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)

Pheochromacytoma is a relatively rare cause of arterial hypertension. Untreated pheochromacytoma may however lead to a fatal hypertensive crisis during anaesthesia or another form of stress. It is therefore important to correctly diagnose this disease. 24-hour monitoring of blood pressure (BP) can already contribute to the diagnosis of pheochromacytoma based on the frequent occurrence of BP variability and the absence of a night-time fall in BP. 5 gene mutations have so far been identified that may be responsible for the familial form of pheochromacytoma: mutation of the von Hippel-Lindau (VHL) gene, leading to the onset of VHL syndrome, mutation of the RET-proto-oncogene in multiple endocrine adenomatosis type 2, mutation of the type 1 gene for neurofibromatosis, which is associated with von Recklinghausen's disease and finally mutation of the genes encoding the B and D subunits of succinated hydrogenase (SDHB, SDHD), which are associated with familial paragangliomas and pheochromacytoma. Genetic analysis should therefore be carried out for all confirmed cases of pheochromacytoma, especially for young people under 50 years of age. Biochemical diagnostics relies mainly on measurements of free metanephrines in plasma or urine, which usually has greater diagnostic weight than plasma, or catecholamines in urine. The diagnosis of extraadrenal or multiple forms can use not only CT/MR but also imaging using the radiopharmaceutical 123I-Metaiodobenzylguanidine (MIBG) or 18F-fluorodopamine PET (only available in the USA). Pharmacological treatment using alpha or beta receptor blockers with subsequent laparoscopic excision of the tumor is usually successful in benign forms of pheochromocytoma. Unfortunately, there are still no convincingly effective therapeutic procedures available for malign forms.
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PMID:[Diagnostic and therapeutic procedures in pheochromocytoma: current trends]. 1757 79

A 38-year-old woman with RET gene mutation presented with tumors in her thyroid and bilateral adrenal glands. I-metaiodobenzylguanidine scintigraphy revealed accumulation of the radioisotope in both adrenal glands. Both plasma adrenaline and noradrenaline levels were elevated. The circadian rhythms for plasma adrenocorticotropic hormone (ACTH) and cortisol levels were disturbed. Plasma ACTH and cortisol levels failed to be suppressed by an overnight dexamethasone test, suggesting autonomic secretion of ACTH and cortisol, although the patient had no typical Cushingoid features, hypertension, or impaired glucose tolerance. Pathological examination showed that these tumors were pheochromocytoma and thyroid medullary carcinoma, respectively, both of which highly expressed corticotropin-releasing factor, urocortin1, and urocortin3. Together with the endocrinological and pathological observations, the patient was diagnosed as multiple endocrine neoplasia type II with corticotropin-releasing factor- and urocortin-producing tumors that stimulated ACTH and glucocorticoid secretion.
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PMID:A case of multiple endocrine neoplasia type II accompanied by thyroid medullary carcinoma and pheochromocytomas expressing corticotropin-releasing factor and urocortins. 1848 Jun 60

The aim of the present study is to provide a review of the expression and action of trophic factors in the carotid body. In glomic type I cells, the following factors have been identified: brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, artemin, ciliary neurotrophic factor, insulin-like growth factors-I and -II, basic fibroblast growth factor, epidermal growth factor, transforming growth factor-alpha and -beta1, interleukin-1beta and -6, tumour necrosis factor-alpha, vascular endothelial growth factor, and endothelin-1 (ET-1). Growth factor receptors in the above cells include p75LNGFR, TrkA, TrkB, RET, GDNF family receptors alpha1-3, gp130, IL-6Ralpha, EGFR, FGFR1, IL1-RI, TNF-RI, VEGFR-1 and -2, ETA and ETB receptors, and PDGFR-alpha. Differential local expression of growth factors and corresponding receptors plays a role in pre- and postnatal development of the carotid body. Their local actions contribute toward producing the morphologic and molecular changes associated with chronic hypoxia and/or hypertension, such as cellular hyperplasia, extracellular matrix expansion, changes in channel densities, and neurotransmitter patterns. Neurotrophic factor production is also considered to play a key role in the therapeutic effects of intracerebral carotid body grafts in Parkinson's disease. Future research should also focus on trophic actions on carotid body type I cells by peptide neuromodulators, which are known to be present in the carotid body and to show trophic effects on other cell populations, that is, angiotensin II, adrenomedullin, bombesin, calcitonin, calcitonin gene-related peptide, cholecystokinin, erythropoietin, galanin, opioids, pituitary adenylate cyclase-activating polypeptide, atrial natriuretic peptide, somatostatin, tachykinins, neuropeptide Y, neurotensin, and vasoactive intestinal peptide.
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PMID:Trophic factors in the carotid body. 1877 56

