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Aldosterone producing adenoma

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https://www.readbyqxmd.com/read/28747387/molecular-characteristics-of-the-kcnj5-mutated-aldosterone-producing-adenomas
#1
Masanori Murakami, Takanobu Yoshimoto, Kazuhiko Nakabayashi, Yujiro Nakano, Takahiro Fukaishi, Kyoichiro Tsuchiya, Isao Minami, Ryotaro Bouchi, Kohji Okamura, Yasuhisa Fujii, Koshi Hashimoto, Ken-Ichiro Hata, Kazunori Kihara, Yoshihiro Ogawa
The pathophysiology of aldosterone-producing adenomas (APAs) has been investigated via genetic approaches and the pathogenic significance of a series of somatic mutations, including KCNJ5, has been uncovered. However, how the mutational status of an APA is associated with its molecular characteristics, including its transcriptome and methylome, has not been fully understood. This study was undertaken to explore the molecular characteristics of APAs, specifically focusing on APAs with KCNJ5 mutations as opposed to those without KCNJ5 mutations, by comparing their transcriptome and methylome status...
July 26, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28699986/diagnosis-and-management-of-primary-aldosteronism
#2
Leticia A P Vilela, Madson Q Almeida
Primary aldosteronism (PA) is the most common form of secondary hypertension (HTN), with an estimated prevalence of 4% of hypertensive patients in primary care and around 10% of referred patients. Patients with PA have higher cardiovascular morbidity and mortality than age- and sex-matched patients with essential HTN and the same degree of blood pressure elevation. PA is characterized by an autonomous aldosterone production causing sodium retention, plasma renin supression, HTN, cardiovascular damage, and increased potassium excretion, leading to variable degrees of hypokalemia...
May 2017: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28688648/nationwide-review-of-hormonally-active-adrenal-tumors-highlights-high-morbidity-in-pheochromocytoma
#3
Punam P Parikh, Gustavo A Rubio, Josefina C Farra, John I Lew
BACKGROUND: Adrenal adenomas are benign tumors often discovered incidentally, and >70% are hormonally inactive. The remaining subset may produce excess aldosterone, cortisol, or catecholamine. Perioperative outcomes after adrenalectomy for such "hormonally active" tumors remain unclear. This study examines in-hospital outcomes after unilateral adrenalectomy for hormonally active tumors. METHODS: A retrospective review was performed using the Nationwide Inpatient Sample (2006-2011) to identify patients undergoing unilateral adrenalectomy for hormonally active or inactive tumors...
July 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28661412/risk-of-new-onset-diabetes-mellitus-in-primary-aldosteronism-a-population-study-over-5-years
#4
Vin-Cent Wu, Shih-Chieh J Chueh, Likwang Chen, Chia-Hui Chang, Ya-Hui Hu, Yen-Hung Lin, Kwan-Dun Wu, Wei-Shiung Yang
OBJECTIVE: Abnormal glucose metabolism due to insulin resistance has been linked to aldosterone overproduction. However, the long-term incidence of new-onset diabetes mellitus (NODM) among patients with primary aldosteronism after targeted treatment has not been well documented. METHODS: The diagnosis of primary aldosteronism and essential hypertension were identified, and then the occurrence of NODM, all-cause mortality among these patients, was ascertained by a validated algorithm from a 23-million population insurance registry...
August 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28604387/macrolides-selectively-inhibit-mutant-kcnj5-potassium-channels-that-cause-aldosterone-producing-adenoma
#5
Ute I Scholl, Laura Abriola, Chengbiao Zhang, Esther N Reimer, Mark Plummer, Barbara I Kazmierczak, Junhui Zhang, Denton Hoyer, Jane S Merkel, Wenhui Wang, Richard P Lifton
Aldosterone-producing adenomas (APAs) are benign tumors of the adrenal gland that constitutively produce the salt-retaining steroid hormone aldosterone and cause millions of cases of severe hypertension worldwide. Either of 2 somatic mutations in the potassium channel KCNJ5 (G151R and L168R, hereafter referred to as KCNJ5MUT) in adrenocortical cells account for half of APAs worldwide. These mutations alter channel selectivity to allow abnormal Na+ conductance, resulting in membrane depolarization, calcium influx, aldosterone production, and cell proliferation...
