Endocrinology and Metabolism

Review Articles

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

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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.

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Cortisol quantification in human plasma and urine by liquid chromatography coupled to mass spectrometry: Validation, analysis and application in a reference population and patients with adrenal incidentalomas
Andressa Cristina dos Santos Marques, Bruna Brito, Jéssica Gorett Brito Fontes, Gabriel Reis Alves Carneiro, João Felipe Dickson Rebelo, Aline Barbosa Moraes, Leonardo Vieira Neto, Monica Costa Padilha
Clinica Chimica Acta.2025; 566: 120055. CrossRef
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; 85(1): 321. 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
The role of thyroid hormones in assessing the survival of intensive care unit patients
Daniela Bartolovic, Snezana Jovicic, Branka Terzic
Vojnosanitetski pregled.2024; 81(5): 318. CrossRef
Current Challenges and Future Directions in the Assessment of Glucocorticoid Status
Sophie A Clarke, Pei Chia Eng, Alexander N Comninos, Katharine Lazarus, Sirazum Choudhury, Christie Tsang, Karim Meeran, Tricia M Tan, Waljit S Dhillo, Ali Abbara
Endocrine Reviews.2024; 45(6): 795. CrossRef
Exaggerated Increases in the Serum Cortisol Level in a Woman Following Oral Contraceptive Treatment
Run Yu
AACE Clinical Case Reports.2024; 10(5): 206. CrossRef
A systematic review and meta-analysis of cortisol levels in Plasmodium infections
Kwuntida Uthaisar Kotepui, Frederick Ramirez Masangkay, Kinley Wangdi, Aongart Mahittikorn, Hideyuki J. Majima, Manas Kotepui
Scientific Reports.2024;[Epub] CrossRef
Effects of a veterinary functional music-based enrichment program on the psychophysiological responses of farm pigs
Juliana Zapata Cardona, Santiago Duque Arias, Edimer David Jaramillo, Alexandre Surget, Yadira Ibargüen-Vargas, Berardo de Jesús Rodríguez
Scientific Reports.2024;[Epub] CrossRef
Post traumatic stress disorder associated hypothalamic-pituitary-adrenal axis dysregulation and physical illness
Stephanie Lawrence, R. Hal Scofield
Brain, Behavior, & Immunity - Health.2024; 41: 100849. CrossRef
Neurobiological Implications of Chronic Stress and Metabolic Dysregulation in Inflammatory Bowel Diseases
Aleksandar Sic, Kiana Cvetkovic, Eshanika Manchanda, Nebojsa Nick Knezevic
Diseases.2024; 12(9): 220. CrossRef
Altered sleep and inflammation are related to outcomes in neonatal encephalopathy
Tim Hurley, Philip Stewart, Robert McCarthy, Mary O'Dea, Lynne Kelly, Mandy Daly, John Butler, Rob McCarthy, Jan Miletin, Deirdre Sweetman, Angela Byrne, Gabrielle Colleran, Megan Ni Bhroin, Arun L. W. Bokde, Eleanor J. Molloy
Acta Paediatrica.2024;[Epub] 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

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

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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.

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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; 85(3): 1379. CrossRef
Cardiometabolic Aspects of Congenital Adrenal Hyperplasia
Robert Krysiak, Hedi L Claahsen-van der Grinten, Nicole Reisch, Philippe Touraine, Henrik Falhammar
Endocrine Reviews.2024;[Epub] CrossRef
Fasting GLP-1 Levels in Women with PCOS and CAH
R. Robeva, G. Kirilov, A. Elenkova, S. Zacharieva
Acta Medica Bulgarica.2024; 51(4): 8. 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

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

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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

Long‐term health consequences of congenital adrenal hyperplasia
Riccardo Pofi, Xiaochen Ji, Nils P. Krone, Jeremy W. Tomlinson
Clinical Endocrinology.2024; 101(4): 318. CrossRef
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
Cardiometabolic Aspects of Congenital Adrenal Hyperplasia
Robert Krysiak, Hedi L Claahsen-van der Grinten, Nicole Reisch, Philippe Touraine, Henrik Falhammar
Endocrine Reviews.2024;[Epub] CrossRef
Proof of concept for a superior therapeutic index of corticosterone compared with hydrocortisone in patients with congenital adrenal hyperplasia
Catriona J Kyle, Luke D Boyle, Mark Nixon, Natalie Z M Homer, Joanna P Simpson, Alison Rutter, Lynne E Ramage, Alexandra Kelman, Ellen Marie Freel, Ruth Andrew, Brian R Walker, Roland H Stimson
European Journal of Endocrinology.2024; 191(6): 535. 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
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

