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Aldosterone producing adenoma

Nathan Elie Frenk, Fernando Sebastianes, Antonio Marcondes Lerario, Maria Candida Barisson Villares Fragoso, Berenice Bilharinho Mendonca, Marcos Roberto de Menezes
OBJECTIVES: To evaluate the safety and long-term efficacy of computed tomography-guided percutaneous ethanol ablation for benign primary and secondary hyperfunctioning adrenal disorders. METHOD: We retrospectively evaluated the long-term results of nine patients treated with computed tomography-guided percutaneous ethanol ablation: eight subjects who presented with primary adrenal disorders, such as pheochromocytoma, primary macronodular adrenal hyperplasia and aldosterone-producing adenoma, and one subject with Cushing disease refractory to conventional treatment...
October 1, 2016: Clinics
Koshiro Nishimoto, Minae Koga, Tsugio Seki, Kenji Oki, Elise P Gomez-Sanchez, Celso E Gomez-Sanchez, Mitsuhide Naruse, Tomokazu Sakaguchi, Shinya Morita, Takeo Kosaka, Mototsugu Oya, Tadashi Ogishima, Masanori Yasuda, Makoto Suematsu, Yasuaki Kabe, Masao Omura, Tetsuo Nishikawa, Kuniaki Mukai
Our group previously purified human and rat aldosterone synthase (CYP11B2 and Cyp11b2, respectively) from their adrenals and verified that it is distinct from steroid 11β-hydroxylase (CYP11B1 or Cyp11b1), the cortisol- or corticosterone-synthesizing enzyme. We now describe their distributions immunohistochemically with specific antibodies. In rats, there is layered functional zonation with the Cyp11b2-positive zona glomerulosa (ZG), Cyp11b1-positive zona fasciculata (ZF), and Cyp11b2/Cyp11b1-negative undifferentiated zone between the ZG and ZF...
October 14, 2016: Molecular and Cellular Endocrinology
Christoph Degenhart, Julia Schneller, Andrea Osswald, Anna Pallauf, Anna Riester, Maximilian F Reiser, Martin Reincke, Felix Beuschlein
OBJECTIVE: To evaluate volumetric and densitometric properties of the adrenal glands in patients with unilateral and bilateral disease in comparison to normal controls. DESIGN: 77 patients (56 male and 21 female) diagnosed with primary aldosteronism (PA) with a mean age of 53±10 years were prospectively enrolled. Unenhanced and contrast enhanced CT scans were analyzed for adrenal volumes and mean densities. f These values were compared with normal controls and between PA subtypes...
October 17, 2016: Clinical Endocrinology
Georgios Daniil, Fabio L Fernandes-Rosa, Jean Chemin, Iulia Blesneac, Jacques Beltrand, Michel Polak, Xavier Jeunemaitre, Sheerazed Boulkroun, Laurence Amar, Tim M Strom, Philippe Lory, Maria-Christina Zennaro
Primary aldosteronism (PA) is the most common form of secondary hypertension. Mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D are found in aldosterone producing adenoma (APA) and familial hyperaldosteronism (FH). A recurrent mutation in CACNA1H (coding for Cav3.2) was identified in a familial form of early onset PA. Here we performed whole exome sequencing (WES) in patients with different types of PA to identify new susceptibility genes. Four different heterozygous germline CACNA1H variants were identified. A de novo Cav3...
October 4, 2016: EBioMedicine
Ayako Moriya, Masaaki Yamamoto, Shunsuke Kobayashi, Tomoko Nagamine, Naomi Takeichi-Hattori, Mototsugu Nagao, Taro Harada, Kyoko Tanimura-Inagaki, Shiro Onozawa, Satoru Murata, Hideki Tamura, Izumi Fukuda, Shinichi Oikawa, Hitoshi Sugihara
The diagnostic steps for primary aldosteronism (PA) include case screening tests, confirmatory tests, and localization. The aim of this study was to identify useful confirmatory tests and their cut-off values for differentiating the subtype of primary aldosteronism, especially in unilateral PA, such as aldosterone-producing adenoma, and bilateral PA, such as idiopathic hyperaldosteronism. Seventy-six patients who underwent all four confirmatory tests, the captopril-challenge test (CCT), furosemide upright test (FUT), saline infusion test (SIT), and ACTH stimulation test (AST), and who were confirmed to have an aldosterone excess by adrenal venous sampling (AVS) were recruited...
