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 major phenotypes of multiple endocrine neoplasia type 1 (MEN 1) consist of three lesions characterized by hyperparathyroidism, pituitary tumors, and endocrine pancreatic tumors. The endocrine pancreatic tumors are a significant cause of disease-related mortality in MEN 1. Although symptomatic pancreatic tumors such as insulinoma and gastrinoma should be resected, the management of asymptomatic pancreatic tumors is not established. In asymptomatic pancreatic tumors, the most important factor is the propensity for malignant transformation of the tumors. Although there are no means to foresee it, the size of the pancreatic tumors might be predictive of malignant development in MEN 1. We report here a patient with MEN 1 who had a large asymptomatic pancreatic tumor. The patient (72-yr-old man) was diagnosed with primary hyperparathyroidism and underwent a total parathyroidectomy. Genetic examination showed a germline mutation of the MEN1 gene (E45G). Abdominal magnetic resonance imaging revealed a large (>6 cm) tumor with a heterogeneous pattern in the tail of the pancreas. No metastases of the tumor were evident. Serum levels of insulin, gastrin, and glucagon were normal, and the patient had no symptoms. Operative resection was performed, and microscopic examination revealed that the tumor was an islet cell tumor stained with multiple hormones. This is a case indicating that asymptomatic pancreatic tumors associated with MEN 1 might be indolent independent of their size.
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PMID:Large and asymptomatic pancreatic islet cell tumor in a patient with multiple endocrine neoplasia type 1. 1121 36

Primary hyperparathyroidism (pHPT) is commonly seen in postmenopausal women. Along with the clinical characterisation of the disease, studies of molecular genetics have contributed to increased understanding of the etiology of pHPT. Genetic association studies have revealed that certain vitamin D receptor polymorphisms relate to the development of sporadic pHPT. A new type of familial pHPT was recently discovered. Studies of parathyroid adenomas have demonstrated that the tumor suppressor gene MEN1 and the oncogene cyclinD1 are of importance for the tumorigenesis.
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PMID:[Primary hyperparathyroidism is common among postmenopausal women. Identification of genetic risk factors can contribute to individualized treatment]. 1140 99

We report the kindred with familial isolated hyperparathyroidism with parathyroid cancer. The proband was diagnosed as having primary hyperparathyroidism at age 43. The same disorder was also found in his daughter who had low bone mass. His son was found to have primary hyperparathyroidism by family screening. The pathological diagnosis of the resected parathyroid in both father and daughter was parathyroid cancer, and that in son was parathyroid adenoma. The right lower gland of the proband and the left lower gland of the son were present in thymus. No mutations were found in the sequences of MEN1 gene, hence gene(s) other than MEN1 gene may have contributed to the malignant potency in our cases.
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PMID:A case of familial isolated hyperparathyroidism with ectopic parathyroid cancer. 1160 67

Loss of heterozygosity (LOH) in the MEN1 region on chromosome 11q13 and MEN1 gene mutations have been found in a subset of sporadic parathyroid tumors. The question of whether these genetic abnormalities in the parathyroid tumors might influence the clinical and biochemical characteristics of primary hyperparathyroidism (PHPT) remains to be elucidated. The aim of the present study was to correlate the presence of MEN1 gene alterations in PHPT tumors with the clinical phenotype. Using microsatellite analysis for LOH at 11q13 and DNA sequencing of the coding exons, the MEN1 gene was studied in 38 parathyroid tumors of patients with sporadic PHPT. Fourteen tumors showed LOH at 11q13, and mutations of MEN1 gene were detected in 7 cases. The clinical and biochemical characteristics of patients were unrelated to the presence or absence of LOH and/or MEN1 gene mutations. In conclusion, MEN1 gene alterations are rather common in sporadic PHPT and their presence does not correlate with the clinical manifestations of the disease.
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PMID:MEN1 gene alterations do not correlate with the phenotype of sporadic primary hyperparathyroidism. 1210 21

