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Review Article
Adrenal gland
A Contemporary Approach to the Diagnosis and Management of Adrenal Insufficiency
Suranut Charoensri, Richard J. Auchus
Endocrinol Metab. 2024;39(1):73-82.   Published online January 22, 2024
DOI: https://doi.org/10.3803/EnM.2024.1894
  • 2,514 View
  • 246 Download
AbstractAbstract PDFPubReader   ePub   
Adrenal insufficiency (AI) can be classified into three distinct categories based on its underlying causes: primary adrenal disorders, secondary deficiencies in adrenocorticotropin, or hypothalamic suppression from external factors, most commonly glucocorticoid medications used for anti-inflammatory therapy. The hallmark clinical features of AI include fatigue, appetite loss, unintentional weight loss, low blood pressure, and hyponatremia. Individuals with primary AI additionally manifest skin hyperpigmentation, hyperkalemia, and salt craving. The diagnosis of AI is frequently delayed due to the non-specific symptoms and signs early in the disease course, which poses a significant challenge to its early detection prior to an adrenal crisis. Despite the widespread availability of lifesaving glucocorticoid medications for decades, notable challenges persist, particularly in the domains of timely diagnosis while simultaneously avoiding misdiagnosis, patient education for averting adrenal crises, and the determination of optimal replacement therapies. This article reviews recent advancements in the contemporary diagnostic strategy and approaches to optimal treatment for AI.
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Original Article
Miscellaneous
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
Endocrinol Metab. 2023;38(6):750-759.   Published online November 13, 2023
DOI: https://doi.org/10.3803/EnM.2023.1785
  • 1,451 View
  • 122 Download
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study investigated the incidence of endocrine immune-related adverse events (irAEs) for recently developed immune checkpoint inhibitor (ICI) drugs.
Methods
We collected studies on newly developed ICI drugs using PubMed/Medline, Embase, and Cochrane Library from inception through January 31, 2023. Among ICI drugs, nivolumab, pembrolizumab, and ipilimumab were excluded from the new ICI drugs because many papers on endocrine-related side effects have already been published.
Results
A total of 44,595 patients from 177 studies were included in this analysis. The incidence of hypothyroidism was 10.1% (95% confidence interval [CI], 8.9% to 11.4%), thyrotoxicosis was 4.6% (95% CI, 3.8% to 5.7%), hypophysitis was 0.8% (95% CI, 0.5% to 1.1%), adrenal insufficiency was 0.9% (95% CI, 0.7% to 1.1%), and hyperglycemia was 2.3% (95% CI, 1.6% to 3.4%). Hypothyroidism and thyrotoxicosis occurred most frequently with programmed cell death protein-1 (PD-1) inhibitors (13.7% and 7.5%, respectively). The rate of endocrine side effects for the combination of a programmed death-ligand 1 inhibitor (durvalumab) and cytotoxic T lymphocyte-associated antigen 4 inhibitor (tremelimumab) was higher than that of monotherapy. In a meta-analysis, the combination of tremelimumab and durvalumab had a 9- to 10-fold higher risk of pituitary and adrenal-related side effects than durvalumab alone.
Conclusion
Newly developed PD-1 inhibitors had a high incidence of thyroid-related irAEs, and combined treatment with durvalumab and tremelimumab increased the risk of pituitary- and adrenal-related irAEs. Based on these facts, it is necessary to predict the endocrine side effects corresponding to each ICI drug, diagnose and treat them appropriately, and try to reduce the morbidity and mortality of patients.
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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
  • 7,303 View
  • 1,455 Download
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.
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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
  • 3,516 View
  • 321 Download
  • 2 Web of Science
  • 2 Crossref
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

