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Adrenal Gland
Long-Term Outcomes of Congenital Adrenal Hyperplasia
Anna Nordenström, Svetlana Lajic, Henrik Falhammar
Endocrinol Metab. 2022;37(4):587-598.   Published online July 8, 2022
DOI: https://doi.org/10.3803/EnM.2022.1528
  • 30,590 View
  • 283 Download
  • 12 Web of Science
  • 15 Crossref
AbstractAbstract PDFPubReader   ePub   
A plethora of negative long-term outcomes have been associated with congenital adrenal hyperplasia (CAH). The causes are multiple and involve supra-physiological gluco- and mineralocorticoid replacement, excess adrenal androgens both intrauterine and postnatal, elevated steroid precursor and adrenocorticotropic hormone levels, living with a congenital condition as well as the proximity of the cytochrome P450 family 21 subfamily A member 2 (CYP21A2) gene to other genes. This review aims to discuss the different long-term outcomes of CAH.

Citations

Citations to this article as recorded by  
  • Increased Prevalence of Accidents and Injuries in Congenital Adrenal Hyperplasia: A Population-based Cohort Study
    Henrik Falhammar, Angelica Lindén Hirschberg, Agneta Nordenskjöld, Henrik Larsson, Anna Nordenström
    The Journal of Clinical Endocrinology & Metabolism.2024; 109(3): e1175.     CrossRef
  • International Newborn Screening Practices for the Early Detection of Congenital Adrenal Hyperplasia
    Tracey A. Conlon, Colin P. Hawkes, Jennifer J. Brady, J. Gerard Loeber, Nuala Murphy
    Hormone Research in Paediatrics.2024; 97(2): 113.     CrossRef
  • Low renin forms of monogenic hypertension: review of the evidence
    Ugochi Chinenye Okorafor, Uchechi Chioma Okorafor
    Journal of Clinical Medicine of Kazakhstan.2024; 21(1): 14.     CrossRef
  • Increased risk of nephrolithiasis: an emerging issue in children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency
    Mariangela Chiarito, Crescenza Lattanzio, Vito D’Ascanio, Donatella Capalbo, Paolo Cavarzere, Anna Grandone, Francesca Aiello, Giorgia Pepe, Malgorzata Wasniewska, Thomas Zoller, Mariacarolina Salerno, Maria Felicia Faienza
    Endocrine.2024; 84(2): 727.     CrossRef
  • Memory in female adolescents with congenital adrenal hyperplasia due to 21-hydroxylase deficiency
    Tania M. Espinosa Reyes, Dainy Cordero Martín, Miguel Ángel Álvarez, Henrik Falhammar
    Endocrine.2024;[Epub]     CrossRef
  • Congenital adrenal hyperplasia: New biomarkers and adult treatments
    Bleuenn Dreves, Yves Reznik, Antoine Tabarin
    Annales d'Endocrinologie.2023; 84(4): 472.     CrossRef
  • Interpretation of Steroid Biomarkers in 21-Hydroxylase Deficiency and Their Use in Disease Management
    Kyriakie Sarafoglou, Deborah P Merke, Nicole Reisch, Hedi Claahsen-van der Grinten, Henrik Falhammar, Richard J Auchus
    The Journal of Clinical Endocrinology & Metabolism.2023; 108(9): 2154.     CrossRef
  • Impact of Newborn Screening on Adult Height in Patients With Congenital Adrenal Hyperplasia (CAH)
    Heike Hoyer-Kuhn, Alexander J Eckert, Gerhard Binder, Walter Bonfig, Angelika Dübbers, Stefan Riedl, Joachim Woelfle, Helmuth G Dörr, Reinhard W Holl
    The Journal of Clinical Endocrinology & Metabolism.2023; 108(11): e1199.     CrossRef
  • Specialty grand challenge in adrenal endocrinology
    Henrik Falhammar
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Contexts of care for people with differences of sex development
    Alexandra E. Kulle, Martina Jürgensen, Ulla Döhnert, Lisa Malich, Louise Marshall, Olaf Hiort
    Medizinische Genetik.2023; 35(3): 181.     CrossRef
  • Cardiovascular risk in Cuban adolescents and young adults with congenital adrenal hyperplasia
    Tania M. Espinosa Reyes, Alba Katherine Pesántez Velepucha, Julio Oscar Cabrera Rego, Wendy Valdés Gómez, Emma Domínguez Alonso, Henrik Falhammar
    BMC Endocrine Disorders.2023;[Epub]     CrossRef
  • Landscape of Adrenal Tumours in Patients with Congenital Adrenal Hyperplasia
    Mara Carsote, Ana-Maria Gheorghe, Claudiu Nistor, Alexandra-Ioana Trandafir, Oana-Claudia Sima, Anca-Pati Cucu, Adrian Ciuche, Eugenia Petrova, Adina Ghemigian
    Biomedicines.2023; 11(11): 3081.     CrossRef
  • Editorial: Recent advances in diagnosis and treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency
    Semra Çaglar Çetinkaya
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Approach of Heterogeneous Spectrum Involving 3beta-Hydroxysteroid Dehydrogenase 2 Deficiency
    Andreea Gabriela Nicola, Mara Carsote, Ana-Maria Gheorghe, Eugenia Petrova, Alexandru Dan Popescu, Adela Nicoleta Staicu, Mihaela Jana Țuculină, Cristian Petcu, Ionela Teodora Dascălu, Tiberiu Tircă
    Diagnostics.2022; 12(9): 2168.     CrossRef
  • Effetti di Crinecerfont sulla secrezione di ACTH nell’iperplasia surrenalica congenita: uno studio di fase 2
    Marianna Rita Stancampiano, Silvia Laura Carla Meroni, Giovanna Weber, Gianni Russo
    L'Endocrinologo.2022; 23(6): 662.     CrossRef
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Adrenal Gland
Clinical and Technical Aspects in Free Cortisol Measurement
Man Ho Choi
Endocrinol Metab. 2022;37(4):599-607.   Published online August 19, 2022
DOI: https://doi.org/10.3803/EnM.2022.1549
  • 4,948 View
  • 302 Download
  • 9 Web of Science
  • 12 Crossref
AbstractAbstract PDFPubReader   ePub   
Accurate measurement of cortisol is critical in adrenal insufficiency as it reduces the risk associated with misdiagnosis and supports the optimization of stress dose. Comprehensive assays have been developed to determine the levels of bioactive free cortisol and their clinical and analytical efficacies have been extensively discussed because the level of total cortisol is affected by changes in the structure or circulating levels of corticoid-binding globulin and albumin, which are the main reservoirs of cortisol in the human body. Antibody-based immunoassays are routinely used in clinical laboratories; however, the lack of molecular specificity in cortisol assessment limits their applicability to characterize adrenocortical function. Improved specificity and sensitivity can be achieved by mass spectrometry coupled with chromatographic separation methods, which is a cutting-edge technology to measure individual as well as a panel of steroids in a single analytical run. The purpose of this review is to introduce recent advances in free cortisol measurement from the perspectives of clinical specimens and issues associated with prospective analytical technologies.

