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 one (MEN 1) is characterized by tumours of the parathyroid glands, pancreatic islet cells and the anterior pituitary and follows an autosomal dominant pattern of inheritance. We report identical twins born to a family known to have the MEN 1 syndrome. The twins were identical until puberty. The first twin underwent puberty normally; the second, however, suffered an early pubertal arrest and was subsequently found to have a prolactinoma. Both were also subsequently shown to have primary hyperparathyroidism. Genetic studies have since confirmed the twins identical for the affected haplotype and show that this is inherited from the father who also has MEN 1. The gene for MEN 1 has now been localized to the long arm of chromosome 11. The current hypothesis is that expression of the syndrome involves two separate genetic mutations. The first mutation is inherited and thus present in all cells but the tumour manifests itself in the endocrine tissue only after a second mutation that represents elimination of the normal allele. In the case described the twins are proven genetically identical. The marked phenotypic difference between the two must, by inference, represent a second somatic mutation and is further supportive evidence of the two-mutation model of tumour expression.
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PMID:Prolactinoma presenting in identical twins with multiple endocrine neoplasia type 1. 884 98

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disease characterized by neoplasia involving the parathyroid glands, the endocrine pancreas, the duodenum, and the anterior pituitary. The most commonly involved gland is the parathyroid gland, which has been found to be abnormal in 90% to 95% of all patients with MEN 1. The disease process is invariably multiglandular and histologically described as either hyperplasia or multiple adenoma, although the histological distinction between the 2 entities remains difficult and controversial. The prevalence of MEN 1 is approximately 0.002 in 100, whereas the prevalence of sporadic primary hyperparathyroidism due to a solitary adenoma is estimated to be as high as 1 in 100.(2.3) We report herein the first case of sporadic primary hyperparathyroidism in the setting of MEN 1 based on clinical, biochemical, pathological, and genetic studies.
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PMID:Sporadic primary hyperparathyroidism in the setting of multiple endocrine neoplasia type 1. 891 Dec 66

A 49-year-old female with multiple endocrine neoplasia (MEN) type 1 associated with malignant lymphoma, lipoma, functioning adenomatous goiter, non-functioning adrenal tumor, polyneuropathy, postoperative primary hyperparathyroidism, and hepatitis B virus was a human T lymphotropic virus type 1 (HTLV-1) carrier. She underwent parathyroidectomy for primary hyperparathyroidism at age 44. At age 49, examinations of the enlarged para-aortic lymph nodes revealed diffuse small non-cleaved B cell lymphoma in stage II, and other various complications were also found. Multiple tumorigenetic factors were considered to be involved in the present case.
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PMID:Multiple endocrine neoplasia type 1 associated with malignant lymphoma and other complications. 896 95

Acromegaly is uncommon in kindreds with multiple endocrine neoplasia type 1 (MEN1), whereas primary hyperparathyroidism (PHP) has the highest penetrance of any endocrinopathy. We report an unusual MEN1 kindred with frequent expression of pituitary tumors and a low penetrance of PHP. Four members were found to have disease: PHP in generation I, acromegaly (2 cases) in generation II, and hyperprolactinemia associated with a pituitary tumor in generation III. There was no evidence for PHP in 1 patient with acromegaly (age 60 yr), the patient with hyperprolactinemia and the pituitary tumor (age 22 yr), and 1 asymptomatic obligate carrier (age 50 yr). Screening of 26 members revealed the possible diagnosis of PHP in 1 family member in generation II and possible early acromegaly in 2 members of generation III with elevated serum concentrations of insulin-like growth factor I and insulin-like growth factor-binding protein-3 but normal patterns of pulsatile GH release. Although the predisposing genetic defect in typical MEN1 families has previously been mapped to chromosome location 11q13 without evidence of heterogeneity among the 87 families analyzed, linkage of disease in this family to the MEN1 region is unlikely based on haplotype analysis. Localization of the gene(s) responsible for disease in such atypical families may aid in the understanding of the pathogenesis of MEN1. In addition, further study of the earliest changes in patterns of pulsatile GH release in familial acromegaly may allow more insight into the pathogenesis and natural history of this disease.
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PMID:A kindred with a variant of multiple endocrine neoplasia type 1 demonstrating frequent expression of pituitary tumors but not linked to the multiple endocrine neoplasia type 1 locus at chromosome region 11q13. 902 41

