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 link between hyperparathyroidism and the growth of hematopoietic stem cells is suggested by this report of a parathyroid carcinoma with polycythemia vera. A 56-year-old white woman presented with splenomegaly, a palpable neck mass and hypercalcemia, recurrent six years after resection of a parathyroid tumor. She had pancytosis with a subnormal serum concentration of erythropoietin. Radiographs showed subperiosteal erosions an dosteopenia. Nephrocalcinosis was absent. Bone biopsy showed a decreased cortical width with many intracortical osteoclasts. The cancellous bone area remained normal, but the osteoid area/bone area, osteoblast perimeter and osteoclast perimeter were increased. At surgery, a parathyroid carcinoma was found in the same location operated on previously. As in two other reported cases, postoperative improvement in the hypercalcemia was associated with remission of the blood dyscrasia. A novel finding in this case is that when the hypercalcemia eventually recurred, it was again accompanied by pancytosis. With bisphosphonate therapy, the serum intact parathyroid hormone level increased in response to a decrease in the ionized calcium level, indicating that the cancer was not autonomous. This case suggests that in the presence of the ionized hypercalcemia, the parathyroid tumor may have produced or induced production of a growth factor that can stimulate pancytosis. The differential diagnosis of polycythemia and hypercalcemia should be expanded to include parathyroid tumors in addition to hepatic, adrenal, renal, and ovarian neoplasms.
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PMID:Parathyroid carcinoma associated with polycythemia vera. 179 72

It is generally accepted that some patients affected by mild asymptomatic primary hyperparathyroidism need not be treated with surgery, but may be medically managed without risk. However, our experience regarding 5 of these cases observed in the last two years, suggests a different approach. These patients, initially diagnosed as having mild hyperparathyroidism based on only moderately elevated serum concentrations of calcium and followed medically for years, were referred to us for a sudden worsening of their clinical course. One 35-year-old man presented hemorrhagic gastritis with severe anemia and type II AV block with syncopal attacks. Three women, aged 51, 64 and 65 years, presented with severe hypercalcemia associated with renal failure in two and with marked bone disease in another. In all these cases parathyroid neoplasms were preoperatively localized (by ultrasonography, CT scan and radioactive 201-Tl 99-Tc scan) and surgically removed. Histological examination showed a parathyroid carcinoma in the male patient and single gland enlargements in the three females. A fifth patient, a 65-year-old woman, was referred to us in critical condition: severe hypercalcemia, osteopenia with femur fracture, myocardial infarction and renal failure. She died in a few days, in spite of intensive medical care. These cases suggest that patients with hyperparathyroidism initially diagnosed as "mild" need close medical observation and preferably, in our opinion, should undergo surgery.
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PMID:Acute complications in the course of "mild" hyperparathyroidism. 180 15

We report our experience in the clinical presentation and management of 12 patients with primary hyperparathyroidism, who underwent successful surgery. Comparing our results with those previously reported in the literature, we have attempted to correlate the kind of parathyroid lesion, the magnitude of hypercalcemia and PTH increase, and clinical symptoms. Often these relationships are intriguing; we have tried to classify our patients describing four groups, according to clinical and humoral findings: 1) patients with very mild hypercalcemia and aspecific symptoms; 2) patients with a finding of recurrent hypercalcemia and prevalent renal involvement; 3) patients with severe hypercalcemia, plurisystemic involvement and general decay; 4) patients with medical emergencies. Finally, some considerations on rare histological pictures (hyperfunctioning carcinoma, oxyphil cell adenoma) are reported.
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PMID:Primary hyperparathyroidism. Our experience. 180 7

Three patients aged between 31 and 59 were treated with pamidronic acid (APD) due to severe hypercalcemia caused by parathyroid carcinoma. APD was given in 250 cm3 intravenous saline over a 2 h period in a dose of 0.45 to 0.50 mg/kg per day. Two patients received 6 and the other 9 infusions. Mean serum calcium diminished from 15.7 +/- 1.3 mg/dl to 11.7 +/- 0.6 mg/dl (p less than 0.05). Mean serum ionized calcium decreased from 8.1 mg/dl to 5.5 mg/dl, urinary calcium excretion from 478 mg/24 h to 229 mg/24 h and hydroxyproline from 204 mg/24 h to 117 mg/24 h. Serum calcium returned to pretreatment levels after 5 and 15 days post intravenous APD in two patients. In the third patient treated with 900 mg/day of oral APD, after the intravenous therapy the relapse occurred during the fourth month. The three patients received a second course of intravenous (iv) APD. The effect upon serum calcium (14.6 +/- 1.1 mg/dl to 11.8 +/- 0.6 mg/dl, p less than 0.05) was similar to the one obtained with the first course. Intravenous APD administration appears to be an effective and safe treatment of the severe hypercalcemia due to parathyroid carcinoma. To sustain levels of serum calcium attained in patients with non resectable tumors, a suitable program of iv APD pulses should be established.
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PMID:Intravenous pamidronic acid in hypercalcemia due to parathyroid carcinoma. 182 Apr 95

