Endocrinology and Metabolism

Brief Report

Adrenal Gland
Aldosterone Immunoassay-Specific Cutoff Value for Seated Saline Suppression Test for Diagnosing Primary Aldosteronism: So Yoon Kwon, Jiyun Park, So Hee Park, So Hyun Cho, You-Bin Lee, Soo-Youn Lee, Jae Hyeon Kim; Endocrinol Metab. 2022;37(6):938-942. Published online December 6, 2022; DOI: https://doi.org/10.3803/EnM.2022.1535

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A seated saline loading test (SLT) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is one of the most accepted confirmatory tests of primary aldosteronism. However, LC-MS/MS is time-consuming and is not widely available in diagnostic laboratories compared to immunoassay. With immunoassay, it is unknown whether SLT in the seated position is more accurate than that of the supine position, and a cutoff value of post-seated SLT plasma aldosterone concentration (PAC) must be established in the Korean population. Ninety-eight patients underwent SLT in both positions, and post-SLT PAC was measured by LC-MS/MS and radioimmunoassay. We confirmed primary aldosteronism if post-seated SLT PAC by LC-MS/MS exceeded 5.8 ng/dL. The area under the receiver operating characteristic curve was greater for seated than supine SLT (0.928 vs. 0.834, P=0.003). The optimal cutoff value of post-seated SLT by radioimmunoassay was 6.6 ng/dL (sensitivity 83.3%, specificity 92.2%).

Citations

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Investigating the cut-off values of captopril challenge test for primary aldosteronism using the novel chemiluminescent enzyme immunoassay method: a retrospective cohort study
Yuta Tezuka, Kei Omata, Yoshikiyo Ono, Kengo Kambara, Hiroki Kamada, Sota Oguro, Yuto Yamazaki, Celso E. Gomez-Sanchez, Akihiro Ito, Hironobu Sasano, Kei Takase, Tetsuhiro Tanaka, Hideki Katagiri, Fumitoshi Satoh
Hypertension Research.2024;[Epub] CrossRef

Review Article

Adrenal Gland
Adrenal Venous Sampling for Subtype Diagnosis of Primary Hyperaldosteronism: Mitsuhide Naruse, Akiyo Tanabe, Koichi Yamamoto, Hiromi Rakugi, Mitsuhiro Kometani, Takashi Yoneda, Hiroki Kobayashi, Masanori Abe, Youichi Ohno, Nobuya Inagaki, Shoichiro Izawa, Masakatsu Sone; Endocrinol Metab. 2021;36(5):965-973. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1192

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Adrenal venous sampling (AVS) is the key procedure for lateralization of primary hyperaldosteronism (PA) before surgery. Identification of the adrenal veins using computed tomography (CT) and intraoperative cortisol assay facilitates the success of catheterization. Although administration of adrenocorticotropic hormone (ACTH) has benefits such as improving the success rate, some unilateral cases could be falsely diagnosed as bilateral. Selectivity index of 5 with ACTH stimulation to assess the selectivity of catheterization and lateralization index (LI) >4 with ACTH stimulation for unilateral diagnosis is used in many centers. Co-secretion of cortisol from the tumor potentially affects the lateralization by the LI. Patients aged <35 years with hypokalemia, marked aldosterone excess, and unilateral adrenal nodule on CT have a higher probability of unilateral disease. Patients with normokalemia, mild aldosterone excess, and no adrenal tumor on CT have a higher probability of bilateral disease. Although no methods have 100% specificity for subtype diagnosis that would allow bypassing AVS, prediction of the subtype should be considered when recommending AVS to patients. Methodological standardization and strict indication improve diagnostic quality of AVS. Development of non-invasive imaging and biochemical markers will drive a paradigm shift in the clinical practice of PA.