October 1, 2016: Endocrine Journal
Takashi Okamura, Yasuyo Nakajima, Akiko Katano-Toki, Kazuhiko Horiguchi, Shunichi Matsumoto, Satoshi Yoshino, Eijiro Yamada, Takuya Tomaru, Sumiyasu Ishii, Tsugumichi Saito, Atsushi Ozawa, Nobuyuki Shibusawa, Tetsurou Satoh, Shuichi Okada, Rin Nagaoka, Daisuke Takada, Jun Horiguchi, Tetsunari Oyama, Masanobu Yamada
Somatic mutations in KCNJ5 gene have been identified in patients with adrenal aldosterone-producing adenomas (APAs). We previously reported that Japanese patients with APAs had distinct characteristics from patients in Western countries; i.e. they had a high frequency of KCNJ5 mutations and exhibited a frequent association with cortisol co-secretion. Therefore, APAs among Japanese patients may have different features from those in Western countries. We added recent cases, examined 47 cases (43% male) of APAs, including clinicopathological features, KCNJ5 mutations, and the mRNA levels of several steroidogenic enzymes, and compared the results obtained to those reported in other countries...
September 28, 2016: Endocrine Journal
Julien Vouillarmet, Fabio Fernandes-Rosa, Julia Graeppi-Dulac, Pierre Lantelme, Myriam Decaussin-Petrucci, Charles Thivolet, Jean-Louis Peix, Sheerazed Boulkroun, Eric Clauser, Maria-Christina Zennaro
CONTEXT: Recurrent somatic mutations in KCNJ5, CACNA1D, ATP1A1 and ATP2B3 have been identified in aldosterone producing adenomas (APA). The question as to whether they are responsible for both nodulation and aldosterone production is not solved. CASE DESCRIPTION: We describe the case of a young patient who was diagnosed with severe arterial hypertension due to primary aldosteronism at age 26, followed by hemorrhagic stroke four years later. Abdominal computed tomography showed bilateral macronodular adrenal hyperplasia...
September 20, 2016: Journal of Clinical Endocrinology and Metabolism
Elena Azizan, Norlela Sukor, Nor Azmi Kamaruddin, A Rahman A Jamal, Jiri Ceral, Miroslav Solar, Isa Mohamed Rose, Geok Chin Tan
OBJECTIVE: Aldosterone-producing adenoma (APA) is a common curable cause of hypertension. Somatic mutations in five genes (KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1) have been found to cause the excess aldosterone production of two thirds of APAs [1-4]. KCNJ5 mutant APAs, the most common and largest, had explicit genotype-phenotype relationship - a low protein expression of KCNJ5 relative to their peritumoural zona glomerulosa (ZG) and a zona fasciculata-like composition [5-6]. Conversely for the other genes, controversy arises on whether they have the opposite cell phenotype [4,7-8]...
September 2016: Journal of Hypertension
Giuseppe Maiolino, Alberto Flego, Gian Paolo Rossi
OBJECTIVE: PA causes excess cardiovascular (CV) damage, but whether it worsens prognosis remained uncertain as there are no prospective studies. To compare long-term outcome of the 1125 patients recruited in the PAPY study. DESIGN AND METHOD: 11.2% of the PAPY study patients had PA: 6.4% idiopathic hyperaldosteronism (IHA) received medical therapy; 4,8% aldosterone-producing adenoma (APA) required adrenalectomy. Endpoints were total and CV mortality, major adverse cardiovascular events (MACE) and total CV events...
