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

Serial measurements of urinary sodium excretion, sodium space, plasma volume, and plasma renin concentration were made during the development of hypertension in patients who were exposed to an excess of endogenous or exogenous mineralocorticoid activity. Five patients with primary aldosteronism due to adenoma were followed during spironolactone treatment, for 35-55 days after the drug had been stopped, and finally, after surgery. Blood pressure rose continuously after stopping spironolactone. Sodium balance, however, showed an initial phase of sodium gain, followed by a phase of gradual sodium loss. Sodium space and exchangeable sodium rose by 5.0 +/- 0.48 liters/1.73 m2 of body surface area (BSA) (P less than 0.005) and by 865 +/- 97 mEq/1.73 m2 BSA (P less than 0.005), respectively; the values were maximal after 10-15 days, declined afterward, but remained higher than during spironolactone treatment. Plasma and blood volumes rose by 624 +/- 90 ml/1.73 m2 BSA (P less than 0.005) and by 327 +/- 74 ml/1.73 m2 BSA (P less than 0.01), respectively; they were maximal after 20-25 days, and then returned to their initial values. Exchangeable sodium, during the phase of sodium loss, was inversely correlated with the rise in blood pressure (P less than 0.01). Renin fell during the phase of sodium gain, and remained low afterwards. Blood pressure and sodium space declined after surgery, but plasma volume showed no change. The postsurgery values of these parameters were not significantly different from those measured during spironolactone treatment. Two subjects with adrenocortical insufficiency, who were followed for 45-60 days during treatment with dexamethasone and 9alpha-fluorocortisol acetate, also showed a transient rise in sodium space and plasma volume. The results suggest a redistribution of body fluids during development of hypertension. They also suggest that the tendency of body fluid volumes to return to normal is pressure-dependent. The long-term effects of mineralocorticoid excess on the interrelations between pressure, volume, and renin bear some resemblance to the pattern observed in patients with established essential hypertension, i.e., pressure remains elevated despite a decrease of volume, and renin is "inappropriately" suppressed in relation to the sodium and volume status.
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PMID:Volume-pressure relationships during development of mineralocorticoid hypertension in man. 85 75

The presence of the two components of the renin-angiotensin system (RAS) has been systematically investigated in human normal and pathological adrenal tissues with two aims: 1) the detection of renin and especially angiotensinogen, which has not been reported before; and 2) to study possible differences in the coexpression of renin and angiotensinogen in tissue of cortical and medullary origin. The relative levels of renin and angiotensinogen mRNAs were determined by Northern blot analysis in normal (n = 5) and pathological adrenal tissues of cortical (n = 23) and medullary (n = 10) origin. Renin, prorenin, and angiotensinogen levels were also measured. Renin concentrations in normal and pathological adrenals were around 30-fold higher than those in the plasma of normal subjects, except for a Cushing's adenoma, which contains an extremely high renin content. Renin accounted for 56% of the total renin in normal adrenals and up to 87% in neoplastic tissues. This high proportion of renin indicates a likely conversion of prorenin to renin within these tissues. Renin mRNA was detected in each group of adrenal tissues. There was a significant correlation between the concentration of renin and its mRNA (r = 0.75; P less than 0.05). Angiotensinogen and its mRNA were detected in all normal and pathological adrenals. Compared to normal adrenal tissues, the relative amount of angiotensinogen mRNA was significantly higher in pheochromocytomas. However, the increased mRNA level in these tissues was not accompanied by a parallel increase in tissue angiotensinogen levels. Since the translational efficiency of angiotensinogen was verified by in vitro cell-free translation, the low level of angiotensinogen compared to the relatively high amount of its mRNA suggests a lack of storage of this protein in adrenal cells, as in liver cells. This study demonstrates that renin and angiotensinogen are coexpressed in normal and pathological tissues. Tissues of different cellular origin (zona glomerulosa, fasciculata, and medullary tissue), were able to express, store, and process renin and synthesize angiotensinogen. There was no obvious relationship between the expression of these proteins and the pathophysiology of the adrenal gland.
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PMID:Coexpression of renin, angiotensinogen, and their messenger ribonucleic acids in adrenal tissues. 138 71

