Endocrinology and Metabolism

Special Article

Pituitary gland
Consensus on the Diagnosis of Cushing’s Disease: A Collaborative Statement from the Korean Endocrine Society and Japan Endocrine Society: Jeongmin Lee, Hidenori Fukuoka, Seung Shin Park, A Ram Hong, Jung Hee Kim, Sang Ouk Chin, Han-Sang Baek, Dong-Jun Lim, Kazunori Kageyama, Mitsuru Nishiyama, Shigeyuki Tahara, Kenichi Oyama, Akira Sugawara, Miho Yamashita, Naoko Inoshita, Hiroshi Arima, Byung-Joon Kim, Yoon-Sok Chung, Soon Jib Yoo, Michio Otsuki, Mi-kyung Kim, The Committee of Clinical Practice Guideline of Korean Endocrine Society, Korean Neuroendocrine Study Group of Korean Endocrine Society; Endocrinol Metab. 2026;41(1):1-13. Published online January 1, 2026; DOI: https://doi.org/10.3803/EnM.2025.2707

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Abstract PDF PubReader ePub: Cushing’s disease (CD) is a rare but serious endocrine disorder caused by excessive cortisol secretion due to adrenocorticotropic hormone–secreting pituitary tumors. Despite recent developments in diagnostic criteria and treatment options, CD remains associated with substantial comorbidities and mortality. Early and accurate diagnosis is thus essential. Both the Korean Endocrine Society (KES) and Japan Endocrine Society (JES) guidelines are intended to standardize diagnostic approaches to CD, and they share common principles; however, notable differences exist, particularly in biochemical testing thresholds and imaging recommendations. This consensus statement integrates clinical evidence and expert practice from both the KES and JES to establish harmonized recommendations for biochemical evaluation, imaging, and differential testing. This unified framework is intended to enhance diagnostic precision and improve clinical outcomes across East Asian populations.

Review Articles

Hypothalamus and pituitary gland
Medical Treatment of Cushing’s Syndrome: Laurence Guignat, Jerome Bertherat; Endocrinol Metab. 2025;40(1):26-38. Published online January 13, 2025; DOI: https://doi.org/10.3803/EnM.2024.501

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Endogenous Cushing’s syndrome (CS) refers to the manifestations of chronic cortisol excess. This rare disease is associated with multiple comorbidities, impaired quality of life, and increased mortality. The management of CS remains challenging. Regardless of the underlying cause, surgical resection of the tumor is typically the first-line and preferred treatment. However, when surgery is not feasible or has been unsuccessful, medical therapies may be employed to control CS. The therapeutic strategy should be individualized based on the recommendations of a multidisciplinary team of experts and the patient’s preferences, informed by detailed information on the available options. All medications require careful monitoring, along with adequate instructions for patients and caregivers. The aim of this mini-review is to provide an overview of the main medical therapies currently used to treat CS, including their efficacy, safety, and management. Despite the availability of new drugs in recent years, the need remains for more effective specific targeted pharmacological therapies.

Citations

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Advances in the medical management of hypercortisolism: current strategies, monitoring, and emerging therapies
Jorge Esteban Mosquera, Leili Rahimi, Oksana Hamidi
Current Opinion in Endocrinology, Diabetes & Obesity.2025; 32(5): 222. CrossRef
Update in the Management of ACTH-Secreting Gastroenteropancreatic and Thoracic Neuroendocrine Neoplasms
Marina Tsoli, Anat Bel-Ange, Karine Atlan, Simona Ben-Haim, Gregory Kaltsas, Simona Grozinsky-Glasberg
Current Treatment Options in Oncology.2025; 26(11): 1010. CrossRef

Miscellaneous
Toward Systems-Level Metabolic Analysis in Endocrine Disorders and Cancer: Aliya Lakhani, Da Hyun Kang, Yea Eun Kang, Junyoung O. Park; Endocrinol Metab. 2023;38(6):619-630. Published online November 21, 2023; DOI: https://doi.org/10.3803/EnM.2023.1814

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Metabolism is a dynamic network of biochemical reactions that support systemic homeostasis amidst changing nutritional, environmental, and physical activity factors. The circulatory system facilitates metabolite exchange among organs, while the endocrine system finely tunes metabolism through hormone release. Endocrine disorders like obesity, diabetes, and Cushing’s syndrome disrupt this balance, contributing to systemic inflammation and global health burdens. They accompany metabolic changes on multiple levels from molecular interactions to individual organs to the whole body. Understanding how metabolic fluxes relate to endocrine disorders illuminates the underlying dysregulation. Cancer is increasingly considered a systemic disorder because it not only affects cells in localized tumors but also the whole body, especially in metastasis. In tumorigenesis, cancer-specific mutations and nutrient availability in the tumor microenvironment reprogram cellular metabolism to meet increased energy and biosynthesis needs. Cancer cachexia results in metabolic changes to other organs like muscle, adipose tissue, and liver. This review explores the interplay between the endocrine system and systems-level metabolism in health and disease. We highlight metabolic fluxes in conditions like obesity, diabetes, Cushing’s syndrome, and cancers. Recent advances in metabolomics, fluxomics, and systems biology promise new insights into dynamic metabolism, offering potential biomarkers, therapeutic targets, and personalized medicine.