June 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28592038/-the-application-of-captopril-challenge-test-in-the-diagnosis-of-primary-aldosteronism
#6
S Chen, Z P Zeng, A L Song, L Zhu, L Lu, A L Tong, C Shi, H Z Li
Objective: To evaluate the value of captopril challenge test (CCT) in the diagnosis of primary aldosteronism (PA). Methods: A total of 674 patients [(45.0±13.7) years, men 341, women 333] admitted to Peking Union Medical College Hospital from 2000 to 2015 were analyzed. Among them, 222 subjects were with essential hypertension (EH), 28 were with pheochromocytoma (PHEO), 246 were with idiopathic hyperaldosteronism (IHA) and 178 were with aldosterone producing adenoma (APA). All patients received CCT. 24 h urine sodium was measured in partial patients...
June 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28584016/aldosterone-producing-adenomas-histopathology-genotype-correlation-and-identification-of-a-novel-cacna1d-mutation
#7
Geok Chin Tan, Giulia Negro, Alexandra Pinggera, Nur Maya Sabrina Tizen Laim, Isa Mohamed Rose, Jiri Ceral, Ales Ryska, Long Kha Chin, Nor Azmi Kamaruddin, Norfilza Mohd Mokhtar, A Rahman A Jamal, Norlela Sukor, Miroslav Solar, Joerg Striessnig, Morris Jonathan Brown, Elena Aisha Azizan
Mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1 are thought to cause the excessive autonomous aldosterone secretion of aldosterone-producing adenomas (APAs). The histopathology of KCNJ5 mutant APAs, the most common and largest, has been thoroughly investigated and shown to have a zona fasciculata-like composition. This study aims to characterize the histopathologic spectrum of the other genotypes and document the proliferation rate of the different sized APAs. Adrenals from 39 primary aldosteronism patients were immunohistochemically stained for CYP11B2 to confirm diagnosis of an APA...
July 2017: Hypertension
https://www.readbyqxmd.com/read/28584015/aldosterone-producing-adenomas-genotypes-and-phenotypes
#8
EDITORIAL
Fumitoshi Satoh, Hironobu Sasano, Yuto Yamazaki, Sadayoshi Ito
No abstract text is available yet for this article.
July 2017: Hypertension
https://www.readbyqxmd.com/read/28584012/nefm-neurofilament-medium-polypeptide-a-marker-for-zona-glomerulosa-cells-in-human-adrenal-inhibits-d1r-dopamine-d1-receptor-mediated-secretion-of-aldosterone
#9
Carmela Maniero, Sumedha Garg, Wanfeng Zhao, Timothy Isaac Johnson, Junhua Zhou, Mark Gurnell, Morris J Brown
Heterogeneity among aldosterone-producing adenomas (APAs) has been highlighted by the discovery of somatic mutations. KCNJ5 mutations predominate in large zona fasciculata (ZF)-like APAs; mutations in CACNA1D, ATP1A1, ATP2B3, and CTNNB1 are more likely to be found in small zona glomerulosa (ZG)-like APAs. Microarray comparison of KCNJ5 mutant versus wild-type APAs revealed significant differences in transcriptomes. NEFM, encoding a neurofilament subunit which is a D1R (dopamine D1 receptor)-interacting protein, was 4-fold upregulated in ZG-like versus ZF-like APAs and 14-fold more highly expressed in normal ZG versus ZF...
June 5, 2017: Hypertension
https://www.readbyqxmd.com/read/28529209/quantitative-value-of-aldosterone-renin-ratio-for-detection-of-aldosterone-producing-adenoma-the-aldosterone-renin-ratio-for-primary-aldosteronism-aquarr-study
#10
Giuseppe Maiolino, Giacomo Rossitto, Valeria Bisogni, Maurizio Cesari, Teresa Maria Seccia, Mario Plebani, Gian Paolo Rossi
BACKGROUND: Current guidelines recommend use of the aldosterone-renin ratio (ARR) for the case detection of primary aldosteronism followed by confirmatory tests to exclude false-positive results from further diagnostic workup. We investigated the hypothesis that this could be unnecessary in patients with a high ARR value if the quantitative information carried by the ARR is taken into due consideration. METHODS AND RESULTS: We interrogated 2 large data sets of prospectively collected patients studied with the same predefined protocol, which included the captopril challenge test...
May 21, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28514805/expression-and-histopathological-significance-of-disabled-2-in-aldosterone-producing-adenoma
#11
Ping Li, Min Zhang, Jian-Qiang Ma, Qi Sun, Guang-Xiang Liu, Xiao-Zhi Zhao, Wen-Huan Feng, Shan-Mei Shen, Hong-Qian Guo, Da-Long Zhu
The current pathological diagnosis of aldosterone-producing adenoma (APA) is challenging because no histological markers of aldosterone production are available in routine practice. A previous study demonstrated that Disabled-2 (DAB2) is a specific marker of the zona glomerulosa (ZG) in rodents. The aim of the present study was to investigate the significance of immunohistochemical staining to detect DAB2 in the adrenal tissue of patients with APA. We investigated the expression of DAB2 in 36 adrenal glands with APA, 23 adrenal glands with cortisol-producing adenoma (CPA), and 33 adrenal glands with non-functioning adenoma (NFA)...