We have identified a subgroup of patients with aldosterone-producing adenoma (APA) who are responsive to angiotensin. Thus, a fall in plasma aldosterone (PA) during saline infusion may cause confusion with low-renin essential hypertension. Responsiveness of PA to angiotensin infusion and to upright posture may cause confusion with bilateral hyperplasia. Renin levels were not as completely suppressed in this angiotensin-responsive subgroup, leading to speculation that non-tumorous adrenal glomerulosa might also be less suppressed and might respond to angiotensin. This is unlikely, since angiotensin infusion soon after removal of the adenoma produced aldosterone levels of less than 10% of those achieved preoperatively. A biosynthetic peculiarity of the tumours is more likely, since urinary 18-oxo-cortisol levels were normal in this subgroup (as in bilateral hyperplasia) and raised in the more typical angiotensin-unresponsive subgroup (as in glucocorticoid-suppressible hyperaldosteronism). Since angiotensin-responsive tumours respond just as well to surgery as angiotensin-unresponsive tumours, it is important not to misdiagnose this subgroup as bilateral hyperplasia or low-renin essential hypertension.
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PMID:Angiotensin-responsive aldosterone-producing adenoma masquerades as idiopathic hyperaldosteronism (IHA: adrenal hyperplasia) or low-renin essential hypertension. 283 71

Renin, angiotensinogen, and converting enzyme were detected in 10 normal human pituitary glands by immunohistochemical techniques. Renin was stained by polyclonal and monoclonal antibodies directed against human renin, and an antibody directed against the renin prosegment revealed the presence of prorenin. Immunoreactive angiotensinogen and angiotensin I-converting enzyme were found in the same cells as renin. Using serial sections and double immunohistochemical labeling with a PRL antiserum, all of the proteins of the renin-angiotensin system appeared to be localized within the lactotroph cells, and no component of the renin system was detected in any of the other pituitary cells. Renin, angiotensinogen, and angiotensin I-converting enzyme also were found in 6 PRL-secreting adenomas as well as in a mixed PRL/GH-secreting adenoma. The renin content of a PRL adenoma was about 1/100th that of a normal kidney. Renin activity could be blocked by an anticatalytic human renin antibody. No renin, angioten-sinogen, or angiotensin I-converting enzyme was found in 6 GH-secreting adenomas, 1 corticotroph adenoma, or 10 nonsecreting pituitary adenomas. The colocalization of proteins of the renin-angiotensin system suggests production of angiotensin II within the lactotroph cells and favors the hypothesis of a paracrine action of this peptide.
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PMID:Presence of renin, angiotensinogen, and converting enzyme in human pituitary lactotroph cells and prolactin adenomas. 301 40

Metoclopramide, a dopaminergic inhibitor, injected in 9 normal volunteers, was followed by a prompt decrease of serum potassium (10--20 min; p less than 0.01) and by an increase of plasma aldosterone (p less than 0.01). Renin slightly increased at 45 min (p less than 0.05); insulin and cortisol did not show any significant increase. The urinary excretion of potassium rose after metoclopramide (p less than 0.05). A bolus of aldosterone (250 micrograms i.v.) in 4 normal subjects was not followed by any modification of serum potassium, but increased urinary potassium excretion (p less than 0.05); the injection of metoclopramide in two patients with an aldosterone-secreting adenoma of the adrenal and in one patient with Addison's disease induced a decrease of serum potassium in absence of any modification of plasma aldosterone. The decrease of serum potassium after metoclopramide is not explained by changes of aldosterone or insulin, considered the most important hormonal controls of potassium. The rapidity of potassium decrease implies a change of distribution of potassium between extra- and intracellular compartments, which, in turn, may stimulate aldosterone secretion. It is conceivable that the dopaminergic system has a role in the control of serum potassium.
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PMID:Dopaminergic control of serum potassium. 699 Jan 71