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Development and validation of an interpretable machine learning model for predicting intraoperative HDI in PPGL based on intratumoral and peritumoral CT radiomics
Shurong Li, Zhiqiang Zhang, Yubing Zhang, Yulong Chen, Jian Ling, Qingfen Hong, Xuanling Wu, Fufu Zheng, Cheng Luo
European Journal of Radiology.2026; 195: 112559. CrossRef
Features of bioenergetic metabolism in physiological and pathological conditions: focus on oncogenesis
A. S. Zhdanova, Z. E. Belaya, G. A. Melnichenko
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Original Articles

Adrenal Gland
Clinical and Molecular Characteristics of PRKACA L206R Mutant Cortisol-Producing Adenomas in Korean Patients: Insoon Jang, Su-jin Kim, Ra-Young Song, Kwangsoo Kim, Seongmin Choi, Jang-Seok Lee, Min-Kyeong Gwon, Moon Woo Seong, Kyu Eun Lee, Jung Hee Kim; Endocrinol Metab. 2021;36(6):1287-1297. Published online December 2, 2021; DOI: https://doi.org/10.3803/EnM.2021.1217

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Background
An activating mutation (c.617A>C/p.Lys206Arg, L206R) in protein kinase cAMP-activated catalytic subunit alpha (PRKACA) has been reported in 35% to 65% of cases of cortisol-producing adenomas (CPAs). We aimed to compare the clinical characteristics and transcriptome analysis between PRKACA L206R mutants and wild-type CPAs in Korea.
Methods
We included 57 subjects with CPAs who underwent adrenalectomy at Seoul National University Hospital. Sanger sequencing for PRKACA was conducted in 57 CPA tumor tissues. RNA sequencing was performed in 13 fresh-frozen tumor tissues.
Results
The prevalence of the PRKACA L206R mutation was 51% (29/57). The mean age of the study subjects was 42±12 years, and 87.7% (50/57) of the patients were female. Subjects with PRKACA L206R mutant CPAs showed smaller adenoma size (3.3±0.7 cm vs. 3.8±1.2 cm, P=0.059) and lower dehydroepiandrosterone sulfate levels (218±180 ng/mL vs. 1,511±3,307 ng/mL, P=0.001) than those with PRKACA wild-type CPAs. Transcriptome profiling identified 244 differentially expressed genes (DEGs) between PRKACA L206R mutant (n=8) and wild-type CPAs (n=5), including five upregulated and 239 downregulated genes in PRKACA L206R mutant CPAs (|fold change| ≥2, P<0.05). Among the upstream regulators of DEGs, CTNNB1 was the most significant transcription regulator. In several pathway analyses, the Wnt signaling pathway was downregulated and the steroid biosynthesis pathway was upregulated in PRKACA mutants. Protein-protein interaction analysis also showed that PRKACA downregulates Wnt signaling and upregulates steroid biosynthesis.
Conclusion
The PRKACA L206R mutation in CPAs causes high hormonal activity with a limited proliferative capacity, as supported by transcriptome profiling.

Citations

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Sexual dimorphism in benign adrenocortical tumours
Onnicha Suntornlohanakul, Cristina L Ronchi, Wiebke Arlt, Alessandro Prete
European Journal of Endocrinology.2025; 192(5): R1. CrossRef

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

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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.

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Review Articles

Miscellanenous
Cushing Syndrome Associated Myopathy: It Is Time for a Change: Martin Reincke; Endocrinol Metab. 2021;36(3):564-571. Published online June 18, 2021; DOI: https://doi.org/10.3803/EnM.2021.1069

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Cushing syndrome is the result of excessive levels of glucocorticoids. Endogenous Cushing syndrome is rare with an incidence of two to three cases per million per year. Clinically, the presentation consists of a characteristic phenotype including skin symptoms and metabolic manifestations. A frequent co-morbidity with high impact on quality of life is Cushing syndrome associated myopathy. It characteristically affects the proximal myopathy, impairing stair climbing and straightening up. The pathophysiology is complex and involves protein degradation via the forkhead box O3 (FOXO3) pathway, intramuscular fat accumulation, and inactivity-associated muscle atrophy. Surgical remission of Cushing syndrome is the most important step for recovery of muscle function. Restoration depends on age, co-morbidities and postoperative insulin-like growth factor concentrations. At average, functionality remains impaired during the long-term compared to age and sex matched control persons. Growth hormone therapy in individuals with impaired growth hormone secretion could be an option but has not been proved in a randomized trial.