Citations

Citations to this article as recorded by  
  • Highly Responsive Bioassay for Quantification of Glucocorticoids
    Mathias Flensted Poulsen, Martin Overgaard, Christian Brix Folsted Andersen, Andreas Lodberg
    Analytical Chemistry.2024; 96(5): 2000.     CrossRef
  • An LC-MS/MS Method for the Simultaneous Quantification of Insulin, Cortisol, Glucagon-like Peptide 1, Ghrelin, and Osteocalcin
    Zhichao Zhang, Hareem Siddiqi, Yu-Ping Huang, Shannon McClorry, Peng Ji, Daniela Barile, Carolyn M. Slupsky
    Separations.2024; 11(2): 41.     CrossRef
  • Determination of cortisol cut-off limits and steroid dynamics in the ACTH stimulation test: a comparative analysis using Roche Elecsys Cortisol II immunoassay and LC-MS/MS
    Sema Okutan, Nanna Thurmann Jørgensen, Lars Engers Pedersen, Stina Willemoes Borresen, Linda Hilsted, Lennart Friis Hansen, Ulla Feldt-Rasmussen, Marianne Klose
    Endocrine.2024;[Epub]     CrossRef
  • Advancements in Cortisol Detection: From Conventional Methods to Next-Generation Technologies for Enhanced Hormone Monitoring
    Visesh Vignesh, Bernardo Castro-Dominguez, Tony D. James, Julie M. Gamble-Turner, Stafford Lightman, Nuno M. Reis
    ACS Sensors.2024; 9(4): 1666.     CrossRef
  • Comparative analysis of salivary cortisol measurements using different assay methods in relation to serum-free cortisol measurement
    Anna Lee, Sooah Jang, Sanghoo Lee, Hyun-Kyung Park, In-Young Kim, Ryunsup Ahn, Jeong-Ho Seok, Kyoung-Ryul Lee
    Practical Laboratory Medicine.2024; 40: e00393.     CrossRef
  • A dilute and shoot method for urinary free cortisol analysis by LC-MS/MS
    Ying Shen, Xia Luo, Qing Guan, Liming Cheng
    Journal of Chromatography B.2024; 1239: 124127.     CrossRef
  • Osteopathic Manipulation as a Method of Cortisol Modification: A Systematic Review
    Dylan Thibaut, Valentine Santarlas, Joseph Hoppes, Alejandra Vásquez-Castillo, Alexa Morrow, Eddie Oviedo, James Toldi
    Cureus.2023;[Epub]     CrossRef
  • Pitfalls in the Diagnosis and Management of Hypercortisolism (Cushing Syndrome) in Humans; A Review of the Laboratory Medicine Perspective
    Kade C. Flowers, Kate E. Shipman
    Diagnostics.2023; 13(8): 1415.     CrossRef
  • Electrochemical sensors for cortisol detection: Principles, designs, fabrication, and characterisation
    Gopi Karuppaiah, Min-Ho Lee, Shekhar Bhansali, Pandiaraj Manickam
    Biosensors and Bioelectronics.2023; 239: 115600.     CrossRef
  • The role of the hypothalamic-pituitary-adrenal axis in depression across the female reproductive lifecycle: current knowledge and future directions
    Liisa Hantsoo, Kathleen M. Jagodnik, Andrew M. Novick, Ritika Baweja, Teresa Lanza di Scalea, Aysegul Ozerdem, Erin C. McGlade, Diana I. Simeonova, Sharon Dekel, Sara L. Kornfield, Michelle Nazareth, Sandra J. Weiss
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • РІВЕНЬ СТРЕСУ В ДІТЕЙ ШКІЛЬНОГО ВІКУ З COVID-19
    Г. А. Павлишин, О. І. Панченко
    Здобутки клінічної і експериментальної медицини.2023; (4): 119.     CrossRef
  • Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study
    Josef Briegel, Patrick Möhnle, Didier Keh, Johanna M. Lindner, Anna C. Vetter, Holger Bogatsch, Dorothea Lange, Sandra Frank, Ludwig C. Hinske, Djillali Annane, Michael Vogeser, Michael Bauer, Thorsten Brenner, Patrick Meybohm, Markus Weigand, Matthias Gr
    Critical Care.2022;[Epub]     CrossRef
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Original Articles
Adrenal Gland
Big Data Articles (National Health Insurance Service Database)
Epidemiology and Long-Term Adverse Outcomes in Korean Patients with Congenital Adrenal Hyperplasia: A Nationwide Study
Jung Hee Kim, Sunkyu Choi, Young Ah Lee, Juneyoung Lee, Sin Gon Kim
Endocrinol Metab. 2022;37(1):138-147.   Published online February 28, 2022
DOI: https://doi.org/10.3803/EnM.2021.1328
  • 3,534 View
  • 154 Download
  • 9 Web of Science
  • 10 Crossref
AbstractAbstract PDFPubReader   ePub   
Background
Previous studies on the epidemiology and complications of congenital adrenal hyperplasia (CAH) were conducted in Western countries and in children/adolescents. We aimed to explore the epidemiology of CAH, as well as the risk of comorbidities and mortality, in a Korean nationwide case-control study.
Methods
CAH patients (n=2,840) were included between 2002 and 2017 from the National Health Insurance Service database and the Rare Intractable Disease program. CAH patients were compared, at a 1:10 ratio, with age-, sex-, and index year-matched controls (n=28,400).
Results
The point prevalence of CAH patients in Korea was 1 in 18,745 persons in 2017. The annual incidence rate declined between 2003 and 2017 from 3.25 to 0.41 per 100,000 persons. CAH patients were at elevated risk for cardiovascular disease (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.4 to 1.9), stroke (OR, 1.7; 95% CI, 1.3 to 2.0), diabetes mellitus (OR, 2.8; 95% CI, 2.6 to 3.1), dyslipidemia (OR, 2.4; 95% CI, 2.2 to 2.6), and psychiatric disorders (OR, 1.5; 95% CI, 1.3 to 1.6). Fracture risk increased in CAH patients aged over 40 years (OR, 1.4; 95% CI, 1.1 to 1.7). CAH patients were at higher risk of mortality than controls (hazard ratio, 1.6; 95% CI, 1.3 to 2.0).
Conclusion
Our nationwide study showed a recent decline in the incidence of CAH and an elevated risk for cardiovascular, metabolic, skeletal, and psychiatric disorders in CAH patients. Lifelong management for comorbidity risk is a crucial component of treating CAH patients.