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A controlled trial of percutaneous adrenal arterial embolization for hypertension in patients with idiopathic hyperaldosteronism
Yaqiong Zhou, Xinquan Wang, Jixin Hou, Jindong Wan, Yi Yang, Sen Liu, Tao Luo, Qiting Liu, Qiang Xue, Peijian Wang
Hypertension Research.2024; 47(2): 311. CrossRef
Screening and diagnosis of primary aldosteronism. Consensus document of all the Spanish Societies involved in the management of primary aldosteronism
Marta Araujo-Castro, Jorge Gabriel Ruiz-Sánchez, Paola Parra Ramírez, Patricia Martín Rojas-Marcos, Almudena Aguilera-Saborido, Jorge Francisco Gómez Cerezo, Nieves López Lazareno, María Eugenia Torregrosa Quesada, Jorge Gorrin Ramos, Josep Oriola, Esteba
Endocrine.2024;[Epub] CrossRef
Diagnostic accuracy of using multiple cytokines to predict aldosterone-producing adenoma
Fei Qin, Hong Wen, Xiaoge Zhong, Yajin Pan, Xiaomei Lai, Tingting Yang, Jing Huang, Jie Yu, Jianling Li
Scientific Reports.2023;[Epub] CrossRef
A clinical assessment of portable point-of-care testing for quick cortisol assay during adrenal vein sampling
Ko Aiga, Mitsuhiro Kometani, Shigehiro Karashima, Seigo Konishi, Takuya Higashitani, Daisuke Aono, Xurong Mai, Mikiya Usukura, Takahiro Asano, Ayako Wakayama, Yuko Noda, Wataru Koda, Tetsuya Minami, Satoshi Kobayashi, Toshinori Murayama, Takashi Yoneda
Scientific Reports.2023;[Epub] CrossRef
2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism
Jeonghoon Ha, Jung Hwan Park, Kyoung Jin Kim, Jung Hee Kim, Kyong Yeun Jung, Jeongmin Lee, Jong Han Choi, Seung Hun Lee, Namki Hong, Jung Soo Lim, Byung Kwan Park, Jung-Han Kim, Kyeong Cheon Jung, Jooyoung Cho, Mi-kyung Kim, Choon Hee Chung
Endocrinology and Metabolism.2023; 38(6): 597. CrossRef
Correlation of Histopathologic Subtypes of Primary Aldosteronism with Clinical Phenotypes and Postsurgical Outcomes
Chang Ho Ahn, You-Bin Lee, Jae Hyeon Kim, Young Lyun Oh, Jung Hee Kim, Kyeong Cheon Jung
The Journal of Clinical Endocrinology & Metabolism.2023;[Epub] CrossRef
The Entity of Connshing Syndrome: Primary Aldosteronism with Autonomous Cortisol Secretion
Mara Carsote
Diagnostics.2022; 12(11): 2772. CrossRef

Original Articles

Adrenal Gland
Aldosterone Inhibits In Vitro Myogenesis by Increasing Intracellular Oxidative Stress via Mineralocorticoid Receptor: Jin Young Lee, Da Ae Kim, Eunah Choi, Yun Sun Lee, So Jeong Park, Beom-Jun Kim; Endocrinol Metab. 2021;36(4):865-874. Published online July 30, 2021; DOI: https://doi.org/10.3803/EnM.2021.1108

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Background
Despite clinical evidence indicating poor muscle health in subjects with primary aldosteronism (PA), it is still unclear whether the role of aldosterone in muscle metabolism is direct or mediated indirectly via factors, such as electrolyte imbalance or impaired glucose uptake. As one approach to clarify this issue, we investigated the effect of aldosterone on in vitro myogenesis and the potential mechanism explaining it.
Methods
Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Immunofluorescence, quantitative reversetranscription polymerase chain reaction, Western blot, viability, and migration analyses were performed for experimental research.
Results
Recombinant aldosterone treatment suppressed muscle differentiation from mouse C2C12 myoblasts in a dose-dependent manner, and consistently reduced the expression of myogenic differentiation markers. Furthermore, aldosterone significantly increased intracellular reactive oxygen species (ROS) levels in myotubes, and treatment with N-acetyl cysteine, a potent biological thiol antioxidant, reversed the decrease of myotube area, myotube area per myotube, nucleus number per myotube, and fusion index due to aldosterone through decreasing oxidative stress. A binding enzyme-linked immunosorbent assay confirmed that mineralocorticoid receptor (MR) interacted with aldosterone in C2C12 myoblasts, while eplerenone, an MR inhibitor, blocked aldosterone-stimulated intracellular ROS generation during myogenesis and markedly attenuated the suppression of in vitro myogenesis by aldosterone.
Conclusion
These findings support the hypothesis that hypersecretion of aldosterone, like PA, directly contributes to muscular deterioration and suggest that antioxidants and/or MR antagonists could be effective therapeutic options to reduce the risk of sarcopenia in these patients.

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Cody A. Rutledge
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Role of glucocorticoid and mineralocorticoid receptors in rainbow trout (Oncorhynchus mykiss) skeletal muscle: A transcriptomic perspective of cortisol action
Jorge E. Aedo, Rodrigo Zuloaga, Daniela Aravena-Canales, Alfredo Molina, Juan Antonio Valdés
Frontiers in Physiology.2023;[Epub] CrossRef
Effect of 11-Deoxycorticosterone in the Transcriptomic Response to Stress in Rainbow Trout Skeletal Muscle
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Heart Failure Medication and Muscle Wasting
Yasuhiro Izumiya
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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
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Higher Plasma Stromal Cell-Derived Factor 1 Is Associated with Lower Risk for Sarcopenia in Older Asian Adults
Sunghwan Ji, Kyunggon Kim, So Jeong Park, Jin Young Lee, Hee-Won Jung, Hyun Ju Yoo, Il-Young Jang, Eunju Lee, Ji Yeon Baek, Beom-Jun Kim
Endocrinology and Metabolism.2023; 38(6): 701. CrossRef
The Role of Aldosterone in OSA and OSA-Related Hypertension
Yi Wang, Chuan Xiang Li, Ying Ni Lin, Li Yue Zhang, Shi Qi Li, Liu Zhang, Ya Ru Yan, Fang Ying Lu, Ning Li, Qing Yun Li
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Daiji Kawanami, Yuichi Takashi, Yoshimi Muta, Naoki Oda, Dai Nagata, Hiroyuki Takahashi, Makito Tanabe
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Clinical Study
Diagnostic Accuracy of Computed Tomography in Predicting Primary Aldosteronism Subtype According to Age: Seung Hun Lee, Jong Woo Kim, Hyun-Ki Yoon, Jung-Min Koh, Chan Soo Shin, Sang Wan Kim, Jung Hee Kim; Endocrinol Metab. 2021;36(2):401-412. Published online March 31, 2021; DOI: https://doi.org/10.3803/EnM.2020.901

