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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pheochromocytoma is a rare but important tumor of chromaffin cells that is frequently considered in the evaluation of hypertension, arrhythmias, or panic disorder and in the follow-up of patients with particular genetic diseases. This report provides an update about the genetics, neurochemical diagnosis, localization by imaging, and surgical management of pheochromocytoma. Specific mutations of the RET proto-oncogene cause familial predisposition to pheochromocytoma in multiple endocrine neoplasia type II, and mutations in the von Hippel-Lindau tumor suppressor gene cause familial disposition to pheochromocytoma in von Hippel-Lindau disease. Recent findings demonstrating extraordinarily high sensitivity of plasma levels of metanephrines for detecting pheochromocytoma have led to an algorithm for clinical diagnostic steps. Nuclear imaging approaches, such as(123) I-metaiodobenzylguanidine scintigraphy and 6-[(18) F]fluorodopamine positron emission tomography, enhance both diagnosis and localization of the tumor, as described in an algorithm for patients with positive biochemical test results. Since pheochromocytoma is often benign, surgical resection by laparoscopic adrenalectomy can be curative. Areas requiring further work include determining appropriate follow-up of patients with familial pheochromocytoma, elucidating the bases for phenotypic differences, improving both specificity and sensitivity of biochemical tests, optimizing cost-effectiveness of diagnostic imaging, and testing the risk for tumor recurrence after partial adrenalectomy.
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PMID:Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma. 1118 43

This study examined the mechanisms linking different biochemical and clinical phenotypes of pheochromocytoma in multiple endocrine neoplasia type 2 (MEN 2) and von Hippel-Lindau (VHL) syndrome to underlying differences in the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, and of phenylethanolamine N-methyltransferase (PNMT), the enzyme that converts norepinephrine to epinephrine. Signs and symptoms of pheochromocytoma, plasma catecholamines and metanephrines, and tumor cell neurochemistry and expression of TH and PNMT were examined in 19 MEN 2 patients and 30 VHL patients with adrenal pheochromocytomas. MEN 2 patients were more symptomatic and had a higher incidence of hypertension (mainly paroxysmal) and higher plasma concentrations of metanephrines, but paradoxically lower total plasma concentrations of catecholamines, than VHL patients. MEN 2 patients all had elevated plasma concentrations of the epinephrine metabolite, metanephrine, whereas VHL patients showed specific increases in the norepinephrine metabolite, normetanephrine. The above differences in clinical presentation were largely explained by lower total tissue contents of catecholamines and expression of TH and negligible stores of epinephrine and expression of PNMT in pheochromocytomas from VHL than from MEN 2 patients. Thus, mutation-dependent differences in the expression of genes controlling catecholamine synthesis represent molecular mechanisms linking the underlying mutation to differences in clinical presentation of pheochromocytoma in patients with MEN 2 and the VHL syndrome.
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PMID:Pheochromocytomas in von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2 display distinct biochemical and clinical phenotypes. 1134 98

The pheochromocytoma is a medullo-adrenal tumor which develops at the cost of the chromaffin cells. It appears in 11-19% of cases of von Hippel-Lindau's disease (VHL), is often bilateral, and the symptomatology is often crude: arterial hypertension is frequently isolated and unstable, and the classic triad of headache, palpitations and sweating is quite rarely observed. We report four observations of bilateral pheochromocytomas in patients with von Hippel-Lindau's disease (three with phenotype IIA and one with phenotype IIB). The tumor was bilateral during the diagnosis in three cases; in the fourth patient, the attack on the contralateral adrenal gland came two years after the first adrenalectomy. All the patients had undergone an adrenalectomy by open surgery after a short preparation of 48 hours; replacement therapy was begun in each patient. Morbidity was low, and the patients submitted to a prolonged follow-up in order to screen for the onset of future lesions of VHL.
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PMID:[Bilateral adrenal pheochromocytomas in von Hippel-Lindau disease]. 1177 64

Loss of von Hippel-Lindau (VHL) gene function leads to VHL disease, which is characterized by vascular tumors of the central nervous system, renal clear cell carcinomas, and pheochromocytomas. Pheochromocytomas express high levels of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. PC12 cells that express VHL antisense RNA had 5-10-fold reduced levels of endogenous pVHL and 2-3-fold increased levels of TH protein and mRNA. Nuclear run-on analysis revealed an augmentation of TH gene transcription with enhanced efficiency of transcript elongation in the 3' region of the gene. Transient coexpression of the VHL antisense RNA with a TH promoter reporter construct increased TH promoter activity by 2-3-fold. A decrease in pVHL accumulation also resulted in an increase in TH mRNA accumulation and transcription of the TH gene during hypoxia. This is the first evidence that endogenous pVHL is a physiological regulator of the catecholaminergic phenotype. Thus, loss of pVHL function may be causative in pheochromocytoma-associated hypercatecholaminemia and arterial hypertension.
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PMID:Endogenous von Hippel-Lindau tumor suppressor protein regulates catecholaminergic phenotype in PC12 cells. 1191 40