Citations

Citations to this article as recorded by  
  • Hyperandrogenism and Cardiometabolic Risk in Pre- and Postmenopausal Women—What Is the Evidence?
    Angelica Lindén Hirschberg
    The Journal of Clinical Endocrinology & Metabolism.2024; 109(5): 1202.     CrossRef
  • Case report: Development of central precocious puberty in a girl with late-diagnosed simple virilizing congenital adrenal hyperplasia complicated with Williams syndrome
    Eun Young Joo, Myung Ji Yoo, Su Jin Kim, Woori Jang, Ji-Eun Lee
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Анализ распространенности и заболеваемости надпочечниковой недостаточностью в мире
    М. Ю. Юкина, Н. Ф. Нуралиева, Е. А. Трошина
    Ateroscleroz.2023; 18(4): 426.     CrossRef
  • Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database
    Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee
    Endocrinology and Metabolism.2023; 38(1): 10.     CrossRef
  • Long-term cardiometabolic morbidity in young adults with classic 21-hydroxylase deficiency congenital adrenal hyperplasia
    Beatrice Righi, Salma R. Ali, Jillian Bryce, Jeremy W. Tomlinson, Walter Bonfig, Federico Baronio, Eduardo C. Costa, Guilherme Guaragna-Filho, Guy T’Sjoen, Martine Cools, Renata Markosyan, Tania A. S. S. Bachega, Mirela C. Miranda, Violeta Iotova, Henrik
    Endocrine.2023; 80(3): 630.     CrossRef
  • Serum steroid profile captures metabolic phenotypes in adults with classic congenital adrenal hyperplasia
    Chang Ho Ahn, Jaeyoon Shim, Han Na Jang, Young Ah Lee, Sang-Won Lee, Man Ho Choi, Jung Hee Kim
    The Journal of Steroid Biochemistry and Molecular Biology.2023; 234: 106374.     CrossRef
  • Long‐term health consequences of congenital adrenal hyperplasia
    Riccardo Pofi, Xiaochen Ji, Nils P. Krone, Jeremy W. Tomlinson
    Clinical Endocrinology.2023;[Epub]     CrossRef
  • Predictors of Cardiovascular Morbidities in Adults With 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia
    Suranut Charoensri, Richard J Auchus
    The Journal of Clinical Endocrinology & Metabolism.2023;[Epub]     CrossRef
  • Multiplexed Serum Steroid Profiling Reveals Metabolic Signatures of Subtypes in Congenital Adrenal Hyperplasia
    Jaeyoon Shim, Chang Ho Ahn, Seung Shin Park, Jongsung Noh, Chaelin Lee, Sang Won Lee, Jung Hee Kim, Man Ho Choi
    Journal of the Endocrine Society.2023;[Epub]     CrossRef
  • Long-Term Outcomes of Congenital Adrenal Hyperplasia
    Anna Nordenström, Svetlana Lajic, Henrik Falhammar
    Endocrinology and Metabolism.2022; 37(4): 587.     CrossRef
Close layer
Adrenal Gland
Adrenal Morphology as an Indicator of Long-Term Disease Control in Adults with Classic 21-Hydroxylase Deficiency
Taek Min Kim, Jung Hee Kim, Han Na Jang, Man Ho Choi, Jeong Yeon Cho, Sang Youn Kim
Endocrinol Metab. 2022;37(1):124-137.   Published online February 8, 2022
DOI: https://doi.org/10.3803/EnM.2021.1278
  • 4,358 View
  • 127 Download
  • 6 Web of Science
  • 6 Crossref
AbstractAbstract PDFPubReader   ePub   
Background
Monitoring adults with classical 21-hydroxylase deficiency (21OHD) is challenging due to variation in clinical and laboratory settings. Moreover, guidelines for adrenal imaging in 21OHD are not yet available. We evaluated the relationship between adrenal morphology and disease control status in classical 21OHD.
Methods
This retrospective, cross-sectional study included 90 adult 21OHD patients and 270 age- and sex-matched healthy controls. We assessed adrenal volume, width, and tumor presence using abdominal computed tomography and evaluated correlations of adrenal volume and width with hormonal status. We investigated the diagnostic performance of adrenal volume and width for identifying well-controlled status in 21OHD patients (17α-hydroxyprogesterone [17-OHP] <10 ng/mL).
Results
The adrenal morphology of 21OHD patients showed hypertrophy (45.6%), normal size (42.2%), and hypotrophy (12.2%). Adrenal tumors were detected in 12 patients (13.3%). The adrenal volume and width of 21OHD patients were significantly larger than those of controls (18.2±12.2 mL vs. 7.1±2.0 mL, 4.7±1.9 mm vs. 3.3±0.5 mm, P<0.001 for both). The 17-OHP and androstenedione levels were highest in patients with adrenal hypertrophy, followed by those with normal adrenal glands and adrenal hypotrophy (P<0.05 for both). Adrenal volume and width correlated positively with adrenocorticotropic hormone, 17-OHP, 11β-hydroxytestosterone, progesterone sulfate, and dehydroepiandrosterone sulfate in both sexes (r=0.33–0.95, P<0.05 for all). For identifying well-controlled patients, the optimal cut-off values of adrenal volume and width were 10.7 mL and 4 mm, respectively (area under the curve, 0.82–0.88; P<0.001 for both).
Conclusion
Adrenal volume and width may be reliable quantitative parameters for monitoring patients with classical 21OHD.