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Background
Guidelines by the Endocrine Society Guideline on bypassing adrenal vein sampling (AVS) in patients <35 years old with marked primary aldosteronism (PA) (hypokalemia and elevated plasma aldosterone concentration [PAC]) and a unilateral lesion on computed tomography (CT) are based on limited number of studies. We aimed to determine the accuracy of CT in PA patients according to age.
Methods
In this retrospective study, we investigated the concordance between CT and AVS in 466 PA patients from two tertiary centers who successfully underwent AVS.
Results
CT had an overall accuracy of 64.4% (300/466). In the group with unilateral lesion, patients with hypokalemia had higher concordance than those without hypokalemia (85.0% vs. 43.6%, P<0.001). In the group with marked PA (hypokalemia and PAC >15.9 ng/dL) and unilateral lesion, accuracy of CT was 84.6% (11/13) in patients aged <35 years; 100.0% (20/20), aged 35 to 39 years; 89.4% (59/66), aged 40 to 49 years; and 79.8% (79/99), aged ≥50 years. Cut-off age and PAC for concordance was <50 years and >29.6 ng/dL, respectively. The significant difference in accuracy of CT in 198 patients with marked PA and a unilateral lesion between the <50-year age group and ≥50-year age group (90.9% vs. 79.8%, P=0.044) disappeared in 139 of 198 patients with PAC > 30.0 ng/dL (91.9% vs. 87.7%, P=0.590).
Conclusion
Patients with hypokalemia, PAC >30.0 ng/dL, and unilateral lesion were at high risk of unilateral PA regardless of age.

Citations

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Predicting Bilateral Subtypes of Primary Aldosteronism Without Adrenal Vein Sampling: A Systematic Review and Meta-analysis
Elisabeth Ng, Stella May Gwini, Winston Zheng, Peter J Fuller, Jun Yang
The Journal of Clinical Endocrinology & Metabolism.2024; 109(2): e837. CrossRef
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
Imaging Concordance With Vein Sampling for Primary Aldosteronism: A Cohort Study and Literature Review
Sara Cartwright, MaKayla Gordon, Jessica Shank, Abbey Fingeret
Journal of Surgical Research.2024; 296: 1. CrossRef
Best Practices: Indications and Procedural Controversies of Adrenal Vein Sampling for Primary Aldosteronism
Keith B. Quencer, Abhilasha Singh, Anu Sharma
American Journal of Roentgenology.2023; 220(2): 190. CrossRef
Accuracy of Gallium-68 Pentixafor Positron Emission Tomography–Computed Tomography for Subtyping Diagnosis of Primary Aldosteronism
Jinbo Hu, Tingting Xu, Hang Shen, Ying Song, Jun Yang, Aipin Zhang, Haoyuan Ding, Naiguo Xing, Zhuoyuan Li, Lin Qiu, Linqiang Ma, Yi Yang, Zhengping Feng, Zhipeng Du, Wenwen He, Yue Sun, Jun Cai, Qifu Li, Yue Chen, Shumin Yang, Mei Mei, Suxin Luo, Kangla
JAMA Network Open.2023; 6(2): e2255609. CrossRef
Adrenal Vein Sampling in the Young – Necessary or Not?
Eleftheria Gkaniatsa, Oskar Ragnarsson
Experimental and Clinical Endocrinology & Diabetes.2023; 131(07/08): 435. CrossRef
2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism
Jeonghoon Ha, Jung Hwan Park, Kyoung Jin Kim, Jung Hee Kim, Kyong Yeun Jung, Jeongmin Lee, Jong Han Choi, Seung Hun Lee, Namki Hong, Jung Soo Lim, Byung Kwan Park, Jung-Han Kim, Kyeong Cheon Jung, Jooyoung Cho, Mi-kyung Kim, Choon Hee Chung
Endocrinology and Metabolism.2023; 38(6): 597. CrossRef
Correlation of Histopathologic Subtypes of Primary Aldosteronism with Clinical Phenotypes and Postsurgical Outcomes
Chang Ho Ahn, You-Bin Lee, Jae Hyeon Kim, Young Lyun Oh, Jung Hee Kim, Kyeong Cheon Jung
The Journal of Clinical Endocrinology & Metabolism.2023;[Epub] CrossRef
Indices of ACTH‐stimulated adrenal venous sampling as predictors of postsurgical outcomes in primary aldosteronism
Seung Hun Lee, Jong Woo Kim, Hyun‐Ki Yoon, Sang Wan Kim, Su Jin Kim, Kyu Eun Lee, Yu‐Mi Lee, Tae‐Yon Sung, Suck Joon Hong, Chan Soo Shin, Jung‐Min Koh, Jung Hee Kim
Clinical Endocrinology.2022; 96(4): 521. CrossRef
Expression of CYP11B1 and CYP11B2 in adrenal adenoma correlates with clinical characteristics of primary aldosteronism
Chang Ho Ahn, Hee Young Na, So Yeon Park, Hyeong Won Yu, Su‐Jin Kim, June Young Choi, Kyu Eun Lee, Sang Wan Kim, Kyeong Cheon Jung, Jung Hee Kim
Clinical Endocrinology.2022; 96(1): 30. CrossRef
Letter to the Editor From Singhania et al: “Increasing Incidence of Primary Aldosteronism in Western Sweden During 3 Decades—Yet an Underdiagnosed Disorder”
Pankaj Singhania, Rana Bhattacharjee
The Journal of Clinical Endocrinology & Metabolism.2022; 107(3): e1315. CrossRef
Development and validation of model for sparing adrenal venous sampling in diagnosing unilateral primary aldosteronism
Ying Song, Jun Yang, Hang Shen, Elisabeth Ng, Peter J. Fuller, Zhengping Feng, Jinbo Hu, Linqiang Ma, Yi Yang, Zhipeng Du, Yue Wang, Ting Luo, Wenwen He, Qifu Li, Fei-Fei Wu, Shumin Yang
Journal of Hypertension.2022; 40(9): 1692. CrossRef
Validation of Existing Clinical Prediction Tools for Primary Aldosteronism Subtyping
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Review Article

