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Aldosterone producing adenoma

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https://www.readbyqxmd.com/read/29016532/kcnj5-mutation-as-a-predictor-for-resolution-of-hypertension-after-surgical-treatment-of-aldosterone-producing-adenoma
#1
Takumi Kitamoto, Masao Omura, Sachiko Suematsu, Jun Saito, Tetsuo Nishikawa
OBJECTIVE: To investigate the effect of KCNJ5 mutations on the cure of hypertension in patients with aldosterone-producing adenoma (APA) after unilateral adrenalectomy. METHODS: Our study included 142 patients with APA, who were detected with an endocrinological abnormality and diagnosed with hypertension, as confirmed by pathological analysis. We sequenced KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1 from APA tissue samples, and performed a retrospective analysis to determine correlations between wild-type or mutated KCNJ5 and patient clinical characteristics...
October 7, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28994759/a-novel-method-super-selective-adrenal-venous-sampling
#2
Kohzoh Makita, Koshiro Nishimoto, Kanako Kiriyama-Kitamoto, Shigehiro Karashima, Tsugio Seki, Masanori Yasuda, Seishi Matsui, Masao Omura, Tetsuo Nishikawa
Primary aldosteronism (PA) and subclinical Cushing's syndrome (SCS) are conditions in which the adrenal glands autonomously produce excessive amounts of aldosterone and cortisol, respectively. The conventional adrenal venous sampling (cAVS) method collects blood samples from both adrenal central veins and is useful for identifying the laterality of excess hormone production in a unilateral lesion(s), as documented in PA cases. In cAVS, plasma cortisol concentrations (PCCs) are used to normalize plasma aldosterone concentrations (PACs)...
September 15, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28993452/macrolides-blunt-aldosterone-biosynthesis-a-proof-of-concept-study-in-kcnj5-mutated-adenoma-cells-ex-vivo
#3
Brasilina Caroccia, Selene Prisco, Teresa Maria Seccia, Maria Piazza, Giuseppe Maiolino, Gian Paolo Rossi
Aldosterone-producing adenoma (APA), a major subtype of primary hyperaldosteronism, the main curable cause of human endocrine hypertension, involves somatic mutations in the potassium channel Kir3.4 (KCNJ5) in 30% to 70% of cases, typically the more florid phenotypes. Because KCNJ5 mutated channels were reported to be specifically sensitive to inhibition by macrolide antibiotics, which concentration dependently blunts aldosterone production in HAC15 transfected with the G151R and L168R mutated channel, we herein tested the effect of clarithromycin on aldosterone synthesis and secretion in a pure population of aldosterone-secreting cells obtained by immunoseparation (CD56(+) cells) from APA tissues with/without the 2 most common KCNJ5 mutations...
October 9, 2017: Hypertension
https://www.readbyqxmd.com/read/28978442/mechanisms-responsible-for-%C3%AF-pore-currents-in-cav-calcium-channel-voltage-sensing-domains
#4
Stefania Monteleone, Andreas Lieb, Alexandra Pinggera, Giulia Negro, Julian E Fuchs, Florian Hofer, Jörg Striessnig, Petronel Tuluc, Klaus R Liedl
Mutations of positively charged amino acids in the S4 transmembrane segment of a voltage-gated ion channel form ion-conducting pathways through the voltage-sensing domain, named ω-current. Here, we used structure modeling and MD simulations to predict pathogenic ω-currents in CaV1.1 and CaV1.3 Ca(2+) channels bearing several S4 charge mutations. Our modeling predicts that mutations of CaV1.1-R1 (R528H/G, R897S) or CaV1.1-R2 (R900S, R1239H) linked to hypokalemic periodic paralysis type 1 and of CaV1.3-R3 (R990H) identified in aldosterone-producing adenomas conducts ω-currents in resting state, but not during voltage-sensing domain activation...