Citations

Citations to this article as recorded by  
  • Long‐term health consequences of congenital adrenal hyperplasia
    Riccardo Pofi, Xiaochen Ji, Nils P. Krone, Jeremy W. Tomlinson
    Clinical Endocrinology.2023;[Epub]     CrossRef
  • Landscape of Adrenal Tumours in Patients with Congenital Adrenal Hyperplasia
    Mara Carsote, Ana-Maria Gheorghe, Claudiu Nistor, Alexandra-Ioana Trandafir, Oana-Claudia Sima, Anca-Pati Cucu, Adrian Ciuche, Eugenia Petrova, Adina Ghemigian
    Biomedicines.2023; 11(11): 3081.     CrossRef
  • Multiplexed Serum Steroid Profiling Reveals Metabolic Signatures of Subtypes in Congenital Adrenal Hyperplasia
    Jaeyoon Shim, Chang Ho Ahn, Seung Shin Park, Jongsung Noh, Chaelin Lee, Sang Won Lee, Jung Hee Kim, Man Ho Choi
    Journal of the Endocrine Society.2023;[Epub]     CrossRef
  • Long-Term Outcomes of Congenital Adrenal Hyperplasia
    Anna Nordenström, Svetlana Lajic, Henrik Falhammar
    Endocrinology and Metabolism.2022; 37(4): 587.     CrossRef
  • Congenital adrenal hyperplasia in patients with adrenal tumors: a population-based case–control study
    F. Sahlander, J. Patrova, B. Mannheimer, J. D. Lindh, H. Falhammar
    Journal of Endocrinological Investigation.2022; 46(3): 559.     CrossRef
  • Fully automatic volume measurement of the adrenal gland on CT using deep learning to classify adrenal hyperplasia
    Taek Min Kim, Seung Jae Choi, Ji Yeon Ko, Sungwan Kim, Chang Wook Jeong, Jeong Yeon Cho, Sang Youn Kim, Young-Gon Kim
    European Radiology.2022; 33(6): 4292.     CrossRef
Close layer
Hypothalamus and Pituitary Gland
Metabolic Impacts of Discontinuation and Resumption of Recombinant Human Growth Hormone Treatment during the Transition Period in Patients with Childhood-Onset Growth Hormone Deficiency
Yun Jeong Lee, Yunha Choi, Han-Wook Yoo, Young Ah Lee, Choong Ho Shin, Han Saem Choi, Ho-Seong Kim, Jae Hyun Kim, Jung Eun Moon, Cheol Woo Ko, Moon Bae Ahn, Byung-Kyu Suh, Jin-Ho Choi
Endocrinol Metab. 2022;37(2):359-368.   Published online April 25, 2022
DOI: https://doi.org/10.3803/EnM.2021.1384
  • 4,568 View
  • 186 Download
  • 3 Web of Science
  • 4 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Discontinuing growth hormone (GH) treatment during the transition to adulthood has been associated with adverse health outcomes in patients with childhood-onset growth hormone deficiency (CO-GHD). This study investigated the metabolic changes associated with interrupting GH treatment in adolescents with CO-GHD during the transition period.
Methods
This study included 187 patients with CO-GHD who were confirmed to have adult GHD and were treated at six academic centers in Korea. Data on clinical parameters, including anthropometric measurements, metabolic profiles, and bone mineral density (BMD) at the end of childhood GH treatment, were collected at the time of re-evaluation for GHD and 1 year after treatment resumption.
Results
Most patients (n=182, 97.3%) had organic GHD. The median age at treatment discontinuation and re-evaluation was 15.6 and 18.7 years, respectively. The median duration of treatment interruption was 2.8 years. During treatment discontinuation, body mass index Z-scores and total cholesterol, low-density lipoprotein, and non-high-density lipoprotein (HDL) cholesterol levels increased, whereas fasting glucose levels decreased. One year after GH treatment resumption, fasting glucose levels, HDL cholesterol levels, and femoral neck BMD increased significantly. Longer GH interruption (>2 years, 60.4%) resulted in worse lipid profiles at re-evaluation. The duration of interruption was positively correlated with fasting glucose and non-HDL cholesterol levels after adjusting for covariates.
Conclusion
GH treatment interruption during the transition period resulted in worse metabolic parameters, and a longer interruption period was correlated with poorer outcomes. GH treatment should be resumed early in patients with CO-GHD during the transition period.

Citations

Citations to this article as recorded by  
  • Ghrelin regulating liver activity and its potential effects on liver fibrosis and Echinococcosis
    Jiang Zhu, Tanfang Zhou, Meng Menggen, Kalibixiati Aimulajiang, Hao Wen
    Frontiers in Cellular and Infection Microbiology.2024;[Epub]     CrossRef
  • Composición de la microbiota en pacientes con déficit de hormona de crecimiento antes y después de recibir tratamiento
    Patricia García Navas, María Yolanda Ruíz del Prado, Pablo Villoslada Blanco, Emma Recio Fernández, María Ruíz del Campo, Patricia Pérez Matute
    Anales de Pediatría.2024;[Epub]     CrossRef
  • Relationship between the Stimulated Peak Growth Hormone Level and Metabolic Parameters in Children with Growth Hormone Deficiency
    Seong Yong Lee
    The Ewha Medical Journal.2023;[Epub]     CrossRef
  • Dyslipidaemia and growth hormone deficiency – A comprehensive review
    Matthias Hepprich, Fahim Ebrahimi, Emanuel Christ
    Best Practice & Research Clinical Endocrinology & Metabolism.2023; 37(6): 101821.     CrossRef
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Adrenal Gland
Outcome-Based Decision-Making Algorithm for Treating Patients with Primary Aldosteronism
Jung Hee Kim, Chang Ho Ahn, Su Jin Kim, Kyu Eun Lee, Jong Woo Kim, Hyun-Ki Yoon, Yu-Mi Lee, Tae-Yon Sung, Sang Wan Kim, Chan Soo Shin, Jung-Min Koh, Seung Hun Lee
Endocrinol Metab. 2022;37(2):369-382.   Published online April 14, 2022
DOI: https://doi.org/10.3803/EnM.2022.1391
  • 3,939 View
  • 161 Download
  • 4 Web of Science
  • 4 Crossref
AbstractAbstract PDFPubReader   ePub   
Background
Optimal management of primary aldosteronism (PA) is crucial due to the increased risk of cardiovascular and cerebrovascular diseases. Adrenal venous sampling (AVS) is the gold standard method for determining subtype but is technically challenging and invasive. Some PA patients do not benefit clinically from surgery. We sought to develop an algorithm to improve decision- making before engaging in AVS and surgery in clinical practice.
Methods
We conducted the ongoing Korean Primary Aldosteronism Study at two tertiary centers. Study A involved PA patients with successful catheterization and a unilateral nodule on computed tomography and aimed to predict unilateral aldosterone-producing adenoma (n=367). Study B involved similar patients who underwent adrenalectomy and aimed to predict postoperative outcome (n=330). In study A, we implemented important feature selection using the least absolute shrinkage and selection operator regression.
Results
We developed a unilateral PA prediction model using logistic regression analysis: lowest serum potassium level ≤3.4 mEq/L, aldosterone-to-renin ratio ≥150, plasma aldosterone concentration ≥30 ng/mL, and body mass index <25 kg/m2 (area under the curve, 0.819; 95% confidence interval, 0.774 to 0.865; sensitivity, 97.6%; specificity, 25.5%). In study B, we identified female, hypertension duration <5 years, anti-hypertension medication <2.5 daily defined dose, and the absence of coronary artery disease as predictors of clinical success, using stepwise logistic regression models (sensitivity, 94.2%; specificity, 49.3%). We validated our algorithm in the independent validation dataset (n=53).
Conclusion
We propose this new outcome-driven diagnostic algorithm, simultaneously considering unilateral aldosterone excess and clinical surgical benefits in PA patients.

