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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parathyroid cells express a plasma membrane calcium receptor (CaR), which is stimulated by a rise in extracellular calcium concentration ([Ca2+]ext). A decreased sensitivity to [Ca2+]ext occurs in adenomatous parathyroid cells in patients with primary hyperparathyroidism, but the underlying functional mechanism is not yet fully understood. This study explored whether CaR responsiveness is influenced by increasing the affinity of IP3 receptors--a major signalling component of other G-protein-coupled receptors. The sulphydryl reagent thimerosal was used to increase the responsiveness of IP3-receptors. Quantitative fluorescence microscopy in Fura-2-loaded cells was used to investigate the effects of thimerosal on the cytoplasmic calcium concentrations ([Ca2+]i) in human parathyroid cells and to compare its effects in a rat medullary thyroid carcinoma cell line (rMTC6-23) also expressing CaR. During incubation in Ca(2+)-free medium, thimerosal 5 microM induced a rapid sustained rise in [Ca2+]i in human parathyroid cells and no further [Ca2+]i increase appeared in response to the CaR agonist Gd3+ (100 microM). Thimerosal 1 microM induced only slow and minimal changes of basal [Ca2+]i and allowed a rapid response to Gd3+ 20 nM (a concentration without effect in control cells). The slope of the thimerosal-induced [Ca2+]i responses was steeper following exposure to CaR agonists. In the presence of 1 mM [Ca2+]ext, thimerosal (0.5 microM) induced a sharp increase in [Ca2+]i to a peak (within 60 s), followed either by return to basal [Ca2+]i or by a plateau of slightly higher amplitude. Similar results were obtained using rMTC6-23 cells. Thimerosal increases the responsiveness to CaR agonists through modulation of the sensitivity of the IP3 receptor in both parathyroid and rMTC6-23 cells.
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PMID:Thimerosal increases the responsiveness of the calcium receptor in human parathyroid and rMTC6-23 cells. 1059 73

Whether activation of the calcium receptor (CaR) modulates secretory events was investigated by real-time fluorescence and confocal microscopy using fura 2 and FM1-43 fluorescent dye. Two paradigms were used: human parathyroid cells, which are stimulated by a step from a high to a low extracellular calcium concentration ([Ca(2+)](ext)), and rMTC6-23 cells, a rat medullary thyroid carcinoma cell line whose secretion is stimulated by an increase in [Ca(2+)](ext). Parathyroid cells were dispersed from parathyroid adenomas removed from 18 patients with primary hyperparathyroidism. In both cell types, incubation with FM1-43 (2 microM) resulted in staining of the plasma membranes, which was rapidly increased following changes in [Ca(2+)](ext) known to stimulate secretion. A high [Ca(2+)](ext) and lanthanum (La(3+)) decreased the membrane-associated FM1-43 fluorescence. Prolonged incubation (5-30 min) in the presence of FM1-43 resulted in accumulation of the dye in the cytoplasm, its granular distribution suggesting targeting of the secretory compartment. These data suggest that FM1-43 fluorescence is determined by: (i) changes in cell membrane surface area associated with secretion-associated events, (ii) displacement/quenching by extracellular cations and (iii) endocytosis of the dye. In parathyroid cells, a rise in FM1-43 fluorescence occurred during incubation in a high (inhibitory) [Ca(2+)](ext) if the cytoplasmic calcium concentration ([Ca(2+)](i)) was decreased by the calcium chelator BAPTA/AM [bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester)] (10-50 microM). Alternatively, the expected rise in FM1-43 fluorescence did not occur during incubation in a low (stimulatory) [Ca(2+)](ext) if [Ca(2+)](i) was increased by addition of the calcium ionophore A23187 (10-25 microM). These data suggest that [Ca(2+)](i), rather than the absolute value of [Ca(2+)](ext), is the main modulator of secretion from parathyroid cells.
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PMID:Changes in cytoplasmic calcium determine the secretory response to extracellular cations in human parathyroid cells: a confocal microscopy study using FM1-43 dye. 1108 28

The multiple endocrine neoplasia syndromes are divided into two categories: MEN type I and MEN type II. The MEN type II syndrome is further divided into MEN IIa and MEN IIb. The syndromes are characterized by benign and malignant changes in two or more endocrine organs, as well as incidental changes in nervous, muscular and connective tissue. Two main forms can be distinguished: the MEN-I syndrome with hyperplasia of the parathyroid gland, accompanied by islet cell tumor and pituitary adenoma; the MEN-II syndrome with medullary thyroid carcinoma in combination with bilateral pheochromocytoma and hyperplasia of the parathyroid gland (MEN IIa), while type IIb is characterized by the additional appearance of neurocutaneous manifestations without primary hyperparathyroidism. Characteristics shared by these syndromes include the involved cell type, most of the tumors are composed of one or more specific polypeptide- and biogenic amine-producing cell types (APUD--amine precursor uptake and decarboxylation). The second characteristic is the increased incidence in certain families. The hereditary component is autosomal dominant with variable expression but high penetrance. Mechanisms of tumorigenesis differ in these syndromes. While MEN I is caused by an inherited mutation of a tumor suppressor gene, menin, located on the long arm of chromosome 11, MEN II is caused by activation of the RET proto-oncogene. We have reported the case of a young man exhibiting bilateral pheochromocytoma. In addition, the patient showed mild primary hyperparathyroidism and marfanoid habitus, all these stigmata usually being part of the MEN-II syndrome. Although this described patient showed a phenotypic mixture of the MEN-IIa and MEN-IIb syndrome, the genetic analysis for MEN II and von-Hippel-Lindau gene did not reveal any pathologic mutations, the endocrine disorders described here are not related to multiple endocrine neoplasia syndromes.
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PMID:Multiple endocrine neoplasia (MEN)--an overview and case report--patient with sporadic bilateral pheochromocytoma, hyperparathyroidism and marfanoid habitus. 1120 36