Polymorphisms in the vitamin D receptor (VDR) gene have been hypothezised to interfere with VDR expression. VDR alleles (Bb, Aa and Tt) were examined in 254 Caucasian patients with sporadic primary hyperparathyroidism (spHPT, n = 206), HPT of multiple endocrine neoplasia type 1 (MEN-1; n = 17), and HPT of uremia (n = 31). In comparison to age- and sex-matched controls, the b, a and T alleles were overrepresented in 100 menopausal females with spHPT (p = 0.006-0.0004), equivalent to an odds ratio of 2.6-3.4 for spHPT in homozygotes for the b, a and, T alleles. The association between VDR genotypes and spHPT was restricted to female patients and those with parathyroid adenoma (p = 0.0006-0.0001), whereas HPT of MEN 1 and uremia seemed unrelated to the VDR polymorphisms (p = 0.26-0.96). The results suggest that the VDR alleles b, a, and T are novel risk factors in the essentially uncharacterized pathogenesis of spHPT.
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PMID:Vitamin D receptor alleles b, a, and T: risk factors for sporadic primary hyperparathyroidism (HPT) but not HPT of uremia or MEN 1. 907 Feb 72

55 prospectively documented patients aged 20-84 (median 67) years (47 women, 8 males) underwent surgery for primary hyperparathyroidism (pHPT). The most frequent symptoms and associated conditions were nephrolithiasis (42%) and neuropsychiatric symptoms (39%). Only one case of asymptomatic and one case of "normocalcemic" pHPT were found in this series. 47 patients (89%) were cured following initial neck exploration, and 3 further patients (6%) were cured by a second operation. Reoperation also led to cure in 2 patients operated on elsewhere in the first instance. 6 patients (11%) had double adenoma (bilaterally) and 36% of the adenomas had an ectopic location, with an intrathyroidal adenoma in 2 cases. In 2 patients sternotomy was carried out. Persistent pHPT was observed in 3 patients (following initial exploration in 2 cases and reoperation in one). These patients had a supernumerary adenomatous gland with ectopic location in 2 cases and a double adenoma with ectopic position of one adenoma in a further case. One 80-year-old patient died post-operatively from intestinal ischemia. 2 patients had permanent postoperative hypoparathyroidism; in no case was a permanent recurrent laryngeal nerve palsy observed. Bilateral parathyroid exploration with thyroid mobilization by capsular dissection is the procedure of choice for pHPT. In 2 patients with the MEN 2A-syndrome and with medullary thyroid carcinoma thyroidectomy, lymphadenectomy and autotransplantation of normal parathyroids to the arm was performed, with normal parathyroid function in both cases.
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PMID:[Primary hyperthyroidism 1996]. 915 29

Multiple endocrine neoplasia type 1 (MEN-1) is characterized by primary hyperparathyroidism, endocrine pancreatic-duodenal and anterior pituitary tumors. The diagnosis is challenging and involves the exclusion of other endocrine neoplasia syndromes with overlapping features. The predisposing genetic defect was assigned to chromosomal region 11q13 based on linkage analysis. Combined tumor and pedigree genotype analysis showed that allele losses in pancreatic, parathyroid and pituitary tumors eliminated the wild-type allele at the 11q13 loci, suggesting inactivation of a tumor suppressor gene in this region. A 5-Mb integrated map of the region has been established by the European consortium on MEN-1. Based on this mapping the critical interval was restricted to 2 Mb, a region within which eight candidate genes are located.
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PMID:Multiple endocrine neoplasia type 1 and the search for the genetic trigger. 916 50

Multiple endocrine neoplasia type 2 (MEN-2) is an inherited multiglandular disease with age-related penetrance and variable expression. The prognosis of MEN-2 is linked to the carcinological evolution of medullary thyroid cancer (MTC), which depends mainly on the stage of discovery, and to the incidents related to pheochromocytomas. The emphasizes the need for early diagnosis and management of MEN-2. Since 1993, mutations evidenced on the protooncogene RET have allowed subjects at risk to be identified, thus leading to a three-step management of these patients. (1) For all the potentially affected members of a MEN-2 family, screening by molecular genetics of the ret gene enables one to identify the subjects at risk who bear the mutation. When no mutation is observed, a linkage analysis study may be proposed. (2) In the subjects at risk, early screening for the various types of endocrine lesions may then start in childhood and be performed using specific biological markers of MTC, pheochromocytoma and primary hyperparathyroidism, and particularly, basal and pentagastrin-stimulated calcitonin measurement, which is known to be the most sensitive marker for the monitoring of MTC. (3) This step of biological investigations enables the earliest possible treatment of any endocrine lesion detected before it is expressed clinically, thus improving the prognosis of MEN-2. When genetic screening cannot be performed, only annual clinical and biological monitoring remain available in all members of a family affected with MEN-2.
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PMID:Multiple endocrine neoplasia type 2: management of patients and subjects at risk. French Study Group on Calcitonin-Secreting Tumors (GETC). 916 55

