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 gene for multiple endocrine neoplasia type 1 (MEN1), an inherited predisposition to neuroendocrine neoplasm of the parathyroid glands, the pancreatic islet parenchyma, and the anterior pituitary gland, was recently mapped to chromosome 11q13 based on genetic linkage in families. We now show that the pathogenesis of MEN1-associated parathyroid lesions involves unmasking of a recessive mutation at the disease locus and that sporadic primary hyperparathyroidism shares the same mechanisms. By examination of allele losses in MEN1-associated lesions, we could define deletions of chromosome 11 and map the MEN1 locus to a small region within chromosome band 11q13, telomeric to the PYGM locus. In contrast, a low incidence of deletions involving the MEN1 gene was found in sporadic pituitary adenomas.
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PMID:Localization of the MEN1 gene to a small region within chromosome 11q13 by deletion mapping in tumors. 196 41

The nuclear DNA content of paraffin-embedded parathyroid tumors from 49 patients with proven primary hyperparathyroidism was determined by flow cytometric analysis. The lesions included 14 primary and 11 locally recurrent or metastatic lesions from 16 carcinoma patients, 28 single adenomas from 28 patients, and 15 hyperplastic glands from five patients with familial multiple endocrine neoplasia type 1. No abnormal DNA stemline was found in any of the hyperplastic glands. One (3.6%) of the adenomas was aneuploid. There was no difference in ploidy patterns between the primary and recurrent lesions of the carcinomas and five (31%) of the carcinomas expressed aneuploidy. Four of the five patients with aneuploid carcinoma had recurrences including pulmonary metastases. One of them died of this disease 12 years after the initial operation, and all except one of the others are hypercalcemic even after removal of the successive recurrent or metastatic tumors. Of the 11 patients with diploid carcinoma, four had either local recurrence or pulmonary metastasis. Two of them are living with normocalcemia 3 and 6 years, respectively, after removal of the recurrent tumors and the others are alive with mild hypercalcemia. The remaining seven patients with diploid carcinoma, however, have no recurrence 2 to 5 years after the initial operation. Thus aneuploid parathyroid carcinomas are likely to show more malignant behavior than those with a diploid DNA pattern. All of the patients with adenoma and hyperplasia have been normocalcemic after a mean follow-up interval of 37 months. This study indicates that flow cytometric analysis of nuclear DNA content is a valuable adjunct to histologic examination in the diagnosis of parathyroid carcinoma and the prediction of the clinical outcome.
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PMID:Flow cytometric DNA analysis of parathyroid tumors with special reference to its diagnostic and prognostic value in parathyroid carcinoma. 196 27

In the differential diagnosis of endocrine symptoms, the autosomal dominant multiple endocrine neoplasia (MEN) syndromes are rare but important. We found seven index cases of MEN-I in 176 patients with adenomas of the anterior pituitary and 26 patients with primary hyperparathyroidism. Of 23 cases of medullary thyroid carcinoma and eight cases of pheochromocytoma, 14 patients are classified as MEN-IIa and one as MEN-IIb. Family screening identified six MEN-I and seven MEN-II cases among 32 individuals examined. Because of autosomal dominant inheritance and sometimes-delayed manifestation of the complete syndrome, screening of healthy and affected family members should be repeated at least every other year.
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PMID:The importance of multiple endocrine neoplasia syndromes in differential diagnosis. 197 10

A total of 79 consecutive patients with pituitary tumours were screened for multiple endocrine neoplasia type 1 (MEN-1). The 79 patients included 21 patients with acromegaly, nine with Cushing's disease, 18 with prolactinomas, three with mixed pituitary adenomas (GH and PRL), and 28 patients with no detectable hypersecretion of hormones. The screening consisted of: (1) a family history, (2) a uniform medical history of the patient using a standard questionnaire, and (3) hormonal evaluation including measurements of the serum levels of insulin, gastrin, glucagon, somatostatin, vasoactive intestinal polypeptide and pancreatic polypeptide. Ionized calcium and glucose concentration in serum were also measured. We found no patients with the MEN-1 syndrome. In one patient, we found a transient elevation of serum concentrations of pancreatic polypeptide for which we have no explanation. In another patient, the serum gastrin concentration was elevated secondary to achlorhydria. No other endocrine disorders were found, and no patients had relatives with recognized endocrine pancreatic tumours, primary hyperparathyroidism (HPT), or pituitary adenomas.
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PMID:Screening for multiple endocrine neoplasia type 1 in patients with recognized pituitary adenoma. 198 64