Citations to this article as recorded by  
  • 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
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Review Article
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
  • 4,705 View
  • 290 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
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
  • 3,793 View
  • 159 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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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
  • 3,361 View
  • 149 Download
  • 8 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
  • Predictors of Cardiovascular Morbidities in Adults With 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia
    Suranut Charoensri, Richard J Auchus
    The Journal of Clinical Endocrinology & Metabolism.2024; 109(3): e1133.     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
  • 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
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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
  • 4,254 View
  • 126 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
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Adrenal Gland
Metabolic Subtyping of Adrenal Tumors: Prospective Multi-Center Cohort Study in Korea
Eu Jeong Ku, Chaelin Lee, Jaeyoon Shim, Sihoon Lee, Kyoung-Ah Kim, Sang Wan Kim, Yumie Rhee, Hyo-Jeong Kim, Jung Soo Lim, Choon Hee Chung, Sung Wan Chun, Soon-Jib Yoo, Ohk-Hyun Ryu, Ho Chan Cho, A Ram Hong, Chang Ho Ahn, Jung Hee Kim, Man Ho Choi
Endocrinol Metab. 2021;36(5):1131-1141.   Published online October 21, 2021
DOI: https://doi.org/10.3803/EnM.2021.1149
  • 5,116 View
  • 209 Download
  • 8 Web of Science
  • 8 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Conventional diagnostic approaches for adrenal tumors require multi-step processes, including imaging studies and dynamic hormone tests. Therefore, this study aimed to discriminate adrenal tumors from a single blood sample based on the combination of liquid chromatography-mass spectrometry (LC-MS) and machine learning algorithms in serum profiling of adrenal steroids.
Methods
The LC-MS-based steroid profiling was applied to serum samples obtained from patients with nonfunctioning adenoma (NFA, n=73), Cushing’s syndrome (CS, n=30), and primary aldosteronism (PA, n=40) in a prospective multicenter study of adrenal disease. The decision tree (DT), random forest (RF), and extreme gradient boost (XGBoost) were performed to categorize the subtypes of adrenal tumors.
Results
The CS group showed higher serum levels of 11-deoxycortisol than the NFA group, and increased levels of tetrahydrocortisone (THE), 20α-dihydrocortisol, and 6β-hydroxycortisol were found in the PA group. However, the CS group showed lower levels of dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) than both the NFA and PA groups. Patients with PA expressed higher serum 18-hydroxycortisol and DHEA but lower THE than NFA patients. The balanced accuracies of DT, RF, and XGBoost for classifying each type were 78%, 96%, and 97%, respectively. In receiver operating characteristics (ROC) analysis for CS, XGBoost, and RF showed a significantly greater diagnostic power than the DT. However, in ROC analysis for PA, only RF exhibited better diagnostic performance than DT.
Conclusion
The combination of LC-MS-based steroid profiling with machine learning algorithms could be a promising one-step diagnostic approach for the classification of adrenal tumor subtypes.