Thirty-eight normocalcemic patients with bone metastases from breast carcinoma were randomized to receive dichloromethylene diphosphonate (CL2MDP) in addition to their specific antitumor treatment (chemotherapy and/or hormone therapy), at a dose of 300 mg/day/i.v. or placebo for the first 7 dys. The CL2MDP treatment then continued at a dose of 100 mg day/i.m. for 3 weeks and finally at 100 mg i.m. on alternate days for at least another 2 months. In both groups of patients there was a reduction in the intensity of pain (Scott-Huskisson analog), but there was a more frequent reduction in the daily consumption of analgesics in patients treated with CL2MDP (p = 0.02). Unlike the controls, the patients who received CL2MDP presented a significant reduction in urinary calcium (p = 0.003) and in hydroxyproline (p = 0.05) on the 7th day. As regards the clinical evolution, negative events such as the appearance of hypercalcemia, pathological fractures, new bone lesions or a substantial increase in the preexisting ones, were observed in 9 of the 12 evaluable patients treated with placebo and in 3 out of 9 treated with CL2MDP. Thickening of the preexisting osteolytic lesions was reported in 2 patients treated with CL2MDP. Tolerance was excellent: only a few patients complained of pain at the intramuscular drug injection site.
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PMID:Controlled clinical study on the use of dichloromethylene diphosphonate in patients with breast carcinoma metastasizing to the skeleton. 182 15

Nine patients (median age, 81 years) with primary hyperparathyroidism were treated with intravenous infusions of disodium pamidronate (APD), which is a bisphosphonate drug. Six patients had severe hypercalcemia (serum calcium concentration, greater than 3 mmol/L) persisting after rehydration with saline and treatment with furosemide; three patients had moderate hypercalcemia with pronounced symptoms (serum calcium concentration 2.8 to 2.9 mmol/L). Three of the patients were considered to have hypercalcemic crises. In all patients, the raised serum calcium levels were lowered by the disodium pamidronate infusions. One week after a single infusion of 15 to 60 mg disodium pamidronate, six of the nine patients had serum calcium concentrations within the normal reference interval and two patients had slightly raised values. Transient asymptomatic hypocalcemia was noted in one patient. All patients tolerated the infusions well, and no side effects were noted. In the patients with verified parathyroid adenomas, a temporary increase in parathyroid hormone levels were observed concomitant with the drop in serum calcium level. The patient with parathyroid cancer displayed no such effect indicating an autonomous parathyroid hormone secretion from the parathyroid carcinoma tumor. The good effect of treatment with the osteoclast inhibitor disodium pamidronate on hypercalcemia caused by primary hyperparathyroidism suggests that this hypercalcemia is mainly due to an increased osteoclast activity. The number of patients in this series is yet too small to allow general conclusions. But the case histories in this series show that disodium pamidronate promises to be of value in different clinical situations for the treatment of severe hypercalcemia in patients with hyperparathyroidism. It can be used (1) preoperatively to investigate whether the patient's symptoms are related to the hypercalcemia, (2) in the treatment of hypercalcemic crises when "forced diuresis" has failed to normalize the serum calcium, (3) after unsuccessful parathyroid surgery when it can be used as a long-term treatment before reoperation, giving time for localization studies and healing of the scar reaction, and (4) in aged and fragile patients where it can be tried as an alternative to surgery.
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PMID:Disodium pamidronate in the preoperative treatment of hypercalcemia in patients with primary hyperparathyroidism. 848 82

Although 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has been shown to inhibit the growth of certain malignant cells, its hypercalcemic effect has prevented clinical application. We have recently developed a novel vitamin D3 analog, 22-oxa-1,25-(OH)2D3 (OCT), that is capable of promoting differentiation and inhibiting proliferation without inducing hypercalcemia. The present study was undertaken to determine whether OCT could be applied for the treatment of breast cancer with or without estrogen receptor (ER). OCT inhibited the proliferation of both ER-positive (MCF-7, T-47D, and ZR-75-1) and ER-negative breast cancer cells (MDA-MB-231 and BT-20) in vitro in a time- and dose-dependent manner, as determined by cell number and [3H]thymidine uptake. The antiproliferative effect was observed with a concentration as low as 10(-11) M OCT, and treatment of MCF-7 cells with 10(-8) M OCT for 8 days caused more than a 50% reduction in cell number compared with that of vehicle-treated cells. OCT was approximately 1 order of magnitude more potent than 1,25-(OH)2D3 in inhibiting the proliferation of MCF-7 cells. The in vivo effect of OCT was examined in athymic mice implanted with ER-negative MX-1 tumor, which was established as the xenograft derived from human breast carcinoma. Intratumor administration of OCT three times a week remarkably delayed the growth of MX-1 tumor in a time- and dose-dependent manner. The antitumor effect of 1 microgram/kg BW OCT was greater than that of 500 microgram/kg BW adriamycin, and the relative tumor weights in each group on day 26 were 29.7% and 50.5% of that in the vehicle-treated group, respectively. The effects of OCT and adriamycin were additive, and the relative tumor weight after 26 days of combined treatment was 21.7% of that in the vehicle-treated group. Oral administration of OCT was also effective, and the relative tumor weight in the OCT-treated group (1 microgram/kg BW) was 54.6 +/- 0.1% (mean +/- SEM) of that in the vehicle-treated group. Neither intratumor nor oral administration of OCT raised the serum calcium level in these animals. These results demonstrate that OCT is a potent inhibitor of the proliferation of breast cancer cells with or without ER and that OCT inhibits the growth of breast cancer in vivo without inducing hypercalcemia. We suggest that OCT may provide a new strategy for the treatment of breast carcinoma regardless of ER status.
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PMID:A novel vitamin D3 analog, 22-oxa-1,25-dihydroxyvitamin D3, inhibits the growth of human breast cancer in vitro and in vivo without causing hypercalcemia. 185 78