October 3, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28973103/genetic-causes-of-functional-adrenocortical-adenomas
#5
Maria-Christina Zennaro, Sheerazed Boulkroun, Fabio Fernandes-Rosa
Aldosterone and cortisol, the main mineralocorticoid and glucocorticoid hormones in humans, are produced in the adrenal cortex, which is composed of three concentric zone with specific functional characteristics. Adrenocortical adenomas (ACA) may lead to the autonomous secretion of aldosterone responsible for primary aldosteronism, the most frequent form of secondary arterial hypertension. In the case of cortisol production, ACA lead to overt or subclinical Cushing syndrome. Genetic analysis driven by next generation sequencing technology has enabled the discovery, during the last seven years, of the genetic causes of a large subset of ACA...
August 2, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28957852/the-subtyping-of-primary-aldosteronism-by-adrenal-vein-sampling-sequential-blood-sampling-causes-factitious-lateralization
#6
Giacomo Rossitto, Michele Battistel, Giulio Barbiero, Valeria Bisogni, Giuseppe Maiolino, Miotto Diego, Teresa M Seccia, Gian Paolo Rossi
BACKGROUND: The pulsatile secretion of adrenocortical hormones and a stress reaction occurring when starting adrenal vein sampling (AVS) can affect the selectivity and also the assessment of lateralization when sequential blood sampling is used. We therefore tested the hypothesis that a simulated sequential blood sampling could decrease the diagnostic accuracy of lateralization index for identification of aldosterone-producing adenoma (APA), as compared with bilaterally simultaneous AVS...
September 27, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28956362/ctnnb1-mutation-in-aldosterone-producing-adenoma
#7
REVIEW
Jian Jhong Wang, Kang Yung Peng, Vin Cent Wu, Fen Yu Tseng, Kwan Dun Wu
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...
September 2017: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28947616/review-of-markers-of-zona-glomerulosa-and-aldosterone-producing-adenoma-cells
#8
REVIEW
Teresa M Seccia, Brasilina Caroccia, Elise P Gomez-Sanchez, Paul-Emmanuel Vanderriele, Celso E Gomez-Sanchez, Gian Paolo Rossi
No abstract text is available yet for this article.
September 25, 2017: Hypertension
https://www.readbyqxmd.com/read/28931750/adrenal-gipr-expression-and-chromosome-19q13-microduplications-in-gip-dependent-cushing-s-syndrome
#9
Anne-Lise Lecoq, Constantine A Stratakis, Say Viengchareun, Ronan Chaligné, Lucie Tosca, Vianney Deméocq, Mirella Hage, Annabel Berthon, Fabio R Faucz, Patrick Hanna, Hadrien-Gaël Boyer, Nicolas Servant, Sylvie Salenave, Gérard Tachdjian, Clovis Adam, Vanessa Benhamo, Eric Clauser, Anne Guiochon-Mantel, Jacques Young, Marc Lombès, Isabelle Bourdeau, Dominique Maiter, Antoine Tabarin, Jérôme Bertherat, Hervé Lefebvre, Wouter de Herder, Estelle Louiset, André Lacroix, Philippe Chanson, Jérôme Bouligand, Peter Kamenický
GIP-dependent Cushing's syndrome is caused by ectopic expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in cortisol-producing adrenal adenomas or in bilateral macronodular adrenal hyperplasias. Molecular mechanisms leading to ectopic GIPR expression in adrenal tissue are not known. Here we performed molecular analyses on adrenocortical adenomas and bilateral macronodular adrenal hyperplasias obtained from 14 patients with GIP-dependent adrenal Cushing's syndrome and one patient with GIP-dependent aldosteronism...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28918446/favorable-surgical-outcomes-of-aldosterone-producing-adenoma-based-on-lateralization-by-ct-imaging-and-hypokalemia-a-non-avs-based-strategy
#10
Hai Li, Jianbin Liu, Xiujuan Feng, Liehua Liu, Guohong Wei, Xiaopei Cao, Yanbing Li
PURPOSE: To test the efficacy of a strategy based on CT imaging and clinical characteristics on lateralizing origin of excess aldosterone secretion in primary aldosteronism. PATIENTS AND METHODS: Consecutive patients with diagnosed primary hyperaldosteronism from June 2006 to July 2012 in our center underwent adrenal surgeries without pre-operational adrenal venous sampling (AVS) if all the three criteria were met: (1) round- or oval-shaped occupational lesion of low density after contrast enhancement with diameter >1 cm on CT scan was located in one adrenal gland; (2) unequivocally normal contralateral adrenal gland; (3) serum potassium level lower than 3...
