Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031511 (pheochromocytoma)
 14,622 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This is a consensus statement from an international group, mostly of clinical endocrinologists. MEN1 and MEN2 are hereditary cancer syndromes. The commonest tumors secrete PTH or gastrin in MEN1, and calcitonin or catecholamines in MEN2. Management strategies improved after the discoveries of their genes. MEN1 has no clear syndromic variants. Tumor monitoring in MEN1 carriers includes biochemical tests yearly and imaging tests less often. Neck surgery includes subtotal or total parathyroidectomy, parathyroid cryopreservation, and thymectomy. Proton pump inhibitors or somatostatin analogs are the main management for oversecretion of entero-pancreatic hormones, except insulin. The roles for surgery of most entero-pancreatic tumors present several controversies: exclusion of most operations on gastrinomas and indications for surgery on other tumors. Each MEN1 family probably has an inactivating MEN1 germline mutation. Testing for a germline MEN1 mutation gives useful information, but rarely mandates an intervention. The most distinctive MEN2 variants are MEN2A, MEN2B, and familial medullary thyroid cancer (MTC). They vary in aggressiveness of MTC and spectrum of disturbed organs. Mortality in MEN2 is greater from MTC than from pheochromocytoma. Thyroidectomy, during childhood if possible, is the goal in all MEN2 carriers to prevent or cure MTC. Each MEN2 index case probably has an activating germline RET mutation. RET testing has replaced calcitonin testing to diagnose the MEN2 carrier state. The specific RET codon mutation correlates with the MEN2 syndromic variant, the age of onset of MTC, and the aggressiveness of MTC; consequently, that mutation should guide major management decisions, such as whether and when to perform thyroidectomy.
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PMID:Guidelines for diagnosis and therapy of MEN type 1 and type 2. 1205 Feb 90

Multiple endocrine neoplasia Type 2 is a rare familial cancer syndrome transmitted in an autosomal dominant manner. It is characterized by the association of medullary thyroid carcinoma with pheochromocytoma and hyperparathyroidism. Medullary thyroid carcinoma, present in virtually all patients, is the principal cause of death. In 1993, germline mutations in the RET proto-oncogene were identified as the underlying cause of the syndrome. Genetic screening of at-risk family members can now be performed with high specificity and sensitivity. The ability to determine gene carrier status at a preclinical stage is of great value as it allows early prophylactic thyroidectomy. The specific RET codon mutation correlates with clinical variants of the syndrome, age at onset and aggressiveness of medullary thyroid carcinoma. This review will focus on mutational spectrum, genotype-phenotype correlations and clinical decisions based on genetic information.
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PMID:Molecular diagnosis of multiple endocrine neoplasia Type 2. 1462 4

Hereditary medullary thyroid carcinoma (MTC) is caused by autosomal dominant gain-of-function mutations in the RET proto-oncogene. Associations between specific RET mutations (genotype) and the aggressiveness of MTC and presence or absence of other endocrine neoplasms (phenotype) are well documented. Mutations in six exons (10, 11, 13, 14, 15, and 16) located in either cysteine-rich or tyrosine kinase domains cause one of three distinctive clinical subtypes: familial MTC, multiple endocrine neoplasia (MEN) type 2A (including variants with Hirschsprung's disease and cutaneous lichen amyloidosis), and MEN 2B. Hallmarks of MEN 2A include MTC, pheochromocytoma, and hyperparathyroidism. MEN 2B is associated with an earlier onset of MTC and pheochromocytoma, the absence of hyperparathyroidism, and the presence of striking physical stigmata (e.g., coarse facies, ganglioneuromatosis, and marfanoid habitus). Familial MTC is not associated with other endocrine neoplasms; however, the accurate distinction between familial MTC and MEN 2A may be difficult in kindreds with small size, incomplete histories, or a predominance of young individuals who may not have yet fully manifested the syndrome. Genetic testing detects greater than 95% of mutation carriers and is considered the standard of care for all first-degree relatives of patients with newly diagnosed MTC. Recommendations on the timing of prophylactic thyroidectomy and the extent of surgery are based upon a model that utilizes genotype- phenotype correlations to stratify mutations into three risk levels.
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PMID:RET proto-oncogene: a review and update of genotype-phenotype correlations in hereditary medullary thyroid cancer and associated endocrine tumors. 1602 19

