Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary aldosteronism is the most common cause of secondary hypertension, most frequently due to an aldosterone-producing adenoma or idiopathic hyperaldosteronism. Somatic mutations of the potassium channel KCNJ5 in the region of the selectivity filter have been found in a significant number of aldosterone-producing adenomas. There are also familial forms of primary aldosteronism, one of which, familial hyperaldosteronism type 3 which to date has been found in one family who presented with a severe abnormality in aldosterone and 18-oxocortisol production and hypertrophy and hyperplasia of the transitional zone of the adrenal cortex. In familial hyperaldosteronism type 3, there is a genomic mutation causing a T158A change of amino acids within the selectivity filter region of the KCNJ5 gene. We are reporting our studies demonstrating that lentiviral-mediated expression of a gene carrying the T158A mutation of the KCNJ5 in the HAC15 adrenal cortical carcinoma cell line causes a 5.3-fold increase in aldosterone secretion in unstimulated HAC15-KCNJ5 cells and that forskolin-stimulated aldosterone secretion was greater than that of angiotensin II. Expression of the mutated KCNJ5 gene decreases plasma membrane polarization, allowing sodium and calcium influx into the cells. The calcium channel antagonist nifedipine and the calmodulin inhibitor W-7 variably inhibited the effect. Overexpression of the mutated KCNJ5 channel resulted in a modest decrease in HAC15 cell proliferation. These studies demonstrate that the T158A mutation of the KCNJ5 gene produces a marked stimulation in aldosterone biosynthesis that is dependent on membrane depolarization and sodium and calcium influx into the HAC15 adrenal cortical carcinoma cells.
 ...
PMID:Potassium channel mutant KCNJ5 T158A expression in HAC-15 cells increases aldosterone synthesis. 2244 11

Primary aldosteronism is the most common form of secondary hypertension. Case detection is based on an abnormal plasma aldosterone:plasma renin activity ratio and the diagnosis must be confirmed with an aldosterone suppression test. Subtype differentiation should be performed using adrenal venous sampling. Approximately 50% of patients with primary aldosteronism will have a unilateral aldosterone-producing adenoma; laparoscopic adrenalectomy results in cure of hypertension in 60% and improvement in blood pressure control in the remainder.
 ...
PMID:Primary aldosteronism. 2309 Aug 93

A 24-year-old woman presented with severe hypertension. A diagnostic evaluation for secondary hypertension was undertaken. A duplex ultrasonography followed by a magnetic angiography suspected fibromuscular dysplasia. Unexpectedly, a contrast-enhanced angiography performed for renal angioplasty showed normal renal arteries. Primary aldosteronism was then evoked on the basis of decreased plasma renin and increased plasma aldosterone and aldosterone/renin ratio. After a CT-scan disclosed a left adrenal tumour, the patient underwent a left laparoscopic adrenalectomy. Pathological findings confirmed a benign adrenocortical adenoma. Blood pressure and aldosterone levels were normalized after surgery. Thus, clinicians should be aware of false-positive results of magnetic resonance angiography that could hide other causes of secondary hypertension.
 ...
PMID:Misleading diagnosis of renal artery stenosis by magnetic resonance angiography in a patient with primary aldosteronism. 2300 96

Endocrine hypertension is the most common cause of secondary hypertension affecting ~3 % of the population, with primary hyperaldosteronism and pheochromocytoma being the principal conditions. Both diseases share an increased cardiovascular risk in comparison with essential hypertension patients (at the same blood pressure level). This augmented cardiovascular risk as well as the availability of specific treatment emphasize the importance of timely and correct diagnosis. Primary hyperaldosteronism, representing one tenth of hypertensive patients, is an under-diagnosed disease partly because of difficult diagnostic steps and absence of standard criteria. Recently, the description of somatic mutations in KCNJ5 gene in Conn adenomas had precipitated a resurgence of research activity to understand the pathophysiology of this common disease. Research had confirmed the role of these mutations in aldosterone hypersecretion; however, its role in adenoma formation is still to be elucidated. Elsewhere, much remains to be done in order to understand the pathogenesis of bilateral idiopathic hyperaldosteronism, the other common subtype of primary hyperaldosteronism. In pheochromocytoma, the revolution of genetics has led to major advances in the characterization of this rare disease. It is now clear that up to 50 % of patients with pheochromocytoma have a genetic abnormality and that different pheochromocytomas segregate into two clusters with distinct genotypes, signal transduction pathways and expression of biomarkers (phenotype). This continuing progress has huge effects on patient's management and follow-up. In this article we will shed light on the recent developments in both diseases with emphasis on their role in patient care.
 ...
PMID:[Update on endocrine hypertension]. 2308 79

