Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wider application of the aldosterone/plasma renin activity ratio among hypertensives has facilitated the detection of primary aldosteronism at earlier stages of evolution (with most patients normokalemic), and found prevalence rates far greater than those previously reported. Reliable detection of patients with PAL requires that 1) the diagnosis is considered in all hypertensives; 2) blood samples are collected under standardized conditions of diet, posture, and time of day; 3) medications known to alter the ratio are avoided or their effects taken into account; 4) aldosterone and plasma renin activity are measured using consistently accurate assay techniques; and 5) reliable methods (such as fludrocortisone suppression testing) are used to confirm primary aldosteronism. Adrenal venous sampling is the only dependable way to differentiate aldosterone-producing adenoma from bilateral adrenal hyperplasia. As has occurred in familial hyperaldosteronism type I, the elucidation of genetic mutations causing other forms of primary aldosteronism should further facilitate detection of this potentially curable or specifically treatable variety of hypertension.
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PMID:Primary aldosteronism: rare bird or common cause of secondary hypertension? 1135 74

1. Evidence from recent experimental and clinical studies suggests that excessive circulating levels of aldosterone can bring about adverse cardiovascular sequelae independent of the effects on blood pressure. Examples of these sequelae are the development of myocardial and vascular fibrosis in uninephrectomized, salt-loaded rats infused with mineralocorticoids and, in humans, an association of aldosterone with left ventricular hypertrophy, impaired diastolic and systolic function, salt and water retention causing aggravation of congestion in patients with established congestive cardiac failure (CCF), reduced vascular compliance and an increased risk of arrhythmias (resulting from intracardiac fibrosis, hypokalaemia, hypomagnesaemia, reduced baroreceptor sensitivity and potentiation of catecholamine effects). 2. These sequelae of aldosterone excess may contribute to the pathogenesis and worsen the prognosis of CCF and hypertension. 3. The heart and blood vessels may be capable of extra-adrenal aldosterone biosynthesis, raising the possibility that aldosterone may have paracrine or autocrine (and not just endocrine) effects on cardiovascular tissues. 4. The high prevalence of CCF, which is associated with secondary aldosteronism, and primary aldosteronism (PAL; recently recognized to be a much more common cause of hypertension than was previously thought) argue for an important role for aldosterone excess as a cause of cardiovascular injury. 5. The recognition of non-blood pressure-dependent adverse sequelae of aldosterone excess raises the question as to whether normotensive individuals with PAL, who have been detected as a result of genetic or biochemical screening among families with inherited forms of PAL, are at excess risk of cardiovascular events. 6. Provided that patients are carefully investigated in order to permit the appropriate selection of specific surgical (laparoscopic adrenalectomy for PAL that lateralizes on adrenal venous sampling) or medical (treatment with aldosterone antagonist medications) management and safety considerations for the use of aldosterone antagonists are kept in mind, the appreciation of a widening role for aldosterone in cardiovascular disease should provide a substantially better outlook for many patients with CCF and hypertension.
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PMID:New perspectives on the role of aldosterone excess in cardiovascular disease. 1155 16

Pindolol is a non-selective beta-adrenergic antagonist (beta-blocker) for the treatment of cardiovascular diseases such as hypertension and angina pectoris. It has one chiral center, and, therefore, two optical isomers. It was essential to develop an enantioselective assay to measure each enantiomer in human plasma. However, separation of enantiomers using chiral chromatography usually requires relatively long retention times. This can pose a problem for rapid turnaround of a large number of samples (i.e., clinical studies). In the present study, a simple and sensitive chiral liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method was developed and validated for the determination of S-(-)- and R-(+)-pindolol in human plasma. To increase throughput, staggered sample injection was employed using a CTC Trio Valve system on a CTC HTS PAL autosampler. The method exhibited good intra- and inter-day accuracy and precision, and was linear over a dynamic range of 250 pg/mL to 250 ng/mL for each pindolol enantiomer. Intra- and inter-day accuracy ranged between 90.0-106% and 91.6-104% for both quality control (QC) samples of S-(-)- and R-(+)-pindolol, respectively. The respective intra- and inter-day precision ranged between 4.24-7.86% and 4.98-10.4%.
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PMID:Enantiomeric separation and quantification of pindolol in human plasma by chiral liquid chromatography/tandem mass spectrometry using staggered injection with a CTC Trio Valve system. 1634 28