July 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28461157/cholesterol-delivery-to-the-adrenal-glands-estimated-by-adrenal-venous-sampling-an-in%C3%A2-vivo-model-to-determine-the-contribution-of-circulating-lipoproteins-to-steroidogenesis-in-humans
#12
Edward Buitenwerf, Robin P F Dullaart, Anneke C Muller Kobold, Thera P Links, Wim J Sluiter, Margery A Connelly, Michiel N Kerstens
BACKGROUND: Cholesterol, required for adrenal steroid hormone synthesis, is at least in part derived from circulating lipoproteins. The contribution of high-density lipoproteins (HDL) and low-density lipoproteins (LDL) to adrenal steroidogenesis in humans is unclear. OBJECTIVE: The aim of the study was to determine the extent to which HDL and LDL are taken up by the adrenal glands using samples obtained during adrenal venous sampling (AVS). METHODS: AVS was successfully performed in 23 patients with primary aldosteronism...
May 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28458337/outcomes-analysis-of-surgical-and-medical-treatments-for-patients-with-primary-aldosteronism
#13
Kyeong Seon Park, Jung Hee Kim, Ye Seul Yang, A Ram Hong, Dong-Hwa Lee, Min Kyong Moon, Sung Hee Choi, Chan Soo Shin, Sang Wan Kim, Seong Yeon Kim
Patients with aldosterone-producing adenomas are treated using surgery, and patients with idiopathic hyperaldosteronism receive medical treatment using mineralocorticoid receptor antagonists (MRAs). However, the outcomes of surgical and medical treatment for primary aldosteronism (PA) remain unclear. Therefore, we compared the outcomes of surgical and medical treatment for PA and aimed to identify a specific subgroup that might benefit from medical treatment. We identified 269 patients who were treated for PA (unilateral excess: 221 cases; bilateral excess: 48 cases) during 2000-2015 at the Seoul National University Hospital and two other tertiary centers...
April 29, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28422753/steroid-metabolome-analysis-reveals-prevalent-glucocorticoid-excess-in-primary-aldosteronism
#14
Wiebke Arlt, Katharina Lang, Alice J Sitch, Anna S Dietz, Yara Rhayem, Irina Bancos, Annette Feuchtinger, Vasileios Chortis, Lorna C Gilligan, Philippe Ludwig, Anna Riester, Evelyn Asbach, Beverly A Hughes, Donna M O'Neil, Martin Bidlingmaier, Jeremy W Tomlinson, Zaki K Hassan-Smith, D Aled Rees, Christian Adolf, Stefanie Hahner, Marcus Quinkler, Tanja Dekkers, Jaap Deinum, Michael Biehl, Brian G Keevil, Cedric H L Shackleton, Jonathan J Deeks, Axel K Walch, Felix Beuschlein, Martin Reincke
BACKGROUND: Adrenal aldosterone excess is the most common cause of secondary hypertension and is associated with increased cardiovascular morbidity. However, adverse metabolic risk in primary aldosteronism extends beyond hypertension, with increased rates of insulin resistance, type 2 diabetes, and osteoporosis, which cannot be easily explained by aldosterone excess. METHODS: We performed mass spectrometry-based analysis of a 24-hour urine steroid metabolome in 174 newly diagnosed patients with primary aldosteronism (103 unilateral adenomas, 71 bilateral adrenal hyperplasias) in comparison to 162 healthy controls, 56 patients with endocrine inactive adrenal adenoma, 104 patients with mild subclinical, and 47 with clinically overt adrenal cortisol excess...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28420172/subtype-diagnosis-of-primary-aldosteronism-is-adrenal-vein-sampling-always-necessary
#15
REVIEW
Fabrizio Buffolo, Silvia Monticone, Tracy A Williams, Denis Rossato, Jacopo Burrello, Martina Tetti, Franco Veglio, Paolo Mulatero
Aldosterone producing adenoma and bilateral adrenal hyperplasia are the two most common subtypes of primary aldosteronism (PA) that require targeted and distinct therapeutic approaches: unilateral adrenalectomy or lifelong medical therapy with mineralocorticoid receptor antagonists. According to the 2016 Endocrine Society Guideline, adrenal venous sampling (AVS) is the gold standard test to distinguish between unilateral and bilateral aldosterone overproduction and therefore, to safely refer patients with PA to surgery...
