Disease relevance of Hypercalcemia

• Parathyroid hormone-related protein (PTHrP) was discovered as a result of a search for the circulating factor secreted by cancers which causes the common paraneoplastic syndrome humoral hypercalcemia of malignancy [1].
• We studied a patient with acute myeloblastic leukemia, hypercalcemia, hypophosphatemia and inappropriately elevated serum parathyroid hormone levels to define the mechanism of the hypercalcemia [2].
• Effective treatment with oral calcitriol is often impossible in patients with osteitis fibrosa, because low doses may cause hypercalcemia [3].
• We measured plasma concentrations of 1,25-dihydroxyvitamin D (1,25-(OH)2D) in the course of a 6-to-37-month survey of four children with hypercalcemia and an elfin facies (Williams syndrome) [4].
• Normal parathyroid hormone activity in hypercalcemia associated with thrombotic thrombocytopenic purpura [5].

Psychiatry related information on Hypercalcemia

• The clinical phenotype of WS includes elfin facies, infantile hypercalcemia, supravalvular aortic stenosis, hyperacusis and mental retardation [6].
• Patients receiving lithium for the management of manic depressive disorders appear to be at increased risk for development of hypercalcemia [7].

High impact information on Hypercalcemia

• In contrast to the situation in humoral hypercalcemia of malignancy in which PTHrP plays the role of a classical "endocrine" hormone, under normal circumstances PTHrP plays predominantly paracrine and/or autocrine roles [1].
• BACKGROUND: Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown [8].
• BACKGROUND: An activating mutation of the receptor for parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) was recently found in a patient with Jansens's metaphyseal chondrodysplasia, a rare form of short-limbed dwarfism associated with hypercalcemia and normal or low serum concentrations of the two hormones [9].
• A mouse model of human familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism [10].
• It appears that production of the bone-resorbing cytokine lymphotoxin is related to osteoclastic bone destruction and hypercalcemia in patients with myeloma [11].

Chemical compound and disease context of Hypercalcemia

• Short-term episodes of hypercalcemia were easily controlled by changes in calcitriol dosage [12].
• Hypercalcemia and increases in serum hormone value during prolonged administration of 1alpha,25-dihydroxyvitamin D [13].
• In patients with hypercalcemia and solid tumors the excretion of the major urinary metabolite of the E prostaglandins, 7 alpha-hydroxy-5, 11-diketotetranorprostane-1, 16-dioic acid (PGE-M), was significantly greater than normal, P LESS THAN 0.01 (median of 58.4 and 7.1 ng per milligram of creatinine respectively) [14].
• Letter: Indomethacin-responsive hypercalcemia [15].
• In 50 consecutive patients with cancer-associated hypercalcemia, we measured nephrogenous cyclic AMP, tubular phosphorus threshold, fasting calcium excretion, plasma 1,25-dihydroxyvitamin D, and immunoreactive parathyroid hormone as determined by four region-specific antiserums [16].

Biological context of Hypercalcemia

• Familial benign hypercalcemia (FBH) and neonatal hyperparathyroidism (NHPT) are disorders of calcium homeostasis that are associated with missense mutations of the calcium-sensing receptor (CaR) [17].
• We conclude that dosage of the gene defect accounts for these widely disparate clinical phenotypes; a single defective allele causes familial hypocalciuric hypercalcemia, while two defective alleles causes neonatal severe hyperparathyroidism [18].
• Markedly reduced activity of mutant calcium-sensing receptor with an inserted Alu element from a kindred with familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism [19].
• In rats fed dihydrotachysterol to induce hypercalcemia, Western blot analysis revealed significant upregulation of both cPLA2 and PGHS-2 in the kidney cortex and the inner and outer medulla [20].
• A tumor-derived factor believed to cause hypercalcemia by acting on the parathyroid hormone (PTH) receptor was recently purified, cloned, and found to have NH2-terminal sequence homology with PTH [21].

Anatomical context of Hypercalcemia

• These characteristics are shared by the parathyroid hormone receptor agonists associated with humoral hypercalcemia of malignancy, which suggests that normal human keratinocytes may produce a factor related to that produced by malignant tumors associated with humoral hypercalcemia of malignancy [22].
• IL-6 stimulates osteoclast formation, causes mild hypercalcemia, and is produced by bone cells in vitro upon exposure to systemic hormones [23].
• In sarcoidosis, 1,25(OH)2D is produced by alveolar macrophages in response to gamma-interferon, and patients may develop hypercalcemia after prolonged exposure to sunlight and increased dermal production of vitamin D3 [24].
• Injection of PTH above the calvaria caused hypercalcemia in wild-type but not PGHS-2(-/-) mice [25].
• Our results suggest that hypercalcemia affects pancreatic, gallbladder, and gastric functions as well as their responses to exogenous CCK [26].

Gene context of Hypercalcemia

• Casr+/- mice, analogous to humans with familial hypocalciuric hypercalcemia, had benign and modest elevations of serum calcium, magnesium and parathyroid hormone levels as well as hypocalciuria [10].
• A synthetic peptide corresponding to the first 34 amino acids of the parathyroid hormone-related protein (PTH-rP) produced by a human tumor associated with hypercalcemia was examined for skeletal and renal effects on calcium metabolism in vivo and in vitro [27].
• ATL cells often abnormally express interleukin 2 (IL-2) receptors, and ATL patients may show clinical evidence of hypercalcemia, osteolytic bone lesions, or increased bone turnover [28].
• Parathyroid hormone-related peptide (PTHrP) was initially identified as a product of malignant tumors that mediates paraneoplastic hypercalcemia [29].
• The inherited disorders, familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT), are caused by inactivating mutations in the CASR gene [30].

Analytical, diagnostic and therapeutic context of Hypercalcemia

• Failure of parathyroid hormone antagonists to inhibit in vitro bone resorbing activity produced by two animal models of the humoral hypercalcemia of malignancy [31].
• These findings suggest that the decline in filtration rate associated with hypercalcemia is due largely to the reduction in Kf, the latter dependent upon the presence of parathyroid hormone [32].
• Pancreatitis in association with hypercalcemia in patients receiving total parenteral nutrition [33].
• In vivo, 22-oxa-calcitriol inhibited the growth of BxPC-3 xenografts more significantly than calcitriol without including hypercalcemia [34].
• Parathyroidectomy in two patients resulted in a decrease in parathyroid hormone concentration to normal, but hypercalcemia persisted [35].

References