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)

A patient with chronic lymphocytic leukemia (CLL) is described in whom hypercalcemia occurred in association with elevation of the peripheral lymphocyte count and expansion of total tumor mass. Hypercalcemia was ameliorated with the institution of chemotherapy for the leukemic process and subsequent fall in WBC count and decrease in total tumor burden; hypercalcemia recurred with relapse of the leukemic process. The serum immunoreactive parathyroid hormone (iPTH) concentration, when measured, was inappropriately elevated for the degree of hypercalcemia. The hypercalcemia would appear to be a direct consequence of the leukemia, and possibly involved secretion of a parathyroid hormone-like polypeptide by the CLL cells. Although a possible role for either an osteoclast-activating substance or prostaglandins was not excluded, they would not account for the elevated serum iPTH levels observed.
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PMID:Hypercalcemia associated with chronic lymphocytic leukemia. 50 29

New information has elucidated many of the biochemical pathways in the formation, release and metabolism of parathyroid hormone (PTH). The hormone is biosynthesized in the parathyroid cells from two distinct precursors, or prohormones, that are modified by specific enzymic cleavages during the synthesis and intracellular transport of the hormonal polypeptide. Release of the hormone from the gland inversely depends on the extracellular calcium concentration, but is regulated over a much narrower range of calcium concentration than was realized previously. This new information points to a pattern of regulation that is more appropriate for homeostasis than was the pattern indicated by earlier studies. The persistence of a basal level of PTH secretion, despite sustained hypercalcaemia, suggests a possible mechanism for the abnormal secretion seen in states of hyperparathyroidism. The discovery of a calium-dependent degradative pathway for PTH in the parathyroid cell indicates that changes in the turnover of PTH may be one means by which calcium regulates the amount of hormone available for secretion. Of the multiple immunoreactive forms of PTH present in the circulation of man and animals, the predominant form in blood appears to be a large biologically-inactive fragment consisting of the middle and carboxy two-thirds of the hormone sequence. At times, smaller biologically-active fragments of PTH may also appear in blood. Most circulating fragments of PTH probably arise from peripheral cleavage of the intact, secreted hormone in kidney and liver, but some forms of the hormone, including prohormones, may also be secreted from the parathyroid gland. The heterogeneity of circulating PTH and the concomitant uncertainties regarding its precise character have introduced difficulties in the interpretation of immunoassay measurements. A further delineation of the pathways and regulation of PTH biosynthesis, secretion and metabolism should lead to the development of more-specific immuno-assays and result in improved diagnosis and management of patients with disorders of the parathyroid glands.
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PMID:New concepts in the formation, regulation of release, and metabolism of parathyroid hormone. 78 74

Transforming growth factor alpha (TGF-alpha) is a polypeptide regulator of cell growth produced by many malignant tumors. It stimulates osteoclastic resorption in bone organ culture and osteoclast-like cell formation in marrow culture. To determine whether tumor production of TGF-alpha can cause hypercalcemia in vivo, we used Chinese hamster ovarian (CHO) cells transfected with the human TGF-alpha gene (TCHO), which stably express and secrete TGF-alpha. We used nontransfected CHO cells as controls (CCHO). TCHO and CCHO were inoculated intramuscularly into one hindlimb of nude mice and grew as local solid tumors. After 4 weeks of TCHO tumor growth, plasma ionized calcium (Ca2+) increased to reach 1.48 +/- 0.03 mM (mean +/- SEM), whereas mice bearing similarly sized CCHO tumors and non-tumor-bearing mice (NTB) remained normocalcemic (normal range for Ca2+, 1.15-1.30 mM). Plasma TGF-alpha was undetectable by an ELIFA assay in all NTB mice, was markedly increased in all TCHO mice (5.75 +/- 0.78 ng/ml), and was slightly increased in CCHO mice (0.50 +/- 0.22 ng/ml). Quantitative bone histomorphometry showed a prominent increase in osteoclastic bone resorption in TCHO mice. These data suggest that TGF-alpha is a mediator of hypercalcemia and increased osteoclastic bone resorption in tumors that produce it in sufficient quantity.
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PMID:Expression of human transforming growth factor alpha by Chinese hamster ovarian tumors in nude mice causes hypercalcemia and increased osteoclastic bone resorption. 164 53