Adrenal gland
The Genotype-Based Morphology of Aldosterone-Producing Adrenocortical Disorders and Their Association with Aging: Xin Gao, Yuto Yamazaki, Yuta Tezuka, Kei Omata, Yoshikiyo Ono, Ryo Morimoto, Yasuhiro Nakamura, Fumitoshi Satoh, Hironobu Sasano; Endocrinol Metab. 2021;36(1):12-21. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2021.101

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Primary aldosteronism (PA) is the most common cause of secondary hypertension, and is associated with an increased incidence of cardiovascular events. PA itself is clinically classified into the following two types: unilateral PA, mostly composed of aldosteroneproducing adenoma (APA); and bilateral hyperaldosteronism, consisting of multiple aldosterone-producing micronodules (APMs) and aldosterone-producing diffuse hyperplasia. Histopathologically, those disorders above are all composed of compact and clear cells. The cellular morphology in the above-mentioned aldosterone-producing disorders has been recently reported to be closely correlated with patterns of somatic mutations of ion channels including KCNJ5, CACNA1D, ATP1A1, ATP2B3, and others. In addition, in non-pathological adrenal glands, APMs are frequently detected regardless of the status of the renin-angiotensin-aldosterone system (RAAS). Aldosterone-producing nodules have been also proposed as non-neoplastic nodules that can be identified by hematoxylin and eosin staining. These non-neoplastic CYP11B2-positive nodules could represent possible precursors of APAs possibly due to the presence of somatic mutations. On the other hand, aging itself also plays a pivotal role in the development of aldosterone-producing lesions. For instance, the number of APMs was also reported to increase with aging. Therefore, recent studies indicated the novel classification of PA into normotensive PA (RAAS-independent APM) and clinically overt PA.