September 2016: Journal of Hypertension
Junhua Zhou, Brian Lam, Sudeshna Neogi, Giles Yeo, Elena Azizan, Morris Brown
OBJECTIVE: Primary aldosteronism (PA) is the most common type of secondary hypertension occurring in ∼10% of hypertensive patients. Up to 50% of PA is caused by aldosterone-producing adenomas (APA). This study is to identify the potential biological processes and canonical pathways involved with aldosterone regulation, APA formation, or APA and ZG cell functions. DESIGN AND METHOD: Gene ontology (GO) and pathway analyses were performed on genes differentially expressed in APAs when compared to ZG and on genes differentially expressed in ZG when compared to ZF...
September 2016: Journal of Hypertension
Martin Wolley, Diane Cowley, Ashraf Ahmed, Richard Gordon, Michael Stowasser
OBJECTIVE: Obstructive sleep apnoea (OSA) is known to commonly co-exist with primary aldosteronism (PA), but it is unknown if treatment via mineralocorticoid receptor blockade or adrenalectomy (for aldosterone producing adenoma, APA), improves sleep apnoea parameters in these patients. We therefore aimed to determine if specific medical or surgical treatment of PA improves OSA, as measured by the apnoea hypopnoea index (AHI). DESIGN AND METHOD: Patients undergoing diagnostic workup for PA were recruited if they had symptoms suggestive of OSA...
September 2016: Journal of Hypertension
Yoshitsugu Iwakura, Ryo Morimoto, Kumi Kikuchi, Yoshikiyo Ono, Yuta Tezuka, Yasuko Tsukada, Masahiro Nezu, Yasuhiro Igarashi, Masataka Kudo, Akira Nishiyama, Sadayoshi Ito, Fumitoshi Satoh
OBJECTIVE: High prevalence of renal damage has been demonstrated in patients with primary aldosteronism (PA). However, the original mechanism and onset still be elucidated. The purpose of this study is to investigate the possible original mechanisms of renal damages in PA. DESIGN AND METHOD: Consecutive 72 patients with aldosterone producing adenoma (APA) and 70 patients with essential hypertension (EH) participated. No patients had renal damages defined as eGFR (based on Cystatin C) < 60 ml/min/1...
September 2016: Journal of Hypertension
Satoshi Umemura
Primary aldosteronism (PA) is a heterogeneous group of disorders including both sporadic and familial forms (familial hyperaldosteronism type I, II and III). PA is the most frequent endocrine cause of secondary hypertension and associated with a higher rate of cardiovascular complications, compared with essential hypertension.Here I review the recent progress in understanding of the genetic and molecular mechanisms leading to autonomous aldosterone production in PA.Systematic screening detects primary aldosteronism in 5 to 10% of all patients with hypertension and in approximately 20% of patients with resistant hypertension...
September 2016: Journal of Hypertension
Vin-Cent Wu, Shuo-Meng Wang, Chia-Hui Chang, Ya-Hui Hu, Lian-Yu Lin, Yen-Hung Lin, Shih-Chieh Jeff Chueh, Likwang Chen, Kwan-Dun Wu
There exists a great knowledge gap in terms of long-term effects of various surgical and pharmacological treatments on outcomes among primary aldosteronism (PA) patients. Using a validated algorithm, we extracted longitudinal data for all PA patients diagnosed in 1997-2010 and treated in the Taiwan National Health Insurance. We identified 3362 PA patients for whom the mean length of follow-up was 5.75 years. PA has higher major cardiovascular events (MACE) than essential hypertension (23.3% vs 19.3%, p = 0...
2016: Scientific Reports
Giacomo Rossitto, Diego Miotto, Michele Battistel, Giulio Barbiero, Giuseppe Maiolino, Valeria Bisogni, Viola Sanga, Gian Paolo Rossi
OBJECTIVE: As metoclopramide stimulates aldosterone secretion, we tested its usefulness in the assessment of lateralization of primary aldosteronism by adrenal vein sampling (AVS). DESIGN: Prospective within-patient study in consecutive patients undergoing AVS for primary aldosteronism subtyping. METHODS: We compared the diagnostic accuracy of baseline and postmetoclopramide lateralization index and relative (to cortisol) aldosterone secretion indices (RASI) for each adrenal gland with aldosterone-producing adenoma (APA) determined by the four corners criteria as the reference diagnosis...