Pheochromocytoma (Pheo) is a rare cause of hypertension (HTN). Classically, a triad of symptoms includes sweating, palpitations, and headache. HTN is often present and labile. Although a triad of symptoms is cited as the most frequent presenting complaints, our clinical experience leads us to question how often these are present. Thirty-two patients with histologically proven pheo or paraganglionoma were evaluated. Around 84.4% patients had adrenal pheos and 15.6% had extra-adrenal pheos. Two patients had bilateral adrenal tumors, two had a history of prior pheos, and four had a family history of pheo. There were 19 (59.4%) female and 13 (40.6%) male patients. Six (18.7%) patients were black and 26 (81.3%) were white. The mean age at presentation was 43.2+/-13.9 years. Two patients were known to have neurofibromatosis type 1, two had von Hippel-Lindau disease, one had multiple endocrine neoplasia 2A, and one PGL/SDHD genetic mutation. Twenty-six patients had sporadic tumors or had not had genetic testing. Biochemical diagnosis was confirmed with 24-h urine measurements. Urine catecholamine measurements were elevated at least 2 to 4 times above normal levels. Mean SBP readings at presentation were 128+/-19 mmHg. Mean DBP readings were 81+/-13 mmHg. Around 65.6% patients were hypertensive at presentation. Fifty percent of the patients had palpitations, 40.6% had tachycardia, 34.4% had sweating, and 31.3% had headaches. Initial presenting symptoms were diverse. Pheo is a rare clinical entity and remains a huge diagnostic challenge for all clinicians.
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PMID:Lack of symptoms in patients with histologic evidence of pheochromocytoma: a diagnostic challenge. 1710 71

To assess the prevalence of genetic mutations in nonsyndromic pheochromocytoma/paraganglioma (PHEO/PGL) patients we have performed a systematic search for mutations in the succinate dehydrogenase (SDH) B, C, and D subunits, von Hippel-Lindau (VHL), and RET genes by direct bidirectional sequencing. Patients were selected from the medical records of hypertension centers. After exclusion of syndromic patients, 45 patients with familial (F+, n=3) and sporadic (F-, n=42) cases of isolated PHEO/PGL were considered. They included 35 patients with PHEO, 7 with PGL, and 3 with head/neck PGL (hnPGL). Three patients with PHEO (2F-, 1F+) presented VHL mutations (P86A, G93C, and R167W), six with PGL (4F-, 2F+) were positive for SDH or VHL mutations (SDHB R230G in two patients, SDHB S8F, R46Q, R90Q, and VHL P81L in one subject each), and one with hnPGL carried the SDHD 348-351delGACT mutation. We have also detected missense (SDHB S163P, SDHD H50R and G12S), synonymous (SDHB A6A, SDHD S68S), and intronic mutations that have been considered nonpathological polymorphic variants. No mutation was found in SDHC or RET genes. Our data indicate that germline mutations of VHL and SDH subunits are not infrequent in familial as well as in sporadic cases of nonsyndromic PHEO/PGL (overall, 12 of 45 probands, 22%). Accordingly, screening for such mutations seems to be justified. However, a more precise characterization of the functional relevance of any observed sequence variant and of other genetic and environmental determinants of neoplastic transformation is essential in order to plan appropriate protocols for family screening and follow-up.
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PMID:Genetic mutation screening in an italian cohort of nonsyndromic pheochromocytoma/paraganglioma patients. 1710 82

Pheochromocytomas/paragangliomas(PHEOs/PGLs) are rare but treacherous catecholamine-producing tumors which, if overlooked or improperly treated, will almost invariably prove fatal. Patients with MEN2 PHEOs have a high incidence of paroxysmal attacks and a higher prevalence of hypertension and other cardiovascular problems than do patients with Von-Hippel-Lindau (VHL) PHEOs. Compared to measurements of deconjugated metanephrines, plasma concentrations of free metanephrines are relatively independent of renal function and therefore more suitable for diagnosis of PHEO/PGL. Recently, the focus of Positron Emission Tomography (PET) imaging for these tumors has been the localization of PHEO. Although a limited number of studies are available, [18F]-fluorodopamine ([18F]DA) PET has been found to be the best overall imaging modality in the localization of PHEO. For adrenal PHEOs, this method seems to be comparable to other functional modalities such as [18F]-fluorodopa ([18F]DOPA) PET or [123I]-metaiodobenzylguanidine ([123I]MIBG)scintigraphy. For extraadrenal PHEOs, data are limited and more extensive studies are needed. In patients with metastatic PHEO, the sensitivity of [18F]DA PET is superior to [123I]MIBG. The so called "flip-flop" imaging showing superiority of non-specific [18F] flurodeoxyglucose (FDG) PET over specific [18F]DA PET has been described in rapidly progressive, often metastatic SDHB-associated PHEOs. Whether these data reflect PHEO cell dedifferentiation (e.g. losing Norepinephrine Transporter-NET) or increased metabolic rate remains to be established.
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PMID:Diagnosis of pheochromocytoma with special emphasis on MEN2 syndrome. 1957 Jul 38