Citations

Citations to this article as recorded by  
  • Subtype-specific Body Composition and Metabolic Risk in Patients With Primary Aldosteronism
    Seung Shin Park, Chang Ho Ahn, Sang Wan Kim, Ji Won Yoon, Jung Hee Kim
    The Journal of Clinical Endocrinology & Metabolism.2024; 109(2): e788.     CrossRef
  • Prognostic models to predict complete resolution of hypertension after adrenalectomy in primary aldosteronism: A systematic review and meta‐analysis
    Luigi Marzano, Amir Kazory, Faeq Husain‐Syed, Claudio Ronco
    Clinical Endocrinology.2023; 99(1): 17.     CrossRef
  • 2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism
    Jeonghoon Ha, Jung Hwan Park, Kyoung Jin Kim, Jung Hee Kim, Kyong Yeun Jung, Jeongmin Lee, Jong Han Choi, Seung Hun Lee, Namki Hong, Jung Soo Lim, Byung Kwan Park, Jung-Han Kim, Kyeong Cheon Jung, Jooyoung Cho, Mi-kyung Kim, Choon Hee Chung
    Endocrinology and Metabolism.2023; 38(6): 597.     CrossRef
  • Correlation of Histopathologic Subtypes of Primary Aldosteronism with Clinical Phenotypes and Postsurgical Outcomes
    Chang Ho Ahn, You-Bin Lee, Jae Hyeon Kim, Young Lyun Oh, Jung Hee Kim, Kyeong Cheon Jung
    The Journal of Clinical Endocrinology & Metabolism.2023;[Epub]     CrossRef
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Review Article
Hypothalamus and Pituitary Gland
Independent Skeletal Actions of Pituitary Hormones
Se-Min Kim, Farhath Sultana, Funda Korkmaz, Daria Lizneva, Tony Yuen, Mone Zaidi
Endocrinol Metab. 2022;37(5):719-731.   Published online September 28, 2022
DOI: https://doi.org/10.3803/EnM.2022.1573
  • 3,906 View
  • 236 Download
  • 4 Web of Science
  • 4 Crossref
AbstractAbstract PDFPubReader   ePub   
Over the past years, pituitary hormones and their receptors have been shown to have non-traditional actions that allow them to bypass the hypothalamus-pituitary-effector glands axis. Bone cells—osteoblasts and osteoclasts—express receptors for growth hormone, follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), prolactin, oxytocin, and vasopressin. Independent skeletal actions of pituitary hormones on bone have been studied using genetically modified mice with haploinsufficiency and by activating or inactivating the receptors pharmacologically, without altering systemic effector hormone levels. On another front, the discovery of a TSH variant (TSH-βv) in immune cells in the bone marrow and skeletal action of FSHβ through tumor necrosis factor α provides new insights underscoring the integrated physiology of bone-immune-endocrine axis. Here we discuss the interaction of each pituitary hormone with bone and the potential it holds in understanding bone physiology and as a therapeutic target.

Citations

Citations to this article as recorded by  
  • New tools for bone health assessment in secreting pituitary adenomas
    Meliha Melin Uygur, Stefano Frara, Luigi di Filippo, Andrea Giustina
    Trends in Endocrinology & Metabolism.2023; 34(4): 231.     CrossRef
  • A Causality between Thyroid Function and Bone Mineral Density in Childhood: Abnormal Thyrotropin May Be Another Pediatric Predictor of Bone Fragility
    Dongjin Lee, Moon Ahn
    Metabolites.2023; 13(3): 372.     CrossRef
  • The mechanism of oxytocin and its receptors in regulating cells in bone metabolism
    Liu Feixiang, Feng Yanchen, Li Xiang, Zhang Yunke, Miao Jinxin, Wang Jianru, Lin Zixuan
    Frontiers in Pharmacology.2023;[Epub]     CrossRef
  • To investigate the mechanism of Yiwei Decoction in the treatment of premature ovarian insufficiency-related osteoporosis using transcriptomics, network pharmacology and molecular docking techniques
    Weisen Fan, Yan Meng, Jing Zhang, Muzhen Li, Yingjie Zhang, Xintian Qu, Xin Xiu
    Scientific Reports.2023;[Epub]     CrossRef
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Original Article
Miscellaneous
Fancd2os Reduces Testosterone Production by Inhibiting Steroidogenic Enzymes and Promoting Cellular Apoptosis in Murine Testicular Leydig Cells
Xiang Zhai, Xin-yang Li, Yu-jing Wang, Ke-ru Qin, Jin-rui Hu, Mei-ning Li, Hai-long Wang, Rui Guo
Endocrinol Metab. 2022;37(3):533-546.   Published online June 29, 2022
DOI: https://doi.org/10.3803/EnM.2022.1431
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AbstractAbstract PDFPubReader   ePub   
Background
It is well-established that serum testosterone in men decreases with age, yet the underlying mechanism of this change remains elusive.
Methods
The expression patterns of Fancd2 opposite-strand (Fancd2os) in BALB/c male mice and testicular tissue derived cell lines (GC-1, GC-2, TM3, and TM4) were assessed using real-time polymerase chain reaction (RT-PCR), Western blot and immunofluorescence. The Fancd2os-overexpressing or knockdown TM3 cells were constructed by infecting them with lentivirus particles and were used to evaluated the function of Fancd2os. The testosterone production was measured using enzyme linked immunosorbent assay (ELISA) and the steroidogenic enzymes such as steroidogenic acute regulatory protein (StAR), P450 cholesterol side-chain cleavage (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD) were analysed using RT-PCR. The apoptosis of TM3 cells induced by ultraviolet light or testicular tissues was detected using flow cytometry, Western blot or dUTP-biotin nick end labeling (TUNEL) assays. Pearson correlation analysis was used to assess the correlation between the Fancd2os expression and TUNEL-positive staining in mouse testicular Leydig cells.
Results
The Fancd2os protein was predominantly expressed in mouse testicular Leydig cells and its expression increased with age. Fancd2os overexpression inhibited testosterone levels in TM3 Leydig cells, whereas knockdown of Fancd2os elevated testosterone production. Fancd2os overexpression downregulated the levels of StAR, P450scc and 3β-HSD, while Fancd2os knockdown reversed this effect. Fancd2os overexpression promoted ultraviolet light-induced apoptosis of TM3 cells. In contrast, Fancd2os knockdown restrained apoptosis in TM3 cells. In vivo assays revealed that higher Fancd2os levels and mouse age were associated with increased apoptosis in Leydig cells and decreased serum testosterone levels. Pearson correlation analysis exhibited a strong positive correlation between the expression of Fancd2os and TUNEL-positive staining in mouse testicular Leydig cells.
Conclusion
Our findings suggest that Fancd2os regulates testosterone synthesis via both steroidogenic enzymes and the apoptotic pathway.