November 2016: Journal of Hypertension
S Y Liu, C M Chu, A P Kong, S K Wong, P W Chiu, F C Chow, E K Ng
BACKGROUND: Radiofrequency ablation (RFA) is an emerging treatment for primary aldosteronism owing to aldosterone-producing adenoma. Whether RFA could be an alternative treatment to laparoscopic adrenalectomy is unknown. METHODS: This was a retrospective comparative study in patients with aldosterone-producing adenoma undergoing either laparoscopic adrenalectomy or CT-guided percutaneous RFA between 2004 and 2012. Short-term outcomes and long-term resolution rates of primary aldosteronism (normalized aldosterone to renin ratio), hypokalaemia and hypertension (BP lower than 140/90 mmHg without antihypertensive medical therapy) were evaluated...
October 2016: British Journal of Surgery
G Maiolino, V Bisogni, G Rossitto, M Cesari, G P Rossi
OBJECTIVE: Guidelines recommend use of the aldosterone-renin ratio (ARR) for the case detection of primary aldosteronism (PA) and "confirmatory" tests in patients with a baseline ARR value above a given cut-off to exclude false positive results from further diagnostic work-up.We tested the hypothesis that the ARR carries important quantitative information, which could avoid confirmatory tests in a substantial proportion of the patients. DESIGN AND METHOD: The study was carried out in two prospectively recruited large cohorts of hypertensive patients who underwent measurement of the ARR and the captopril challenge test, in which a conclusive diagnosis of aldosterone-producing adenoma (APA) was made by the "four corners" criteria...
September 2016: Journal of Hypertension
F Satoh, Y Ono, R Morimoto, Y Iwakura, M Nezu, K Omata, Y Tezuka, Y Igarashi, M Kudo, S Ito
OBJECTIVE: The measurement of plasma aldosterone concentration (PAC) and renin activity (PRA) or active renin concentration (ARC) is clinically important not only for detection of primary aldosteronism but also for the selection of antihypertensive agents to treat patients successfully. However, it has taken approximately 7 days for clinicians to get the results. Of late, we developed the novel rapid non-RIA assays of PAC and ARC, which are measurable in 10 minutes. This study is intended to investigate the utility and accuracy of this new methods...
September 2016: Journal of Hypertension
G Daniil, F L Fernandes-Rosa, J Chemin, X Jeunemaitre, M Polak, S Boulkroun, L Amar, T M Strom, P Lory, M C Zennaro
OBJECTIVE: Primary aldosteronism (PA) is the most common form of secondary hypertension. Mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D are found in aldosterone producing adenomas (APA) and familial hyperaldosteronism (FH). Recently, a recurrent germline mutation in CACNA1H (encoding the T-type voltage-dependent calcium channel Cav3.2) was identified in a new familial form of early onset hypertension and PA. DESIGN AND METHOD: To identify new genes responsible for PA, we have performed whole exome sequencing in 23 patients with APA, 10 patients with FH and in two trios with the proband presenting early onset PA...
September 2016: Journal of Hypertension
S Monticone, F Satoh, A S Dietz, R Goupil, K Lang, F Pizzolo, R D Gordon, R Morimoto, M Reincke, M Stowasser, P Mulatero
OBJECTIVE: Adrenal vein sampling (AVS) is the only reliable means to distinguish between aldosterone-producing adenoma and bilateral adrenal hyperplasia, the two most common subtypes of primary aldosteronism (PA). To distinguish between unilateral and bilateral disease is of fundamental importance because it allows to allocate patients to the correct management: unilateral adrenalectomy for aldosterone-producing adenoma or pharmacotherapy with mineralocorticoid receptor antagonists for individuals with bilateral adrenal hyperplasia...
September 2016: Journal of Hypertension
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