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Adrenal gland
Is Follow-up of Adrenal Incidentalomas Always Mandatory?: Giuseppe Reimondo, Alessandra Muller, Elisa Ingargiola, Soraya Puglisi, Massimo Terzolo; Endocrinol Metab. 2020;35(1):26-35. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.26

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Adrenal masses are mainly detected unexpectedly by an imaging study performed for reasons unrelated to any suspect of adrenal diseases. Such masses are commonly defined as “adrenal incidentalomas” and represent a public health challenge because they are increasingly recognized in current medical practice. Management of adrenal incidentalomas is currently matter of debate. Although there is consensus on the need of a multidisciplinary expert team evaluation and surgical approach in patients with significant hormonal excess and/or radiological findings suspicious of malignancy demonstrated at the diagnosis or during follow-up, the inconsistency between official guidelines and the consequent diffuse uncertainty on management of small adrenal incidentalomas still represents a considerable problem in terms of clinical choices in real practice. The aim of the present work is to review the proposed strategies on how to manage patients with adrenal incidentalomas that are not candidates to immediate surgery. The recent European Society of Endocrinology/European Network for the Study of Adrenal Tumors guidelines have supported the view to avoid surveillance in patients with clear benign adrenal lesions <4 cm and/or without any hormonal secretion; however, newer prospective studies are needed to confirm safety of this strategy, in particular in younger patients.

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An Adrenocortical Carcinoma Evolving After Nine Years of Latency From a Small Adrenal Incidentaloma
Harpreet S Kohli, Sukesh Manthri, Shikha Jain, Rahul Kashyap, Sheng Chen, Thoyaja Koritala, Aysun Tekin, Ramesh Adhikari, Raghavendra Tirupathi, Aram Barbaryan, Simon Zec, Hanyin Wang, Stephanie Welle, Pavan Devulapally, Mack Sheraton, Manpreet Kaur, Vish
Cureus.2021;[Epub] CrossRef
Diagnostic algorithm of the subclinical forms of adrenal neoplasms
Sofya G. Blyumina, Pavel N. Romashchenko, Igor S. Zheleznyak
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Letter

Adrenal gland
An Ectopic Cortisol-Producing Adrenocortical Adenoma Masquerading as a Liposarcoma in the Pararenal Space: Sunyoung Kang, Seung Shin Park, Jae Hyun Bae, Kyu Eun Lee, Jung Hee Kim, Chan Soo Shin; Endocrinol Metab. 2018;33(3):423-424. Published online August 14, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.3.423

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Review Article

Adrenal gland
Recent Updates on the Diagnosis and Management of Cushing's Syndrome: Lynnette K. Nieman; Endocrinol Metab. 2018;33(2):139-146. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.139

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Cushing's syndrome, a potentially lethal disorder characterized by endogenous hypercortisolism, may be difficult to recognize, especially when it is mild and the presenting features are common in the general population. However, there is a need to identify the condition at an early stage, as it tends to progress, accruing additional morbidity and increasing mortality rates. Once a clinical suspicion is raised, screening tests involve timed measurement of urine, serum or salivary cortisol at baseline or after administration of dexamethasone, 1 mg. Each test has caveats, so that the choice of tests must be individualized for each patient. Once the diagnosis is established, and the cause is determined, surgical resection of abnormal tumor/tissue is the optimal treatment. When this cannot be achieved, medical treatment (or bilateral adrenalectomy) must be used to normalize cortisol production. Recent updates in screening for and treating Cushing's syndrome are reviewed here.

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Namgok Lecture 2017

Adrenal gland
Bone Health in Adrenal Disorders: Beom-Jun Kim, Seung Hun Lee, Jung-Min Koh; Endocrinol Metab. 2018;33(1):1-8. Published online March 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.1

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Secondary osteoporosis resulting from specific clinical disorders may be potentially reversible, and thus continuous efforts to find and adequately treat the secondary causes of skeletal fragility are critical to ameliorate fracture risk and to avoid unnecessary treatment with anti-osteoporotic drugs. Among the hyperfunctional adrenal masses, Cushing's syndrome, pheochromocytoma, and primary aldosteronism are receiving particularly great attention due to their high morbidity and mortality mainly by increasing cardiovascular risk. Interestingly, there is accumulating experimental and clinical evidence that adrenal hormones may have direct detrimental effects on bone metabolism as well. Thus, the present review discusses the possibility of adrenal disorders, especially focusing on pheochromocytoma and primary aldosteronism, as secondary causes of osteoporosis.

