Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The second type of multiple endocrine neoplasia syndromes can be described as rare syndromes, heritable in autosomal dominant manner and linking medullary thyroid carcinoma to different tumors of endocrine organ system and endocrinopathies. This syndrome is divided into multiple endocrine neoplasia syndrome type 2A (MEN 2A), characterized with combination of medullary thyroid carcinoma, pheochromocytoma and primary hyperparathyroidism; type 2B (MEN 2B), characterized with combination of medullary thyroid carcinoma, pheochromocytoma, marfanoid habitus and ganglioneuromatosis, and familial medullary thyroid carcinoma syndrome, characterized with the only indication, which is hereditary medullary thyroid carcinoma. Though type 2 multiple endocrine neoplasia syndrome has been known since 1961, yet, the cause of the syndrome, which is germline mutations of c-ret protooncogene, was detected just a decade ago and syndrome pathogenesis with its characterized endocrine neoplasia carcinogenesis machinery were detected. Implementation of progressive genetic researches in clinical practice enabled precise diagnosis of multiple endocrine neoplasia syndrome and its subtypes not only for ill patients but also for healthy syndrome inheritors, e.g. relatives of the sick. Stated genotype link to phenotype helps to prognosticate possible combinations of endocrine neoplasia and endocrinopathies, and to choose purposeful patient observation. Genetic screening of the inheritors of multiple endocrine neoplasia type 2 syndrome enabled purposeful researches and observations of patients with a huge risk of uprising endocrine neoplasia, it also enabled application of effective prophylaxis methods, avoidance or early diagnostic of malignant tumors and life prognosis improvement for patients with malignant tumors while practicing well-timed treatment adaptation. This literature review contains the newest data on multiple endocrine neoplasia syndrome type 2 and its pathogenesis, diagnostics, patient observation, endocrine cancer prophylaxis and methods of treatment, which are characteristic for syndrome and which are being chosen according to biochemical endocrine neoplasia symptoms and genetic diagnosis.
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PMID:[Multiple endocrine neoplasia syndromes. Type 2]. 1586 1

Medullary thyroid carcinoma (MTC) is a rare calcitonin producing tumor. About 70-75% of patients with MTC have sporadic disease while the others suffer from hereditary MTC. Hereditary MTC is divided into three clinical subtypes: multiple endocrine neoplasia (MEN) type 2A is characterized by MTC, pheochromocytoma and primary hyperparathyroidism. MEN 2B is characterized by aggressive MTC, pheochromocytoma, marfanoid habitus and the presence of distinctive mucosal neuromas on the tongue, lips and subconjunctival areas as well as ganglioneuromatosis of the gastrointestinal tract. The third clinical subtype of inherited MTC, familial MTC, is defined as the presence of MTC in families without evidence of adrenal or parathyroid gland involvement. Hereditary MTC is caused by autosomal dominant gain-of-function mutations in the RET proto-oncogene. The first RET germline mutations were identified in 1993 in patients with MEN 2A and FMTC. Initially a codon 634 (exon 11) mutation was found in approximately 85% of patients with MEN 2A, and germline mutations in FMTC kindreds were more equally distributed throughout the RET proto-onocogene. In about 5% of families in these earlier series, mutations did not reside in exons 10 and 11. We now report a change in the spectrum of mutations detected in the RET proto-oncogene in patients with hereditary MTC from the 'classical' mutation at codon 634 in exon 11 (level 2) to more cases with mutations in the exons 13-15 (level 1) and less aggressive disease. In our series 38.9% of mutations were level 1 mutations, 54.4% level 2, and 5.6% level 3 mutations.
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PMID:Change in the spectrum of RET mutations diagnosed between 1994 and 2006. 1760 1

Multiple endocrine neoplasia type 2 (MEN2) is an hereditary disease with a prevalence of 1/5000. Three phenotypic variants have been identified: MEN2A associates medullary thyroid carcinoma (MTC) to pheochromocytoma in about 20-50% of cases and to primary hyperparathyroidism in 5-20% of cases; MEN2B associates MTC to pheochromocytoma in 50% of cases, to marphanoid habitus and to mucosal and digestive ganglioneuromatosis whereas in familial isolated medullary thyroid carcinoma (FMTC), the other components of the disease are absent. In MEN2, natural history of the disease and a common embryologic origin (neural crest) may explain the phenotypes observed in the organ involved, beginning from the stage of hyperplasia to adenoma and cancer. MEN2 is an inherited autosomal dominant disease with a complete penetrance, related to germline mutation in the proto-oncogene RET. MTC represent the most frequent circumstance of diagnosis. Pheochromocytoma and HPT may reveal the disease unfrequently and are systematically associated to undiagnosed MTC which is present yet. Analysis of the RET gene allows to confirm the diagnosis of MEN2 by identifying the causal germline mutation. Management of MEN2 patients include thyroidectomy associated to cervical central and bilateral lymph nodes dissection for MTC, unilateral adrenalectomy for unilateral pheochromocytoma or bilateral adrenalectomy when both glands are involved, and selective resection of pathologic parathyroid glands for HPT. Familial genetic screening detects at risk subjects who will develop the disease and allows to manage them at the earliest stage of the disease by perform early or prophylactic thyroidectomy such giving them the best chance of cure. Prognosis of MEN2 is mainly related to the stage-dependant prognosis of MTC, thus pointing the necessity of a complete thyroid surgery for index cases with MTC and the earliest thyroidectomy for screened at risk subjects.
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PMID:[Multiple endocrine neoplasia type 2]. 1762 79

Multiple endocrine neoplasia type 2 is historically composed of three clinical subtypes, all of which are associated with germline mutations in the RET proto-oncogene. Multiple endocrine neoplasia type 2A, familial medullary thyroid carcinoma, and multiple endocrine neoplasia type 2B are collectively associated with a 70-100% risk of medullary thyroid carcinoma by age 70 years. Pheochromocytomas are identified in 50% of individuals with multiple endocrine neoplasia type 2A and multiple endocrine neoplasia type 2B. Furthermore, those with multiple endocrine neoplasia type 2A have a 20-30% risk for primary hyperparathyroidism. Individuals with multiple endocrine neoplasia type 2B often have distinct physical features including mucosal neuromas of the lips and tongue, medullated corneal nerve fibers, ganglioneuromatosis of the gastrointestinal tract, distinctive facies with enlarged lips, and a "Marfanoid" body habitus. Clinical recognition and accurate diagnosis of individuals and families who are at risk of harboring a germline RET mutation is critical for the prevention and management of potentially life-threatening neoplasms. This overview summarizes the clinical description of multiple endocrine neoplasia type 2, diagnosis and testing strategies, management and surveillance, and differential diagnosis for other related syndromes.
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PMID:Multiple endocrine neoplasia type 2: an overview. 2155 34