The recent chromosomal mapping of the genes for two different autosomal dominant inherited predispositions to multiple endocrine neoplasias promises to be a significant breakthrough for the understanding of the pathogenesis of such lesions. Multiple endocrine neoplasia type 1 (MEN1) associates primary hyperparathyroidism, lesions of the endocrine pancreas and pituitary adenomas. The first hint that the MEN1 gene is localized on chromosome 11 came from the finding of allele losses in MEN1 associated tumours. Subsequent genetic linkage analysis to restriction fragment length polymorphism (RFLP) markers assigned the gene to chromosome band 11q13. MEN2A is characterized by medullary thyroid carcinoma and phaeochromocytoma. The disease locus was localized to the centromeric region of chromosome 10 by genetic linkage. For both syndromes genetic linkage maps of the flanking regions have been established, and a set of RFLP markers is now available for premorbid identification of gene carriers in affected families. Analysis of allele losses showed that tumorigenesis of parathyroid and pancreatic lesions results from unmasking of a recessive mutation at the MEN1 locus, and by deletion mapping the tentative MEN1 region was restricted to a few million base pairs. In contrast, such losses appear to be relatively rare in MEN2A associated lesions.
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PMID:Multiple endocrine neoplasia. 198 11

The previous cytometric studies on parathyroid tumors have provided conflicting data regarding the relationship between DNA content and histopathology, resulting from differences in technical methods and data analysis. This study measured nuclear DNA of parathyroid tumors by flow cytometry in fresh material and determined whether DNA aneuploidy really assists in making a pathologic diagnosis of carcinoma or not. From May 1987 through April 1989, 65 consecutive patients operated on for primary hyperparathyroidism had DNA analysis of the freshly excised parathyroid tumors. Three of the patients had metastatic lesions of parathyroid carcinoma in the lung, cervical lymph nodes, and lung and mediastinal lymph nodes, respectively. Pathologic classifications of the lesions from the other 62 patients were 54 adenomas, four carcinomas, and four hyperplasias. In all the latter patients, hyperplasia was associated with a multiple endocrine neoplasia syndrome. Unequivocal evidence of aneuploidy was found in all of the metastatic lesions and 60% of the primary lesions of the carcinomas, in 9% of the adenomas and in 50% of the hyperplasias. Therefore, parathyroid carcinomas were more apt to be aneuploid than were adenomas (P = 0.0015, both-sided testing). In each of the cases of aneuploid hyperplasia, a small aneuploid peak was found. The high incidence of aneuploidy in patients with multiple endocrine neoplasia type 1 may indicate the presence of clonal heterogeneity of hyperplastic glands and the presence of an abnormal subset of cells that have malignant potential. Cell distribution analysis did not provide any significant information beyond ploidy level. In conclusion, DNA flow cytometric analysis of DNA ploidy patterns is a valuable adjunct to the histopathologic diagnosis of parathyroid neoplasms.
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PMID:Flow cytometric DNA analysis of parathyroid tumors. Implication of aneuploidy for pathologic and biologic classification. 220 8

Two patients with the rare association of Cushing's syndrome and primary hyperparathyroidism are reported. Initially, both patients suffered from Cushing's syndrome due to adrenal cortical adenomas with typical features and laboratory findings. Five years after treatment of the Cushing's syndrome by removal of the tumor, asymptomatic mild hypercalcemia was incidentally noticed in both patients, which suggested the occurrence of primary hyperparathyroidism. An enlarged parathyroid gland was removed surgically in both cases and was histologically shown to be a parathyroid adenoma. The levels of serum calcium returned to normal after parathyroidectomy. Papillary adenocarcinoma of the thyroid in one patient and adenomatous goiter in the other were also incidentally detected at operation. These findings suggest that Cushing's syndrome resulting from an adrenal cortical adenoma may be another presentation of multiple endocrine neoplasia type I.
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PMID:Hyperparathyroidism associated with Cushing's syndrome due to an adrenal cortical adenoma. 222 44