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Original Articles

Clinical Study
The Eosinophil Count Tends to Be Negatively Associated with Levels of Serum Glucose in Patients with Adrenal Cushing Syndrome: Younghak Lee, Hyon-Seung Yi, Hae Ri Kim, Kyong Hye Joung, Yea Eun Kang, Ju Hee Lee, Koon Soon Kim, Hyun Jin Kim, Bon Jeong Ku, Minho Shong; Endocrinol Metab. 2017;32(3):353-359. Published online September 18, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.3.353

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Abstract PDF PubReader

Background

Cushing syndrome is characterized by glucose intolerance, cardiovascular disease, and an enhanced systemic inflammatory response caused by chronic exposure to excess cortisol. Eosinopenia is frequently observed in patients with adrenal Cushing syndrome, but the relationship between the eosinophil count in peripheral blood and indicators of glucose level in patients with adrenal Cushing syndrome has not been determined.

Methods

A retrospective study was undertaken of the clinical and laboratory findings of 40 patients diagnosed with adrenal Cushing syndrome at Chungnam National University Hospital from January 2006 to December 2016. Clinical characteristics, complete blood cell counts with white blood cell differential, measures of their endocrine function, description of imaging studies, and pathologic findings were obtained from their medical records.

Results

Eosinophil composition and count were restored by surgical treatment of all of the patients with adrenal Cushing disease. The eosinophil count was inversely correlated with serum and urine cortisol, glycated hemoglobin, and inflammatory markers in the patients with adrenal Cushing syndrome.

Conclusion

Smaller eosinophil populations in patients with adrenal Cushing syndrome tend to be correlated with higher levels of blood sugar and glycated hemoglobin. This study suggests that peripheral blood eosinophil composition or count may be associated with serum glucose levels in patients with adrenal Cushing syndrome.

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Association between Eosinophil Count and Cortisol Concentrations in Equids Admitted in the Emergency Unit with Abdominal Pain
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Inverse relationship between eosinophil profiles and serum glucose concentration in dogs with naturally occurring hypercortisolism
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Domestic Animal Endocrinology.2022; 80: 106727. CrossRef
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Daniela Alberghina, Alessandra Statelli, Vincenzo Monteverde, Irene Vazzana, Giuseppe Cascone, Michele Panzera
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Changes in leukocytes and CRP in different stages of major depression
Deepti Singh, Paul C. Guest, Henrik Dobrowolny, Veronika Vasilevska, Gabriela Meyer-Lotz, Hans-Gert Bernstein, Katrin Borucki, Alexandra Neyazi, Bernhard Bogerts, Roland Jacobs, Johann Steiner
Journal of Neuroinflammation.2022;[Epub] CrossRef
HIF1α is a direct regulator of steroidogenesis in the adrenal gland
Deepika Watts, Johanna Stein, Ana Meneses, Nicole Bechmann, Ales Neuwirth, Denise Kaden, Anja Krüger, Anupam Sinha, Vasileia Ismini Alexaki, Luis Gustavo Perez-Rivas, Stefan Kircher, Antoine Martinez, Marily Theodoropoulou, Graeme Eisenhofer, Mirko Peitz
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The Immune System in Cushing’s Syndrome
Valeria Hasenmajer, Emilia Sbardella, Francesca Sciarra, Marianna Minnetti, Andrea M. Isidori, Mary Anna Venneri
Trends in Endocrinology & Metabolism.2020; 31(9): 655. CrossRef

Clinical Study
The Recovery of Hypothalamic-Pituitary-Adrenal Axis Is Rapid in Subclinical Cushing Syndrome: Hee Kyung Kim, Jee Hee Yoon, Yun Ah Jeong, Ho-Cheol Kang; Endocrinol Metab. 2016;31(4):592-597. Published online December 20, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.4.592

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Abstract PDF PubReader

Background

In subclinical Cushing syndrome (SC), it is assumed that glucocorticoid production is insufficient to cause a clinically recognizable syndrome. Differences in hormonal levels or recovery time of the hypothalamic-pituitary-adrenocortical (HPA) axis after adrenalectomy between patients with overt Cushing syndrome (OC) and SC remain unknown.

Methods

Thirty-six patients (10 with OC and 26 with SC) with adrenal Cushing syndrome who underwent adrenalectomy from 2004 to 2014 were reviewed retrospectively. Patients were treated with glucocorticoid after adrenalectomy and were reevaluated every 1 to 6 months using a rapid adrenocorticotropic hormone (ACTH) stimulation test.