Citations

Citations to this article as recorded by  
  • Treating Primary Aldosteronism-Induced Hypertension: Novel Approaches and Future Outlooks
    Nathan Mullen, James Curneen, Padraig T Donlon, Punit Prakash, Irina Bancos, Mark Gurnell, Michael C Dennedy
    Endocrine Reviews.2024; 45(1): 125.     CrossRef
  • Steroid profiling in adrenal disease
    Danni Mu, Dandan Sun, Xia Qian, Xiaoli Ma, Ling Qiu, Xinqi Cheng, Songlin Yu
    Clinica Chimica Acta.2024; 553: 117749.     CrossRef
  • 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
  • Recent Updates on the Management of Adrenal Incidentalomas
    Seung Shin Park, Jung Hee Kim
    Endocrinology and Metabolism.2023; 38(4): 373.     CrossRef
  • LC-MS based simultaneous profiling of adrenal hormones of steroids, catecholamines, and metanephrines
    Jongsung Noh, Chaelin Lee, Jung Hee Kim, Seung Woon Myung, Man Ho Choi
    Journal of Lipid Research.2023; 64(11): 100453.     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
  • Toward Systems-Level Metabolic Analysis in Endocrine Disorders and Cancer
    Aliya Lakhani, Da Hyun Kang, Yea Eun Kang, Junyoung O. Park
    Endocrinology and Metabolism.2023; 38(6): 619.     CrossRef
  • Prevalence and Characteristics of Adrenal Tumors in an Unselected Screening Population
    Ying Jing, Jinbo Hu, Rong Luo, Yun Mao, Zhixiao Luo, Mingjun Zhang, Jun Yang, Ying Song, Zhengping Feng, Zhihong Wang, Qingfeng Cheng, Linqiang Ma, Yi Yang, Li Zhong, Zhipeng Du, Yue Wang, Ting Luo, Wenwen He, Yue Sun, Fajin Lv, Qifu Li, Shumin Yang
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Special Article
Miscellaneous
COVID-19 Vaccination for Endocrine Patients: A Position Statement from the Korean Endocrine Society
Cheol Ryong Ku, Kyong Yeun Jung, Chang Ho Ahn, Jun Sung Moon, Ju Hee Lee, Eun Heui Kim, Hyemi Kwon, Hee Kyung Kim, Sunghwan Suh, Sangmo Hong, Jeonghoon Ha, Eun Roh, Jin Hwa Kim, Mi-kyung Kim, the Committee of Clinical Practice Guideline of the Korean Endocrine Society
Endocrinol Metab. 2021;36(4):757-765.   Published online August 17, 2021
DOI: https://doi.org/10.3803/EnM.2021.404
  • 10,375 View
  • 419 Download
  • 19 Web of Science
  • 21 Crossref
AbstractAbstract PDFPubReader   ePub   
Since the first outbreak of coronavirus disease 2019 (COVID-19), ongoing efforts have been made to discover an efficacious vaccine against COVID-19 to combat the pandemic. In most countries, both mRNA and DNA vaccines have been administered, and their side effects have also been reported. The clinical course of COVID-19 and the effects of vaccination against COVID-19 are both influenced by patients’ health status and involve a systemic physiological response. In view of the systemic function of endocrine hormones, endocrine disorders themselves and the therapeutics used to treat them can influence the outcomes of vaccination for COVID-19. However, there are very limited data to support the development of clinical guidelines for patients with specific medical backgrounds based on large clinical trials. In the current severe circumstances of the COVID-19 pandemic, position statements made by clinical specialists are essential to provide appropriate recommendations based on both medical evidence and clinical experiences. As endocrinologists, we would like to present the medical background of COVID-19 vaccination, as well as precautions to prevent the side effects of COVID-19 vaccination in patients with specific endocrine disorders, including adrenal insufficiency, diabetes mellitus, osteoporosis, autoimmune thyroid disease, hypogonadism, and pituitary disorders.

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Close layer
Original Article
Adrenal Gland
Contralateral Suppression at Adrenal Venous Sampling Is Associated with Renal Impairment Following Adrenalectomy for Unilateral Primary Aldosteronism
Ye Seul Yang, Seung Hun Lee, Jung Hee Kim, Jee Hee Yoo, Jung Hyun Lee, Seo Young Lee, A Ram Hong, Dong-Hwa Lee, Jung-Min Koh, Jae Hyeon Kim, Sang Wan Kim
Endocrinol Metab. 2021;36(4):875-884.   Published online August 11, 2021
DOI: https://doi.org/10.3803/EnM.2021.1047
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  • 150 Download
  • 7 Web of Science
  • 7 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Adrenal venous sampling (AVS) is performed to distinguish the subtype of primary aldosteronism (PA). The clinical implication of contralateral suppression (CS; aldosterone/cortisolnondominantperipheral) at AVS remains unclear. We aimed to investigate the clinical significance of CS and its impact on postoperative outcomes after unilateral adrenalectomy.
Methods
In this retrospective observational multi-center study, we analyzed PA patients who underwent both successful adrenocorticotropin hormone-stimulated AVS and unilateral adrenalectomy. Successful cannulation was defined as the selectivity index (cortisoladrenal/ cortisolperipheral) ≥3. Clinical and biochemical outcomes after unilateral adrenalectomy were evaluated based on the international Primary Aldosteronism Surgical Outcome consensus.
Results
Among 263 patients analyzed, 247 had CS (93.9%). Patients with CS had lower serum potassium levels, higher plasma aldosterone concentration, higher aldosterone-to-renin ratio (ARR), and larger adenoma size than those without CS. Those with CS showed significantly higher lateralization index than those without CS (P<0.001). Although postoperative blood pressure and ARR significantly decreased in those with CS, clinical and biochemical outcomes were comparable in both groups. When the cut-off value of age was determined using receiver operating characteristic (ROC) analysis, patients aged ≥50 years old with contralateral suppression index (CSI; the ratio between aldosterone/cortisolnondominant and aldosterone/cortisolperipheral) ≤0.26 had greater odds ratio (6.43; 95% confidence interval, 1.30 to 31.69) of incident chronic kidney disease than those aged <50 years with CSI >0.26 after adjusting for other factors.
Conclusion
CS may not predict postoperative clinical and biochemical outcomes in subjects with unilateral aldosterone excess, but it is associated with postsurgical deterioration of renal function in subjects over 50 years with CSI ≤0.26.