Citations

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  • An EWAS of dementia biomarkers and their associations with age, African ancestry, and PTSD
    Mark W. Miller, Erika J. Wolf, Xiang Zhao, Mark W. Logue, Sage E. Hawn
    Clinical Epigenetics.2024;[Epub]     CrossRef
  • Gas/Liquid Chromatography–Mass Spectrometry Analysis of Key Functional Substances Regulating Poll Gland Secretion in Male Camels during Seasonal Estrus
    Lijun Dai, Bao Yuan, Bohao Zhang, Wenli Chen, Xixue Yuan, Xinhong Liu, Yuan Gao, Yong Zhang, Quanwei Zhang, Xingxu Zhao
    Animals.2023; 13(12): 2024.     CrossRef
  • Benzo[b]fluoranthene induces male reproductive toxicity and apoptosis via Akt-Mdm2-p53 signaling axis in mouse Leydig cells: Integrating computational toxicology and experimental approaches
    Chao-feng Shi, Fei Han, Xiao Jiang, Zhonghao Zhang, Yingqing Li, Jiankang Wang, Shengqi Sun, Jin-yi Liu, Jia Cao
    Food and Chemical Toxicology.2023; 179: 113941.     CrossRef
  • Induction of apoptosis by cannabidiol and its main metabolites in human Leydig cells
    Yuxi Li, Xilin Li, Patrick Cournoyer, Supratim Choudhuri, Lei Guo, Si Chen
    Archives of Toxicology.2023; 97(12): 3227.     CrossRef
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Review Articles
Miscellaneous
Brown Adipose Tissue: Activation and Metabolism in Humans
Imane Hachemi, Mueez U-Din
Endocrinol Metab. 2023;38(2):214-222.   Published online March 27, 2023
DOI: https://doi.org/10.3803/EnM.2023.1659
  • 6,545 View
  • 469 Download
  • 3 Web of Science
  • 3 Crossref
AbstractAbstract PDFPubReader   ePub   
Brown adipose tissue (BAT) is a thermogenic organ contributing to non-shivering thermogenesis. BAT becomes active under cold stress via sympathetic nervous system activation. However, recent evidence has suggested that BAT may also be active at thermoneutrality and in a postprandial state. BAT has superior energy dissipation capacity compared to white adipose tissue (WAT) and muscles. Thus, it has been proposed that the recruitment and activation of additional BAT may increase the overall energy-expending capacity in humans, potentially improving current whole-body weight management strategies. Nutrition plays a central role in obesity and weight management. Thus, this review discusses human studies describing BAT hyper-metabolism after dietary interventions. Nutritional agents that can potentially recruit brown adipocytes via the process of BAT-WAT transdifferentiation are also discussed.

Citations

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  • Spermidine activates adipose tissue thermogenesis through autophagy and fibroblast growth factor 21
    Yinhua Ni, Liujie Zheng, Liqian Zhang, Jiamin Li, Yuxiang Pan, Haimei Du, Zhaorong Wang, Zhengwei Fu
    The Journal of Nutritional Biochemistry.2024; 125: 109569.     CrossRef
  • A natural sustained-intestinal release formulation of red chili pepper extracted capsaicinoids (Capsifen®) safely modulates energy balance and endurance performance: a randomized, double-blind, placebo-controlled study
    N. Roopashree, Das S. Syam, I. M. Krishnakumar, K. N. Mala, Bradley S. Fleenor, Jestin Thomas
    Frontiers in Nutrition.2024;[Epub]     CrossRef
  • MRI Methods to Visualize and Quantify Adipose Tissue in Health and Disease
    Katerina Nikiforaki, Kostas Marias
    Biomedicines.2023; 11(12): 3179.     CrossRef
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Hypothalamus and Pituitary Gland
Advances in Pituitary Surgery
Yoon Hwan Byun, Ho Kang, Yong Hwy Kim
Endocrinol Metab. 2022;37(4):608-616.   Published online August 19, 2022
DOI: https://doi.org/10.3803/EnM.2022.1546
  • 3,352 View
  • 157 Download
  • 2 Web of Science
  • 3 Crossref
AbstractAbstract PDFPubReader   ePub   
Pituitary surgery has advanced considerably in recent years with the exploration and development of various endoscopic approaches and techniques. Different endoscopic skull base approaches are being applied to access sellar tumors in different locations. Moreover, extracapsular dissection and cavernous sinus exploration have enabled gross total resection of sellar tumors where it could not have been achieved in the past. Techniques for skull base reconstruction have also progressed, allowing surgeons to remove larger and more complicated tumors than before. This review article discusses different endoscopic skull base approaches, surgical techniques for removing pituitary adenomas, and reconstruction methods for repairing postoperative low-flow and high-flow cerebrospinal fluid leakage.