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

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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

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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
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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; 100(6): 404. CrossRef
Composition of the microbiota in patients with growth hormone deficiency before and after treatment with growth hormone
Patricia García Navas, María Yolanda Ruíz del Prado, Pablo Villoslada Blanco, Emma Recio Fernández, María Ruíz del Campo, Patricia Pérez Matute
Anales de Pediatría (English Edition).2024; 100(6): 404. CrossRef
Clinical Management of Postoperative Growth Hormone Deficiency in Hypothalamic-Pituitary Tumors
Pedro Iglesias
Journal of Clinical Medicine.2024; 13(15): 4307. CrossRef
An Overview of Cardiovascular Risk in Pituitary Disorders
Georgia Ntali, Vyron Markussis, Alexandra Chrisoulidou
Medicina.2024; 60(8): 1241. CrossRef
The role of IGF1 in determining body composition in children and adolescents with growth hormone deficiency and those with idiopathic short stature
Hussein Zaitoon, Michal Yackobovitch-Gavan, Eyas Midlej, Adi Uretzky, Irina Laurian, Anna Dorfman, Hagar Interator, Yael Lebenthal, Avivit Brener
Endocrine.2024; 86(3): 1110. CrossRef
Policy for transitioning childhood-onset growth hormone deficiency from pediatric to adult endocrine care in Belgium
Willem Staels, Jean De Schepper, Marianne Becker, Philippe Lysy, Daniel Klink, Karl Logghe, Marieken den Brinker, Anne Rochtus, Bruno Lapauw, Martine Cools, Orsalia Alexopoulou, Marie Bex, Bernard Corvilain, Laurent Crenier, Christophe De Block, Julian Do
Frontiers in Endocrinology.2024;[Epub] CrossRef
Transition Period and Young Adulthood in Patients with Childhood Onset Growth Hormone Deficiency (COGHD): Impact of Growth Hormone Replacement on Bone Mass and Body Composition
Mirjana Doknic, Marko Stojanovic, Aleksandra Markovic
International Journal of Molecular Sciences.2024; 25(19): 10313. CrossRef
Baseline Clinical Factors Associated with Cessation of Growth Hormone Therapy in Patients with Severe Growth Hormone Deficiency - Real World Evidence
Nageswary Nadarajah, Emmanuel Ssemmondo, Shani Brooks, Remi Akinyombo, Kazeem Adeleke, Harshal Deshmukh, Thozhukat Sathyapalan
International Journal of Endocrinology and Metabolism.2024;[Epub] CrossRef
Relationship between the Stimulated Peak Growth Hormone Level and Metabolic Parameters in Children with Growth Hormone Deficiency
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The Ewha Medical Journal.2023;[Epub] CrossRef
Dyslipidaemia and growth hormone deficiency – A comprehensive review
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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

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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.

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Dongjie Zhang, Shouzheng Ma, Liang Wang, Di Liu
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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
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Frontiers in Nutrition.2024;[Epub] CrossRef
Thermogenic Fat as a New Obesity Management Tool: From Pharmaceutical Reagents to Cell Therapies
Ying Cheng, Shiqing Liang, Shuhan Zhang, Xiaoyan Hui
Biomedicines.2024; 12(7): 1474. CrossRef
Ling-gui-zhu-gan granules reduces obesity and ameliorates metabolic disorders by inducing white adipose tissue browning in obese mice
Yuxiu Li, Zimengwei Ye, Yi Zhao, Bingrui Xu, Wanying Xue, Zhufeng Wang, Ran An, Fan Wang, Rui Wu
Frontiers in Physiology.2024;[Epub] CrossRef
When Being Lean Is Not Enough: The Metabolically Unhealthy Normal Weight Phenotype and Cardiometabolic Disease
Dahyun Park, Min-Jeong Shin, Faidon Magkos
CardioMetabolic Syndrome Journal.2024; 4(2): 57. CrossRef
The Interplay between Liver and Adipose Tissue in the Onset of Liver Diseases: Exploring the Role of Vitamin Deficiency
Ivan Tattoli, Aimee Rachel Mathew, Antonella Verrienti, Lucia Pallotta, Carola Severi, Fausto Andreola, Virve Cavallucci, Mauro Giorgi, Mara Massimi, Lapo Bencini, Marco Fidaleo
Cells.2024; 13(19): 1631. CrossRef
Nutrition, hydration and supplementation considerations for mountaineers in high-altitude conditions: a narrative review
Ewa Karpęcka-Gałka, Barbara Frączek
Frontiers in Sports and Active Living.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

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

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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.