Citations

Citations to this article as recorded by

Subtype-specific Body Composition and Metabolic Risk in Patients With Primary Aldosteronism
Seung Shin Park, Chang Ho Ahn, Sang Wan Kim, Ji Won Yoon, Jung Hee Kim
The Journal of Clinical Endocrinology & Metabolism.2024; 109(2): e788. CrossRef
2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism
Jeonghoon Ha, Jung Hwan Park, Kyoung Jin Kim, Jung Hee Kim, Kyong Yeun Jung, Jeongmin Lee, Jong Han Choi, Seung Hun Lee, Namki Hong, Jung Soo Lim, Byung Kwan Park, Jung-Han Kim, Kyeong Cheon Jung, Jooyoung Cho, Mi-kyung Kim, Choon Hee Chung
Endocrinology and Metabolism.2023; 38(6): 597. CrossRef
Correlation of Histopathologic Subtypes of Primary Aldosteronism with Clinical Phenotypes and Postsurgical Outcomes
Chang Ho Ahn, You-Bin Lee, Jae Hyeon Kim, Young Lyun Oh, Jung Hee Kim, Kyeong Cheon Jung
The Journal of Clinical Endocrinology & Metabolism.2023;[Epub] CrossRef
Expression of CYP11B1 and CYP11B2 in adrenal adenoma correlates with clinical characteristics of primary aldosteronism
Chang Ho Ahn, Hee Young Na, So Yeon Park, Hyeong Won Yu, Su‐Jin Kim, June Young Choi, Kyu Eun Lee, Sang Wan Kim, Kyeong Cheon Jung, Jung Hee Kim
Clinical Endocrinology.2022; 96(1): 30. CrossRef
Pathology of Aldosterone Biosynthesis and its Action
Xin Gao, Yuto Yamazaki, Yuta Tezuka, Kei Omata, Yoshikiyo Ono, Ryo Morimoto, Yasuhiro Nakamura, Takashi Suzuki, Fumitoshi Satoh, Hironobu Sasano
The Tohoku Journal of Experimental Medicine.2021; 254(1): 1. CrossRef
Cellular Senescence in Adrenocortical Biology and Its Disorders
Xin Gao, Faping Li, Bin Liu, Yuxiong Wang, Yishu Wang, Honglan Zhou
Cells.2021; 10(12): 3474. CrossRef

Original Articles

A Clinical Observation of Endocrine Adrenal Tumors.: Hye Young Park, Tae Suk Kim, Soo Jin Lee, Dong Gu Choi, Moon Ho Kang; J Korean Endocr Soc. 1994;9(3):228-238. Published online November 6, 2019

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Abstract PDF: Endocrine adrenal tumors are uncommon but clinically significant because they can be managed successfully by surgical therapy. During pregnancy, adrenal tumors can be a cause of death for both mother and baby, unless they diagnoses antenatally and managed properly. To investigate clinical characteristics of endocrine adrenal tumors, we analyzed 26 cases of adrenal tumor diagnosed and managed in Chung Ang Gil Hospital including cases associated with pregnancy and also a rare case of paraganglioma in liver. 1) There were 7 cases of Cushing's syndrome among which two cases were due to Cushing's disease and five cases were due to adrenal adenoma. Six cases were managed successfully by appropriate surgery. Another one case was associated with pregnancy but the patient expired due to sudden development of pulmonary edema and hypotension during preoperative preparation.2) Among 9 cases of primary aldosteronism, 8 cases were aldosterone-producing adenoma(APA) and 1 case was idiopathic hyperaldosteronism(IHA). In differential diagnosis between APA and IHA, diagnostic accuracy of postural study and adrenal CT was 86%, 78% respectively. In each one case of APA and IHA, adrenal venous aldosterone sampling was used for the differential diagnosis. Six cases of APA were managed by appropriate surgery. One patient with APA who refuses surgery and one patient with IHA were placed on spironolactone with good response.3) Among 10 cases of pheochromocytoma, seven cases were from adrenal gland and three cases were paragangliomas including one case originating from liver and two cases from abdominal ganglia. One patient with pheochromocytoma was diagnosed in 1st trimester of pregnancy and she was successfully treated by surgery.We observed 26 cases of endocrine adrenal tumors which were successfully managed except one case. We think that it is important to pay attention to adrenal tumor for early diagnosis particulary when associated with pregnancy. Paraganglioma in liver, although very rare, should be included in the differential diagnosis of space occupying lesion in liver.

Endocrine Research
Aldosterone Rapidly Enhances Levels of the Striatin and Caveolin-1 Proteins in Rat Kidney: The Role of the Mineralocorticoid Receptor: Kevalin Inthachart, Krissanapong Manotham, Somchai Eiam-Ong, Somchit Eiam-Ong; Endocrinol Metab. 2019;34(3):291-301. Published online September 26, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.3.291

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Background

Striatin and caveolin-1 (cav-1) are scaffolding/regulating proteins that are associated with salt-sensitive high blood pressure and promote renal sodium and water reabsorption, respectively. The mineralocorticoid receptor (MR) interacts with striatin and cav-1, while aldosterone increases striatin and cav-1 levels. However, no in vivo data have been reported for the levels of these proteins in the kidney.

Methods

Male Wistar rats were intraperitoneally injected with normal saline solution, aldosterone alone (Aldo: 150 µg/kg body weight), or aldosterone after pretreatment with eplerenone, an MR blocker, 30 minutes before the aldosterone injection (eplerenone [Ep.]+Aldo). Thirty minutes after the aldosterone injection, the amount and localization of striatin and cav-1 were determined by Western blot analysis and immunohistochemistry, respectively.

Results

Aldosterone increased striatin levels by 150% (P<0.05), and cav-1 levels by 200% (P<0.001). Eplerenone had no significant effect on striatin levels, but partially blocked the aldosterone-induced increase in cav-1 levels. Aldosterone stimulated striatin and cav-1 immunoreactivity in both the cortex and medulla. Eplerenone reduced cav-1 immunostaining in both areas; however, striatin intensity was reduced in the cortex, but increased in the medulla.