Phaeochromocytomas are catecholamine-secreting tumours that arise from chromaffin cells of the adrenal medulla and extra-adrenal sites. Extra-adrenal phaeochromocytomas are called paragangliomas. A diagnosis of phaeochromocytoma is suspected by typical paroxysmal symptoms, unusual or refractory hypertension, discovery of an adrenal incidentaloma or a family history of phaeochromocytoma or paraganglioma, possibly associated with other genetic syndromes (multiple endocrine neoplasia type 2 A or B, neurofibromatosis type 1 and von Hippel-Lindau disease). It can be confirmed by measurements of urinary or plasma fractionated catecholamines and metanephrines. The best diagnostic performances are achieved by metanephrines. Twenty-four hour urine fractionated metanephrines are still recommended as a screening test but some experts prefer plasma measurements in high-risk patients. Increased serum chromogranin-A levels, combined with high catecholamine or metanephrine in a patient with normal renal function is also a tool, virtually diagnostic of phaeochromocytoma. Recent studies have suggested that 25% of patients with phaeochromocytoma have germline mutations of several genes (NF1, VHL, SDHD, SDHB and RET). Thus, genetic testing should be carried out according to an algorithm of risk factors and specific characteristics. Once a biochemical diagnosis of phaeochromocytoma is made, a CT scan or MRI of the abdomen and pelvis should be performed first. If these investigations remain negative, the chest and neck should be explored. After anatomical imaging, functional imaging by 123I-MIBG should be considered. If the MIBG scan is negative, other imaging modalities have recently proven to be useful (PET, Octreoscan). After localization, the treatment of phaeochromocytoma is a surgical resection, which may be laparoscopic. Preoperative preparation with alpha- and beta-adrenergic blockade and/or calcium channel blockers associated with volume expansion is essential. Malignant phaeochromocytoma is rare and its treatment still unsatisfying. Phaeochromocytoma during pregnancy is also rare and its diagnosis easily missed because of its clinical resemblance to pre-eclampsia.
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PMID:Phaeochromocytoma: state-of-the-art. 2051 23

Pheochromocytomas and paragangliomas are tumors arising from chromaffin cells. These tumors produce catecholamines and are typically found with symptoms and signs that may include hypertension (persistent or episodic), palpitations, headache and sweating. So far, 10 different genes have been associated with both tumors and other genes are expected to be detected. Pheochromocytoma and paraganglioma can occur as a part of genetic syndromes - familial paragangliomas (SDH genes, SDHAF2 gene), von Hippel-Lindau syndrome (VHL gene), multiple endocrine neoplasia type 2 (RET gene), and neurofibromatosis type 1 (NF1 gene). These tumors may be the first and only manifestation of these genetic syndromes. Patients with SDHB mutations are at high risk to develop malignant disease and unfortunately current therapeutic options for malignant form of disease are poor. Genetic testing plays a key role in the management of these tumors and therefore not only index patients with pheochromocytoma but also relatives should be tested. Management of this disease requires multidisciplinary cooperation and should be performed in the specialized medical centres.
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PMID:[Hereditary pheochromocytoma and paraganglioma]. 2292 Feb 2

The U.S. Food and Drug Administration (FDA) approved vandetanib in April 2011 for the treatment of unresectable, locally advanced or metastatic medullary thyroid cancer (MTC). In Europe it was approved in March 2012, but only for the treatment of aggressive and symptomatic MTC. This small molecule is a tyrosine kinase inhibitor of several growth factors involved in cellular proliferation and angiogenesis, including the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptors 2 and 3 (VEGFR-2, VEGFR-3). In addition, vandetanib is an inhibitor of the RET (rearranged during transfection) gene, a proto-oncogene often mutated in familial MTC. Since MTC is a rare disease, for which no previous medical therapies are approved, vandetanib is the first drug shown to be effective in a large phase III trial treating patients with metastatic or locally advanced MTC. Common adverse events are diarrhea, nausea, hypertension, headache and QT prolongation that are manageable and are commonly outweighed by the benefits of vandetanib in terms of delaying disease progression and inducing tumor response.
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PMID:Vandetanib therapy in medullary thyroid cancer. 2317 Mar 8