The report presents 200 cases of gastrointestinal stromal tumors (GIST). The material originated from six diagnostic centers in Poland and was reclassified according to the current criteria. Among lesions other than GISTs, 14 were identified as smooth muscle tumors and seven as neural tumors. GISTs were located in the stomach (51-63.3% of the investigated series), small intestine (27.4-33.8%), colon (approximately 4.5%), abdominal cavity, i.e. in the peritoneum and omentum (6%), and in the retroperitoneal space (2.5%). A slight predominance of women was noted (53-56%). The age of the patients ranged between 14 and 93 years of life, with the mean age of 62.4 years. Individuals younger than 45 years of age accounted for 10% of the group. In ten patients (five of them less than 45 years of life), multiple tumors were detected, their number ranging from two to less than 20; these individuals constituted 5% of the entire series. Moderately and highly aggressive tumors predominated. In the series, when multiple tumors were excluded, a total of 24 epithelioid GISTs (12%) were observed; of this number, 13 were situated in the stomach, six--in the small intestine, two--in the abdominal cavity and another two in the retroperitoneal space. Synchronic tumors observed in patients with GISTs were seen in seven patients, including an adenocarcinoma of the colon, two adenocarcinomas of the stomach, a carcinoid tumor of the small intestine, a pheochromocytoma of the retroperitoneal space, an anaplastic lymphoma and a disseminated squamous cell carcinoma. In immunohistochemical reactions (CD117, CD34, SMA, S-100, DES), attention was focused on the immunoreactivity of small GISTs, below 2 cm in size, and of multiple tumors. Immunohistochemical reactions were equally differentiated as to their presence and intensity in small tumors and in highly aggressive lesions above 5-10 cm in size. In multiple GISTs, immunohistochemical tests strongly indicated the heterogeneity of neoplastic cells, which, nevertheless, showed no consistent association with the location of the tumor, its aggressiveness, cellular structure or a tendency to form multiple foci.
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PMID:Gastrointestinal stromal tumors. A multicenter experience. 1609 66

A pheochromocytoma is a neoplasm composed of cells which synthesize and release catecholamines. These tumors produce the hypertension which can be cured with surgical excision of the lesion. The pathological picture of pheochromocytomas is varied and nothing but the presence of metastases can determine aggressiveness of this neoplasm. Current studies try to look for other biological markers which can separate malignant tumors before they metastasize. It allows to target with more effective therapy. Many studies analyze details of microscopic features of these tumors, immunohistochemical markers and molecular disorders. It seems that the most important factor in estimation of aggressiveness of pheochromocytomas is PASS scale. The detection of high expression of telomerase and hTERT and high proliferative activity, measured by immunohistochemistry with the MIB-1 antibody supports most strongly biological malignancy of pheochromocytoma.
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PMID:[Markers of malignancy in pheochromocytomas]. 1682 Dec 16

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant tumour syndrome caused by germline activating mutations of the RET proto-oncogene. It has a strong penetrance of medullary thyroid carcinoma (MTC) and can be associated with bilateral pheochromocytoma and primary hyperparathyroidism (MEN2A) within a single patient or family. Based on the phenotype three distinct clinical forms have been described: (1) classical MEN2A, (2) MEN2B, an association of MTC, pheochromocytoma and mucosal neuroma and (3) familial MTC (FMTC), which is associated with a very low incidence of other endocrinopathies. Each variant of MEN2 results from a different RET gene mutation, with a good genotype-phenotype correlation with regard to aggressiveness of MTC, time of onset of MTC and the presence or absence of other endocrine tumours. Recommendations on the timing of prophylactic thyroidectomy and extent of surgery are based on a classification of RET mutations into three risk levels using the genotype-phenotype correlations. MEN2 provides a unique model for early prevention and cure of cancer and for stratified roles of mutation-based diagnosis of carriers.
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PMID:Genotype-phenotype relationship in multiple endocrine neoplasia type 2. Implications for clinical management. 1926 18

Multiple endocrine neoplasia syndromes have since been classified as types 1 and 2, each with specific phenotypic patterns. MEN1 is usually associated with pituitary, parathyroid and paraneoplastic neuroendocrine tumours. The hallmark of MEN2 is a very high lifetime risk of developing medullary thyroid carcinoma (MTC) more than 95% in untreated patients. Three clinical subtypesdMEN2A, MEN2B, and familial MTC (FMTC) have been defined based on the risk of pheochromocytoma, hyperparathyroidism, and the presence or absence of characteristic physical features). MEN2 occurs as a result of germline activating missense mutations of the RET (REarranged during Transfection) proto-oncogene. MEN2-associated mutations are almost always located in exons 10, 11, or 13 through 16. Strong genotype-phenotype correlations exist with respect to clinical subtype, age at onset, and aggressiveness of MTC in MEN2. These are used to determine the age at which prophylactic thyroidectomy should occur and whether screening for pheochromocytoma or hyperparathyroidism is necessary. Specific RET mutations can also impact management in patients presenting with apparently sporadic MTC. Therefore, genetic testing should be performed before surgical intervention in all patients diagnosed with MTC. Recently, Pellegata et al. have reported that germline mutations in CDKN1B can predispose to the development of multiple endocrine tumours in both rats and humans and this new MEN syndrome is named MENX and MEN4, respectively. CDKN1B. A recent report showed that in sporadic MTC, CDKN1B V109G polymorphism correlates with a more favorable disease progression than the wild-type allele and might be considered a new promising prognostic marker. New insights on MEN syndrome pathogenesis and related inherited endocrine disorders are of particular interest for an adequate surgical and therapeutic approach.
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PMID:Multiple endocrine neoplasia, the old and the new: a mini review. 2314 Sep 18