Citations

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  • Treatment decision based on unilateral index from nonadrenocorticotropic hormone-stimulated and adrenocorticotropic hormone-stimulated adrenal vein sampling in primary aldosteronism
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    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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    Sara Mørup, Nathalie Voss, Caroline Clausen, Claus Larsen Feltoft, Mikkel Andreassen, Jesper Krogh
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Close layer
Review Articles
Adrenal Gland
Asian Conference on Tumor Ablation Guidelines for Adrenal Tumor Ablation
Byung Kwan Park, Masashi Fujimori, Shu-Huei Shen, Uei Pua
Endocrinol Metab. 2021;36(3):553-563.   Published online June 1, 2021
DOI: https://doi.org/10.3803/EnM.2021.1008
  • 3,673 View
  • 142 Download
  • 3 Web of Science
  • 4 Crossref
AbstractAbstract PDFPubReader   ePub   
Thermal ablation is a good alternative treatment in patients who are unable to undergo adrenalectomy. Even though the Asian Conference on Tumor Ablation (ACTA) has been held for many years, adrenal ablation guidelines have not been established. No guidelines for adrenal ablation are established in American and European countries, either. The aim of this review was to introduce the first version of ACTA guidelines for adrenal tumor ablation.

Citations

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    Chi-Shin Tseng, Chieh-Kai Chan, Hsiang-Ying Lee, Chien-Ting Pan, Kang-Yung Peng, Shuo-Meng Wang, Kuo-How Huang, Yao-Chou Tsai, Vin-Cent Wu, Jeff S. Chueh
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    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
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Miscellaneous
Clinical Characteristics, Management, and Potential Biomarkers of Endocrine Dysfunction Induced by Immune Checkpoint Inhibitors
Shintaro Iwama, Tomoko Kobayashi, Hiroshi Arima
Endocrinol Metab. 2021;36(2):312-321.   Published online April 27, 2021
DOI: https://doi.org/10.3803/EnM.2021.1007
  • 5,498 View
  • 267 Download
  • 15 Web of Science
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AbstractAbstract PDFPubReader   ePub   
Immune-related adverse events (irAEs) affecting the endocrine glands are among the most frequent irAEs induced by immune checkpoint inhibitors (ICIs) and include hypopituitarism, primary adrenal insufficiency, thyrotoxicosis, hypothyroidism, hypoparathyroidism, and type 1 diabetes mellitus. Since the incidence and clinical features of endocrine irAEs vary according to the ICI used, it is important to understand the characteristics of these irAEs and to manage each one appropriately. Since some endocrine irAEs, including adrenal crisis and diabetic ketoacidosis, are potentially life-threatening, predicting the risk of endocrine irAEs before their onset is critical. Several autoantibodies have been detected in patients who develop endocrine irAEs, among which anti-thyroid antibodies may be predictive biomarkers of thyroid dysfunction. In this review, we describe the clinical features of each endocrine irAE induced by ICIs and discuss their potential biomarkers, including autoantibodies.