The authors present a case of a 36 years old woman applied to them for a follow up of sponge kidney disease and in whom they discovered a primary hyperparathyroidism. Further investigations discovered a medullary thyroid carcinoma. So this patient present multiple endocrine neoplasia (MEN) type 2A confirmed by microscopic and genetic analysis. This observation enlarged the discussion upon the nature of the relationship between kidney disease and primary hyperparathyroidism. Elsewhere it recommended to check systematically genetic markers of MEN type 2A if there is an association with sponge kidney disease and primary hyperparathyroidism.
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PMID:[Description of a case of Cacchi Ricci disease associated with hyperparathyroidism in the setting of multiple endocrine disease]. 1195 91

Multiple endocrine neoplasia type 2A (MEN2A), a dominantly inherited cancer syndrome, is defined by the presence of medullary thyroid carcinoma (MTC), pheochromocytoma (pheo), and primary hyperparathyroidism (p-HPT). Along with multiple endocrine neoplasia type 2B (MEN2B) and familial medullary thyroid carcinoma (FMTC), it is associated with germline mutations of the RETproto-oncogene localized in 10q11.2. In FMTC and MEN2A, point mutations result in the substitution of one of five Cys residues in the extracellular domain of RET. In a larger pedigree from Saarland, several individuals were observed with C-cell thyroid carcinoma. We screened 16 members of this extended family by single-strand conformation polymorphism analysis (SSCP), polymerase chain reaction (PCR), followed by restriction enzyme analysis, and by sequencing the mutated regions. In 7 family members, all of whom had been earlier operated on because of MTC, a DNA transition from T to C was observed, causing an amino acid substitution Cys(634)Arg. Nine members of the kindred did not carry the mutation and may be excluded from yearly biochemical testing. One of these persons seems to have been unnecessarily operated on owing to a borderline pentagastrin test.
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PMID:Molecular Screening for RET Proto-Oncogene Mutations in a German MEN2A Pedigree. 1211 82

MEN-2A is characterized by medullary thyroid carcinoma (MTC) with pheochromocytoma and sometimes parathyroid adenoma. In affected members of the family, the risk of MTC is about 100%. Biochemical screening allows tumors to be detected early but even at this stage treatment is not always curative. Missense mutations in exon 10 and 11 of the RET proto-oncogene are associated with MEN-2A. Early detection of this mutation by DNA analysis allows the identification of the carriers of the gene. We performed genetic screening in 88 members of an extended family with MEN-2A and found 18 members positive for RET mutation (Cys634Gly). Only three of these 18 RET positive cases had a previous diagnosis of medullary cancer and/or pheochromocytoma. Up to now, 12 of the RET positive cases have undergone thyroidectomy. There was extended disease with cervical lymph node metastasis in 6 of them, bilateral medullary microcancer in 3 and c-cell hyperplasia in the remaining 3. Three of the 18 RET positive patients had also pheochromocytoma. Primary hyperparathyroidism was present in only one patient. The mean age of diagnosis of medullary cancer was between 25-50 yr and mean age of death was between 35-95 yr in affected members of the family. The family had many other affected members in other cities in Turkey and in other countries throughout the world from Australia to the Netherlands. So this family is perhaps one of the most extended families with MEN-2A.
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PMID:Clinical characteristics and genetic screening of an extended family with MEN2A. 1215 Mar 34

We report what we believe to be the first case of a patient with multiple endocrine neoplasia type 2A (MEN 2A) and renal dysplasia associated with an RET 634 mutation. The proband presented at the age of 29 with medullary thyroid carcinoma (MTC), bilateral pheochromocytomas, and primary hyperparathyroidism. Screening of family members identified the syndrome in his father. Both the proband and his father carry RET 634 germline mutation resulting in cysteine to arginine amino acid substitution. The proband had a left nephrectomy at the age of 10 years. Histologic examination of the resected kidney revealed severe dysplasia. His father had normal renal tract on ultrasonography. The proband's clinical presentation was unusual, and initially thought to be an atypical pneumonia. Surgical management after pharmacologic alpha- and beta-blockage consisted of bilateral adrenalectomy, total thyroidectomy, and subtotal parathyroidectomy as a single procedure.
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PMID:Multiple endocrine neoplasia type 2A: an unusual clinical presentation and association with renal dysplasia. 1260 35