Patients with resistant hypertension have a higher incidence of secondary causes of hypertension compared with the general hypertensive population. It is important to screen such patients for secondary causes of hypertension because appropriate treatment can lead to improved blood pressure control or even cure these patients, and thus avoid the cardiovascular morbidity and mortality associated with uncontrolled hypertension. One common cause of secondary hypertension, often associated with hypokalemia, is primary hyperaldosteronism or Conn syndrome. Aldosterone is a mineralocorticoid hormone produced in the outer layer of the adrenal cortex (the zona glomerulosa); its primary action is to increase sodium and water reabsorption by the kidney. Once the diagnosis of primary aldosteronism is made, it is necessary to determine if aldosterone production is unilateral or bilateral. When production is unilateral (most often from a functional adenoma), surgery is potentially curative. The authors report a case and review the diagnostic workup of Conn syndrome in which resistant hypertension and hypokalemia were cured by unilateral adrenalectomy.
 ...
PMID:Primary hyperaldosteronism decoded: a case of curable resistant hypertension. 2347 Jun 90

Aldosterone plays a major role in the regulation of sodium and potassium homeostasis and blood pressure. More recently, aldosterone has emerged as a key hormone mediating end organ damage. In extreme cases, dysregulated aldosterone production leads to primary aldosteronism (PA), the most common form of secondary hypertension. However, even within the physiological range, high levels of aldosterone are associated with an increased risk of developing hypertension over time. PA represents the most common and curable form of hypertension, with a prevalence that increases with the severity of hypertension. Although genetic causes underlying glucocorticoid-remediable aldosteronism, one of the three Mendelian forms of PA, were established some time ago, somatic and inherited mutations in the potassium channel GIRK4 have only recently been implicated in the formation of aldosterone-producing adenoma (APA) and in familial hyperaldosteronism type 3. Moreover, recent findings have shown somatic mutations in two additional genes, involved in maintaining intracellular ionic homeostasis and cell membrane potential, in a subset of APAs. This review summarizes our current knowledge on the genetic determinants that contribute to variations in plasma aldosterone and renin levels in the general population and the genetics of familial and sporadic PA. Various animal models that have significantly improved our understanding of the pathophysiology of excess aldosterone production are also discussed. Finally, we outline the cardiovascular, renal, and metabolic consequences of mineralocorticoid excess beyond blood pressure regulation.
 ...
PMID:Genetics of mineralocorticoid excess: an update for clinicians. 2361 Jan 23

Primary aldosteronism is the most frequent form of secondary hypertension. It is characterized by an autonomous, inappropriately high and unsuppressible production of aldosterone. The prevalence of aldosteronism in the general population is from 5-12% with bilateral adrenal hyperplasia and aldosterone-producing adenoma being the two main causes. Primary aldosteronism may either be sporadic or familial, the latter variant occurring in at least three forms: type I (or glucocorticoid-remediable aldosteronism), type II and type III. The diagnosis is based on the aldosterone/renin ratio as a screening test, subsequent confirmatory tests, and on CT/MR imaging studies. Adrenal vein sampling is the gold standard test for diagnosing the major subtypes and for identifying the surgically correctable forms. Genetic testing is used to exclude the familial forms.
 ...
PMID:[Primary hyperaldosteronism: a diagnostic algorithm]. 2383 73