Conclusion

This is the first in vivo study demonstrating that aldosterone rapidly enhances renal levels of striatin and cav-1. Aldosterone increases striatin levels via an MR-independent pathway, whereas cav-1 is partially regulated through MR.

Citations

Citations to this article as recorded by

Aldosterone Inhibits In Vitro Myogenesis by Increasing Intracellular Oxidative Stress via Mineralocorticoid Receptor
Jin Young Lee, Da Ae Kim, Eunah Choi, Yun Sun Lee, So Jeong Park, Beom-Jun Kim
Endocrinology and Metabolism.2021; 36(4): 865. CrossRef

Review Article

CTNNB1 Mutation in Aldosterone Producing Adenoma: Jian-Jhong Wang, Kang-Yung Peng, Vin-Cent Wu, Fen-Yu Tseng, Kwan-Dun Wu; Endocrinol Metab. 2017;32(3):332-338. Published online September 18, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.3.332

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Discoveries of somatic mutations permit the recognition of subtypes of aldosterone-producing adenomas (APAs) with distinct clinical presentations and pathological features. Catenin β1 (CTNNB1) mutation in APAs has been recently described and discussed in the literature. However, significant knowledge gaps still remain regarding the prevalence, clinical characteristics, pathophysiology, and outcomes in APA patients harboring CTNNB1 mutations. Aberrant activation of the Wnt/β-catenin signaling pathway will further modulate tumorigenesis. We also discuss the recent knowledge of CTNNB1 mutation in adrenal adenomas.

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Pathogenesis of Primary Aldosteronism: Impact on Clinical Outcome
Lucas S. Santana, Augusto G. Guimaraes, Madson Q. Almeida
Frontiers in Endocrinology.2022;[Epub] CrossRef
Molecular Mechanisms of Functional Adrenocortical Adenoma and Carcinoma: Genetic Characterization and Intracellular Signaling Pathway
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Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause
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Emanuele Pignatti, Sining Leng, Yixing Yuchi, Kleiton S. Borges, Nick A. Guagliardo, Manasvi S. Shah, Gerard Ruiz-Babot, Dulanjalee Kariyawasam, Makoto Mark Taketo, Ji Miao, Paula Q. Barrett, Diana L. Carlone, David T. Breault
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A. L. Markel
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Genetic Characterization of GnRH/LH-Responsive Primary Aldosteronism
Nadia Gagnon, Katia Y Cáceres-Gorriti, Gilles Corbeil, Nada El Ghoyareb, Natasha Ludwig, Mathieu Latour, André Lacroix, Isabelle Bourdeau
The Journal of Clinical Endocrinology & Metabolism.2018; 103(8): 2926. CrossRef

Original Article

Clinical Study
Diagnostic Role of Captopril Challenge Test in Korean Subjects with High Aldosterone-to-Renin Ratios: Jung Hee Kim, Kyeong Seon Park, A Ram Hong, Chan Soo Shin, Seong Yeon Kim, Sang Wan Kim; Endocrinol Metab. 2016;31(2):277-283. Published online May 13, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.277

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Background

Diagnosis of primary aldosteronism (PA) begins with aldosterone-to-renin ratio (ARR) measurement followed by confirmative tests. However, the ARR has high false positive rates which led to unnecessary confirmatory tests. Captopril challenge test (CCT) has been used as one of confirmatory tests, but the accuracy of it in the diagnosis of PA is still controversial. We aimed to examine the clinical efficacy of CCT as a post-screening test in PA.

Methods

In a prospective study, we enrolled subjects with suspected PA who had hypertension and ARR >20 (ng/dL)/(ng/mL/hr). Sixty-four patients who underwent both the saline infusion test and the CCT were included.

Results

The diagnostic performance of plasma aldosterone concentration (PAC) post-CCT was greater than that of ARR post-CCT and ARR pre-CCT in PA (area under the curve=0.956, 0.797, and 0.748, respectively; P=0.001). A cut-off value of 13 ng/dL showed the highest diagnostic odds ratio considering PAC post-CCT at 60 and 90 minutes. A PAC post-CCT of 19 ng/dL had a specificity of 100%, which can be used as a cut-off value for the confirmative test. Determining the diagnostic performance of PAC post-CCT at 90 minutes was sufficient for PA diagnosis. Subjects with PAC post-CCT at 90 minutes <13 ng/dL are less likely to have PA, and those with PAC post-CCT at 90 minutes ≥13 but <19 ng/dL should undergo secondary confirmatory tests.

Conclusion

The CCT test may be a reliable post-screening test to avoid the hospitalization in the setting of falsely elevated ARR screening tests.