September 16, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28904009/diagnosis-of-endocrine-disease-18-oxocortisol-and-18-hydroxycortisol-is-there-clinical-utility-of-these-steroids
#11
Jacques Lenders, Tracy A Williams, Martin Reincke, Celso E Gomez-Sanchez
Since the early nineteen eighties 18-hydroxycortisol and 18-oxocortisol have attracted attention when it was shown that the urinary excretion of these hybrid steroids was increased in primary aldosteronism. The development and more widespread use of specific assays has improved the understanding of their role in the (patho)physiology of adrenal disorders. The adrenal site of synthesis is not fully understood although it is clear that for the synthesis of 18-hydroxycortisol and 18-oxocortisol the action of both aldosterone synthase (zona glomerulosa) and 17α-hydroxylase (zona fasciculata) is required with cortisol as main substrate...
September 13, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28894201/cortisol-overproduction-results-from-dna-methylation-of-cyp11b1-in-hypercortisolemia
#12
Mitsuhiro Kometani, Takashi Yoneda, Masashi Demura, Hiroshi Koide, Koshiro Nishimoto, Kuniaki Mukai, Celso E Gomez-Sanchez, Tadayuki Akagi, Takashi Yokota, Shin-Ichi Horike, Shigehiro Karashima, Isamu Miyamori, Masakazu Yamagishi, Yoshiyu Takeda
Adrenocortical hormone excess, due to primary aldosteronism (PA) or hypercortisolemia, causes hypertension and cardiovascular complications. In PA, hypomethylation of aldosterone synthase (CYP11B2) is associated with aldosterone overproduction. However, in hypercortisolemia, the role of DNA methylation of 11β-hydroxylase (CYP11B1), which catalyzes cortisol biosynthesis and is highly homologous to CYP11B2, is unclear. The aims of our study were to determine whether the CYP11B1 expression was regulated through DNA methylation in hypercortisolemia with cortisol-producing adenoma (CPA), and to investigate a possible relationship between DNA methylation and somatic mutations identified in CPA...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28893861/adrenal-venous-sampling-for-primary-aldosteronism-laboratory-medicine-best-practice
#13
Gregory Kline, Daniel T Holmes
Primary aldosteronism (PA) is the most common form of secondary hypertension and is critical to identify because when caused by an aldosterone-producing adenoma (APA) or another unilateral form, it is potentially curable, and even when caused by bilateral disease, antihypertensives more specific to PA treatment can be employed (ie, aldosterone antagonists). Identification of unilateral forms is not generally accomplished with imaging because APAs may be small and elude detection, and coincidental identification of a non-functioning incidentaloma contralateral to an APA may lead to removal of an incorrect gland...
September 11, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28879651/preliminary-studies-on-the-differential-expression-of-adrenocorticotropic-hormone-receptor-in-adrenal-adenomas
#14
Dongliang Hu, Tongzu Liu, Xinghuan Wang
INTRODUCTION: The ACTH receptor (ACTHR) is primarily expressed in the adrenal cortex. Previous studies focused on the regulatory function of ACTHR in glucocorticoid secretion, but research on adrenal tumours is rare. The aim of this study was to evaluate ACTHR expression in common adrenal adenomas and investigate its influence on adrenal tumorigenesis using adrenocortical H295R cells. MATERIALS AND M: ETHODS: Real-time polymerase chain reaction and western blot were used to detect the expression of ACTHR in 18 aldosterone-producing adenomas, 16 cortisol-producing adenomas, nine non-functional adenomas, and 12 normal adrenal samples...
