Overview
Tam Dao, Alexander E. Green, Yun A Kim, Sung-Jin Bae, Ki-Tae Ha, Karim Gariani, Mi-ra Lee, Keir J. Menzies, Dongryeol Ryu
Endocrinol Metab. 2020;35(4):716-732.   Published online December 23, 2020
DOI: https://doi.org/10.3803/EnM.2020.405
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AbstractAbstract PDFPubReader   ePub   
The world is facing the new challenges of an aging population, and understanding the process of aging has therefore become one of the most important global concerns. Sarcopenia is a condition which is defined by the gradual loss of skeletal muscle mass and function with age. In research and clinical practice, sarcopenia is recognized as a component of geriatric disease and is a current target for drug development. In this review we define this condition and provide an overview of current therapeutic approaches. We further highlight recent findings that describe key pathophysiological phenotypes of this condition, including alterations in muscle fiber types, mitochondrial function, nicotinamide adenine dinucleotide (NAD+) metabolism, myokines, and gut microbiota, in aged muscle compared to young muscle or healthy aged muscle. The last part of this review examines new therapeutic avenues for promising treatment targets. There is still no accepted therapy for sarcopenia in humans. Here we provide a brief review of the current state of research derived from various mouse models or human samples that provide novel routes for the development of effective therapeutics to maintain muscle health during aging.

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Thyroid
The Revised 2016 Korean Thyroid Association Guidelines for Thyroid Nodules and Cancers: Differences from the 2015 American Thyroid Association Guidelines
Ka Hee Yi
Endocrinol Metab. 2016;31(3):373-378.   Published online September 26, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.3.373
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Increased detection of thyroid nodules using high-resolution ultrasonography has resulted in a world-wide increase in the incidence of differentiated thyroid cancer (DTC). Despite the steep increase in its incidence, the age-standardized mortality rate of thyroid cancer has remained stable, which leads toward a trend of more conservative treatment. The latest American Thyroid Association (ATA) guidelines for thyroid nodules and thyroid cancer revised in 2015 suggested that fine needle aspiration biopsy should be performed for thyroid nodules larger than 1 cm and lobectomy might be sufficient for 1 to 4 cm intrathyroidal DTC. In addition, active surveillance instead of immediate surgical treatment was also recommended as a treatment option for papillary thyroid microcarcinoma based on the results of a few observational studies from Japan. The Korean Thyroid Association (KTA) has organized a task force team to develop revised guidelines for thyroid nodules and DTC after an extensive review of articles and intense discussion on whether we should accept the changes in the 2015 ATA guidelines. This paper introduces and discusses the updated major issues and differences in the ATA and the KTA guidelines.

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Close layer
Original Articles
Clinical Study
Triglyceride Glucose Index Is Superior to the Homeostasis Model Assessment of Insulin Resistance for Predicting Nonalcoholic Fatty Liver Disease in Korean Adults
Sang Bae Lee, Min Kyung Kim, Shinae Kang, Kahui Park, Jung Hye Kim, Su Jung Baik, Ji Sun Nam, Chul Woo Ahn, Jong Suk Park
Endocrinol Metab. 2019;34(2):179-186.   Published online May 20, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.2.179
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AbstractAbstract PDFPubReader   ePub   
Background

Recently, the triglyceride glucose (TyG) index has been considered a surrogate marker of insulin resistance which is a well-known pathogenic factor in nonalcoholic fatty liver disease (NAFLD). However, few studies have investigated the relationship between the TyG index and NAFLD. Thus, we investigated the relationship between the TyG index and NAFLD and the effectiveness of the TyG index compared with the homeostasis model assessment of insulin resistance (HOMA-IR) in identifying NAFLD in Korean adults.

Methods

Participants of 4,986 who underwent ultrasonography in a health promotion center were enrolled. The TyG index was calculated as ln [fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2], and HOMA-IR was estimated. NAFLD was diagnosed by ultrasonography.

Results

Significant differences were observed in metabolic parameters among the quartiles of the TyG index. The prevalence of NAFLD significantly increased with increment in the TyG index. After adjusting for multiple risk factors, a logistic regression analysis was performed. When the highest and lowest quartiles of the TyG index and HOMA-IR were compared, the odds ratios for the prevalence of NAFLD were 2.94 and 1.93 (95% confidence interval, 2.32 to 3.72 and 1.43 to 2.61; both P for trend <0.01), respectively. According to the receiver operating characteristic analysis, the TyG index was superior to HOMA-IR in predicting NAFLD.

Conclusion

The TyG index and prevalence of NAFLD were significantly related and the TyG index was superior to HOMA-IR in predicting NAFLD in Korean adults.

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Thyroid Stimulating Hormone Reference Range and Prevalence of Thyroid Dysfunction in the Korean Population: Korea National Health and Nutrition Examination Survey 2013 to 2015
Won Gu Kim, Won Bae Kim, Gyeongji Woo, Hyejin Kim, Yumi Cho, Tae Yong Kim, Sun Wook Kim, Myung-Hee Shin, Jin Woo Park, Hai-Lin Park, Kyungwon Oh, Jae Hoon Chung
Endocrinol Metab. 2017;32(1):106-114.   Published online January 23, 2017
DOI: https://doi.org/10.3803/EnM.2017.32.1.106
Correction in: Endocrinol Metab 2023;38(3):357
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AbstractAbstract PDFPubReader   
Background

No nationwide epidemiological study evaluating the prevalence of subclinical and overt forms of hypothyroidism and hyperthyroidism has yet been conducted in Korea. This study aimed to evaluate the reference range of serum thyroid stimulating hormone (TSH) and the national prevalence of thyroid dysfunctions in Korea.

Methods

Nation-wide cross-sectional data were analyzed from a representative sample of the civilian, non-institutionalized Korean population (n=6,564) who underwent blood testing for thyroid function and anti-thyroid peroxidase antibody (TPOAb) as part of the Korea National Health and Nutrition Examination Survey VI (2013 to 2015).

Results

The reference interval of serum TSH in the Korean reference population was 0.62 to 6.68 mIU/L. Based on this reference interval, the prevalence of overt and subclinical hypothyroidism was 0.73% (males 0.40%, females 1.10%) and 3.10% (males 2.26%, females 4.04%), respectively. The prevalence of hypothyroidism increased with age until the age group between 50 to 59 years. Positive TPOAb were found in 7.30% of subjects (males 4.33%, females 10.62%). The prevalence of overt and subclinical hypothyroidism TPOAb-positive subjects was 5.16% and 10.88%, respectively. The prevalence of overt and subclinical hyperthyroidism was 0.54% (males 0.30%, females 0.81%) and 2.98% (males 2.43%, females, 3.59%), respectively.

Conclusion

The Serum TSH reference levels in the Korean population were higher than the corresponding levels in Western countries. Differences were found in the prevalence of hypothyroidism and hyperthyroidism according to age, sex, and TPOAb positivity. This study provides important baseline information for understanding patterns of thyroid dysfunction and diseases in Korea.

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