Citations

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Xinyu Liu, Chao Guo, Jin Bian, Sufang Hao, Ying Lou, Huimin Zhang, Xianliang Zhou, Jun Cai, Wenjun Ma
Frontiers in Endocrinology.2023;[Epub] CrossRef
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Hypertension.2022; 79(8): 1835. CrossRef
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Case Reports

A Case of Persistent Hyperkalemia After Unilateral Adrenalectomy for Aldosterone-Producing Adenoma.: Min Jae Yang, Seung Jin Han, Min Seok Lee, Eun Kyung Kim, Hae Jin Kim, Dae Jung Kim, Yoon Sok Chung, Tae Hee Lee, Jang Hee Kim, Kwan Woo Lee; J Korean Endocr Soc. 2009;24(3):201-205. Published online September 1, 2009; DOI: https://doi.org/10.3803/jkes.2009.24.3.201

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Abstract PDF: Primary aldosteronism is a syndrome characterized by various clinical features that are due to excessive autonomous aldosterone secretion not sustained by the activation of the renin-angiotensin system. Aldosterone-producing adrenal adenoma is found in approximately 35% of the patients who suffer with primary aldosteronism. Laparoscopic adrenalectomy is the standard treatment for aldosterone-producing adrenal adenoma, and the result of this operation is normalization of the serum potassium and plasma aldosterone concentrations, as well as correcting the plasma renin activity in most cases. However, it is known that some of the patients with aldosterone-producing adrenal adenoma show transient hyperkalemia postoperatively due to the reversible suppression of the renin-aldosterone axis. We recently experienced the case of a 54-year-old woman with an aldosterone-producing adrenal adenoma, and she presented with severe hyperkalemia after unilateral adrenalectomy. Compared with the previously reported cases that showed transient suppression of the rennin-aldosterone axis for less than 7 months, our patient revealed a prolonged episode of hyperkalemia for 8 months postoperatively, and this required continuous mineralocorticoid replacement.

A Case Of Transient Hyporeninemic Hypoaldosteronism After Unilateral Adrenalrectomy for Aldosterone-Producing Adenoma.: Jungho Suh, Gwanpyo Koh, Keun Yong Park, Jongwook Hong, Suk Chon, Seungjoon Oh, Jeong taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim; J Korean Endocr Soc. 2005;20(5):502-506. Published online October 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.5.502

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Abstract PDF

Primary aldosteronism is due to either a unilateral adrenal adenoma or bilateral hyperplasia of the adrenal cortex in most cases. A unilateral adrenalectomy in hypertensive and hypokalemic patients, with a well-documented adrenal adenoma, is usually followed by the correction of hypokalemia in all subjects, with the cure of hypertension in 60 to 87% of patients. Here, a unique case, in which a unilateral adrenalectomy for the removal of an adrenal adenoma was followed by severe hyperkalemia, low levels of plasma renin activity and serum aldosterone, suggestive of chronic suppression of the renin-aldosterone axis, is reported. In a follow-up Lasix stimulation test on the 70th day after surgery, the suppression of the renin-aldosterone axis was resolved, indicating the suppression was transient. Patients undergoing a unilateral adrenalectomy for an aldosterone-producing adenoma should be closely followed up to avoid severe hyperkalemia.

Citations

Citations to this article as recorded by

A Case of Persistent Hyperkalemia After Unilateral Adrenalectomy for Aldosterone-Producing Adenoma
Min Jae Yang, Seung Jin Han, Min Seok Lee, Eun Kyung Kim, Hae Jin Kim, Dae Jung Kim, Yoon Sok Chung, Tae Hee Lee, Jang Hee Kim, Kwan Woo Lee
Journal of Korean Endocrine Society.2009; 24(3): 201. CrossRef

A Case of Primary Reninism Manifested by Hypertension with Hypokalemia.: Hyung Jin Choi, Eui Sil Hong, Young Min Cho, Do Joon Park, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2005;20(2):168-173. Published online April 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.2.168

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Abstract PDF

Primary reninism is a rare cause of hypertension manifesting along with hypokalemia. A high level of plasma renin activity and a high level of serum aldosterone are the whole markers of primary reninism. Upon making the diagnosis of primary reninism, other more common causes of aldosteronism must be differentiated, such as renovascular hypertension and primary aldosteronism. Primary reninism is commonly caused by juxtaglomerular cell tumor, which is one of the curable causes of hypertension, and this can be successfully treated by conservative surgery. We report here on a case of primary reninism that was caused by juxtaglomerular cell tumor that developed in a 22-year-old female patient. She was recently diagnosed with hypertension and hypokalemia. She had markedly elevated plasma renin activity and an increased serum aldosterone concentration. Computed tomography revealed a mass located in the right kidney and selective renal vein sampling suggested that the mass was secreting an excess of renin. Right nephrectomy was done and her hypertension with hypokalemia was successfully treated. We report here a case of primary reninism that presented with juxtaglomerular cell tumor along with a review of the literature

Citations

Citations to this article as recorded by

Reninoma: a rare cause of curable hypertension
Ji Hye Kim, Ji Hyun Kim, Myung Hyun Cho, Eujin Park, Hye Sun Hyun, Yo Han Ahn, Hee Gyung Kang, Kyung Chul Moon, Il-Soo Ha, Hae Il Cheong
Korean Journal of Pediatrics.2019; 62(4): 144. CrossRef