Primary hyperparathyroidism is a common disorder with an annual incidence of approximately 0.5 in 1,000 (ref. 1). In more than 95% of cases, the disease is caused by sporadic parathyroid adenoma or sporadic hyperplasia. Some cases are caused by inherited syndromes, such as multiple endocrine neoplasia type 1 (MEN1; ref. 2). In most cases, the molecular basis of parathyroid neoplasia is unknown. Parathyroid adenomas are usually monoclonal, suggesting that one important step in tumour development is a mutation in a progenitor cell. Approximately 30% of sporadic parathyroid tumours show loss of heterozygosity (LOH) for polymorphic markers on 11q13, the site of the MEN1 tumour suppressor gene. This raises the question of whether such sporadic parathyroid tumours are caused by sequential inactivation of both alleles of the MEN1 gene. We recently cloned the MEN1 gene and identified MEN1 germline mutations in fourteen of fifteen kindreds with familial MEN1 (ref. 10). We have studied parathyroid tumours not associated with MEN1 to determine whether somatic mutations in the MEN1 gene are present. Among 33 tumours we found somatic MEN1 gene mutation in 7, while the corresponding MEN1 germline sequence was normal in each patient. All tumours with MEN1 gene mutation showed LOH on 11q13, making the tumour cells hemi- or homozygous for the mutant allele. Thus, somatic MEN1 gene mutation for the mutant allele. Thus, somatic MEN1 gene mutation contributes to tumorigenesis in a substantial number of parathyroid tumours not associated with the MEN1 syndrome.
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PMID:Somatic mutation of the MEN1 gene in parathyroid tumours. 924 Dec 76

To elucidate the cellular proliferative kinetics of the parathyroidal gland in patients with hyperparathyroidism, we investigated the expression of proliferating cell nuclear antigen (PCNA) in parathyroidal tissues using an immunohistochemical procedure. The PCNA labeling index (LI; maximum LI, maximal stained area; average LI, evenly distributed stained area) indicating cellular proliferative activity was defined as the number of PCNA-positive cells per 1000 parathyroid cells in the region of interest. We used these indexes to compare and investigate the proliferative activity of parathyroid cells under various conditions. The specimens used for the study were 42 parathyroid glands from 21 patients with primary hyperparathyroidism (19 cases of adenoma and 2 cases of primary hyperplasia due to multiple endocrine neoplasia type 1) and 129 parathyroid glands from 32 patients with secondary hyperparathyroidism. An additional 40 parathyroid glands resected during thyroid surgery of 30 normocalcemic patients were used as normal controls. In normally functioning parathyroids, a small number of cells in the growth phase were found. In primary hyperparathyroidism, proliferative activity was highest in the adenoma followed by primary hyperplasia. In contrast, the PCNA LIs showed a low value in the normal rim of the adenoma and normal glands resected as biopsy specimens from adenoma patients. We, therefore, assumed that proliferative activity was suppressed in these cells compared with that in normally functioning glands. In secondary hyperparathyroidism, when the cell component of the parathyroid tissues was divided into five types, PCNA immunoreactivity was lowest in the dark chief cells. Proliferative activity in cells of the oxyphil series was the same or higher than that in the clear chief cells or vacuolated chief cells. When classified according to the structure of the parathyroid glands, cell proliferation was significantly higher in the nodular type than in the diffuse type (maximum LI, 176 +/- 231 vs. 38.3 +/- 55.7; average LI, 120 +/- 188 vs. 24.8 +/- 43.5; mean +/- SD; P < 0.001). More PCNA-immunoreactive cells were found in autotransplanted glands with recurrence than in glands resected during the initial surgery. To summarize the PCNA expression classified according to the pathological types of hyperparathyroidism, the PCNA LIs were highest in secondary hyperplasia (maximum LI, 144 +/- 212; average LI, 96.0 +/- 169) and adenoma (maximum LI, 102 +/- 81.7; average LI, 67.5 +/- 67.7), followed by primary hyperplasia (maximum LI, 25.0 +/- 25.4; average LI, 19.2 +/- 22.2) and normal glands (maximum LI, 13.6 +/- 23.9; average LI, 4.40 +/- 8.90). These findings suggest that the cellular proliferative kinetics of the parathyroid gland differ depending on the type of hyperparathyroidism, glandular structure, and cell components. As the detection method of intranuclear expression of PCNA in cells is too sensitive, we should be careful not to overestimate the number of cells in the proliferative cycle. However, these results could not have been obtained using a conventional method such as DNA analysis by flow cytometry.
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PMID:Analysis of proliferative activity of the parathyroid glands using proliferating cell nuclear antigen in patients with hyperparathyroidism. 925 54


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