Clinical and genetic epidemiology of inherited renal disease in Newfoundland. Newfoundland's geography, settlement, and socioeconomic development have produced a population useful for the study of genetic diseases. This review examines the clinical and genetic epidemiologic studies of inherited renal diseases undertaken in this population in the past 15 years. Common founder effects and large families through each generation provided very extensive pedigrees with autosomal-dominant diseases, such as polycystic kidney disease (PKD) and von Hippel-Lindau disease. In the former disease the diagnostic utility of renal ultrasound was determined, as was the prognostic impact of genotype, the role of the renin-angiotensin system in the pre-hypertensive phase, the potential for somatic mutations of the PKD2 gene, or the combination of mutations in the PKD1 and PKD2 genes, in single cells to induce cysts, and the demonstration that human transheterozygotes of PKD1 and -2 are not embryonically lethal. The presence of multiple genetic isolates and the high coefficient of kinship have predisposed to autosomal recessive diseases such as Bardet-Biedl syndrome (BBS), autosomal-recessive PKD, primary hyperoxaluria, and dihydroxyadenine urolithiasis. We have reported the clinical manifestations and natural history of the BBS, with particular emphasis on the fact that renal abnormalities are cardinal manifestations of the disease, the presence of at least six different genotypes, the identity and function of the BBS6 gene, and the presence of three different BBS6 mutations. Because of its relatively homogenous origins and high coefficient of kinship, Newfoundland's population also may be useful for the study of complex diseases such as preeclampsia. Using unbiased ascertainment and strict diagnostic criteria, we have found a significant risk of preeclampsia and non-proteinuric gestational hypertension in sisters of probands with preeclampsia, particularly when probands are defined by severity of preeclampsia, an observation that supports a study to search for susceptibility genes. We conclude that collaborations between clinical epidemiologists and molecular geneticists, using the Newfoundland population, have provided important clinical and mechanistic insights into inherited renal diseases.
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PMID:Clinical and genetic epidemiology of inherited renal disease in Newfoundland. 1202 33

A rare case of von Hippel-Lindau (VHL) disease with bilateral pheochromocytomas, right renal cell carcinoma, right pelvic carcinoma, spinal hemangioblastoma and primary hyperparathyroidism is described. A 78-year-old woman had a history of hypertension from her forties. She suffered from headache and body weight loss. Abdominal CT revealed bilateral adrenal tumors and right external renal tumors enhanced in early stage. MIBG scintigraphy exhibited a high accumulation of tracer in both adrenal glands. On the basis of the radiographic findings and endocrinological results, the patient was diagnosed as having bilateral pheochromocytomas and right renal cell carcinoma. A bilateral adrenectomy was performed, followed by surgery for resection of the renal cell carcinoma. The other resected right kidney showed a clear cell subtype that was determined to be renal cell carcinoma, and proved that the pelvic tumor was transient cell carcinoma. Spinal MRI showed spinal hemangioblastoma. von Hippel-Lindau (VHL) gene mutation for the patient was found. We diagnosed the patient as VHL because of the existence of spinal hemangioma and a VHL disease gene. Parathyroid echo revealed a hypoechoic space on the back of the left lobe, and serum calcium and intact PTH to be elevated. The patient was diagnosed as primary hyperparathyroidism. We report the first case of a patient with VHL disease complicated with bilateral pheochromocytomas, right renal cell carcinoma, right renal pelvic carcinoma and primary hyperparathyroidism. The life expectancy of affected individuals has been less than 50 years. Since the prognosis may be improved by an early diagnosis, affected individuals with VHL complexes should undergo cranial, spinal MRI and abdomen CT. The families may benefit from presymptomatic detection of affected gene carriers and the exclusion of at-risk family members by negative test results.
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PMID:A case of von Hippel-Lindau disease with bilateral pheochromocytoma, renal cell carcinoma, pelvic tumor, spinal hemangioblastoma and primary hyperparathyroidism. 1208 Dec 37