Results

Levels of basal 24-hour urine free cortisol (UFC), serum cortisol after an overnight dexamethasone suppression test (DST), and serum cortisol and 24-hour UFC after low-dose DST and high-dose DST were all significantly lower in patients with SC compared with OC. Basal ACTH levels showed significantly higher in patients with SC compared with OC. The probability of recovering adrenal function during follow-up differed significantly between patients with OC and SC (P=0.001), with significant correlations with the degree of preoperative cortisol excess. Patients with OC required a longer duration of glucocorticoid replacement to recover a normal ACTH stimulation test compared with patients with SC (median 17.0 months vs. 4.0 months, P<0.001).

Conclusion

The HPA axis recovery time after adrenalectomy in patients with SC is rapid and is dependent on the degree of cortisol excess. More precise definition of SC is necessary to achieve a better management of patients and to avoid the risk of under- or over-treatment of SC patients.

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Hypothalamic–pituitary–adrenal axis recovery after treatment of Cushing's syndrome
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Serum Cortisol Levels via Radioimmunoassay vs Liquid Chromatography Mass Spectrophotometry in Healthy Control Subjects and Patients With Adrenal Incidentalomas
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Case Report

Adrenal gland
Bilateral Adrenocortical Masses Producing Aldosterone and Cortisol Independently: Seung-Eun Lee, Jae Hyeon Kim, You-Bin Lee, Hyeri Seok, In Seub Shin, Yeong Hee Eun, Jung-Han Kim, Young Lyun Oh; Endocrinol Metab. 2015;30(4):607-613. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.607

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A 31-year-old woman was referred to our hospital with symptoms of hypertension and bilateral adrenocortical masses with no feature of Cushing syndrome. The serum aldosterone/renin ratio was elevated and the saline loading test showed no suppression of the plasma aldosterone level, consistent with a diagnosis of primary hyperaldosteronism. Overnight and low-dose dexamethasone suppression tests showed no suppression of serum cortisol, indicating a secondary diagnosis of subclinical Cushing syndrome. Adrenal vein sampling during the low-dose dexamethasone suppression test demonstrated excess secretion of cortisol from the left adrenal mass. A partial right adrenalectomy was performed, resulting in normalization of blood pressure, hypokalemia, and high aldosterone level, implying that the right adrenal mass was the main cause of the hyperaldosteronism. A total adrenalectomy for the left adrenal mass was later performed, resulting in a normalization of cortisol level. The final diagnosis was bilateral adrenocortical adenomas, which were secreting aldosterone and cortisol independently. This case is the first report of a concurrent cortisol-producing left adrenal adenoma and an aldosterone-producing right adrenal adenoma in Korea, as demonstrated by adrenal vein sampling and sequential removal of adrenal masses.

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Original Articles

Clinical Study
Subclinical Atherosclerosis in Patients with Cushing Syndrome: Evaluation with Carotid Intima-Media Thickness and Ankle-Brachial Index: Luigi Petramala, D'Elia Lorenzo, Gino Iannucci, Antonio Concistré, Laura Zinnamosca, Cristiano Marinelli, Giuseppe De Vincentis, Antonio Ciardi, Giorgio De Toma, Claudio Letizia; Endocrinol Metab. 2015;30(4):488-493. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.488

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Background

Cushing syndrome (CS) has been described as a killing disease due its cardiovascular complications. In fact, chronic cortisol excess leads to a constellation of complications, including hypertension, hyperglycemia, adiposity, and thromboembolism. The main vascular alteration associated with CS is atherosclerosis.

Methods

Aim of this study was to analyze carotid intima-media thickness (cIMT) and ankle-brachial index (ABI), two surrogate markers of subclinical atherosclerosis in a consecutive series of CS patients, compared to patients with essential hypertension (EH) and health subjects (HS).

Results

Patients with CS showed a significant increase (P<0.05) of cIMT (0.89±0.17 mm) compared to EH (0.81±0.16 mm) and HS (0.75±0.4 mm), with a high prevalence of plaque (23%; P<0.03). Moreover, CS patients showed a mean ABI values (1.07±0.02) significantly lower respect to HS (1.12±0.11; P<0.05), and a higher percentage (20%) of pathological values of ABI (≤0.9; P<0.03).

Conclusion

In conclusion, we confirmed and extended the data of cIMT in CS, and showed that the ABI represent another surrogate marker of subclinical atherosclerosis in this disease.