Influence of vasoactive intestinal polypeptide, neuropeptide Y, calcitonin gene-related peptide, and substance P was investigated on dispersed parathyroid cells of adult cattle. At a physiological concentration of extracellular calcium, vasoactive intestinal polypeptide stimulated the parathyroid hormone release in a dose-dependent manner, whereas no effects were noted for the other peptides. The dependency of PTH secretion upon extracellular calcium was shifted to the right by vasoactive intestinal polypeptide at 10(-6) mol/l, with a tendency for greater effects at low (0.5 mmol/l) than high concentrations (2.0-3.0 mmol/l) of the cation. Vasoactive intestinal polypeptide significantly enhanced cAMP release of the parathyroid cells, whereas no influence was noted on cytoplasmic calcium or pH within the cells. The results suggest that vasoactive intestinal polypeptide stimulates the PTH release by interaction with cAMP production of the parathyroid cells. This effect may contribute to the development of hypercalcemia in patients with neuroendocrine tumours secreting vasoactive intestinal polypeptide.
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PMID:Vasoactive intestinal polypeptide stimulates parathyroid hormone release by interaction with cyclic adenosine monophosphate production of bovine parathyroid cells. 170 45

Parathyroid hormone-related peptide (PTHrp), a polypeptide synthesized by tumors associated with hypercalcemia and known to cause bone resorption, was examined for its effects on bone formation in cultures of 21-day fetal rat calvariae. Continuous treatment with PTHrp for 24-72 h stimulated DNA synthesis, but inhibited [3H] proline incorporation into collagen by about 50%. In contrast, transient exposure to PTHrp at 0.1-1.0 nM for 24 h followed by removal of the factor for 48 h caused an increase in [3H]proline incorporation into collagen and noncollagen protein by 2- and 1.6-fold, respectively. The stimulatory effect was seen in the periosteum-free bone, and was decreased, but not prevented by hydroxyurea. PTHrp at 1-10 nM for 24 h increased medium insulin-like growth factor (IGF) I levels by 2.5-4.4-fold, and the effect was sustained 48 h after the removal of the agent. An IGF I neutralizing antibody prevented the stimulatory effect of PTHrp on bone collagen synthesis. PTH had the same stimulatory effects as those of PTHrp on bone collagen synthesis and IGF I concentrations, although slightly lower doses were needed to observe the enhancement of [3H]proline incorporation into collagen. It is concluded that continuous treatment with PTHrp inhibits, whereas transient treatment stimulates, collagen synthesis; the stimulatory effect appears mediated by an enhancement in the local production of IGF I.
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PMID:Differential effects of continuous and transient treatment with parathyroid hormone related peptide (PTHrp) on bone collagen synthesis. 231 43

The clinical features of 20 patients from five families with multiple endocrine neoplasia syndrome type I (MEN-I) were studied. Nineteen patients (95%) had hyperparathyroidism. Five patients who had a diagnosis during surgery of adenoma and who had fewer than 3.5 glands removed had recurrence of hypercalcemia after surgery. Fourteen patients (70%) had pancreatic islet cell tumors. All had one or more elevated serum polypeptide hormones, and six had symptoms related to the hormones produced. Multiple pancreatic tumors were identified in the nine patients who underwent surgery. Three patients who died had a mean survival of 6.3 +/- 2.9 years. Eight patients had pituitary tumors; seven had macroadenomas. Of the eight patients with pituitary tumors, seven had high serum prolactin and responded to bromocriptine therapy, whereas the eighth patient had acromegaly treated with radiotherapy. It was concluded that hypercalcemia due to hyperparathyroidism in MEN-I syndrome patients should be managed by a resection of four glands and transplantation of one half gland into the forearm because none of the patients has shown evidence of a recurrence, and serum calcium levels have been normal. Pancreatic tumors, which are usually multiple, may be asymptomatic. Patients with these tumors usually have long survival rates, even with distant metastasis. Total pancreatectomy may be the method of choice, especially in patients with gastrinoma caused by the diffuse nature of the disease. Long-term follow-up is needed, however, with more patients. Pituitary tumors are primarily prolactin-producing tumors, and medical treatment is the method of choice.
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PMID:Multiple endocrine syndrome type I. Clinical, laboratory findings, and management in five families. 256 65