Pheochromocytomas are chromaffin cell tumors, mostly originating from the adrenal medulla, and represent a rare cause of hypertensiondue to excessive production of catecholamines (norepinephrine and/or epinephrine). More than 10% occur in families with multiple endocrine neoplasia type II, von Hippel-Lindau disease, neurofibromatosis type I, and familial carotid body tumors. Since approximately half of the afflicted patients present without or with only episodic hypertension, detailed clinical evaluation and sensitive biochemical tests are mandatory for the diagnosis, which relies on the detection of increased catecholamine production. Commonly employed tests such as the measurement of free catecholamines in plasma and urine or of their metabolites, vanillylmandelic acid and total metanephrines (= free + conjugated normetanephrine and metanephrine) in urine, suffer from interference from external factors and sometimes low clinical sensitivity and/or specificity. Recent technical advances now allow us to measure plasma free (unconjugated) metanephrines, thus increasing clinical sensitivity and specificity to close to 100%. Plasma free metanephrines offer the following advantages for the detection of pheochromocytomas: (i) independence of short-term changes in catecholamine secretion which may result from change of posture, exercise or intraoperative stress, (ii) information on long-term increase of catecholamine production, (iii) tight correlation with tumor mass, and (iv) only minor interference from drugs. This method does not need time-consuming standardized procedures for blood sampling, which are a prerequisite for the determination of free catecholamines. In conclusion, it is therefore recommended to use plasma free metanephrines--after meticulous clinical screening--as the first-line biochemical test for detecting pheochromocytomas.
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PMID:How to detect pheochromocytomas?--the diagnostic relevance of plasma free metanephrines. 1208 59

Monogenic or single-gene forms of human hypertension result from mutations involving regulatory elements of the renin-angiotensin-aldosterone system (RAAS) or occur in syndromes associated with hereditary pheochromocytoma. RAAS gain-of-function mutations result in sodium retention, suppression of plasma renin activity, and often, but not invariably, hypokalemia. Hereditary RAAS syndromes result from intrinsic renal abnormalities (apparent mineralocorticoid excess and Liddle's syndromes) or from mineralocorticoid excess states (congenital adrenal hyperplasia and glucocorticoid-remediable aldosteronism). In the hereditary pheochromocytoma syndromes many asymptomatic individuals are identified because they are at-risk individuals in kindreds with a pheochromocytoma-predisposing syndrome. On the other hand, up to 25% of subjects with presumed "sporadic" pheochromocytoma have germline mutations in one of four pheochromocytoma susceptibility genes (the RET proto-oncogene, von Hippel-Lindau gene, neurofibromatosis F1 gene, and succinate dehydrogenase subunit D and succinate dehydrogenase subunit B genes). Hereditary pheochromocytomas are typically intra-adrenal and bilateral and patients typically present at younger ages compared with sporadic pheochromocytoma.
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PMID:Screening for genetic causes of hypertension. 1241 72

Laparoscopic adrenalectomy has become the standard treatment for benign adrenal tumors, providing minimal invasiveness and early recovery. In the case of pheochromocytomas, special attention should be paid perioperatively to prevent excessive hypertension or hypotension. The protocol should include sufficient preoperative medication with alpha 1 blockers, early ligation of the adrenal vein, and minimal handling of the tumor itself. A literature review of 227 laparoscopic adrenalectomies for pheochromocytomas revealed that the perioperative data, including the operative time, blood loss, and hemodynamic status, were similar or slightly better in the laparoscopic procedures as compared to the open procedures, although the convalescence period was significantly shorter in the laparoscopic surgery. The majority of surgeons prefer the transperitoneal approach for pheochromocytomas, although some authors use the retroperitoneal approach successfully. A comparison of the perioperative data from laparoscopic surgeries for pheochromocytomas versus those for other adrenal tumors showed that the former had slightly higher demands to complete the procedure safely. In the treatment of familial pheochromocytoma due to multiple endocrine neoplasia type 2 or von Hippel-Lindau disease, a cortical-sparing adrenalectomy can be safely performed laparoscopically. In conclusion, laparoscopic adrenalectomy is the standard for small pheochromocytomas, with a high success rate when the procedure is performed by experienced surgeons.
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PMID:Laparoscopic adrenalectomy for pheochromocytoma: a literature review. 1248 69

A 12-year-old boy presented with severe hypertension, congenital microcephaly, severe hearing loss, developmental delay, cryptorchidism, and bilateral pheochromocytomas, without the phenotypic features of multiple endocrine neoplasia type II syndromes (MEN-2). Sequence analysis of the polymerase chain reaction (PCR)-amplified gnomic DNA identified a missense mutation at nucleotide 451 of the von Hippel-Lindau (VHL) gene (A451G) that changes a codon for serine (AGT) to one for glycine (GGT) at amino acid position 80 (S80G). The sequence DNA analysis of the parents did not show a mutation in the VHL gene that was previously identified in their affected son. The observed constellation of microcephaly, deafness, cryptorchidism, developmental delay, hypertension, and bilateral pheochromocytoma in association with a VHL mutation A451G in a patient with negative family history has not previously been described in the literature. Knowledge that VHL mutation plays a critical role in sporadic pheochromocytoma should aid in the future diagnosis and treatment of this tumor. Genetic testing in known pheochromocytoma families is indicated to identify genetically abnormal subjects that carry the MEN-2, VHL, and glomus tumor gene mutations.
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PMID:Bilateral pheochromocytomas and congenital anomalies associated with a de novo germline mutation in the von Hippel-Lindau gene. 1250 Feb 16


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