September 7, 2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/28877721/a-case-of-adrenocoricotrophic-hormone-independent-bilateral-adrenocortical-macronodular-hyperplasia-concomitant-with-primary-aldosteronism
#15
Mao Tokumoto, Naoyoshi Onoda, Yukie Tauchi, Shinichiro Kashiwagi, Satoru Noda, Norikazu Toi, Masahumi Kurajoh, Masahiko Ohsawa, Yuto Yamazaki, Hironobu Sasano, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: Adrenocoricotrophic hormone (ACTH) - independent bilateral adrenocortical macronodular hyperplasia (AIMAH) is a rare cause of Cushing's syndrome, and is characterized by bilateral adrenal hyperplasia. However, Primary aldosteronism (PA) is a relatively common adrenal disease. CASE PRESENTATION: A 56-year-old man who has been treated hypertension and diabetes mellitus was detected low plasma potassium level with an elevated level of plasma aldosterone concentration and bilateral adrenal swelling...
September 6, 2017: BMC Surgery
https://www.readbyqxmd.com/read/28870781/aberrant-g-protein-receptor-expression-is-associated-with-dna-methylation-in-aldosterone-producing-adenoma
#16
Kiyotaka Itcho, Kenji Oki, Kazuhiro Kobuke, Yoko Yoshii, Haruya Ohno, Masayasu Yoneda, Noboru Hattori
This study aimed to evaluate the methylation levels of G protein-coupled receptor (GPCR) related genes and the effects of methylation on mRNA expression levels in aldosterone-producing adenoma (APA). DNA methylation array and transcriptome analysis were applied in non-functioning adrenocortical adenoma (NFA) and APA. We investigated 192 GPCR-related genes and found hypo-methylation in the promoter region of 66 of these genes in APA. An integration study between microarray and methylation analysis revealed that HTR4, MC2R, TACR1, GRM3, and PTGER1 showed hypo-methylation and up-regulation of mRNA in APA...
September 6, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28852406/regulation-of-corticosteroidogenic-genes-by-micrornas
#17
Stacy Robertson, Louise A Diver, Samantha Alvarez-Madrazo, Craig Livie, Ayesha Ejaz, Robert Fraser, John M Connell, Scott M MacKenzie, Eleanor Davies
The loss of normal regulation of corticosteroid secretion is important in the development of cardiovascular disease. We previously showed that microRNAs regulate the terminal stages of corticosteroid biosynthesis. Here, we assess microRNA regulation across the whole corticosteroid pathway. Knockdown of microRNA using Dicer1 siRNA in H295R adrenocortical cells increased levels of CYP11A1, CYP21A1, and CYP17A1 mRNA and the secretion of cortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycorticosterone, and aldosterone...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28844072/update-in-diagnosis-and-management-of-primary-aldosteronism
#18
REVIEW
Sofia M Dick, Marina Queiroz, Bárbara L Bernardi, Angélica Dall'Agnol, Letícia A Brondani, Sandra P Silveiro
Primary aldosteronism (PA) is a group of disorders in which aldosterone is excessively produced. These disorders can lead to hypertension, hypokalemia, hypervolemia and metabolic alkalosis. The prevalence of PA ranges from 5% to 12% around the globe, and the most common causes are adrenal adenoma and adrenal hyperplasia. The importance of PA recognition arises from the fact that it can have a remarkably adverse cardiovascular and renal impact, which can even result in death. The aldosterone-to-renin ratio (ARR) is the election test for screening PA, and one of the confirmatory tests, such as oral sodium loading (OSL) or saline infusion test (SIT), is in general necessary to confirm the diagnosis...
August 28, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28747387/molecular-characteristics-of-the-kcnj5-mutated-aldosterone-producing-adenomas
#19
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
#20
REVIEW
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
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