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)

The authors present a case of a 37 year old male (proband) with a 13 year history of progressive sight impairment leading to blindness and a 4 year history of a mild hypertension. He was incidentally found to have large adrenal tumors after an ultrasound kidney examination. The tumors were confirmed with CT scan and magnetic resonance imaging. A bilateral pheochromocytoma was biochemically demonstrated and successfully removed. The eye diagnosis of angiomatosis retinae von Hippel-Lindau was ascertained after a search of the patient files in other medical departments, which led to a family screening. Proband's brother, having hypertension and a history of a cerebellar astrocytoma operation, was also diagnosed with CT scan to have a bilateral pheochromocytoma. Unfortunately, at the same time he was found to have a large irremovable neuroendocrine pancreatic carcinoma, which caused complications and his eventual death. Both proband and his brother were affected by the same CGG(Arg167)->CAG(Gln) mutation in the exon 3 of the VHL gene. Other living and examined family members were not affected, which was confirmed by negative genetic testing. One year after the pheochromocytoma operation, proband was diagnosed to have a retroperitoneal tumor left to the aorta, clinically silent, with slightly and non-constantly elevated urine norepinephrine and normetanephrine. Metaiodobenzylguanidine scintigraphy showed that it was a paraganglioma. The old CT and magnetic resonance picture review demonstrated that the tumor had already been present at the time of the operation. It was surgically removed and histologically verified. It is a pity that proband had not been sent by his ophthalmologist for an endocrine examination when the eye diagnosis was determined. Affection of the family would have been discovered earlier, and proband's brother might have possibly been saved.
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PMID:[Hereditary pheochromocytoma--a family affected by von Hippel-Lindau disease]. 1293 43

Pheochromocytomas are rare tumours of catecholamine-producing chromaffin cells leading to hypertension and symptoms of catecholamine excess. They can be benign or malignant, sporadic or familial tumours. Genetic syndromes associated with pheochromocytoma are MEN II, VHL disease and neurofibromatosis type 1. Usually, pheochromocytomas occur in the adrenal medulla. Clinical manifestations include hypertension (which can be intermittent, stable or in the form of hypertensive peaks) and symptoms related to catecholamine excess such as headache, palpitations and tachycardia, pallor, anxiety and nervousness, nausea, vomiting, weight loss. This clinical syndrome can be mimicked by various hyperkinetic and hyperadrenergic states. When pheochromocytoma is suspected, the first diagnostic step is represented by the measurement of catecholamines and their metabolites (metanephrines) in urine and plasma. Chro-mogranin A measurement can be useful. The clonidine suppression test may be helpful in ruling out other conditions that may elevate catecholamines and metanephrines. Localiza-tion and staging of pheochromocytoma is based on MRI, which is more sensitive than CT scan, and (131)I-MIBG scintiscan. The best therapeutic option for pheochromocytoma is surgery with a laparoscopic approach. An appropriate pre-, intra- and postoperative medical management of the patient is mandatory. In the absence of optimal medical treatment, intraoperative mortality reaches 50%.
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PMID:Recent advances in diagnosis and treatment of pheochromocytoma. 1460 91

We have recently proposed lipid peroxidation as a unifying mechanistic pathway by which several seemingly unrelated risk/protective factors (obesity, hypertension, diabetes, smoking, oophorectomy/hysterectomy, parity, antioxidants) affect renal cell carcinoma development. In experimental studies, increased lipid peroxidation is a principal mechanistic pathway in renal carcinogenesis induced by different chemicals. In this communication, we provide additional lines of evidence that further support a role for lipid peroxidation on renal cell cancer development. (1) Lipid peroxidation may explain the role of other risk (analgesic use, pre-eclampsia) or protective (alcohol intake, oral contraceptives) factors for renal cell carcinoma. (2) Additional experimental evidence supports lipid peroxidation as an important mechanism in renal carcinogenesis, and (3) Existing evidence support a cross-talk between the lipid peroxidation pathway and other pathways that are relevant to renal carcinogenesis, such as apoptosis, VHL, and possibly other pathways.
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PMID:Lipid peroxidation and renal cell carcinoma: further supportive evidence and new mechanistic insights. 1645 3

Phaeochromocytoma is a rare catecholamine-secreting tumour that may arise at any age, but is particularly unusual in childhood. The case of a 6-year-old girl who presented with a prolonged history of general malaise, headaches and abdominal pain is reported. On examination, she was noted to have malignant hypertension. Subsequent imaging of the abdomen demonstrated a left adrenal mass, with the diagnosis of phaeochromocytoma being confirmed by serial raised urinary metanephrines. Sympathetic blockade was established prior to definitive surgical treatment, resulting in complete resolution of the patient's symptoms and hypertension. Genetic screening of the family has since identified a previously undocumented missense mutation in the patient's VHL gene. The case raises the importance of routine measurement of blood pressure in all paediatric patients regardless of age, presentation or other factors.
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PMID:Diagnosis at dusk: malignant hypertension and phaeochromocytoma in a 6-year-old girl. 1825 29