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Antonio Musolino, Chiara Parazzoli, Elisa Delle Donne, Vittoria Favero, Carmen Aresta, Grzegorz Bilo, Alessandro Croce, Martino Pengo, Gianfranco Parati, Luca Persani, Alfredo Scillitani, Iacopo Chiodini, Valentina Morelli
Endocrine Practice.2025;[Epub] CrossRef
Endocrine Disorders and Peripheral Arterial Disease – A Series of Reviews Cushing Syndrome-Cortisol Excess
Poredoš P, Schernthaner GH, Blinc A, Mikhailidis DP, Jensterle M, Anagnostis P, Antignani PL, Bajuk Studen K, Šabović M, Ježovnik MK
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Glucocorticoid therapy is a risk factor for cardiovascular diseases
I. S. Dzherieva, N. I. Volkova, I. Y. Davidenko, I. B. Reshetnikov, S. S. Brovkina, S. M. Avakova, Y. V. Tishchenko
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Clare MacLeod, Patrick W. F. Hadoke, Mark Nixon
International Journal of Molecular Sciences.2021; 22(14): 7622. CrossRef
Cardiovascular and metabolic risk factors in patients with subclinical Cushing
Luigi Petramala, Federica Olmati, Antonio Concistrè, Riccardo Russo, Martina Mezzadri, Maurizio Soldini, Giuseppe De Vincentis, Gino Iannucci, Giorgio De Toma, Claudio Letizia
Endocrine.2020; 70(1): 150. CrossRef
Should Cushing's Syndrome be Considered as a Disease with High Cardiovascular Risk in Relevant Guidelines?
Goran Koracevic, Milan Stojkovic, Dragan Lovic, Milan Pavlovic, Tomislav Kostic, Marija Kutlesic, Sladjana Micic, Maja Koracevic, Milan Djordjevic
Current Vascular Pharmacology.2019; 18(1): 12. CrossRef
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Roberta Lupoli, Pasquale Ambrosino, Anna Tortora, Livia Barba, Gelsy Arianna Lupoli, Matteo Nicola Dario Di Minno
Annals of Medicine.2017; 49(3): 206. CrossRef

Adrenal gland
Limited Diagnostic Utility of Plasma Adrenocorticotropic Hormone for Differentiation between Adrenal Cushing Syndrome and Cushing Disease: A Ram Hong, Jung Hee Kim, Eun Shil Hong, I Kyeong Kim, Kyeong Seon Park, Chang Ho Ahn, Sang Wan Kim, Chan Soo Shin, Seong Yeon Kim; Endocrinol Metab. 2015;30(3):297-304. Published online August 4, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.3.297

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Background

Measurement of the plasma adrenocorticotropic hormone (ACTH) level has been recommended as the first diagnostic test for differentiating between ACTH-independent Cushing syndrome (CS) and ACTH-dependent CS. When plasma ACTH values are inconclusive, a differential diagnosis of CS can be made based upon measurement of the serum dehydroepiandrosterone sulfate (DHEA-S) level and results of the high-dose dexamethasone suppression test (HDST). The aim of this study was to assess the utility of plasma ACTH to differentiate adrenal CS from Cushing' disease (CD) and compare it with that of the HDST results and serum DHEA-S level.

Methods

We performed a retrospective, multicenter study from January 2000 to May 2012 involving 92 patients with endogenous CS. The levels of plasma ACTH, serum cortisol, 24-hour urine free cortisol (UFC) after the HDST, and serum DHEA-S were measured.

Results

Fifty-seven patients had adrenal CS and 35 patients had CD. The area under the curve of plasma ACTH, serum DHEA-S, percentage suppression of serum cortisol, and UFC after HDST were 0.954, 0.841, 0.950, and 0.997, respectively (all P<0.001). The cut-off values for plasma ACTH, percentage suppression of serum cortisol, and UFC after HDST were 5.3 pmol/L, 33.3%, and 61.6%, respectively. The sensitivity and specificity of plasma ACTH measurement were 84.2% and 94.3%, those of serum cortisol were 95.8% and 90.6%, and those of UFC after the HDST were 97.9% and 96.7%, respectively.

Conclusion

Significant overlap in plasma ACTH levels was seen between patients with adrenal CS and those with CD. The HDST may be useful in differentiating between these forms of the disease, especially when the plasma ACTH level alone is not conclusive.

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Case Reports

Thyroid
Medullary Thyroid Carcinoma with Ectopic Adrenocorticotropic Hormone Syndrome: Hong Seok Choi, Min Joo Kim, Chae Ho Moon, Jong Ho Yoon, Ha Ra Ku, Geon Wook Kang, Im Il Na, Seung-Sook Lee, Byung-Chul Lee, Young Joo Park, Hong Il Kim, Yun Hyi Ku; Endocrinol Metab. 2014;29(1):96-100. Published online March 14, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.1.96