It is well known that primary aldosteronism (PA) due to aldosterone-producing adenoma (APA) is a surgically curable secondary hypertension. Thus, the differential diagnosis between unilateral hyperaldosteronemia due to APA and bilateral hyperaldosteronemia due to idiopathic hyperaldosteronism (IHA) is crucial to decide surgical indication for treatment in PA patients. Adrenal venous sampling (AVS) can diagnose the laterality of hypersecretion of aldosterone in those patients, while it is still impossible to differentiate bilateral hypersecretion of bilateral aldosterone-producing adenomas (Blt-APAs) from that of bilateral hyperplasia of IHA. To solve the problem, we try to develop a new method of supper-selective ACTH-stimulated adrenal venous sampling (SS-ACTH-AVS). We performed SS-ACTH-AVS by using a strip-tip type 2.2 Fr micro-catheter (Koshin Medical Inc. Japan). Adrenal effluents were sampled super-selectively at the central veins and at one or two tributaries of adrenal veins in each gland. We would like to emphasize that SS-ACTH-AVS can precisely analyze the situation of hyperfunction of steroidogenesis in each side of adrenals as well as in some tiny lesions inside the adrenal cortex which are not visible in the CT images. Moreover, we can differentiate Blt-APAs from IHA, and postulate the decision of surgical treatment, such as partial adrenalectomy. Thus, we should perform SS-ACTH-AVS especially in the case demonstrating the existence of bilateral adrenal lesions such as unilateral and bilateral tumors, or even no tumor in both sides in the patients with PA.
...
PMID:Is it Possible to Extirpate Cardiovascular Events in Primary Aldosteronism After Surgical Treatment. 2394 77

Primary aldosteronism is the most common form of secondary hypertension and has significant cardiovascular consequences. Aldosterone-producing adenomas (APAs) are responsible for half the cases of primary aldosteronism, and about half have mutations of the G protein-activated inward rectifying potassium channel Kir3.4. Under basal conditions, the adrenal zona glomerulosa cells are hyperpolarized with negative resting potentials determined by membrane permeability to K(+) mediated through various K(+) channels, including the leak K(+) channels TASK-1, TASK-3, and Twik-Related Potassium Channel 1, and G protein inward rectifying potassium channel Kir3.4. Angiotensin II decreases the activity of the leak K(+) channels and Kir3.4 channel and decreases the expression of the Kir3.4 channel, resulting in membrane depolarization, increased intracellular calcium, calcium-calmodulin pathway activation, and increased expression of cytochrome P450 aldosterone synthase (CYP11B2), the last enzyme for aldosterone production. Somatic mutations of the selectivity filter of the Kir3.4 channel in APA results in loss of selectivity for K(+) and entry of sodium, resulting in membrane depolarization, calcium mobilization, increased CYP11B2 expression, and hyperaldosteronism. Germ cell mutations cause familial hyperaldosteronism type 3, which is associated with adrenal zona glomerulosa hyperplasia, rather than adenoma. Less commonly, somatic mutations of the sodium-potassium ATPase, calcium ATPase, or the calcium channel calcium channel voltage-dependent L type alpha 1D have been found in some APAs. The regulation of aldosterone secretion is exerted to a significant degree by activation of membrane K(+) and calcium channels or pumps, so it is not surprising that the known causes of disorders of aldosterone secretion in APA have been channelopathies, which activate mechanisms that increase aldosterone synthesis.
 ...
PMID:Minireview: potassium channels and aldosterone dysregulation: is primary aldosteronism a potassium channelopathy? 2424 57

Primary aldosteronism (PA) is the most common form of secondary hypertension, found in about 5% of all hypertension cases, and up to 20% of resistant hypertension cases. The most common forms of PA are an aldosterone-producing adenoma and idiopathic (bilateral) hyperaldosteronism. Rare genetic forms of PA exist and, until recently, the only condition with a known genetic mechanism was familial hyperaldosteronism type 1, also known as glucocorticoid-remediable aldosteronism (FHA1/GRA). FHA type 3 has now been shown to derive from germline mutations in the KCNJ5 gene, which encodes a potassium channel found on the adrenal cells. Remarkably, somatic mutations in KCNJ5 are found in about one-third of aldosterone-producing adenomas, and these mutations are likely to be involved in their pathogenesis. Finally, mutations in the genes encoding an L-type calcium channel (CACNA1D) and in genes encoding a sodium-potassium adenosine triphosphatase (ATP1A1) or a calcium adenosine triphosphatase (ATP2B3) are found in other aldosterone-producing adenomas. These findings provide a working model, in which adenoma formation and/or aldosterone production in many cases derives from increased calcium entry, which drives the pathogenesis of primary aldosteronism.
...
PMID:Gene mutations that promote adrenal aldosterone production, sodium retention, and hypertension. 2439 84


<< Previous 1 2 3 4 5 6 7 8 9 Next >>