Blood pressure (BP) is a dynamic phenotype that varies rapidly to adjust to changing environmental conditions. Standing upright is a recent evolutionary trait, and genetic factors that influence postural adaptations may contribute to BP variability. We studied the effect of posture on the genetics of BP and intermediate BP phenotypes. We included 384 sib-pairs in 64 sib-ships from families ascertained by early-onset hypertension and dyslipidemia. Blood pressure, three hemodynamic and seven neuroendocrine intermediate BP phenotypes were measured with subjects lying supine and standing upright. The effect of posture on estimates of heritability and genetic covariance was investigated in full pedigrees. Linkage was conducted on 196 candidate genes by sib-pair analyses, and empirical estimates of significance were obtained. A permutation algorithm was implemented to study the postural effect on linkage. ADRA1A, APO, CAST, CORIN, CRHR1, EDNRB, FGF2, GC, GJA1, KCNB2, MMP3, NPY, NR3C2, PLN, TGFBR2, TNFRSF6, and TRHR showed evidence of linkage with any phenotype in the supine position and not upon standing, whereas AKR1B1, CD36, EDNRA, F5, MMP9, PKD2, PON1, PPARG, PPARGC1A, PRKCA, and RET were specifically linked to standing phenotypes. Genetic profiling was undertaken to show genetic interactions among intermediate BP phenotypes and genes specific to each posture. When investigators perform genetic studies exclusively on a single posture, important genetic components of BP are missed. Supine and standing BPs have distinct genetic signatures. Standardized maneuvers influence the results of genetic investigations into BP, thus reflecting its dynamic regulation.
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PMID:Dynamic genetic linkage of intermediate blood pressure phenotypes during postural adaptations in a founder population. 2326 1

This multi centre observational cohort study gives a view about the occurrence, clinical and laboratory presentation, localization, histological type and genetic background of pheochromocytoma (PHEO) and paraganglioma (PGL) in Eastern Slovakia. It included 28 patients (18 women + 10 men), of which 23 were diagnosed to have PHEO (82,1%) and 7 patients (25%) suffered from PGL with retroperitoneal, inguinal/pelvic and mediastinal distribution. Arterial hypertension was the major symptom present in 86 % with slight dominance of paroxysmal form (58%). In 3 cases (10,7%), the diagnosis was gained after differentiation of adrenal incidentaloma in asymptomatic patients. Five patients (17,8%) were classified to have malignant form of the disease. 9 patients (32,1%) were confirmed to have hereditary form - five of them (17,8%) with familiar medullar thyroid cancer (FMTC) and mutations in RET gene classified as multiple endocrine neoplasia 2A and 4 patients (14,3%) with germline mutations of SDHB gene, respectively. There was found a relatively high occurrence of other co-morbidities: thyroid disease in 20 patients (71,4%), impairment of glucose metabolism in 11 patients (39,3%) and apart from FMTC, 4 patients (14,3%) suffered also from other malignancy. Together with a bigger size of the primary tumor (6,6 cm), higher concentrations of metanephrines and prevalence of extra-adrenal tumors, malignant and hereditary forms, we suppose genetic and environmental factors of Eastern Slovakia may play a role in the etiopathogenesis of the tumors.
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PMID:Analysis of pheochromocytomas / paragangliomas from Eastern Slovakia. 2358 19

The lack of valid clinical management options for patients affected by metastatic colorectal cancer, which has progressed after all approved standard treatments, has lead to research into new active molecules. Regorafenib is an oral small-molecule multi kinase inhibitor, binding to several intracellular kinases, with powerful inhibitory activity against vascular endothelial growth factor receptors (VEGFR-1,VEGFR-2, and VEGFR-3), platelet-derived growth factor receptor, fibroblast growth factor receptor 1, Raf, TIE-2, and the kinases KIT, RET, and BRAF. The antitumor activity of regorafenib has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in several cancer models, particularly colorectal cancer and gastrointestinal stromal tumors. The most frequent adverse events of grade 3 or higher related to regorafenib were hand-foot skin reaction, fatigue, diarrhea, hypertension, and rash or desquamation. Only a few Phase I-II trials, and most recently a Phase III trial in pretreated colorectal cancer, have been carried out to date. Several ongoing trials are testing the efficacy of regorafenib in combination with chemotherapy. At this point in time, regorafenib is the first small-molecule tyrosine kinase inhibitor to gain approval by the US Food and Drug Administration for pretreated metastatic colorectal cancer patients.
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PMID:Critical appraisal of the use of regorafenib in the management of colorectal cancer. 2361 May 28

Multiple endocrine neoplasia (MEN) type 2A, a dominant inherited syndrome caused by germline activating mutations in the RET protooncogene, is characterized by association of medullary thyroid carcinoma, pheochromocytoma and primary hyperparathyroidism. There is limited data on this disease in the Middle East region. In this paper, we present clinical and genetic studies of an Iranian patient and her family members. The patient was a 49-year old Iranian woman who presented with hypertension due to bilateral pheochromocytoma. She had history of a medullary carcinoma of thyroid which had been operated 28 years ago. Analysis of the RET gene in the family revealed a C634R mutation in codon 11 and 3 polymorphisms, G691S, S836S and S904S in codons 11, 14 and 15, respectively, that might have been important in modifying the clinical picture. Due to paucity of information on MEN type 2 in the area, this study can be helpful in portraying the clinical and cytogenetic characteristics of the disease in the region.
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PMID:Multiple endocrine neoplasia type 2A in an Iranian family: clinical and genetic studies. 2478 69


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