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 multiple endocrine neoplasia syndromes are divided into two categories: MEN type I and MEN type II. The MEN type II syndrome is further divided into MEN IIa and MEN IIb. The syndromes are characterized by benign and malignant changes in two or more endocrine organs, as well as incidental changes in nervous, muscular and connective tissue. Two main forms can be distinguished: the MEN-I syndrome with hyperplasia of the parathyroid gland, accompanied by islet cell tumor and pituitary adenoma; the MEN-II syndrome with medullary thyroid carcinoma in combination with bilateral pheochromocytoma and hyperplasia of the parathyroid gland (MEN IIa), while type IIb is characterized by the additional appearance of neurocutaneous manifestations without primary hyperparathyroidism. Characteristics shared by these syndromes include the involved cell type, most of the tumors are composed of one or more specific polypeptide- and biogenic amine-producing cell types (APUD--amine precursor uptake and decarboxylation). The second characteristic is the increased incidence in certain families. The hereditary component is autosomal dominant with variable expression but high penetrance. Mechanisms of tumorigenesis differ in these syndromes. While MEN I is caused by an inherited mutation of a tumor suppressor gene, menin, located on the long arm of chromosome 11, MEN II is caused by activation of the RET proto-oncogene. We have reported the case of a young man exhibiting bilateral pheochromocytoma. In addition, the patient showed mild primary hyperparathyroidism and marfanoid habitus, all these stigmata usually being part of the MEN-II syndrome. Although this described patient showed a phenotypic mixture of the MEN-IIa and MEN-IIb syndrome, the genetic analysis for MEN II and von-Hippel-Lindau gene did not reveal any pathologic mutations, the endocrine disorders described here are not related to multiple endocrine neoplasia syndromes.
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PMID:Multiple endocrine neoplasia (MEN)--an overview and case report--patient with sporadic bilateral pheochromocytoma, hyperparathyroidism and marfanoid habitus. 1120 36

Since 1969 to 2000 twenty one patients from 16 families with syndrome of multiple endocrine neoplasia (MEN) type 2 were examined. Medullary cancer of the thyroid gland (MCTG) was diagnosed in 18 patients, pheochromocytoma--in 15 (in 13 of them--two-sided), primary hyperparathyroidism--in 2. In 9 patients from 5 families syndrome MEN 2 was confirmed genetically (mutation in codon 634 of 11th exon RET in 7 patients with MEN 2a and in codon 918 in 2 patients with MEN 2b). None of the patients had extraadrenal pheochromocytoma, in 9 (60%) patients multicentric tumors within one adrenal gland were diagnosed. All the 18 patients with MCTG underwent extrafascial thyroidectomy with removal of fat and lymph nodes of paratracheal zone, 9 patients--one-sided (6) or two-sided (3) removal of fat and lymph nodes of lateral triangle of neck. Prophylactic thyreoidectomy was performed in 11-year old patient with genetically verified MEN 2a and without topical data of MCTG, 2 patients of 3 and 19 years of age with genetically verified MEN 2 are to undergo prophylactic thyroidectomy. Prophylactic thyroidectomy is necessary in the presence of genetic disorders in members of families with MEN 2 despite absence of structural changes in thyroid gland. Level of basal and stimulated calcitonin may be used as marker of recurrence or metastatic growth only. In MEN 2 after organ-saving operation rate of true recurrence of tumor is high because of genetic damage of medullary layer of adrenal gland.
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PMID:[Diagnosis and treatment of syndrome of multiple endocrine neoplasia type 2]. 1241 13

Multiple endocrine neoplasia (MEN) syndromes comprise the group of heritable endocrinopathies, MEN 1, MEN 2A, and MEN 2B. Primary hyperparathyroidism caused by multiglandular involvement is usually the initial manifestation in MEN 1, occurring in more than 90% of patients. In patients with MEN 2A, hyperparathyroidism develops less commonly and is usually milder than in MEN 1. Advances in genetics and molecular biology aid in confirming the diagnosis and screening relatives who are carriers or at risk for the disease. Surgery plays an important role in the management of hyperparathyroidism in both MEN 1 and MEN 2A,although the timing and extent of surgery are areas of controversy.Long-term follow-up reveals a high rate of recurrent hyperparathyroidism in MEN 1 despite surgical intervention.
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PMID:Hyperparathyroidism and multiple endocrine neoplasia. 1526 11

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

The genotype and phenotype characteristics of Hungarian patients with RET proto-oncogene mutations operated on for hereditary medullary thyroid cancer (MTC) were studied. The genetic screening was performed in two centers and 40 patients with hereditary MTC or C-cell hyperplasia (CCH) from 18 unrelated families were analyzed. One patient having a mutation in exon 16 (Met918Thr) presented with the MEN2B phenotype, six patients from two families had hereditary MTC without pheochromocytoma (pheo) and primary hyperparathyroidism (PHPT), whereas 33 patients from 15 families showed the MEN2A phenotype. Two different mutations were identified in exon 10 (Cys609Tyr and Cys609Ser), five different mutations were present in exon 11 (Cys634Phe, Cys634Arg, Cys634Tyr, Cys634Trp and Cys634Ser), and two different mutations were localized in exon 14 (Val804Met and Val804Leu). Mutations in exon 10 were associated with hereditary MTC (Cys609Tyr) or with MEN2A syndrome (Cys609Ser). Mutations in exon 11 were always associated with the MEN2A phenotype. PHPT was present in one patient with mutation in exon 14 (Val804Met), whereas all other patients affected with mutations in exon 14 had hereditary MTC without PHPT and/or pheos.
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PMID:Genotype-phenotype correlations in Hungarian patients with hereditary medullary thyroid cancer. 1686 47

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 (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 type 2 (MEN2) is a autosomal dominat inherited tumour-syndrome caused by germline activating mutations of the RET proto-oncogene on chromosome 10. It is clinically characterized by the presence of medullary thyroid carcinoma (MTC), bilateral pheochromocytoma and primary hyperparathyroidism (MEN2A) within a single patient. Three distinct clinical forms have been described depending on the phenotype: the classical MEN 2A, MEN 2B, an association of MTC, pheochromocytoma and mucosal neuroma, (FMTC) familial MTC with a low incidence of other endocrinopathies. Each variant of MEN2 results from different RET gene mutation, with a good genotype phenotype correlation. Genetic testing detects nearly 100% 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 extent of surgery are based on a classification into four risk levels utilizing the genotype-phenotype correlations. MEN 2 gives 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:Update multiple endocrine neoplasia type 2. 2008 66

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal, dominantly inherited disease characterized by medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism and is divided into types 2A and 2B. Familial medullary thyroid carcinoma (FMTC) is characterized by the presence of medullary thyroid carcinoma alone in family members and is considered to be one of the subtypes of MEN2. Clinical and genetic data on 505 Japanese patients from 275 MEN2 or FMTC families registered at 54 medical institutions were collected by the MEN Consortium of Japan. The diagnosis was MEN2A in 343 (67.9%) patients, MEN2B in 29 (5.7%), FMTC in 103 (20.4%), and unclassified in 30 (5.9%). Medullary thyroid carcinoma was found in 91.2% of patients (437/479), pheochromocytoma in 45.6% (212/465), and primary hyperparathyroidism in 8.1% (37/457). RET genetic testing was performed in 410 patients, and the germline RET mutation was found in 98.8% (397/402).
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PMID:[Multiple endocrine neoplasia type 2 in Japan: large-scale analysis of data from the MEN consortium of Japan]. 2292 41


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