Original Articles

Interaction of Pituitary Adenylate Cyclase-Activating Polypeptide and Angiotensin II on Aldosterone Production in Human Adrenocortical H295R Cells.: Seong Yeon Kim, Sang Wan Kim, Young Min Cho, Do Joon Park, Chan Soo Shin, Kyung Soo Park, Bo Youn Cho, Hong Kye Lee; J Korean Endocr Soc. 2003;18(3):272-282. Published online June 1, 2003

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Abstract PDF: BACKGROUND
Evidence is accumulating that aldosterone secretion can be regulated in a paracrine and/or an autocrine manner by several neuropeptides locally released within the adrenal gland. Among neuropeptides, pituitary adenylate cyclase-activating polypeptide (PACAP) is present in high concentration in the human adrenal gland. The purpose of this study was to investigate the action of PACAP and the interaction between PACAP and angiotensin II (AII), the main physiologic aldosterone secretagogue, in aldosterone production in human H295R adrenocortical cells. METHODS: H295R cells were incubated with increasing concentrations of PACAP (10(-11)M~10(-7)M) in the absence or presence of 10(-7)M AII. Aldosterone concentration in the supernatant was determined by RIA. Intracellular cAMP content was measured by RIA and total inositol phosphate (IP) production by anion exchange chromatography. Gene expression of CYP11B2 was studied by RT-PCR. RESULTS: In H295R cells, PACAP stimulated aldosterone production in a dose-dependent manner. Incubation of H295R cells with PACAP in the presence of AII significantly increased aldosterone production, compared with that of PACAP alone. PACAP dose-dependently increased cAMP production, but 10(-7)M AII had no effect on either basal or PACAP-stimulated cAMP production. Total IP production was not affected by PACAP, but was increased by 10(-7)M AII; an increase that was not further increased by addition of PACAP. RT-PCR analysis of H295R cells which were exposed to 10-7M PACAP or 10(-7)M AII showed an increase in CYP11B2 transcript signal. Induction of CYP11B2 mRNA expression in response to treatment with both PACAP and AII was significantly more than that resulting from using PACAP alone. CONCLUSION: The present study demonstrates that PACAP exerts a direct stimulatory effect on aldosterone production through induction of CYP11B2 mRNA expression by adenylate cyclase activation as the main intracellular signal pathway in H295R cells. Furthermore, there may be some additive effects between PACAP and AII on aldosterone production.

Mechanism of Angiotensin 2-Stimulated Aldosterone Secretion in Adrenal Glomerulosa Cells of Diabetic Rats ; Normal Phospholipase Activity and Intracellular Calcium Mobilization.: Yeon Ah Sung, Nan Ho Kyung; J Korean Endocr Soc. 1997;12(2):230-244. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Diabetic patients develop hypoaldosteronism which frequently caused hyperkalemia and metabolic acidosis and diabetic hypoaldosteronism is associated with selective unresponsiveness of aldosterone to angiotensin A-II, but mechanism of defect in A-II stimulated aldosterone response still remain unclear. METHODS: To elucidate the mechanism of defect in A-II stimulated aldosterone response, author evaluated the responses of aldosterone production to A-II, K+, and ACTH in adrenal glomerulosa cells prepared from streptozotocin induced diabetic rats, Inositol triphosphate (IP3) generated by activation of phospholipase C (PLC) and arachidonic acid and lysophospholipids generated by activation of phospholipase A2 (PLA2) were measured in A-II stimulated glomerulosa cells. Radiocalcium efflux and aldosterone response to second messenger of A-II such as PLC, IP3, PLA, AA and protein kinase C activator, 12-o-tetradecanoylphorbol 13 acetate (TPA). RESULTS: 1. Plasma renin activity and aldosterone levels were not different among control rats, untreated and insulin treated diabetic rats. 2. Basal, ACTH and K+ -stimulated aldosterone production were similar in cells from the three groups (p<0.05), but A-II stimulated aldosterone production was significantly decreased in cells from untreated diabetic rats compared with control and insulin treated diabetic rats (p0.05). 4. Aldosterone responses to PLC, IP3, AA and TPA were significantly decreased in glomerulosa cells from diabetic rats compared with control and insulin treated diabetic rats (p<0.05), but aldosterone response to PLA2 was similar among the three groups (p>0.05). 45Ca efflux to PLC, IP3 PLA2 and AA were similar among the three groups (p>0.05). CONCLUSION: These results suggested that decreased A-II-stimulated aldosterone response was present in glomerulosa cells from streptozotocin induced diabetic rats and reversed by insulin treatments. The main defect of altered A-II response of zona glomerulosa might be located in the step after activation of phospholipase and increase of intracellular calcium, and activation of PKC, or distal to that could be one of the causative mechanism.

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