Multiple parathyroid tumors, as opposed to hyperplasia, have been reported in a subset of patients with sporadic primary hyperparathyroidism (PHPT). It is not clear whether these multiple tumors are representative of a neoplastic process or whether they merely represent hyperplasia that has affected the parathyroid glands differentially and resulted in asynchronous growth. The molecular genetic techniques of comparative genomic hybridization (CGH), loss of heterozygosity (LOH), and MEN1 mutation analysis were performed on a series of five patients with multiglandular PHPT, each of which had two parathyroid tumors removed. Analysis of these multiple parathyroid tumors from patients with PHPT revealed that independent genetic events were associated with the development of a subset of these tumors. The DNA sequence copy number changes, identified by CGH analyses, either involved different chromosomal regions in the paired glands of a patient (two patients), or those regions implicated in one gland were not changed in a second gland from the same patient (two patients). Each of the three patients exhibiting LOH demonstrated different changes between the paired glands. Where LOH was detected in one gland from a patient, the other gland from the same patient either exhibited no allelic loss or the loss detected was in another region. Each of the three tumors exhibiting LOH at 11q13 was found to contain a somatic MEN1 mutation in the remaining allele, however these mutations were not present in the germline or in the paired gland from the same patient. Although it is possible that a separate series of genetic changes has arisen randomly in two separate glands within the same individual, it seems more likely that the development of these multiple tumors has arisen because of the involvement of other unknown factors. These factors may be genetic [such as the involvement of one or more germline mutations in an unknown low-penetrance gene(s), germline mosaicism or alterations in calcium-sensing receptor gene(s)], epigenetic, physiological, or environmental.
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PMID:Independent genetic events associated with the development of multiple parathyroid tumors in patients with primary hyperparathyroidism. 1236 3

Genetic abnormalities responsible for primary (pHPT) and secondary hyperparathyroidism (sHPT) are not well described, especially those underlying the autonomous and refractory behaviour of glands from uremic patients with glandular hyperplasia and nodular growth. Comparative Genomic Hybridization (CGH) is a molecular cytogenetic technique based on a double-color in situ fluorescent analysis, allowing a global description of gains and losses of genomic material. It is a useful tool that localizes unstable genetic areas whose alteration could modify the expression of one or several genes related to the pathology in study. Results on primary hyperparathyroidism adenomas have shown a series of genetic changes correlating with areas where genes related to pHPT are located, such as MEN1 and cyclin D1. A large number of chromosomal aberrations in glands from patients with secondary hyperparathyroidism have also been found, and although some of them are common with those described for primary hyperparathyroidism, most of them are located in different areas or in a different proportion. These results confirm that although severe sHPT hyperplasias can evolve into neoplasias similar to pHPT adenomas, both parathyroid alterations must be considered, from a genetic point of view, as unrelated.
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PMID:[Chromosome abnormalities in hyperparathyroidism: utility of comparative genomic hybridization in the study of parathyroid hyperplasias]. 1277 45

We report here a dialysis patient with secondary hyperparathyroidism who had a history of parathyroidectomy for primary hyperparathyroidism 27 years previously. The patient was a 48-year-old male. In 1974, he was diagnosed as having primary hyperparathyroidism and an adenoma was completely resected in the Department of Urology, Osaka University Hospital. In 1997, he started hemodialysis for chronic renal failure by diabetic nephropathy. Since his intact-PTH was high, we started intravenous vitamin-D pulse therapy, but intact-PTH did not decrease. We could not detect any parathyroid glands by ultrasonography and 201TlCl-99mTcO4-scintigraphy around the thyroid gland. Finally, chest-CT and 99mTc-MIBI scintigraphy revealed a ectopic parathyroid gland in the mediastine, and the ectopic parathyroid gland was successfully resected in July, 2001. In order to distinguish whether the resected ectopic parathyroid gland was due to primary adenoma or secondary hyperplasia, we used an immunohistochemical technique to examine the expression of PRAD1/cyclin D1, Ki67, and p27 and sequence analysis of the MEN1 gene. As a result, the labeling index (LI) of PRAD1/cyclin D1 was 4, LI of Ki67 was 36, and LI of p27 was 257. Moreover, germline-mutation and somatic-mutation of MEN1 gene was not detected. These findings suggested that the resected parathyroid gland was a nodular hyperplasia of secondary hyperparathyroidism. In conclusion, immunohistochemical findings of parathyroid tissue and sequence analysis of MEN1 gene could be useful for the differential diagnosis of primary adenoma and secondary hyperplasia.
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PMID:[A hemodialysis patient with secondary hyperparathyroidism in whom primary parathyroid adenoma was resected 27 years previously]. 1463 67