Spironolactone, a competitive aldosterone receptor antagonist (ARA), has traditionally been the treatment of first choice in idiopathic hyperaldosteronism (IHA) and for preoperative management of aldosterone producing adenoma (APA). Spironolactone is partially absorbed, is extensively metabolized mainly by the liver and its therapeutic properties are attributable to active metabolite canrenone. At therapeutic doses of 25 to 400 mg per day, spironolactone effectively controls blood pressure and hypokalemia in the majority of cases. Endocrine side effect are often associated and mainly consist of gynecomastia, decreased libido and impotence in man and menstrual irregularities in women. Canrenone and the K+ salt of canrenoate are also in clinical use: they avoid the formation of intermediate products with anti-androgenic and progestational actions, resulting in a decreased incidence of side effects. Furthermore, a relatively new selective ARA compound (eplerenone) with reduced affinity for androgen and progesterone receptors, is currently undergoing clinical trials. In essential hypertension aldosterone can contribute to hypertension and increases the incidence of myocardial hypertrophy and cardiovascular events. On the other hand, inhibition of Renin-Angiotensin-Aldosterone System (RAAS) is associated with a decrease in blood pressure, with a regression of left ventricular hypertrophy and a reduction of target organ damage. Thus, ARA have been proposed as complementary treatment associated to ACE inhibitors and angiotensin receptor antagonists. Aldosterone is also known to play an important role in pathophysiolgy of congestive heart failure (CHF). In vitro and in vivo evidences suggest that aldosterone promotes myocardial fibrosis. This effect reflects direct, extra-epithelial actions of aldosterone via cardiac MR which are counteracted by ARAs in animal models. The RAAS is chronically activated in CHF. Non potassium-sparing diuretics further stimulate the RAAS and cause hypokalemia. Thus, use of ARAs in CHF was first proposed to correct potassium and magnesium depletion. At present ARAs are indicated in the management of primary hyperaldosteronism, in oedematous conditions in patients with CHF, in cirrhosis of the liver accompanied by oedema and ascites, in essential hypertension and in hypokalemic states. Its indication as adjunctive therapy of heart failure is currently under investigation. In fact, it is well known that even high doses of ACE inhibitors may not completely suppress the RAAS; aldosterone 'escape' may occur through non angiotensin II dependent mechanisms. Addition of spironolactone to an ACE inhibitor causes marked diuresis and symptomatic improvement. During the last few years, the RALES study (Randomized Aldactone Evaluation Study) was organized to explore the efficacy of combination therapy with spironolactone and ACE inhibitor in patients with CHF, class III or IV NYHA. The study was stopped 18 months early because the results were so statistically and clinically significant that it would be unethical to continue the trial. It is reported a 30 percent decrease in mortality and hospitalisation for cardiac causes in spironolactone-treated group vs placebo group.
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PMID:Aldosterone antagonists in hypertension and heart failure. 1079 May 93

Primary hyperaldosteronism is characterized by high plasma and urinary aldosterone and suppressed PRA. Renin suppression is due to aldosterone-dependent sodium retention and mild extracellular volume expansion. We observed three patients with primary hyperaldosteronism, severe refractory hypertension, and normal to high normal PRA levels whose aldosterone/renin ratios were still elevated because of disproportionately high aldosterone levels. All available medical data on the patients as well as publications on the aldosterone/renin relationship in primary hyperaldosteronism were reviewed to explain the unusual findings. In one patient, histologically proven renal arteriolosclerosis was the probable cause of the escape of PRA from suppression by an aldosterone-producing adenoma. In the other two patients, hypertensive kidney damage due to primary hyperaldosteronism was the most likely explanation for the inappropriately high PRA, as in patient 1. All patients had high normal or slightly elevated serum creatinine levels and responded to 200 mg spironolactone/day with increased serum creatinine and hyperkalemia. Hyperkalemia was probably due to a decreased filtered load of sodium and a spironolactone-induced decrease in mineralocorticoid function. Two patients were cured of hyperaldosteronism by unilateral adrenalectomy but still need some antihypertensive therapy, whereas one patient has probable bilateral adrenal disease, with normal blood pressure on a low dose of spironolactone. In patients with severe hypertension due to primary hyperaldosteronism, PRA can escape suppression if hypertensive kidney damage supervenes. An increased aldosterone/PRA ratio is still useful in screening for primary hyperaldosteronism. These patients may respond to spironolactone therapy with a strong increase in serum creatinine and potassium. Early specific treatment of primary hyperaldosteronism is therefore indicated, and even a patient with advanced hypertension will profit from adrenalectomy or cautious spironolactone treatment.
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PMID:Primary hyperaldosteronism without suppressed renin due to secondary hypertensive kidney damage. 1099 20