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    Tomoko Kobayashi, Shintaro Iwama, Ayana Yamagami, Yoshinori Yasuda, Takayuki Okuji, Masaaki Ito, Xin Zhou, Masahiko Ando, Takeshi Onoue, Takashi Miyata, Mariko Sugiyama, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Masahiro Morise, Taka
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    Fabiana Pani, Yoshinori Yasuda, Sylvie T Rousseau, Kevin C Bermea, Solmaz Roshanmehr, Rulin Wang, Srinivasan Yegnasubramanian, Patrizio Caturegli, Luigi Adamo
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Close layer
Hypothalamus and Pituitary gland
Best Achievements in Pituitary and Adrenal Diseases in 2020
Chang Ho Ahn, Jung Hee Kim
Endocrinol Metab. 2021;36(1):51-56.   Published online February 24, 2021
DOI: https://doi.org/10.3803/EnM.2021.108
  • 4,508 View
  • 162 Download
  • 2 Web of Science
  • 2 Crossref
AbstractAbstract PDFPubReader   ePub   
Significant progress in pituitary and adrenal diseases was made in 2020. This review presents major translational and clinical advances in research on pituitary and adrenal diseases, encompassing their epidemiology, pathogenesis, diagnosis, and clinical management. We address the controversy regarding the nomenclature of pituitary neuroendocrine tumors, omics-based molecular classification of pituitary adenomas, and novel drugs for Cushing’s disease in the field of pituitary diseases. In the field of adrenal diseases, we cover big data-driven epidemiology of adrenal tumors, steroid profiling as a new diagnostic tool, and the utility of scoring systems in the decision-making process of managing primary aldosteronism. This brief article will broaden readers’ understanding of pituitary and adrenal diseases.

Citations

Citations to this article as recorded by  
  • Surgical management and outcomes of spinal metastasis of malignant adrenal tumor: A retrospective study of six cases and literature review
    Xiangzhi Ni, Jing Wang, Jiashi Cao, Kun Zhang, Shuming Hou, Xing Huang, Yuanjin Song, Xin Gao, Jianru Xiao, Tielong Liu
    Frontiers in Oncology.2023;[Epub]     CrossRef
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    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
Close layer
Adrenal gland
The Genotype-Based Morphology of Aldosterone-Producing Adrenocortical Disorders and Their Association with Aging
Xin Gao, Yuto Yamazaki, Yuta Tezuka, Kei Omata, Yoshikiyo Ono, Ryo Morimoto, Yasuhiro Nakamura, Fumitoshi Satoh, Hironobu Sasano
Endocrinol Metab. 2021;36(1):12-21.   Published online February 24, 2021
DOI: https://doi.org/10.3803/EnM.2021.101
  • 4,796 View
  • 194 Download
  • 6 Web of Science
  • 6 Crossref
AbstractAbstract PDFPubReader   ePub   
Primary aldosteronism (PA) is the most common cause of secondary hypertension, and is associated with an increased incidence of cardiovascular events. PA itself is clinically classified into the following two types: unilateral PA, mostly composed of aldosteroneproducing adenoma (APA); and bilateral hyperaldosteronism, consisting of multiple aldosterone-producing micronodules (APMs) and aldosterone-producing diffuse hyperplasia. Histopathologically, those disorders above are all composed of compact and clear cells. The cellular morphology in the above-mentioned aldosterone-producing disorders has been recently reported to be closely correlated with patterns of somatic mutations of ion channels including KCNJ5, CACNA1D, ATP1A1, ATP2B3, and others. In addition, in non-pathological adrenal glands, APMs are frequently detected regardless of the status of the renin-angiotensin-aldosterone system (RAAS). Aldosterone-producing nodules have been also proposed as non-neoplastic nodules that can be identified by hematoxylin and eosin staining. These non-neoplastic CYP11B2-positive nodules could represent possible precursors of APAs possibly due to the presence of somatic mutations. On the other hand, aging itself also plays a pivotal role in the development of aldosterone-producing lesions. For instance, the number of APMs was also reported to increase with aging. Therefore, recent studies indicated the novel classification of PA into normotensive PA (RAAS-independent APM) and clinically overt PA.

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
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    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
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    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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    Chang Ho Ahn, Hee Young Na, So Yeon Park, Hyeong Won Yu, Su‐Jin Kim, June Young Choi, Kyu Eun Lee, Sang Wan Kim, Kyeong Cheon Jung, Jung Hee Kim
    Clinical Endocrinology.2022; 96(1): 30.     CrossRef
  • Pathology of Aldosterone Biosynthesis and its Action
    Xin Gao, Yuto Yamazaki, Yuta Tezuka, Kei Omata, Yoshikiyo Ono, Ryo Morimoto, Yasuhiro Nakamura, Takashi Suzuki, Fumitoshi Satoh, Hironobu Sasano
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Endocrinol Metab : Endocrinology and Metabolism