April 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28416583/physiological-and-pathological-roles-in-human-adrenal-of-the-glomeruli-defining-matrix-protein-npnt-nephronectin
#16
Ada Ee Der Teo, Sumedha Garg, Timothy Isaac Johnson, Wanfeng Zhao, Junhua Zhou, Celso Enrique Gomez-Sanchez, Mark Gurnell, Morris Jonathan Brown
Primary aldosteronism is a common cause of hypertension, which becomes refractory if undiagnosed, but potentially curable when caused by an aldosterone-producing adenoma (APA). The discovery of somatic mutations and differences in clinical presentations led to recognition of small but common zona glomerulosa (ZG)-like adenomas, distinct from classical large zona fasciculata-like adenomas. The inverse correlation between APA size and aldosterone synthase expression prompted us to undertake a systematic study of genotype-phenotype relationships...
June 2017: Hypertension
https://www.readbyqxmd.com/read/28415786/arterial-stiffness-and-blood-pressure-improvement-in-aldosterone-producing-adenoma-harboring-kcnj5-mutations-after-adrenalectomy
#17
Chia-Hui Chang, Ya-Hui Hu, Yao-Chou Tsai, Che-Hsiung Wu, Shuo-Meng Wang, Lian-Yu Lin, Yen-Hung Lin, Fumitoshi Satoh, Kwan-Dun Wu, Vin-Cent Wu
The aim of this study was to show the effect of KCNJ5 mutational status on arterial stiffness in aldosterone-producing adenomas after adrenalectomy. Between February 2008 and January 2010, we prospectively enrolled 108 aldosterone-producing adenoma patients undergoing adrenalectomy. We conducted repeated measurements of pulse wave velocity at baseline, 6 months, and 12 months after adrenalectomy, grouped by KCNJ5 mutational status. Prognostic factors of arterial stiffness and risk for hypertension at 12 months after adrenalectomy were analyzed after propensity score matching in a 1:1 ratio...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405879/histopathological-and-genetic-characterization-of-aldosterone-producing-adenomas-with-concurrent-subclinical-cortisol-hypersecretion-a-case-series
#18
Francesco Fallo, Isabella Castellano, Celso E Gomez-Sanchez, Yara Rhayem, Catia Pilon, Valentina Vicennati, Donatella Santini, Valeria Maffeis, Ambrogio Fassina, Paolo Mulatero, Felix Beuschlein, Martin Reincke
PURPOSE: Aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion are reported in an increasing number of patients. Five aldosterone-producing adenomas from patients with primary aldosteronism and subclinical hypercortisolism were examined. THE AIMS OF OUR STUDY WERE: (1) to analyze pathological features and immunohistochemical expression of CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) in these tumors; (2) to investigate somatic mutations involved in adrenal steroid hypersecretion and/or tumor growth...
April 12, 2017: Endocrine
https://www.readbyqxmd.com/read/28400483/somatic-and-inherited-mutations-in-primary-aldosteronism
#19
Fabio Luiz Fernandes-Rosa, Sheerazed Boulkroun, Maria-Christina Zennaro
Primary aldosteronism (PA), the most common form of secondary hypertension, is caused in the majority of cases by unilateral aldosterone producing adenoma (APA) or bilateral adrenal hyperplasia. In the last years, recurrent somatic mutations in KCNJ5, CACNA1D, ATP1A1, and ATP2B3 were proved to be associated with APA development, explaining more than 50% of sporadic APA. The identification of these mutations have allowed the establishment of a model for APA development involving modifications in the intracellular ionic equilibrium and in the regulation of cell membrane potential, leading to autonomous aldosterone overproduction...
April 11, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28385310/prevalence-and-clinical-manifestations-of-primary-aldosteronism-encountered-in-primary%C3%A2-care%C3%A2-practice
#20
Silvia Monticone, Jacopo Burrello, Davide Tizzani, Chiara Bertello, Andrea Viola, Fabrizio Buffolo, Luisa Gabetti, Giulio Mengozzi, Tracy A Williams, Franco Rabbia, Franco Veglio, Paolo Mulatero
BACKGROUND: Despite being widely recognized as the most common form of secondary hypertension, among the general hypertensive population the true prevalence of primary aldosteronism (PA) and its main subtypes, aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH), remains a matter of debate. OBJECTIVES: This study sought to determine the prevalence and clinical phenotype of PA in a large cohort of unselected patients with hypertension, consecutively referred to our hypertension unit, by 19 general practitioners from Torino, Italy...
April 11, 2017: Journal of the American College of Cardiology
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