A rare case of primary hyperparathyroidism associated with primary aldosteronism and breast cancer is reported. A 44-year-old woman was admitted to our hospital to undergo surgical removal of breast cancer. She had hypertension with low serum potassium, and slightly but significantly elevated serum calcium levels. Further studies demonstrated an enlarged left superior parathyroid gland and a left aldosterone-producing adrenocortical adenoma. Blood pressure was controlled with spironolactone and nifedipine, and left mastectomy was done for breast cancer. The pathological diagnosis was scirrhous breast carcinoma. Although the postoperative course was uneventful, her serum calcium gradually and progressively rose to higher levels. Left superior parathyroidectomy and left adrenalectomy were then performed simultaneously. The pathological diagnoses of the resected parathyroid gland and adrenal gland were parathyroid chief cell adenoma and adrenocortical adenoma with hyperplasia of zona glomerulosa, respectively. To clarify if the occurence of these tumors may be related to MEN1 gene mutations, we analyzed MEN1 gene in this patient, and found a loss of heterozygosity of the MEN1 locus in the parathyroid adenoma and breast cancer. Thus, we conclude that an alteration of the MEN1 gene and/or another tumor suppressor gene located at the MEN1 locus on chromosome 11q13 may be responsible for the development of parathyroid adenoma and breast cancer in our patient suggesting that the clinical spectrum of MEN1 might include breast cancer. In addition, serum calcium should be interpreted with caution in primary aldosteronism, because hypercalcemia may be masked in the presence of aldosterone excess.
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PMID:Primary hyperparathyroidism associatiated with aldosterone-producing adrenocortical adenoma and breast cancer: relation to MEN1 gene. 1516 74

We report an unusual presentation of multiple endocrine neoplasia type 1 (MEN 1) in a young woman who was subsequently proven to have a novel mutation of the MEN1 gene. The young patient, aged 25 years, was investigated for abdominal discomfort and left upper abdominal pain. Her family history was unremarkable, except an unknown disorder of her father causing early death. Abdominal ultrasonography (USG) and computed tomography revealed a giant pancreatic tumor measuring 10 cm in diameter. The diagnosis of a clinically nonfunctioning pancreatic neuroendocrine tumor was established by clinical and other studies, including USG-guided aspiration biopsy and octreotide scintigraphy, and the patient underwent a distal pancreatectomy. Histology proved a well-differentiated multinodular neuroendocrine tumor of the pancreas. During surgery, a subcutaneous lipoma was also removed from the abdominal wall. Two years later, the patient developed primary hyperparathyroidism, and two enlarged parathyroid glands were surgically removed. Magnetic resonance imaging of the pituitary gland was normal. Screening for MEN1 gene mutation by temperature gradient gel electrophoresis revealed heterozygosities in exons 3, 8, and 9, while direct sequencing indicated a novel germline mutation (C354X) resulting in a stop codon in exon 8 and polymorphisms in exon 3 (R171Q) and exon 9 (D418D and L432L). Genetic screening revealed no mutation in living family members. Our unusual case suggests that a multinodular pancreatic neuroendocrine tumor in a young patient may justify screening for MEN 1 syndrome, even in the absence of other endocrinopathy or family history.
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PMID:Unusual presentation of multiple endocrine neoplasia type 1 in a young woman with a novel mutation of the MEN1 gene. 1520 94

As molecular biology and genetic mapping receive wider application to human disease, genetic alterations have been identified with increased frequency in some patients with primary hyperparathyroidism(HPT). These alterations have been found in molecules related to cellular signaling and growth (RET proto-oncogene)and in tumor suppressors that control cell cycle progression and gene transcription (cyclin D1 and the MEN1 gene product. Although primary HPT can usually be treated surgically without knowledge of which specific genetic alteration has occurred, this information may assist clinicians in identifying which patients will go on to develop multiglandular or recurrent disease. In addition,such an approach would facilitate more appropriate postoperative surveillance, as well as counseling and screening of family members who may be at high risk for HPT.
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PMID:Molecular biology of primary hyperparathyroidism. 1526 18


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