Cultures of a cell line derived from a murine mammary carcinoma that induces hypercalcemia were examined for soluble products that could induce osteoclasts to differentiate from murine bone marrow cells. The serum-free culture supernatant of this cell line stimulated growth of colonies from bone marrow cells that exhibited tartrate-resistant acid phosphatase (TRAPase) activity. These TRAPase-positive cells demonstrated essential features of osteoclasts when cultured with mineralized bone or dentin. The culture period required for colony development and the frequency of colony-forming cells indicated that relatively primitive marrow progenitors were stimulated by a tumor-derived factor(s) to form immature osteoclasts. Other colony-stimulating factors (CSFs), including granulocyte CSF, macrophage CSF, granulocyte-macrophage CSF and interleukin 3, were ruled out as the source of the activity produced by the tumor cells. The biological activity was successfully purified by gel filtration chromatography and reverse-phase HPLC. By SDS/PAGE, the activity was traced to a protein of approximately 17 kDa. Functional and biochemical studies of the purified factor suggest that it is distinct from any known CSF of myeloid cells. This protein appears to be a CSF for the osteoclast lineage, osteoclast CSF (O-CSF).
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PMID:Isolation of a murine osteoclast colony-stimulating factor. 192 9

To elucidate the actual incidence of hypercalcemia in patients with esophageal carcinoma, 382 consecutive cases admitted to the National Cancer Center Hospital (Tokyo, Japan) from 1983 to 1988 were investigated. Hypercalcemia was detected in 5 patients of 376 (1.3%) at the time of primary detection of cancer, and in 45 patients of 120 (38%) patients with recurrent or unresectable cancer who were monitored within 2 months of death. These observations demonstrated that this electrolyte imbalance is a frequent paraneoplastic syndrome observed in patients with advanced esophageal carcinoma. With regard to the etiology, bone metastases were detected in 13 of 49 patients with hypercalcemia; the remaining 36 patients were assumed to be induced by the production of hypercalcemic substance(s) by tumor tissues. Parathyroid hormone-related protein (PTHrP) is a newly discovered factor which increases serum calcium in vivo. The detection of PTHrP mRNA in tumor tissues as well as the production of PTHrP-like immunoreactivity by tumor tissues were closely associated with the development of hypercalcemia, suggesting that PTHrP is the major cause of hypercalcemia in patients with esophageal carcinoma.
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PMID:Hypercalcemia in patients with esophageal carcinoma. The pathophysiologic role of parathyroid hormone-related protein. 193 13

Glucocorticoids are widely used for the treatment of malignancy-associated hypercalcemia to delay the occurrence of an escape phenomenon inherent in calcitonin therapy. Using parathyroid hormone-related protein (PTHrP)-producing squamous carcinoma cells (T3M-1 and EC-GI) established in our laboratory, we investigated the in vitro effects of glucocorticoids and calcitonin on PTHrP mRNA expression in the cells and release of PTHrP into the culture medium. The PTHrP gene was constitutively expressed in the logarithmic growth phase in both squamous carcinoma cell lines. When these cells became superconfluent, PTHrP mRNA expression was greatly diminished in T3M-1 cells but was not distinctly diminished in EC-GI cells. Hydrocortisone inhibited the PTHrP mRNA expression in T3M-1 cells and EC-GI cells in a dose-dependent manner. In accordance with the decreased expression of PTHrP mRNA, the release of immunoreactive as well as bioactive PTHrP also decreased in the conditioned medium of glucocorticoid-treated cells. The minimal effective concentration of prednisolone was about 10(-7) M, which is readily attainable in the serum of patients treated with the agent. Calcitonin and indomethacin did not affect the PTHrP mRNA expression or PTHrP release into the medium. Calcitonin did not modulate the hydrocortisone-induced inhibition of PTHrP production. These in vitro findings suggest that the combined use of glucocorticoids and calcitonin plays a beneficial role in the treatment of malignancy-associated hypercalcemia, since the steroid hormone can suppress PTHrP mRNA expression and release of bioactive PTHrP in certain PTHrP-producing tumors.
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PMID:Effects of glucocorticoids and calcitonin on parathyroid hormone-related protein (PTHrP) gene expression and PTHrP release in human cancer cells causing humoral hypercalcemia. 193 95


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