Various pathological disorders have been associated with primary aldosteronism, including glucagonoma, phaeochromocytoma and primary hyperparathyroidism. In this report, a case of adrenal myelolipoma (a rare non-functioning tumour composed of mature adipose tissue and normal haematopoietic elements similar to bone marrow cells), aldosterone-producing adenoma and a pituitary microadenoma coexisting in a 62-year-old man with a 15-year history of arterial hypertension, previous ablation of an autonomously-functioning thyroid adenoma, multiple lipomas and an heterozygosity of the retinoblastoma (RB) susceptibility gene is reported. We believe that this case probably represents another variant of the multiple neoplasia syndrome and we speculate that structural alteration of the RB gene may play a role in the tumorogenesis.
J Renin Angiotensin Aldosterone Syst 2004 Mar
PMID:A rare combination consisting of aldosterone-producing adenoma and adrenal myelolipoma in a patient with heterozygosity for retinoblastoma (RB) gene. 1513 74

Obstructive sleep apnoea (OSA) is a sleep disorder characterized by recurrent episodes of oxygen desaturation during sleep, representing an independent risk factor for cardiovascular disease, such as myocardial infarction, stroke, congestive heart failure and resistant hypertension. Several neurohormonal mechanisms have been suggested to account for blood pressure increases, such as sympathetic nervous system hyperactivity, oxidative stress, renin-angiotensin-aldosterone system (RAAS) activation, endothelin system activation, and endothelial dysfunction. The aim of this study was to evaluate the behaviour of RAAS and the presence of primary aldosteronism (PA) in these patients and possible correlations between RAAS and the severity of OSA. From October 2007 to November 2008 we studied 325 consecutive newly diagnosed hypertensive patients; 71 patients (21.8%) presented with clinical signs of sleep disorders, evaluated also through a specific questionnaire (Epworth Sleepiness Scale). In hypertensive patients with sleep disorders, 53 patients were affected by OSA; in this group 18 patients were affected by PA (five with aldosterone-producing adenoma (APA) and 13 with bilateral hyperplasia (IHA)); obesity was also demonstrated (BMI > 30 kg/m(2)). Overall, in patients with OSA PRA levels correlated positively with apnoea/hypopnoea index (AHI; r = 0.35; p<0.01), and in all groups the waist circumference and the neck circumference were correlated positively with AHI (r = 0.3 p<0.02 and r = 0.3 p<0.03, respectively). We revealed a high prevalence of PA in patients with OSA, and we can conclude that patients with hypertension and OSA, especially those who are newly diagnosed, must be evaluated for PA.
J Renin Angiotensin Aldosterone Syst 2010 Sep
PMID:Renin-angiotensin-aldosterone system in patients with sleep apnoea: prevalence of primary aldosteronism. 2048 24

Primary hyperaldosteronism (PHA) is characterized by an increased Aldosterone synthesis which is independent of the Renin-Angiotensin-Aldosterone-System (RAAS). The prevalence of PHA in patients who present in specialized hypertension centers is approx. 10 %. Besides patients with the classical symptoms known as "Conn-Trias" (hypertension, hypokalemia, metabolic alkalosis), the more frequent normokalemic patients with PHA also show a worse outcome compared to patients with essential hypertension. Identifying these patients is an important task in the evaluation of hypertension since targeted treatment options are available. Screening for PHA using the Aldosterone-Renin-Ratio (ARR) should be performed in patients with hypokalemic, severe or resistant hypertension. In addition, young patients with early onset of severe hypertension and/or positive family history should be screened. A positive screening result should be followed by a confirmatory test. The saline infusion test is the preferred clinical test for confirming a suspected PHA since it is accessible and time efficient. Other confirmatory tests are not used on a regular basis. After any confirmatory test, CT- or MRI-imaging and adrenal vein sampling (AVS) is used in order to differentiate between a unilateral adenoma, a bilateral hyperplasia or another cause of PHA. CT or MRI usually cannot discriminate smaller tumors form hyperplasia. Therefore AVS is used to detect lateralization of autonomous aldosterone production. Lateralization of aldosterone production indicates a unilateral adenoma. In these cases, laparoscopic adrenalectomy is the therapeutic option of choice with a hypertension cure rate of up to 60 %. If no lateralization is detectable, bilateral hyperplasia as the underlying cause of PHA is likely. Pharmacological inhibition of the mineralocorticoid receptor is the preferred treatment option in these cases. If Spironolactone is not well tolerated, Eplerenone and potassium-sparing diuretics should be prescribed. Often, however, in order to fully control hypertension, additional antihypertensive therapy is necessary.
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PMID:[Primay hyperaldosteronism--diagnostic and treatment]. 2316 80


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