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Ectopic adrenocorticotropic hormone (ACTH) syndrome is caused most frequently by a bronchial carcinoid tumor or by small cell lung cancer. Medullary thyroid carcinoma (MTC) is a rare etiology of ectopic ACTH syndrome. We describe a case of Cushing syndrome due to ectopic ACTH production from MTC in a 48-year-old male. He was diagnosed with MTC 14 years ago and underwent total thyroidectomy, cervical lymph node dissection and a series of metastasectomies. MTC was confirmed by the pathological examination of the thyroid and metastatic mediastinal lymph node tissues. Two years after his last surgery, he developed Cushingoid features, such as moon face and central obesity, accompanied by uncontrolled hypertension and new-onset diabetes. The laboratory results were compatible with ectopic ACTH syndrome. A bilateral adrenalectomy improved the clinical and laboratory findings that were associated with Cushing syndrome. This is the first confirmed case of ectopic ACTH syndrome caused by MTC in Korea.

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Adrenal gland
Adrenocorticotropic Hormone-Independent Cushing Syndrome with Bilateral Cortisol-Secreting Adenomas: Eu Jeong Ku, A Ram Hong, Ye An Kim, Jae Hyun Bae, Mee Soo Chang, Sang Wan Kim; Endocrinol Metab. 2013;28(2):133-137. Published online June 18, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.2.133

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A 48-year-old woman was incidentally found to have bilateral adrenal masses, 2.8 cm in diameter on the right, and 2.3 cm and 1.7 cm in diameter on the left, by abdominal computed tomography. The patient had a medical history of hypertension, which was not being controlled by carvedilol, at a dose of 25 mg daily. She presented with signs and symptoms that suggested Cushing Syndrome. We diagnosed adrenocorticotropic hormone (ACTH)-independent Cushing Syndrome based on the results of basal and dynamic hormone tests. Adrenal vein sampling (AVS) was performed to localize a functioning adrenal cortical mass. AVS results were consistent with hypersecretion of cortisol from both adrenal glands, with a cortisol lateralization ratio of 1.1. Upon bilateral laparoscopic adrenalectomy, bilateral ACTH-independent adrenal adenomas were found. The patient's signs and symptoms of Cushing Syndrome improved after surgery just as the blood pressure was normalized. After surgery, the patient was started on glucocorticoid and mineralocorticoid replacement therapy.

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Original Article

Adrenal gland
Clinical Characteristics for 348 Patients with Adrenal Incidentaloma: Jongho Kim, Kwi Hyun Bae, Yeon Kyung Choi, Ji Yun Jeong, Keun Gyu Park, Jung Guk Kim, In Kyu Lee; Endocrinol Metab. 2013;28(1):20-25. Published online March 25, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.1.20

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Background

Adrenal incidentaloma is an adrenal neoplasm frequently encountered in clinical practice for which detection rates have recently increased. We describe here the clinical characteristics of adrenal incidentalomas.

Methods

A retrospective study was performed examining the age, sex, location, size, function, and the histological findings for 348 patients with an adrenal mass discovered incidentally on computed tomography (CT) undertaken for health examination or nonadrenal disease from August 2005 to May 2012.

Results

Patients consisted of 156 males (44.8%) and 192 females (55.2%), aged between 20 and 86. Adrenal masses were most commonly found in patients in their sixth decade (32.5%). Regarding the location of the masses, 62.0% were found in the left adrenal gland, 30.2% were found in the right, and 7.8% were found bilaterally. Of all of the masses analyzed, 87.1% were 1 to 4 cm in size, and an adenoma-like appearance was the most common finding (75.3%) seen on CT scans. Hormonal analysis showed that 82.2% of the masses were nonfunctioning, 6.0% were diagnosed as subclinical Cushing's syndrome, 4.6% were aldosterone-producing adenomas, and 7.2% were pheochromocytomas. Adrenalectomy was performed in a total of 69 patients having adenoma (50.7%), pheochromocytoma (24.6%), and carcinoma (4.3%).

Conclusion

The characteristics of benign, malignant, nonfunctional, and functional adrenal masses that were incidentally found at our hospital were similar to those presented in other studies.

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Case Reports

A Case of Adrenal Cystic Pheochromocytoma with Contralateral Adrenocortical Adenoma Causing Subclinical Cushing's Syndrome.: Chang Jun Park, Joo Wan Seo, Hyeog Gyu Seoung, Jung Hee Koh, Yong Jae Lee, Bo Hyun Kim, In Ju Kim; Endocrinol Metab. 2012;27(4):323-328. Published online December 20, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.4.323

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Abstract PDF

Bilateral adrenal neoplasms are associated with metastatic cancer, pheochromocytoma and lymphoma. The coexistence of a unilateral functioning adrenocortical adenoma with contralateral pheochromocytoma is extremely rare. A 52-year-old woman complained of fatigue, headache, palpitation, and progressive weight gain. Hormonal assessment demonstrated high 24 hours urine epinephrine, norepinephrine, and free cortisol. A dexamethasone suppression test (overnight 1 mg, low dose 2 mg) showed insuppressible cortisol. Computerized tomographic scanning revealed a bilateral adrenal tumor. To preserve adrenal function, right adrenalectomy along with left adrenal tumorectomy was performed. Histological finding of the right adrenal tumor was pheochromocytoma and the left adrenal tumor was adrenocortical adenoma. This patient was the first case of a functional adrenocortical adenoma with contralateral cystic pheochromocytoma in Korea. We report the case with a review of the literature.