Several novel therapies have been approved recently in advanced renal cell carcinoma (RCC). These agents inhibit pathways downstream of loss of the von Hippel-Lindau gene VHL. They target the vascular endothelial growth factor (VEGF) ligand, VEGF receptor (VEGFR), mammalian target of rapamycin (mTOR), and other potentially important pathways. Even with improvements in survival, disease progresses in all patients. There is a critical need to increase complete responses (now rare). One such strategy is combining several agents to block different levels of the VEGF-VEGFR axis (vertical blockade). Alternatively, combination of a VEGF-VEGFR inhibitor with an mTOR inhibitor is attractive. Finally, horizontal blockade of VEGFR with epidermal growth factor receptor and/or platelet-derived growth factor receptor, all signaling pathways activated by hypoxia-inducible factor, is another approach. Already trials have revealed difficulties with combination therapy. By combining agents, the toxicity of 1 or both can be enhanced. The authors of this article report their experience with sorafenib plus bevacizumab, which produced increases in hand-foot syndrome, hypertension, and proteinuria, all known toxic effects. Clinical activity was impressive with 25 responses in 48 patients (52% response rate). Other combinations also required dose reductions (sorafenib with temsirolimus) or were intolerable (sunitinib with temsirolimus or sunitinib with bevacizumab). Unexpected toxicity characterized by microangiopathic hemolytic anemia occurred late in treatment with sunitinib and bevacizumab. Toxicity may be more severe in patients with RCC, who frequently have 1 kidney and poor renal function. Once tolerability for combination regimens has been established, it will be critical to design informative phase 2 trials and address the benefit of combination versus sequential therapy.
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PMID:Combination targeted therapy in advanced renal cell carcinoma. 1940 58

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

Although hypertension occurring during pregnancies is not uncommon and its prognosis is generally excellent, some of its unusual causes can lead to catastrophic consequences, especially in undiagnosed cases. Here, we report a pregnant woman who presented with hypertension in her early pregnancy. It was subsequently found to be caused by bilateral pheochromocytoma. After removal of both tumors, catecholamine levels unexpectedly and unexplainably remained elevated. At 23 weeks of gestation, the fetus was found dead in utero. After the fetal death, additional studies were performed and revealed a thoracic paraganglioma. To our knowledge, this is the first report of a case of three catecholamine-producing tumors occurring concurrently during a pregnancy. Genetic analysis helped identify this unprecedented condition; the patient harbored a heterozygous missense mutation c.482G>A in exon 3 of the VHL gene, indicating von Hippel-Lindau syndrome. Physicians who care for hypertensive pregnant patients should be aware of this condition as its diagnosis would probably lead to a better outcome.
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PMID:Concurrent bilateral pheochromocytoma and thoracic paraganglioma during pregnancy. 2096 Feb 61

An 18-year-old woman with a 2-year history of hypertension and headache was diagnosed with noradrenalin-secreting bilateral adrenal pheochromocytomas with paragangliomas in the background of von Hippel-Lindau disease with family histories and a missense mutation, 712C to T (Arg167Trp) in the VHL gene. She had optic disc hemangioma in the left eye which gradually enlarged and caused serous retinal detachment on the macula in one year. Low-dose external beam radiation (20 Gy) was administered to the left eye using a lens-sparing single lateral technique. She underwent craniotomy for cerebellar hemangioblastoma at the age of 22 years and total pancreatectomy for multiple neuroendocrine tumors at the age of 24 years. In the 6-year follow-up period after the radiotherapy, the optic disc hemangioma gradually reduced in size and its activity remained low, allowing good central vision to be maintained. External beam radiation is recommended as a treatment option for the initial therapy for optic disc hemangioma.
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PMID:Long-term effect of external beam radiotherapy of optic disc hemangioma in a patient with von Hippel-Lindau disease. 2151 72

Laparoscopic adrenalectomy has become the preferred method for removal of almost all adrenal tumors. An important component in selecting patients for this operation is a thorough understanding of the clinical presentation (mainly hypertension) and diagnostic workup for the full variety of functioning and nonfunctioning adrenal tumors including genetic evaluation when necessary (MEN2, VonHippel-Landau [VHL], type 1 neurofibromatosis [NF1], succinate dehydrogenase mutations [SDH], and MEN1). The indications and contraindications for a laparoscopic approach are discussed with regard to each tumor type. Relevant literature about partial and bilateral adrenalectomy is also summarized. Main areas of controversy are discussed including the size threshold to avoid risk of adrenal capsular effraction and the appropriateness of laparoscopic resection for suspected and known malignancy. This article presents recent data to help the surgeon make well-informed decisions and to optimize the operative approach for a wide variety of adrenal pathologies (secreting vs. non-secreting, benign vs. malignant tumors).
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PMID:Surgical management of adrenal tumors. 2182 Sep 84

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


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