Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parathyroid adenomas are benign neoplasms that over-secrete parathyroid hormone and cause hypercalcemia. A subset of parathyroid adenomas contain a clonal chromosomal rearrangement in which the cyclin D1 oncogene is juxtaposed to the upstream region of the PTH gene, resulting in cyclin D1 overexpression. To examine whether cyclin D1 oncogene can drive primary hyperparathyroidism, transgenic mice were created carrying the human cyclin D1 gene ligated to the upstream region of human PTH gene, mimicking the human tumor gene rearrangement. These mice provide an animal model of primary hyperparathyroidism to understand the molecular pathogenesis and pathophysiology of the disease.
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PMID:[Cyclin D1 in sporadic parathyroid adenomas]. 1577 80

The CASR, a cell surface glycoprotein expressed in parathyroid gland and kidney, is critical for maintaining extracellular calcium homeostasis. The inherited disorders, familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT), are caused by inactivating mutations in the CASR gene. The CASR has an N-terminal, 19 amino acid signal peptide that is predicted to direct the nascent polypeptide chain, as it emerges from the ribosome, into the endoplasmic reticulum (ER). Here, we report the functional characterization of three CASR mutations identified in hypercalcemic/hyperparathyroid patients. The mutations, L11S, L13P and T14A, lie within the signal peptide hydrophobic core. When transiently transfected into kidney cells, L11S and L13P mutants demonstrated reduced intracellular and plasma membrane expression and signaling to the mitogen-activated protein kinase pathway in response to extracellular calcium relative to wild-type CASR and the T14A mutant. All mutant CASR RNAs translated into protein normally. In cotranslational processing assays, which test the functionality of the signal peptide in the early secretory pathway, the wild-type CASR and mutant T14A nascent polypeptides were targeted to microsomal vesicles, representing the ER, translocated into the vesicular lumen and underwent core N-glycosylation. In contrast, the L11S and L13P mutants failed to be inserted in the microsomes and undergo glycosylation. This is the first study examining the function of the CASR signal sequence and reveals that both L11S and L13P mutants are markedly impaired with respect to cotranslational processing, accounting for the observed parathyroid dysfunction.
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PMID:Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia. 1587 34

Hypoparathyroidism following thyroidectomy or due to autoimmune process is the most common cause of hypocalcaemia. If untreated, maternal hypocalcaemia may stimulate fetal parathyroids which results in bone demineralization. Calcium supplementation may also reduce the risk of hypertension. Moreover, hypocalcaemia may inhibit the synthesis of calcium gene-related peptide (CGRP), which, in turn, decreases blood pressure and uterus contractions. In women of reproductive age hypercalcaemia is mostly due to hyperparathyroidism. The complications include toxemia, vomiting, and hypercalcaemic crisis. Maternal hypercalcaemia can suppress fetal parathyroid function and cause neonatal hypocalcaemia. The pharmacotherapy involves diuretics, fluids and oral phosphates. Bisphosphonates are contraindicated. Parathyroid surgery may be performed in the second trimester of pregnancy.
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PMID:[Disorders of calcium metabolism during pregnancy and breast feeding]. 1601 45

Bone disease associated with primary hyperparathyroidism, known as osteitis fibrosa cystica, is now very rarely encountered, since the parathyroid disorder is most often diagnosed at the early stage of asymptomatic hypercalcemia. Here, we report the case of a patient with multiple pleural-based masses and hypercalcemia, which led to the presumptive diagnosis of malignancy. However, histological and laboratory data were consistent with the development of brown tumors of the ribs due to underlying severe hyperparathyroidism.
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PMID:Multiple brown tumors of the ribs simulating malignancy. 1627 71

Parathyroid cysts rarely cause primary hyperparathyroidism. In most cases, the resultant hypercalcemia is mild and detected before any significant skeletal disease develops. We report a patient with severe hypercalcemia, a synchronous brown tumor (osteitis fibrosa cystica) of the maxilla, and a large benign functional parathyroid cyst. The unusual patient presentation and management are described and illustrated. The pertinent literature is reviewed.
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PMID:Malignant hypercalcemia associated with a parathyroid macrocyst and the early genesis of a giant cell tumor. 1636 Aug 25

Primary hyperparathyroidism is a clinical condition related to an excessive and abnormally regulated secretion of parathyroid hormone (PTH) from the parathyroid glands which is responsible for an alteration of the calcium and phosphorus metabolism. Parathyroid adenomas are the most important cause of primary hyperparathyroidism (80-85%). A case of parathyroid adenoma observed in a patient aged 47, admitted to the Emergency Medicine Department of our Hospital with a diagnosis of hypertensive crisis, cephalea, vomiting, and a clinical history of recurrent episodes of severe abdominal and renal pain, is presented. Lab data showed severe hypercalcemia and a progressive worsening of the renal function. A severe neurological involvement with stupor, derangement of mind, the arising of acute respiratory depression, lethargy compelled the colleagues to transfer him to the Intensive Care Unit; a neck ultrasonography showed a poor-echogenous area under the right thyroid inferior pole, with signs of vascularization. The suspect of a primary hyperparathyroidism related to a single adenoma of the parathyroid gland suggested a surgical treatment. A ''concise parathyroidectomy'' was performed. Our surgical approach was confirmed by the comparison of the preintervention and the post-intervention iPTH values: 2080 pg/mL (normal range: 12-65 pg/mL) before excision vs 101 pg/mL after the removal. The histologycal exam reported a parathyroid adenoma with large areas with haemorrage. Three days after surgery the patient was in good general conditions. Patients affected by primary hyperparathyroidism are often misdiagnosed because their clinical conditions can create differential diagnosis problems with other diseases. However the surgical option remains the gold standard treatment.
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PMID:Primary hyperparathyroidism related to a parathyroid adenoma: the dramatic clinical evolution of a misdiagnosed patient and its surgical solution. 1656 23

