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)

Multiple endocrine neoplasia type 2 (MEN-2) is an inherited tumor syndrome that includes medullary thyroid carcinoma (MTC), primary hyperparathyroidism, pheochromocytoma and other non-endocrine diseases. Since the first RET missense mutations in association with MEN-2 were identified, RET mutation analysis had a great impact in the clinical management of MEN-2, such as in early diagnosis and treatment of MTC. Presently, early total thyroidectomy provides real cure of MTC for cases in which molecular diagnosis has been performed at early ages. After RET mutation identification, family members should be screened for this mutation by using methods as DGGE, SSCP, restriction enzyme, genetic sequencing or mini-sequencing. In this paper, we briefly review our experience with the direct RET gene sequencing and DGGE approaches. In 50 typical MEN-2 patients analyzed using both methods, we found no false results suggesting that DGGE is a reliable screening method for RET proto-oncogene mutation analysis.
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PMID:[Genetic screening of multiple endocrine neoplasia type 2: experience of the USP Endocrine Genetics Unit]. 1662 70

Since the majority of multiple endocrine neoplasia type 2A (MEN 2A) patients have missense mutations at codon 634 and those with the Cys630 RET genotype mutations are extremely rare, limited clinical information is available about this rare type. We report here three members of one Japanese MEN 2A family with the Cys630Tyr genotype. A 67-year-old woman presented a firm thyroid nodule, and preoperative examination revealed medullary thyroid carcinoma with primary hyperparthyoidism and no pheochromocytoma. At surgery, bilateral medullary thyroid carcinomas and parathyroid adenoma were found. No lymph node metastasis was identified. Computed tomography scans and laboratory examination of blood have shown no evidence of tumor recurrence and no abnormality of parathyroid function during the 4 years after surgery. A 40-year-old man, the proband's son, was shown to have the same RET mutation, underwent total thyroidectomy prophylactically, and only microscopic foci of medullary thyroid carcinoma were found. A 10-year-old boy, the proband's grandson also having the same RET mutation, showed normal basal serum calcitonin level and has been followed up conservatively. To our knowledge, 18 patients of 6 families with the Cys630 mutations have been reported so far. This is only the second reported case with primary hyperparathyroidism. RET 630 mutations might be associated with lower penetrance of primary hyperparthyoidism and pheochromocytoma.
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PMID:A family of multiple endocrine neoplasia type 2A (MEN 2A) with Cys630Tyr RET germline mutation: report of a case. 1752 3

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

The aim of this paper is to report an atypical presentation of MEN2A, in a patient carrying the C634R mutation of the RET-protooncogene. A 41-year-old Tunisian woman was admitted to our department with newly diagnosed hyperglycemia. She had a history of bilateral urinary stone recurrence, managed successfully on two occasions. On physical examination a thyroid node of 1cm on the left side was found. Laboratory evaluation and imaging findings confirmed the diagnosis of primary hyperparathyroidism. During cervicotomy, the parathyroid adenoma was resected and the thyroid node was suspected to be a carcinoma. Total thyroidectomy, with appropriate neck nodal resection, was performed. Histological examination confirmed the diagnosis of parathyroid adenoma and revealed a multifocal and bilateral medullary carcinoma. These findings led to the diagnosis of multiple endocrine neoplasia. DNA-analysis demonstrated a germline Cys634Arg mutation in the RET-protooncogene. During the postoperative follow-up, blood pressure as well as the level of urinary methoxylated metabolites increased progressively. Imaging findings were compatible with the diagnosis of bilateral pheochromocytoma. In conclusion, this case report of MEN 2A linked to a 634 RET mutation was peculiar by its revelation mode (1) hyperparathyroidism moreover linked to an adenoma and (2) associated with diabetes, mechanisms of which are probably multifactorial (familial type 2 diabetes, hypercalcemia, catecholamines excess).
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PMID:Unusual presentation of multiple endocrine neoplasia type 2A in a patient with the C634R mutation of the RET-protooncogene. 1875 92

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

RET codon 609 point mutations are rare and may predispose to aggressive medullary thyroid carcinoma (MTC). In a kindred with 15 carriers of the Cys609Ser RET mutation we observed no MTC before 17 years of age, no lymph node metastases before 30 years and no distant metastases before 60 years. Two patients developed pheochromocytoma and one had primary hyperparathyroidism as the first sign of the syndrome. In conclusion, at variance from what already known, in this large kindred the Cys609Ser RET mutation predispose to a scarcely aggressive, highly penetrant MTC and a low penetrance of pheochromocytoma and primary hyperparathyroidism.
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PMID:Characterization of the largest kindred with MEN2A due to a Cys609Ser RET mutation. 1947 97

Primary hyperparathyroidism (PHPT) is one of the most frequent endocrinological disorders. In PHPT, there is abnormal regulation of parathyroid hormone (PTH) by calcium, which translates into inappropriately high PTH secretion for the level of calcemia. Most patients with PHPT have increased serum PTH levels, with increases in serum calcium, especially ionic calcium. The incidence of PHPT rises with age, the mean age at diagnosis being 55 years. This disorder affects mainly women with a female-to-male ratio of approximately 3:1. Most (80-85%) of cases are produced by chief cell parathyroid adenomas. The factors involved in the genesis of PHPT are largely unknown. Gene mutations affecting oncogenes (cyclin D1, RET) or tumor suppressor genes (MEN1, HRPT2) are found in a minority of cases. These mutations are especially important in familial forms of PHPT, such as multiple endocrine neoplasia syndrome (MEN1, MEN2A). No mutations affecting the calcium-sensing receptor (CaSR) or vitamin D receptor (VDR) gene have been found. In parathyroid adenomas and hyperplasias, there may be abnormal Wnt signalling, with mutations of the coreceptor LRP5 gene and beta-catenin accumulation. Expression of the Klotho protein, which intervenes in serum calcium regulation, is reduced. Low levels of 25(OH) vitamin D frequently coexist, although whether vitamin D deficiency plays a pathogenic role in PHPT is unknown.
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PMID:[Concept, etiology and epidemiology of primary hyperparathyroidism]. 1962 54

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

Primary hyperparathyroidism (HPT) results from the excessive secretion of parathyroid hormone from parathyroid tumours. While most HPT is sporadic, it is associated with a familial syndrome in a minority of cases. The study of these syndromes has helped define the pathophysiology of both familial and sporadic parathyroid neoplasms. Investigation of kindred with multiple endocrine neoplasia type 1 (MEN1) and the hyperparathyroidism-jaw tumour syndrome (HPT-JT) led to the discovery of the tumour suppressor genes MEN1 and HRPT2. We now recognise that somatic mutations in MEN1 and HRPT2 tumour suppressor genes are frequent events in sporadic parathyroid adenomas and carcinomas, respectively. Parathyroid tumours in the MEN2A syndrome result from mutational activation of the RET oncogene. The CCND1/PRAD1 oncogene was discovered by analysis of sporadic parathyroid tumours. Studies of familial isolated HPT and analysis of chromosomal loss and gain in parathyroid tumours suggest that other genes relevant to parathyroid neoplasia await identification.
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PMID:Clinical and molecular genetics of parathyroid neoplasms. 2083 39


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