Multiple endocrine neoplasia type 2A (MEN 2A) is an autosomal dominant disorder characterized by medullary thyroid carcinoma, pheochromocytoma and primary hyperparathyroidism. The first tumor is usually a medullary thyroid carcinoma. MEN 2A is caused by mutations in the RET proto-oncogene. The detection of mutations in the gene has important diagnostic and therapeutic impacts. Genetic testing of at-risk family members allows one to identify individuals carrying the mutant alleles with very high specificity and sensitivity. Subsequently, total thyroidectomy, recommended at 5 years of age, can be performed in a prophylactic attempt. The authors performed a molecular analysis to identify a mutation in a Thai woman with MEN 2A. She was found to be heterozygous for 1900T>C (C634R). The patient had two daughters who were not found to carry the mutation. The newly available genetic test for patients with MEN 2A in Thailand makes possible accurate DNA-based diagnosis of their at-risk family members before development of the disease, which has important therapeutic impacts for them.
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PMID:A RET C634R mutation in a Thai female with multiple endocrine neoplasia type 2A. 1293 27

Multiple endocrine neoplasia type 2 (MEN-2) is a hereditary syndrome that is transmitted in an autosomal dominant pattern. MEN-2A, MEN-2B, and familial medullary thyroid cancer (MTC) comprise the MEN-2 syndrome. A germline mutation in the RET proto-oncogene is responsible for the MEN-2 syndrome. Recent data indicate that in 99% of MEN-2 cases, a germline RET mutation can be identified by genetic testing. The phenotypic variation of MEN-2 is diverse and partly related to the codon and specific point mutation in the RET proto-oncogene. There are increasing data on the genotype-phenotype correlations in patients with MEN-2 and this information should be used for screening at-risk patients and treatment of RET mutation carriers. All patients (especially if young) with MTC or bilateral pheochromocytoma should have a careful family history taken and genetic screening for RET germline mutations. Patients who are RET germline mutation carriers but without clinical or biochemical evidence of MTC should have a prophylactic total thyroidectomy. The optimal age of thyroidectomy should be based on the RET genotype (eg, high-risk mutations within the first year of life, intermediate-risk mutations by 5 years of age, and low-risk mutations by 10 years of age). Patients who are diagnosed with clinical or biochemical evidence of MTC should have a total or a near total thyroidectomy and at least a central neck lymph node dissection. Patients who have pheochromocytoma and a unilateral adrenal tumor on a localizing study should have a unilateral laparoscopic adrenalectomy after preoperative alpha-blockade. However, patients with bilateral adrenal tumors on localizing studies should have bilateral laparoscopic adrenalectomy. A cortical-sparing (subtotal) adrenalectomy may be considered, if technically feasible, to avoid long-term steroid dependence and to reduce the risk of Addisonian crisis. Patients with biochemical evidence of primary hyperparathyroidism should have a bilateral neck exploration and total parathyroidectomy and autotransplantation (30-60 mg of the most normal parathyroid tissue) to the nondominant forearm if asymmetric parathyroid hyperplasia is present. Rarely, patients may have only single-gland disease and excision may be performed if the other parathyroid glands are not found with biopsy to be hyperplastic. All unresected parathyroid glands should be marked with a clip because patients with MEN-2A have a high risk of persistent and recurrent primary hyperparathyroidism. Patients with familial MTC may have not manifested the other features of MEN-2A, thus these patients should have continued follow-up for pheochromocytoma and primary hyperparathyroidism.
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PMID:Multiple endocrine neoplasia type 2. 1523 8

Concomitant thyroid disease is not unusual among patients with primary hyperparathyroidism. However, the simultaneous occurrence of parathyroid and thyroid carcinoma is extremely rare. We report a 38-year-old man with primary hyperparathyroidism who presented with osteitis fibrosa cystica complicated with pathologic femoral neck fracture. Preoperative investigation for exclusion of multiple endocrine neoplasia did not find evidence of medullary thyroid carcinoma or pheochromocytoma, but imaging studies revealed the presence of nodules in the right lobe and a parathyroid lesion over the left inferior pole of the thyroid gland. Total thyroidectomy, left parathyroidectomy, and bipolar hemiarthroplasty of the left hip were then performed simultaneously. The resected specimens were pathologically identified as papillary thyroid carcinoma and parathyroid carcinoma, respectively. After the operation, 131I ablation therapy was administered at a dose of 120 mCi. Additional doses of 30 mCi were given yearly as serum thyroglobulin level became elevated. Serum calcium level remained normal during yearly follow-up. Although parathyroid carcinoma is an uncommon cause of parathyroid hormone-dependent hypercalcemia, it should nonetheless be given due consideration because its surgical approach differs from that of parathyroid adenoma. As the coexistence of parathyroid and non-medullary thyroid carcinoma has previously been reported, the possibility of both malignancies must also be considered in the setting of primary hyperparathyroidism with thyroid nodules. If confirmed with preoperative parathyroid scintigraphic and other laboratory studies, an optimal outcome may be achieved with complete resection of both tumors at the time of initial operation, followed by adjunctive therapy.
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PMID:Synchronous parathyroid and papillary thyroid carcinoma. 1575 21


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