Intrathyroidal parathyroid carcinoma is an exceedingly rare cause of primary hyperparathyroidism with difficulties in the diagnosis and management. We report a case of hypercalcemia from intrathyroidal parathyroid carcinoma in a 63-year-old Saudi female. She was diagnosed 2 years earlier with osteoporosis in a primary care clinic and was on alendronate since then. This year she was noted to have hypercalcemia, but in retrospect she had more than 10 years history of multiple medical problems related to hypercalcemia. Parathyroid 99mTc-SestaMIBI scintigraphy revealed parathyroid adenoma in the left inferior parathyroid gland. She had successful video-assisted parathyroidectomy that relieved most of her symptoms. The extreme rarity of such a case, the interesting clinical presentation and review of the literature are discussed.
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PMID:Hyperfunctioning intrathyroidal parathyroid carcinoma. 1688 57

Secondary hyperparathyroidism (SHPT) leads not only to bone disorders, but also to cardiovascular complications in long-term dialysis patients. Conventional treatment with calcium (Ca) supplement, phosphate (P) binders and active vitamin D analogs lead in part to amelioration of SHPT, but are simultaneously associated with unacceptable side-effects, including hypercalcemia, hyperphosphatemia, and increased Ca x P products, which are the risk factors for cardiovascular disease in dialysis patients. Conventional treatment has been unable to facilitate the attainment of optimal management of SHPT proposed in the K/DOQI guidelines. Cinacalcet HCl (cinacalcet), a novel calcimimetic compound, restores the sensitivity of the Ca-sensing receptor in parathyroid cells, and decreases serum parathyroid hormone (PTH) without introducing hypercalcemia or hyperphosphatemia. Cinacalcet treatment enables a significant number of patients to achieve the K/DOQI guideline. Based on experimental data, calcimimetics could ameliorate cardiovascular calcification and remodeling in uremic rats with SHPT. Clinical trials have shown that cinacalcet significantly reduced the risks of parathyroidectomy, fracture and cardiovascular hospitalization among long-term dialysis patients with SHPT. Parathyroid intervention therapy (parathyroidectomy and percutaneous direct injection) is also a useful alternative. In the present article, we review novel therapeutic strategies for SHPT.
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PMID:Therapeutic strategies for secondary hyperparathyroidism in dialysis patients. 1691 Nov 89

Fine-needle aspiration (FNA) is a procedure that is increasingly being performed. Artefacts occurring after FNA are reported to complicate the histological analysis of the tissue, mainly in the thyroid; WHAFFT (worrisome histologic alterations following FNA of thyroid) is well documented in the literature. The case of a male patient with hypercalcaemia who was subsequently found to have a nodule in the thyroid gland is reported here. He underwent FNA, followed by a total thyroidectomy and parathyroidectomy. The abnormality in the parathyroid gland showed worrisome histological changes that were suspicious of a malignant lesion, resembling the changes seen in the thyroid gland after FNA. Parathyroid cells were identified by a review of the previous FNA. The concept of WHAFFT, which can mimic the features of malignancy in the parathyroid gland, is therefore introduced.
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PMID:Worrisome histologic alterations following fine-needle aspiration of the parathyroid. 1702 Nov 34

Secondary hyperparathyroidism commonly develops in patients with chronic kidney disease (CKD) in response to high phosphate, low calcium and low 1alpha,25-dihydroxyvitamin D(3) (calcitriol) levels. High levels of parathyroid hormone (PTH) accelerate bone turnover, with efflux of calcium and phosphate that can lead to vascular calcification. Treatment of secondary hyperparathyroidism with calcitriol and calcium-based phosphate binders can produce hypercalcemia and oversuppression of PTH, which results in adynamic bone that cannot buffer calcium and phosphate levels, and increased risk of vascular calcification. PTH levels must, therefore, be reduced to within a range that supports normal bone turnover and minimizes ectopic calcification. Vitamin D analogs that inhibit PTH gene transcription and parathyroid hyperplasia (and have reduced calcemic activity) are a safer treatment for secondary hyperparathyroidism than calcitriol; these agents enhance the survival of patients with CKD. Several such analogs are now in use, and analogs with even greater selectivity than those currently used are in development. Parathyroid glands express both 25-hydroxylase and 1alpha-hydroxylase, which suggests that these enzymes might suppress parathyroid function by an autocrine mechanism. The risk of hypercalcemia with vitamin D analog therapy is reduced by the introduction of non-calcium-based phosphate binders and cinacalcet; furthermore, recent trials indicate that early intervention with vitamin D analogs in stage 3 and 4 CKD can correct PTH levels, and could prevent renal bone disease and prolong patient survival.
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PMID:Drug insight: vitamin D analogs in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease. 1723 40


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