Multiple endocrine neoplasia (MEN) are clinical inherited syndromes affecting different endocrine glands. Three different patterns of MEN syndromes can occur (MEN 1, MEN 2A, and MEN 2B). MEN syndromes are very rare, affect all ages and both sexes are equally affected. MEN 1 is characterized by the neoplastic transformation of the parathyroid glands, pancreatic islets, anterior pituitary, and gastrointestinal tract. Heterozygous MEN 1 germline mutations have been detected in about 70-80% of patients with MEN 1. The mutations are scattered throughout the entire genomic sequence of the gene. MEN 1 patients are characterized by variable clinical features, thus suggesting the lack of a genotype-phenotype correlation. Therapeutical approaches are different according to the different endocrinopathies. The prognosis is generally good if adequate treatment is provided. In MEN 2 syndromes, the medullary thyroid cancer (MTC) is almost invariably present and can be associated with pheochromocytoma (PHEO) and/or multiple adenomatosis of parathyroid glands with hyperparathyroidism (PHPT). The different combination of the endocrine neoplasia gives origin to 3 syndromes: MEN 2A, MEN 2B, and FMTC. The clinical course of MTC varies considerably in the three syndromes. It is very aggressive in MEN 2B, almost indolent in the majority of patients with FMTC and with variable degrees of aggressiveness in patients with MEN 2A. Activating germline point mutations of the RET protooncogene are present in 98% of MEN 2 families. A strong genotype-phenotype correlation has been observed and a specific RET mutation may be responsible for a more or less aggressive clinical course. The treatment of choice for primary MTC is total thyroidectomy with central neck lymph nodes dissection. Nevertheless, 30% of MTC patients, especially in MEN 2B and 2A, are not cured by surgery. Recently, developed molecular therapeutics that target the RET pathway have shown very promising activity in clinical trials of patients with advanced MTC. MEN 2 prognosis is strictly dependent on the MTC aggressiveness and thus on the success of the initial treatment.
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PMID:Genetic and clinical features of multiple endocrine neoplasia types 1 and 2. 2320 66

Malignant peripheral nerve sheath tumor (MPNST) of the adrenal gland is extremely rare. Most of them occur in association with neurofibromatosis, ganglioneuroma or as part of a composite tumor such as pheochromocytoma. Only seven cases of MPNST of the adrenal gland have been reported in the literature till date. Discriminating this entity from other soft tissue sarcomas and gastrointestinal stromal tumor of the adrenal gland has important diagnostic and therapeutic implications. Moreover, the tumor size and pattern of expression for certain immunohistochemical markers may serve as independent predictors of aggressiveness. Herein we present a 24-years-old male with features of Von Recklinghausen's disease who presented with large left adrenal gland malignant peripheral nerve sheath tumor.
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PMID:Malignant peripheral nerve sheath tumor of adrenal gland with heterologus osseous differentiation in a case of Von Recklinghausen's disease. 2473 52

The discovery of SDHD as a pheochromocytoma/paraganglioma susceptibility gene was the prismatic event that led to all of the subsequent work highlighting the key roles played by mitochondria in the pathogenesis of these tumors and other solid cancers. Alterations in the function of tricarboxylic acid cycle enzymes can cause accumulation of intermediate substrates and subsequent changes in cell metabolism, activation of the angiogenic pathway, increased reactive oxygen species production, DNA hypermethylation, and modification of the tumor microenvironment favoring tumor growth and aggressiveness. The elucidation of these tumorigenic mechanisms should lead to novel therapeutic targets for the treatment of the most aggressive forms of pheochromocytoma/paraganglioma.
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PMID:15 YEARS OF PARAGANGLIOMA: Metabolism and pheochromocytoma/paraganglioma. 2611 5


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