Citations

Citations to this article as recorded by

A Case of Bilateral ACTH-independent Adrenal Adenomas with Cushing's Syndrome Treated by Ipsilateral Total and Contralateral Partial Laparoscopic Adrenalectomy
Seung Ah Park, Dong min Jung, Soon young Kim, Nan Young Choi, Tae-jun Kim, Yong kyun Kim, Seong kyun Na, Chul Sik Kim, Seong Jin Lee, Sung-Hee Ihm, Jun Goo Kang
The Korean Journal of Obesity.2013; 22(4): 254. CrossRef

A Case of Ectopic ACTH Syndrome Associated with Bronchial Carcinoid.: Young Jin Choi, Sang hyen Joo, Sun Hye Shin, Ok Nyu Kong, Jun Hyeop An, Young Dae Kim, Seok Man Son, In Joo Kim, Yong Ki Kim; J Korean Endocr Soc. 2004;19(1):76-81. Published online February 1, 2004

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Abstract PDF: Fifteen percent of patients with Cushing's syndrome could be accompanied with nonpituitary tumors that secrets ACTH-the ectopic ACTH syndrome. Among them, bronchial carcinoid is one of the rare causes of the ectopic ACTH syndrome. We experienced a 60-year-old woman who showed conditions of weight gain, generalized edema, hypokalemia, diabetes mellitus, and right middle lung mass. Histologically, the tumor was diagnosed with bronchial carcinoid and was confirmed as an ectopic ACTH syndrome through immunohistochemical staining of ACTH. After resection of the lung mass, blood sugar, electrolytes, generalized weakness, and blood pressure improved.

Original Article

Usefullness of Urinary Free Cortisol Measurement in Diagnosis of Iatrogenic Cushing Syndrome.: Yong Hyun Kim, Sang Jin Kim, Dong Seop Choi; J Korean Endocr Soc. 2000;15(2):162-169. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Although insulin induced hypoglycemia test is a standard diagnostic method in assessment of hypothalamo-pituitary-adrenal axis, rapid ACTH stimulation test using 250microgram has been used as a first line diagnostic test especially in secondary adrenal insufficiency due to iatrogenic Cushing syndrome because it is easy and safe. However, it was suggested that a maximal cortisol response can be achieved with a much lower ACTH dose and 1microgram ACTH enhances the sensitivity without decreasing specificity of test. Also recently, there was a report that midnight to morning urine cortisol increment is more accurate, noninvasive method can be used for measurement of hypothalmo-pituitary-adrenal axis. In this study, we compared the 1microgram ACTH stimulation test with midnight to morning urinary free cortisol increment in secondary adrenal insufficiency due to iatrogenic Cushing syndrome to study the agreement of two test and accuracy of increment of urinary free cortisol in diagnosis of adrenal insufficiency. METHODS: Double voided urine sample were collected at midnight and 8 A.M. in 12 patients who have Cushing-like feature and history of taking glucocorticoids and in 12 normal controls. Urinary free cortisol was measured and cortisol increment was defined as the morning urine free cortisol minus the midnight urine free cortisol. The 1microgram ACTH stimulation test was performed in 12 iatrogenic Cushing syndrome patients at the same day and compard with the result of cortisol increment. RESULTS: Using the results of 12 controls, normal urine free cortisol increment was defined as greater than 165.5nmol/L(6.0microgram/dL). Subnormal cortisol response in 1microgram ACTH stimulation test was noted in 8 out of 12 patients group and urinary free cortisol increment was not observed in 7 out of 8 subnormal response group. Normal cortisol response in 1microgram ACTH stimulation test was noted in 4 out of 12 patients group and urinary free cortisol increment was observed in 3 out of 4 normal response group. So 83% of concordance rate between 1microgram ACTH stimulation test and urine free cortisol increment was recorded. CONCLUSION: Urinary free cortisol increment has high concordance rate with 1microgram ACTH stimulation test and simple, easy test in diagnosing secondary adrenal insufficiency due to iatrogenic Cushing syndrome. Further study including more patients will be helpful to know the adequacy and reliability of test in evaluation of hypothalamo-pituitary-adrenal axis.

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