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
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
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
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
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 Annals of Internal Medicine.2022; 175(10): 1383. CrossRef
The adrenal gland plays a pivotal role in an organism’s health span by controlling the endocrine system. Decades of research on the adrenal gland have provided multiscale insights into the development and maintenance of this essential organ. A particularly interesting finding is that founder stem/progenitor cells participate in adrenocortical development and enable the adult adrenal cortex to regenerate itself in response to hormonal stress and injury. Since major advances have been made in understanding the dynamics of the developmental process and the remarkable regenerative capacity of the adrenal gland, understanding the mechanisms underlying adrenal development, maintenance, and regeneration will be of interest to basic and clinical researchers. Here, we introduce the developmental processes of the adrenal gland and discuss current knowledge regarding stem/progenitor cells that regulate adrenal cortex remodeling and regeneration. This review will provide insights into the fascinating ongoing research on the development and regeneration of the adrenal cortex.
Citations
Citations to this article as recorded by
Update on Adrenarche—Still a Mystery Philipp Augsburger, Jani Liimatta, Christa E Flück The Journal of Clinical Endocrinology & Metabolism.2024;[Epub] CrossRef
Aging induces region-specific dysregulation of hormone synthesis in the primate adrenal gland Qiaoran Wang, Xuebao Wang, Beibei Liu, Shuai Ma, Feng Zhang, Shuhui Sun, Yaobin Jing, Yanling Fan, Yingjie Ding, Muzhao Xiong, Jiaming Li, Qiaocheng Zhai, Yandong Zheng, Chengyu Liu, Gang Xu, Jiayin Yang, Si Wang, Jinlin Ye, Juan Carlos Izpisua Belmonte, Nature Aging.2024; 4(3): 396. CrossRef
Adrenal Dysfunction in Mitochondrial Diseases Madeleine Corkery-Hayward, Louise A. Metherell International Journal of Molecular Sciences.2023; 24(2): 1126. CrossRef
Effects of very low-calorie ketogenic diet on hypothalamic–pituitary–adrenal axis and renin–angiotensin–aldosterone system L. Barrea, L. Verde, E. Camajani, A. S. Šojat, L. Marina, S. Savastano, A. Colao, M. Caprio, G. Muscogiuri Journal of Endocrinological Investigation.2023; 46(8): 1509. CrossRef
Post‐hatching developmental changes in the adrenal gland of the Japanese quail (Coturnix coturnix japonica): Histological, immunohistochemical, and electron microscopic studies Fatma M. Abdel‐maksoud, Saher Fadl, Ahmed Abou‐Elmagd, Abdelmohaimen M.M. Saleh Microscopy Research and Technique.2023; 86(11): 1461. CrossRef
Interactive metabolic signatures of testicular testosterone with bilateral adrenalectomy in mice Hae Lim Cho, Ji-Hoon Kim, Seuk-Min Ryu, Jongsung Noh, Sang Won Lee, Man Ho Choi The Journal of Steroid Biochemistry and Molecular Biology.2023; 231: 106333. CrossRef
Construction of a novel clinical nomogram to predict cancer-specific survival in patients with primary malignant adrenal tumors: a large population-based retrospective study Mingzhen Li, Xiaoying Duan, Di You, Linlin Liu Frontiers in Medicine.2023;[Epub] CrossRef
The anti-platelet drug cilostazol enhances heart rate and interrenal steroidogenesis and exerts a scant effect on innate immune responses in zebrafish Wei-Chun Chang, Mei-Jen Chen, Chung-Der Hsiao, Rong-Ze Hu, Yu-Shan Huang, Yu-Fu Chen, Tsai-Hua Yang, Guan-Yi Tsai, Chih-Wei Chou, Ren-Shiang Chen, Yung-Jen Chuang, Yi-Wen Liu, Mohammed Fouad El Basuini PLOS ONE.2023; 18(10): e0292858. CrossRef
Regulation of Morphogenetic Processes during Postnatal Development and Physiological Regeneration of the Adrenal Medulla S. S. Obernikhin, N. V. Yaglova, E. P. Timokhina, S. V. Nazimova, V. V. Yaglov Bulletin of Experimental Biology and Medicine.2023; 175(4): 549. CrossRef
Distinct HAND2/HAND2-AS1 Expression Levels May Fine-Tune Mesenchymal and Epithelial Cell Plasticity of Human Mesenchymal Stem Cells Rachel Vazana-Netzarim, Yishay Elmalem, Shachar Sofer, Hod Bruck, Naama Danino, Udi Sarig International Journal of Molecular Sciences.2023; 24(22): 16546. CrossRef
An Update on Genetics of Adrenal Gland and Associated Disorders Chester Gauss, Dustin Rowland, Berrin Ergun-Longmire Endocrines.2022; 3(2): 187. CrossRef
Immune dysfunction after spinal cord injury – A review of autonomic and neuroendocrine mechanisms Kyleigh A. Rodgers, Kristina A. Kigerl, Jan M. Schwab, Phillip G. Popovich Current Opinion in Pharmacology.2022; 64: 102230. CrossRef
Clinical and Technical Aspects in Free Cortisol Measurement Man Ho Choi Endocrinology and Metabolism.2022; 37(4): 599. CrossRef
Surrénalectomies Isabelle Valin, Dan Rosenberg Le Nouveau Praticien Vétérinaire canine & féline.2022; 19(82): 50. CrossRef
Adrenal medulla development and medullary-cortical interactions Nicole Bechmann, Ilona Berger, Stefan R. Bornstein, Charlotte Steenblock Molecular and Cellular Endocrinology.2021; 528: 111258. CrossRef
Theory: Treatments for Prolonged ICU Patients May Provide New Therapeutic Avenues for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Dominic Stanculescu, Lars Larsson, Jonas Bergquist Frontiers in Medicine.2021;[Epub] CrossRef
Unravelling Polycystic Ovary Syndrome and Its Comorbidities Kyung-Wook Kim Journal of Obesity & Metabolic Syndrome.2021; 30(3): 209. CrossRef