The state of the renin-aldosterone system in 100 patients with hypertonic form of chronic glomerulonephritis (CGN) with the preserved renal function was assessed by RIA. The control group comprised 35 patients with CGH without arterial hypertension (AH). The study showed that plasma active renin (PAR) and aldosterone (PAL) levels remained unaltered in normotensive CGN patients with the preserved renal function but tended to increase in patients with AH. PAR levels correlated with the severity of AH. The PAL level was significantly elevated in CGN patients with grade II and III AH. Results of the study suggest an important role of elevated PAR levels in the development of AH in patients with CGN and preserved renal function. Moreover, such patients show a tendency toward a rise in their PAL level.
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PMID:[Renin-aldosterone system in patients with hypertensive form of chronic glomerulonephritis and preserved renal function]. 1982 34

Pheochromocytomas/paragangliomas (PHEOs/PGLs) in patients with MEN 2 are usually found in the adrenals after the manifestation of medullary thyroid cancer. These PHEOs are commonly bilateral and hormonally active. Tachycardia, diaphoresis and cephalalgia are encountered in 40 %-80 % of patients with PHEOs; hypertension is very prevalent. Plasma concentrations of free metanephrines (or free metanephrines in urine) are best used for the biochemical diagnosis of PHEO/PGL. In patients with biochemically-proven PHEOs/PGLs, anatomical imaging with computed tomography (CT) and/or magnetic resonance imaging (MRI) should be used. False-positive CT/MRI studies can ensue and the specificity of CT/MRI may vary from 50%-90%. Functional imaging (implementing nuclear medicine modalities) should follow anatomical imaging; modalities with PHEO/PGL-specific ligands are a first choice. Among these specific modalities positron emission tomography (PET) with [18F]-fluorodopamine ([18F]DA) stands out as the best overall method. If PHEO/PGL-specific modalities turn out to be negative functional imaging should follow with nonspecific modalities (particularly if recurrent, metastatic or malignant disease is suspected). Treatment is surgical, with expanding use of laparoscopic approaches. Overall half of the patients with malignant PHEOs remain alive for 5 years.
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PMID:Diagnosis, localization and treatment of pheochromocytoma in MEN 2 syndrome. 1985 14

Polycystic ovary syndrome (PCOS) is a common endocrinological disorder in female reproductive age. Insulin resistance (IR) and compensatory hyperinsulinemia seem to be the main pathophysiologies of this syndrome. Therefore, PCOS is at risk for abnormal glucose tolerance, dyslipidemia, central obesity and hypertension. Also, plasminogen activator-inhibitor-1 (PAL-1), hemostatic factor and C-reactive protein (CRP), inflammatory factor have been reported in PCOS women. The metabolic syndrome (MS), a clustering of several metabolic abnormalities, is more prevalent in PCOS. One-third to 46% of PCOS women with MS have been reported. Since these metabolic abnormalities as well as MS are the important risk factors of cardiovascular disease (CVD), PCOS is at risk for CVD.
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PMID:Polycystic ovary syndrome and the metabolic syndrome. 2121 22

Pheochromocytoma and functional paraganglioma (PH/PGL) are classical causes of secondary hypertension. The clinical practice guidelines for PH/PGL have been changed by the recent identification of a dozen of susceptibility genes. PH/PGL is the neuroendocrine tumor most affected by genetics. Total metanephrin should be measured in every young patient suffering of a resistant hypertension. The diagnosis is based on conventional imaging assciated with nuclear imaging. Genetic testing should be offered to every patient diagnosed for PH/PGL because the identification of a germline mutation, which is found in over 30% of the cases, will change his work-up and follow-up as well as offer the opportunity of a familial genetic testing in relatives. A specialized management is indicated, especially for patients with hereditary or metastatic PH/PGL, and should be performed in an expert center with a multidisciplinary team.
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PMID:[Pheochromocytoma and paraganglioma]. 2629 9


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