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Cushing’s disease and bone
Aleksandra Zdrojowy-Wełna, Barbara Stachowska, Marek Bolanowski
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Skeletal fragility in pituitary disease: how can we predict fracture risk?
Fabio Bioletto, Alessandro Maria Berton, Marco Barale, Luigi Simone Aversa, Lorenzo Sauro, Michela Presti, Francesca Mocellini, Noemi Sagone, Ezio Ghigo, Massimo Procopio, Silvia Grottoli
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Role of oxytocin in bone
Tianming Wang, Jianya Ye, Yongqiang Zhang, Jiayi Li, Tianxiao Yang, Yufeng Wang, Xiao Jiang, Qingqiang Yao
Frontiers in Endocrinology.2024;[Epub] CrossRef
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Modern approach to bone comorbidity in prolactinoma
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Dongjin Lee, Moon Ahn
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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
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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

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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.

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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.2024; 109(8): e1582. CrossRef
Temporal trends in clinical features of patients with primary aldosteronism over 20 years
Seung Shin Park, Chang Ho Ahn, Sang Wan Kim, Jung-Min Koh, Seung Hun Lee, Jung Hee Kim
Hypertension Research.2024; 47(8): 2019. CrossRef
Primary aldosteronism: An underdiagnosed clinical entity
Peeyush Jain, Atul Kaushik, Nilashish Dey, Ashwani Mehta, Shaloo Kapoor, Chhavi Agrawal
Journal of Current Cardiology.2024; 2(2): 65. CrossRef
Historical changes in the clinical features of primary aldosteronism
Takamasa Ichijo
Hypertension Research.2024; 47(10): 2926. CrossRef
Comparing ARR Versus Suppressed PRA as Screening Tests for Primary Aldosteronism
Marco Marcelli, Caixia Bi, John W. Funder, Michael J. McPhaul
Hypertension.2024; 81(10): 2072. CrossRef
Screening and treatment of endocrine hypertension focusing on adrenal gland disorders: a narrative review
Seung Min Chung
Journal of Yeungnam Medical Science.2024; 41(4): 269. CrossRef
Differences in target organ damage between captopril challenge test-defined definitive-positive and borderline-range groups among patients with primary aldosteronism
Naoki Fujiwara, Tatsuya Haze, Hiromichi Wakui, Kouichi Tamura, Mika Tsuiki, Kohei Kamemura, Daisuke Taura, Takamasa Ichijo, Yutaka Takahashi, Minemori Watanabe, Hiroki Kobayashi, Toshifumi Nakamura, Shoichiro Izawa, Norio Wada, Tetsuya Yamada, Kenichi Yok
Hypertension Research.2024;[Epub] CrossRef

Original Article

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

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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.

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Long‐term health consequences of congenital adrenal hyperplasia
Riccardo Pofi, Xiaochen Ji, Nils P. Krone, Jeremy W. Tomlinson
Clinical Endocrinology.2024; 101(4): 318. 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

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

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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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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
Temporal trends in clinical features of patients with primary aldosteronism over 20 years
Seung Shin Park, Chang Ho Ahn, Sang Wan Kim, Jung-Min Koh, Seung Hun Lee, Jung Hee Kim
Hypertension Research.2024; 47(8): 2019. CrossRef
Steroid Profiling in the Differential Diagnosis of Cushing's Syndrome and Diagnosis of MACS
A. Nankova, T. Kamenova, V. Vasilev, At. Elenkova, D. Svinarov, G. Kirilov, S. Zaharieva
Acta Medica Bulgarica.2024; 51(2): 1. CrossRef
Adrenal incidentalomas
Ivana Ságová
Vnitřní lékařství.2024; 70(5): E9. CrossRef
Ectopic Mediastinal Thyroid: A Crossroad Between a Multi-Layered Endocrine Perspective and a Contemporary Approach in Thoracic Surgery
Claudiu Nistor, Mihai-Lucian Ciobica, Oana-Claudia Sima, Anca-Pati Cucu, Florina Vasilescu, Lucian-George Eftimie, Dana Terzea, Mihai Costachescu, Adrian Ciuche, Mara Carsote
Life.2024; 14(11): 1374. CrossRef

Original Article

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

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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.