Citations

Citations to this article as recorded by  
  • Serum and hair steroid profiles in patients with nonfunctioning pituitary adenoma undergoing surgery: A prospective observational study
    Seung Shin Park, Yong Hwy Kim, Ho Kang, Chang Ho Ahn, Dong Jun Byun, Man Ho Choi, Jung Hee Kim
    The Journal of Steroid Biochemistry and Molecular Biology.2023; 230: 106276.     CrossRef
  • Pituitary disease and anaesthesia
    Kim Rhodes, Robert John, Astri Luoma
    Anaesthesia & Intensive Care Medicine.2023; 24(6): 348.     CrossRef
  • Орфанні ендокринні захворювання: сучасні тенденції хірургічного лікування в Україні
    M.D. Tronko, B.B. Guda
    Endokrynologia.2022; 27(4): 287.     CrossRef
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Original Article
Adrenal gland
Big Data Articles (National Health Insurance Service Database)
Mortality and Severity of Coronavirus Disease 2019 in Patients with Long-Term Glucocorticoid Therapy: A Korean Nationwide Cohort Study
Eu Jeong Ku, Keeho Song, Kyoung Min Kim, Gi Hyeon Seo, Soon Jib Yoo
Endocrinol Metab. 2023;38(2):253-259.   Published online March 21, 2023
DOI: https://doi.org/10.3803/EnM.2022.1607
  • 2,766 View
  • 103 Download
  • 3 Web of Science
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AbstractAbstract PDFPubReader   ePub   
Background
The severity of coronavirus disease 2019 (COVID-19) among patients with long-term glucocorticoid treatment (LTGT) has not been established. We aimed to evaluate the association between LTGT and COVID-19 prognosis.
Methods
A Korean nationwide cohort database of COVID-19 patients between January 2019 and September 2021 was used. LTGT was defined as exposure to at least 150 mg of prednisolone (≥5 mg/day and ≥30 days) or equivalent glucocorticoids 180 days before COVID-19 infection. The outcome measurements were mortality, hospitalization, intensive care unit (ICU) admission, length of stay, and mechanical ventilation.
Results
Among confirmed patients with COVID-19, the LTGT group (n=12,794) was older and had a higher proportion of comorbidities than the control (n=359,013). The LTGT group showed higher in-hospital, 30-day, and 90-day mortality rates than the control (14.0% vs. 2.3%, 5.9% vs. 1.1%, and 9.9% vs. 1.8%, respectively; all P<0.001). Except for the hospitalization rate, the length of stay, ICU admission, and mechanical ventilation proportions were significantly higher in the LTGT group than in the control (all P<0.001). Overall mortality was higher in the LTGT group than in the control group, and the significance remained in the fully adjusted model (odds ratio [OR], 5.75; 95% confidence interval [CI], 5.31 to 6.23) (adjusted OR, 1.82; 95% CI, 1.67 to 2.00). The LTGT group showed a higher mortality rate than the control within the same comorbidity score category.
Conclusion
Long-term exposure to glucocorticoids increased the mortality and severity of COVID-19. Prevention and early proactive measures are inevitable in the high-risk LTGT group with many comorbidities.

Citations

Citations to this article as recorded by  
  • Outpatient glucocorticoid use and COVID-19 outcomes: a population-based study
    Almudena Rodríguez-Fernández, Irene Visos-Varela, Maruxa Zapata-Cachafeiro, Samuel Pintos-Rodríguez, Rosa M. García-Álvarez, Teresa M. Herdeiro, María Piñeiro-Lamas, Adolfo Figueiras, Ángel Salgado-Barreira, Rosendo Bugarín-González, Eduardo Carracedo-Mar
    Inflammopharmacology.2024;[Epub]     CrossRef
  • Glucocorticoids as a Double-Edged Sword in the Treatment of COVID-19: Mortality and Severity of COVID-19 in Patients Receiving Long-Term Glucocorticoid Therapy
    Eun-Hee Cho
    Endocrinology and Metabolism.2023; 38(2): 223.     CrossRef
  • Pituitary Diseases and COVID-19 Outcomes in South Korea: A Nationwide Cohort Study
    Jeonghoon Ha, Kyoung Min Kim, Dong-Jun Lim, Keeho Song, Gi Hyeon Seo
    Journal of Clinical Medicine.2023; 12(14): 4799.     CrossRef
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Special Article
Miscellaneous
Immune Checkpoint Inhibitors and Endocrine Disorders: A Position Statement from the Korean Endocrine Society
Hyemi Kwon, Eun Roh, Chang Ho Ahn, Hee Kyung Kim, Cheol Ryong Ku, Kyong Yeun Jung, Ju Hee Lee, Eun Heui Kim, Sunghwan Suh, Sangmo Hong, Jeonghoon Ha, Jun Sung Moon, Jin Hwa Kim, Mi-kyung Kim, The Committee of Clinical Practice Guideline of the Korean Endocrine Society
Endocrinol Metab. 2022;37(6):839-850.   Published online December 26, 2022
DOI: https://doi.org/10.3803/EnM.2022.1627
  • 3,689 View
  • 323 Download
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AbstractAbstract PDFPubReader   ePub   
Immune checkpoint inhibitors (ICIs) including an anti-cytotoxic T-lymphocyte-associated antigen 4 inhibitor, anti-programmed cell death protein 1 (PD-1) inhibitors, and anti-PD-ligand 1 inhibitors are representative therapeutics for various malignancies. In oncology, the application of ICIs is currently expanding to a wider range of malignancies due to their remarkable clinical outcomes. ICIs target immune checkpoints which suppress the activity of T-cells that are specific for tumor antigens, thereby allowing tumor cells to escape the immune response. However, immune checkpoints also play a crucial role in preventing autoimmune reactions. Therefore, ICIs targeting immune checkpoints can trigger various immune-related adverse events (irAEs), especially in endocrine organs. Considering the endocrine organs that are frequently involved, irAEs associated endocrinopathies are frequently life-threatening and have unfavorable clinical implications for patients. However, there are very limited data from large clinical trials that would inform the development of clinical guidelines for patients with irAEs associated endocrinopathies. Considering the current clinical situation, in which the scope and scale of the application of ICIs are increasing, position statements from clinical specialists play an essential role in providing the appropriate recommendations based on both medical evidence and clinical experience. As endocrinologists, we would like to present precautions and recommendations for the management of immune-related endocrine disorders, especially those involving the adrenal, thyroid, and pituitary glands caused by ICIs.

