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

Multiple endocrine neoplasia (MEN) type 2A, or Sipple syndrome, is a rare autosomal dominantly inherited syndrome, which is characterized as combination of medullary thyroid carcinoma, pheochromocytoma, primary hyperparathyroidism, sometimes with rarer inherited disorders like Hirschsprung disease and cutaneous lichen amyloidosis. Syndrome is caused by germinative mutations in c-ret protooncogene, which are typical for different MEN 2 syndromes. We report a clinical case of MEN 2A. A 43-year-old female patient was operated on for pheochromocytoma 7 years after diagnosis and treatment of spread medullary thyroid carcinoma. This is the most common combination of MEN 2A tumors. Diagnosis was based upon clinical data, tumors combinations and analysis of inherited endocrine pathology in first-line relatives. This syndrome has already been diagnosed in Lithuania, but in the last decade after determining the genetic basis of MEN 2 and applying modern genetic examinations in clinical praxis, the strategy of diagnostics and prophylaxis of this syndrome has changed and survival prognosis for patients with this syndrome has improved. Conception of pathogenesis and clinical features of MEN 2A syndrome, genetic selection of inheritors of this syndrome is one more step in early cancer diagnosis, which allows to use cancer prevention measures in time, to apply effective treatment and improve patients' prognosis. Reporting this clinical case of MEN 2A we aimed to pay attention of general practitioners to this rare, but in Lithuania diagnosed too, syndrome and its clinic, diagnostic, and treatment features.
 ...
PMID:[Multiple endocrine neoplasia type 2A]. 1660 64

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.
 ...
PMID:[Genetic screening of multiple endocrine neoplasia type 2: experience of the USP Endocrine Genetics Unit]. 1662 70

Pheochromocytoma may infrequently lead to dilated cardiomyopathy, which may reverse partially or completely after treatment. Progressive dyspnea, palpitations, and paroxysmal attacks of severe hypertension leading to cardiac failure had developed in a 25-yr-old woman. Chest radiography and echocardiography revealed a massive 4-chamber dilatation of the heart with an ejection fraction of 12%. Twenty-four-h urinary vanillylmandelic acid and metanephrine levels were elevated. Magnetic resonance imaging detected a large mass lesion in the right adrenal gland. Oral glucose tolerance testing revealed diabetes mellitus. Medical drug therapy with alpha-blocker, angiotensin converting enzyme inhibitor, beta-blocker, digoxin, and diuretic rapidly improved her cardiac condition. Repeat echocardiogram showed that the left ventricular function had improved substantially. The clinical condition of excess catecholaminemia (and thus, arterial hypertension and the abnormality of the glucose metabolism) subsided with complete resolution of the congestive heart failure following the surgical removal of the tumor. Evaluation for medullary thyroid carcinoma (MTC) revealed an elevated calcitonin level demonstrated by fine needle aspiration biopsy. There were no biochemical evidences for primary hyperparathyroidism. Multiple endocrine neoplasia 2 (MEN 2A) syndrome was diagnosed. An overwhelming secretion of catecholamine might cause severe cardiomyopathy and impair glucose metabolism, as evidenced by the improvement of both conditions following the medical treatment of catecholaminemia and surgical resection of the tumor.
 ...
PMID:Severe reversible dilated cardiomyopathy in a patient with multiple endocrine neoplasia 2A syndrome. 1669 5

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.
 ...
PMID:Genotype-phenotype correlations in Hungarian patients with hereditary medullary thyroid cancer. 1686 47

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.
 ...
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.
 ...
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.
 ...
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).
 ...
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 2A (MEN2A) is an autosomal dominant inherited condition that predisposes to the triad of medullary thyroid cancer (MTC), pheochromocytoma (Pheo), and primary hyperparathyroidism (PHT). Nearly 100% of MEN2A are associated with germ line mutation of the RET proto-oncogene (RET), and DNA-based RET genotype analysis is now considered essential for earlier diagnosis. The first manifestation of MEN2A is most often due to MTC, and less frequently to Pheo. Rarely, MEN2A is recognized during the search for PHT associated conditions. Most patients with primary hyperparathyroidism are asymptomatic, and the focus of the presentation may be the side effects of chronic hypercalcemia, osteoporosis, renal lithiasis, peptic ulcer disease, and hypertension. Hypercalcemic pancreatitis is rare, being an uncommon first manifestation of PHT. Here, we report on a patient who presented recurrent pancreatitis as the first manifestation of MEN2A. In the present case, prompt sequential dosage of calcium, diagnosis of PHT, and genetic analysis would have resulted in pancreatitis prevention and early MEN2A management.
 ...
PMID:Pancreatitis as the first manifestation of multiple endocrine neoplasia type 2A. 1916 90

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.
 ...
PMID:Genotype-phenotype relationship in multiple endocrine neoplasia type 2. Implications for clinical management. 1926 18


<< Previous 1 2 3 4 5 6 7 8 9 Next >>