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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
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.2024; 109(8): e1582. CrossRef
Predicting the resolution of hypertension following adrenalectomy in primary aldosteronism: Controversies and unresolved issues a narrative review
Luigi Marzano
Langenbeck's Archives of Surgery.2024;[Epub] 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

Review Articles

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

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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.

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The Impact of Surgical Telementoring on Reducing the Complication Rate in Endoscopic Endonasal Surgery of the Skull Base
Janez Ravnik, Hojka Rowbottom, Carl H. Snyderman, Paul A. Gardner, Tomaž Šmigoc, Matic Glavan, Urška Kšela, Nenad Kljaić, Boštjan Lanišnik
Diagnostics.2024; 14(17): 1874. CrossRef
Obstructive Sleep Apnea Screening and Effects of Surgery in Acromegaly: A Prospective Study
Jaeyoung Cho, Jung Hee Kim, Yong Hwy Kim, Jinwoo Lee
Endocrinology and Metabolism.2024; 39(4): 641. 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
Pituitary disease and anaesthesia
Kim Rhodes, Robert John, Astri Luoma
Anaesthesia & Intensive Care Medicine.2023; 24(6): 348. CrossRef
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M.D. Tronko, B.B. Guda
Endokrynologia.2022; 27(4): 287. CrossRef

Hypothalamus and pituitary gland
Update on Current Evidence for the Diagnosis and Management of Nonfunctioning Pituitary Neuroendocrine Tumors: Elizabeth Whyte, Masahiro Nezu, Constance Chik, Toru Tateno; Endocrinol Metab. 2023;38(6):631-654. Published online November 15, 2023; DOI: https://doi.org/10.3803/EnM.2023.1838

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Pituitary neuroendocrine tumors (PitNETs) are the third most frequently diagnosed intracranial tumors, with nonfunctioning PitNETs (nfPitNETs) accounting for 30% of all pituitary tumors and representing the most common type of macroPitNETs. NfPitNETs are usually benign tumors with no evidence of hormone oversecretion except for hyperprolactinemia secondary to pituitary stalk compression. Due to this, they do not typically present with clinical syndromes like acromegaly, Cushing’s disease or hyperthyroidism and instead are identified incidentally on imaging or from symptoms of mass effects (headache, vision changes, apoplexy). With the lack of effective medical interventions, first-line treatment is transsphenoidal surgical resection, however, nfPitNETs often have supra- or parasellar extension, and total resection of the tumor is often not possible, resulting in residual tumor regrowth or reoccurrence. While functional PitNETs can be easily followed for recurrence using hormonal biomarkers, there is no similar parameter to predict recurrence in nfPitNETs, hence delaying early recognition and timely management. Therefore, there is a need to identify prognostic biomarkers that can be used for patient surveillance and as therapeutic targets. This review focuses on summarizing the current evidence on nfPitNETs, with a special focus on potential new biomarkers and therapeutics.

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Phenotype Transformation of PitNETs
Zhenwei Li, Yinzi Wu, Guannan He, Renzhi Wang, Xinjie Bao
Cancers.2024; 16(9): 1731. CrossRef
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Zhongyu Wang, Li Wei, Junfeng Lin, Can Huang, Huitong Chen, Dong Fan, Weiyu Hu, Jing Liu, Huaiyi Huang, Zongming Wang, Xin Wang
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Editorial: Prognostic factors in pituitary tumors: clinical, biochemical, imaging, and pathological aspects
Toru Tateno, Roxana-Ioana Dumitriu Stan, Stephanie Du Four
Frontiers in Endocrinology.2024;[Epub] CrossRef

Original Articles

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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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.

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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
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Lijun Dai, Bao Yuan, Bohao Zhang, Wenli Chen, Xixue Yuan, Xinhong Liu, Yuan Gao, Yong Zhang, Quanwei Zhang, Xingxu Zhao
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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
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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

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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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Saedis Saevarsdottir, Kristbjörg Bjarnadottir, Thorsteinn Markusson, Jonas Berglund, Thorunn A. Olafsdottir, Gisli H. Halldorsson, Gudrun Rutsdottir, Kristbjorg Gunnarsdottir, Asgeir Orn Arnthorsson, Sigrun H. Lund, Lilja Stefansdottir, Julius Gudmundsson
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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

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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.

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