Chromogranin-A (CgA), also termed secretory protein-I, is an acidic glycoprotein that is synthesized and secreted by cells of the diffuse endocrine and neuroendocrine system. Several previous studies had suggested that plasma levels of CgA were elevated in patients with primary hyperparathyroidism. In the present study we sought to examine expression of the CgA gene in human parathyroid tissue from patients with primary hyperparathyroidism. We characterized the mRNAs coding for CgA and beta-actin in parathyroid tissue fragments obtained from 12 patients with parathyroid adenomas, 11 patients with familial multiple endocrine neoplasia type I (FMEN I) with parathyroid hyperplasia, and 11 normal subjects. The mRNAs were detected and analyzed by dot and Northern blot hybridization using cDNA probes. CgA mRNA transcripts of 2.1 kilobases were detected in normal and pathological parathyroids. Similarly, beta-actin mRNA species of 2.1 kilobases was present in all tissues. The relative level of parathyroid tissue CgA mRNA, calculated as the CgA/beta-actin mRNA ratio, was 73 +/- 18 in parathyroid adenoma, 73 +/- 20 in FMEN I, and 100 +/- 9 in controls (mean +/- SE; expressed as a percentage of the control reference group value). There were no significant differences among the steady state levels of CgA mRNA levels in these three groups (F = 0.98; P = 0.39). These results demonstrate that expression of CgA mRNA is qualitatively and quantitatively normal in parathyroid tumors from patients with FMEN I and parathyroid adenoma.
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PMID:Expression of chromogranin-A messenger ribonucleic acid in parathyroid tissue from patients with primary hyperparathyroidism. 234

The diagnosis of multiple endocrine neoplasia (MEN) in patients with presumed hyperparathyroidism has important ramifications for patient management especially since as many as 20% of patients with hyperparathyroidism may have associated MEN. Gut hormone levels were measured before and after surgery in 28 patients who underwent resection of a single parathyroid adenoma for biochemical or clinical evidence of hyperparathyroidism. The mean serum calcium level was 11.9 +/- 0.2 mg/dl before surgery and 9.3 +/- 0.3 mg/dl after surgery (p less than 0.001). Two or more hormone levels were elevated in 32% of patients before surgery and 21% after surgery. The same hormone abnormalities (pancreatic polypeptide [PP] and gastrin) occurred 56% of the time. Of elevated preoperative levels of PP, 91% were in the normal range after surgery. In patients with elevated preoperative PP levels, the postoperative level of PP decreased by an average of 64% of the preoperative level. In 27% of patients the level increased more than double the preoperative value. In two of four patients with high levels of PP after surgery the serum calcium level failed to fall. Of 18 patients whose PP levels fell, 17 had a fall in serum calcium levels. Of six patients whose PP levels rose, four had a significant fall in calcium levels. There was no correlation between the absolute levels or the decremental change of calcium and the change in PP. Several abnormalities in gut hormone secretion occur in patients with primary hyperparathyroidism and a parathyroid adenoma. An elevated serum level of PP does not signify MEN syndrome and must be reevaluated after resection of the parathyroid adenoma. Failure of adequate tumor resection is attended by persistent elevation of serum calcium and PP levels.
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PMID:Hyperparathyroidism and gastroenteropancreatic hormone levels. 241 70

Endocrine tumors of the pancreas are rare disorders that can cause life-threatening symptoms related to the excessive hormonal secretion and the malignant nature of the neoplasm. In addition, these neoplasms can present as part of familial endocrinopathy syndromes, especially multiple endocrine neoplasia type 1 (MEN-1). The initial step in evaluation of a patient with an islet cell tumor is definitive diagnosis of the hormonal syndrome that usually can be achieved biochemically. The next step is to reverse the life-threatening hormonal syndrome medically to allow radiographic localization of the islet cell neoplasm and to prepare the patient for elective surgery. In general, the goal of surgery is to accurately stage the extent of disease and to totally resect the tumor resulting in complete correction of the excessive hormonal condition and freedom from malignant progression of the tumor. Resection of the neoplasm should encompass metastatic disease in select individuals in whom complete or nearly complete resection can be achieved. Surgery must be performed with acceptable morbidity and mortality because the medical management of the excessive hormonal secretion in most patients is adequate and the progression rate of malignant islet cell carcinomas is usually slow. Patients with MEN-1 should be identified during evaluation by careful history and should be managed differently. These patients always have multiple islet cell tumors and may have malignant islet cell carcinomas. Large (3 cm) imageable pancreatic neoplasms in patients with MEN-1 should be resected because nearly 50 per cent are malignant. Zollinger-Ellison syndrome in patients with MEN-1 and primary hyperparathyroidism is best managed initially by surgery directed at the hyperparathyroidism. It may be impossible to correct the biochemical abnormalities of Zollinger-Ellison syndrome by islet cell tumor resection in patients with MEN-1. However, insulinoma or VIPoma syndromes can often be corrected by islet cell tumor resection. Portal venous sampling for hormones may be helpful in determining what hormone a specific tumor is secreting.
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PMID:The role of surgery in the management of islet cell tumors. 255 34


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