Parathyroid hormone related protein (PTHrP) has been demonstrated in the tumour cells of squamous cell carcinomas originating in a variety of organs, in undifferentiated small cell tumours of the bronchus, and in carcinoma of the kidney. The protein hormone is thought to produce the hypercalcaemia which may complicate some of these malignancies. By using an antibody raised in rabbits against the N-terminal portion of the molecule, the polypeptide may be demonstrated in cells of the prickle cell layer of normal skin and in the cells of hair follicles. Skin tumours showing squamous or hair follicle differentiation are shown to contain the protein antigen, while basal cell carcinomas and tumours with sweat gland differentiation do not. The hormone may be primordial in origin and the progenitor of parathyroid hormone.
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PMID:Expression of parathyroid hormone related protein in normal skin and in tumours of skin and skin appendages. 276 87

A 20-yr-old black woman presented in 1969 with headache, amenorrhea, hyperprolactinemia, hypogonadotropism, hypogonadism, and hypercalcemia due to a chromophobe adenoma. She received 5000 rads to the sella. One year later she was found to have hyperparathyroidism due to parathyroid adenoma and three and a half glands were removed. Thirteen years later she presented with 3 months of profuse watery diarrhea, hypokalemia, hypercalcemia, hyperchloremic metabolic acidosis, and a normal anion gap. A vasoactive intestinal polypeptide-producing tumor of the pancreas was found and successfully removed, after which hypercalcemia resolved. This is an unusual case of the multiple endocrine neoplasia syndrome, type 1, being associated with a vasoactive intestinal polypeptide-oma and pancreatic cholera.
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PMID:Multiple endocrine neoplasia, type 1, with pancreatic cholera. 288 44

For the purpose of examining the role of calcium ion in the secretory process of atrial natriuretic polypeptide (ANP), we studied the effects of hypercalcemia and ouabain on plasma concentration of immunoreactive ANP (irANP). Pentobarbital sodium-anesthetized dogs were treated with calcium chloride infusion (0.136 mmol.kg-1.min-1, 10 min) or ouabain injection (30 micrograms/kg), and plasma irANP concentration, right atrial pressure, mean arterial pressure, heart rate, and serum calcium concentration were measured. To evaluate the effect of rising arterial pressure, plasma irANP concentration was also measured in dogs treated with phenylephrine hydrochloride (10 micrograms/kg). With calcium chloride infusion, serum calcium concentration and plasma irANP concentration, respectively, increased to about three times and about four times their basal levels. This increase of plasma irANP concentration was not attenuated by pretreatment with adrenoceptor blockers. Ouabain increased plasma irANP concentration to approximately 2.5 times the initial level. Neither calcium chloride nor ouabain produced any effect on right atrial pressure and heart rate, but both significantly increased mean atrial pressure. Phenylephrine caused a greater increase in mean arterial pressure than both calcium chloride and ouabain. However, there was no significant increase in plasma irANP concentration. These results suggest that the calcium ion may play a key role in the secretory process of ANP.
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PMID:Effects of hypercalcemia and ouabain on plasma atrial natriuretic polypeptide in anesthetized dogs. 297 11

A study is reported of the estimation of plasma chloride concentration and acid-base status in the differentiation of primary hyperparathyroidism from all other causes of hypercalcaemia. In the two groups of patients studied, all of whom had hypercalcaemia, there was complete separation between the two groups on the basis of plasma chloride concentration and acid-base status. In 16 patients with primary hyperparathyroidism the increase in plasma chloride concentration and associated metabolic acidosis could have been accounted for by the known renal tubular effects of parathyroid hormone. In 13 patients with hypercalcaemia due to various other causes the decrease in plasma chloride concentration and associated metabolic alkalosis could be accounted for either by the known effects of an excess of calcium-ion on the renal tubules, or perhaps by suppression of endogenous parathyroid hormone secretion. In patients with hypercalcaemia and hypophosphataemia of ;pseudohyperparathyroidism' associated with non-endocrine tumours it is postulated that the low plasma chloride concentrations and metabolic alkalosis found in these patients were due either to a differing biological activity of the parathyroid-hormone-like polypeptide secreted by the tumour cells, or possibly to simultaneous secretion by these cells of an ACTH-like polypeptide.
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PMID:Value of plasma chloride concentration and acid-base status in the differential diagnosis of hyperparathyroidism from other causes of hypercalcaemia. 557 36


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