Citations

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  • Pembrolizumab plus lenvatinib for radically unresectable or metastatic renal cell carcinoma in the Japanese population
    Ryo Fujiwara, Takeshi yuasa, kenichi kobayashi, tetsuya yoshida, susumu kageyama
    Expert Review of Anticancer Therapy.2023; 23(5): 461.     CrossRef
  • Incidence of Endocrine-Related Dysfunction in Patients Treated with New Immune Checkpoint Inhibitors: A Meta-Analysis and Comprehensive Review
    Won Sang Yoo, Eu Jeong Ku, Eun Kyung Lee, Hwa Young Ahn
    Endocrinology and Metabolism.2023; 38(6): 750.     CrossRef
Close layer
Review Article
Adrenal Gland
Recent Updates on the Management of Adrenal Incidentalomas
Seung Shin Park, Jung Hee Kim
Endocrinol Metab. 2023;38(4):373-380.   Published online August 16, 2023
DOI: https://doi.org/10.3803/EnM.2023.1779
  • 7,973 View
  • 1,545 Download
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AbstractAbstract PDFPubReader   ePub   
Adrenal incidentalomas represent an increasingly common clinical conundrum with significant implications for patients. The revised 2023 European Society of Endocrinology (ESE) guideline incorporates cutting-edge evidence for managing adrenal incidentalomas. This paper provides a concise review of the updated contents of the revised guideline. In the 2023 guideline, in patients without signs and symptoms of overt Cushing’s syndrome, a post-dexamethasone cortisol level above 50 nmol/L (>1.8 μg/dL) should be considered as mild autonomous cortisol secretion. Regarding the criteria of benign adrenal adenomas, a homogeneous adrenal mass with ≤10 Hounsfield units on non-contrast computed tomography requires no further follow-up, irrespective of its size. The updated guideline also discusses steroid metabolomics using tandem mass spectrometry to discriminate malignancy. It underscores the importance of high-volume surgeons performing adrenalectomy and emphasizes the pivotal role of a multidisciplinary team approach in deciding the treatment plan for indeterminate adrenal masses. The guideline advocates for more proactive surgical treatment for indeterminate adrenal masses in young patients (<40 years) and pregnant women. This review of the 2023 ESE guideline underscores the ongoing evolution of the adrenal incidentaloma management landscape, emphasizing the need for further research and adaptation of diagnostic and therapeutic strategies.

Citations

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  • Personalized Management of Malignant and Non-Malignant Ectopic Mediastinal Thyroid: A Proposed 10-Item Algorithm Approach
    Mara Carsote, Mihai-Lucian Ciobica, Oana-Claudia Sima, Adrian Ciuche, Ovidiu Popa-Velea, Mihaela Stanciu, Florina Ligia Popa, Claudiu Nistor
    Cancers.2024; 16(10): 1868.     CrossRef
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Special Article
Adrenal gland
2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism
Jeonghoon Ha, Jung Hwan Park, Kyoung Jin Kim, Jung Hee Kim, Kyong Yeun Jung, Jeongmin Lee, Jong Han Choi, Seung Hun Lee, Namki Hong, Jung Soo Lim, Byung Kwan Park, Jung-Han Kim, Kyeong Cheon Jung, Jooyoung Cho, Mi-kyung Kim, Choon Hee Chung, The Committee of Clinical Practice Guideline of Korean Endocrine Society, The Korean Adrenal Study Group of Korean Endocrine Society
Endocrinol Metab. 2023;38(6):597-618.   Published online October 13, 2023
DOI: https://doi.org/10.3803/EnM.2023.1789
  • 3,880 View
  • 526 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFPubReader   ePub   
Primary aldosteronism (PA) is a common, yet underdiagnosed cause of secondary hypertension. It is characterized by an overproduction of aldosterone, leading to hypertension and/or hypokalemia. Despite affecting between 5.9% and 34% of patients with hypertension, PA is frequently missed due to a lack of clinical awareness and systematic screening, which can result in significant cardiovascular complications. To address this, medical societies have developed clinical practice guidelines to improve the management of hypertension and PA. The Korean Endocrine Society, drawing on a wealth of research, has formulated new guidelines for PA. A task force has been established to prepare PA guidelines, which encompass epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and follow-up care. The Korean clinical guidelines for PA aim to deliver an evidence-based protocol for PA diagnosis, treatment, and patient monitoring. These guidelines are anticipated to ease the burden of this potentially curable condition.

Citations

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  • Correlation of Histopathologic Subtypes of Primary Aldosteronism with Clinical Phenotypes and Postsurgical Outcomes
    Chang Ho Ahn, You-Bin Lee, Jae Hyeon Kim, Young Lyun Oh, Jung Hee Kim, Kyeong Cheon Jung
    The Journal of Clinical Endocrinology & Metabolism.2023;[Epub]     CrossRef
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Original Article
Miscellaneous
DN200434 Inhibits Vascular Smooth Muscle Cell Proliferation and Prevents Neointima Formation in Mice after Carotid Artery Ligation
Sudeep Kumar, Jonghwa Jin, Hyeon Young Park, Mi-Jin Kim, Jungwook Chin, Sungwoo Lee, Jina Kim, Jung-Guk Kim, Yeon-Kyung Choi, Keun-Gyu Park
Endocrinol Metab. 2022;37(5):800-809.   Published online September 28, 2022
DOI: https://doi.org/10.3803/EnM.2022.1462
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  • 201 Download
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AbstractAbstract PDFPubReader   ePub   
Background
Excessive proliferation and migration of vascular smooth muscle cells (VSMCs), which contributes to the development of occlusive vascular diseases, requires elevated mitochondrial oxidative phosphorylation to meet the increased requirements for energy and anabolic precursors. Therefore, therapeutic strategies based on blockade of mitochondrial oxidative phosphorylation are considered promising for treatment of occlusive vascular diseases. Here, we investigated whether DN200434, an orally available estrogen receptor-related gamma inverse agonist, inhibits proliferation and migration of VSMCs and neointima formation by suppressing mitochondrial oxidative phosphorylation.
Methods
VSMCs were isolated from the thoracic aortas of 4-week-old Sprague-Dawley rats. Oxidative phosphorylation and the cell cycle were analyzed in fetal bovine serum (FBS)- or platelet-derived growth factor (PDGF)-stimulated VSMCs using a Seahorse XF-24 analyzer and flow cytometry, respectively. A model of neointimal hyperplasia was generated by ligating the left common carotid artery in male C57BL/6J mice.
Results
DN200434 inhibited mitochondrial respiration and mammalian target of rapamycin complex 1 activity and consequently suppressed FBS- or PDGF-stimulated proliferation and migration of VSMCs and cell cycle progression. Furthermore, DN200434 reduced carotid artery ligation-induced neointima formation in mice.
Conclusion
Our data suggest that DN200434 is a therapeutic option to prevent the progression of atherosclerosis.

Citations

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  • Jatrorrhizine inhibits Piezo1 activation and reduces vascular inflammation in endothelial cells
    Tianying Hong, Xianmei Pan, Han Xu, Zhijuan Zheng, Lizhen Wen, Jing Li, Mingfeng Xia
    Biomedicine & Pharmacotherapy.2023; 163: 114755.     CrossRef
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Endocrinol Metab : Endocrinology and Metabolism