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)

Parenteral application of the active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3, has been anticipated to have remarkable efficacy in secondary hyperparathyroidism. However, in a reproduction seg. I study in rats, poor reproductive performance was reflected in a decrease in the number of matings, implantations and live births. These changes were though reversible after treatment with the compound was discontinued. In order to clarify the mechanism of these reversible toxicities, the following were examined in female rats treated with the D3 metabolite: 1. effect on the estrous cycle (no treatment for 2 weeks, treatment for 3 weeks and recovery for 2 weeks), and 2. effect on the maintenance of pregnancy (treatment for 2 weeks before mating and during the gestation period). In both groups, the levels of calcium, calcitonin, PTH and progesterone in serum were measured, and histopathological examination of the thyroid, parathyroid, ovary and uterus was carried out. The following results were observed: 1) disturbance of the estrous cycle, 2) hypofunctional changes in the corpus luteum in the ovary, and the epithelium, endometrium and uterine gland in the uterus with a decrease in the serum progesterone level and 3) hypercalcemia with a decrease in calcitonin or PTH levels in serum with morphological changes including atrophy and cyst-formation in the parathyroid. However, the above changes were reversible, and recovery was observed after administration of the compound was discontinued. These results indicate that the hypercalcemia caused by 1,25-dihydroxyvitamin D3 disrupts endocrinological homeostasis which in turn temporarily disrupts the female reproductive system. Furthermore, it was suggested that 1,25-dihydroxyvitamin D3 itself directly influences on endocrinological organs (hypothalamus, pituitary, parathyroid and thyroid) and reproductive organs (ovary and uterus).
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PMID:Effect of 1,25-dihydroxyvitamin D3 on the female reproductive system in rats. 145 99

Intravenous calcitriol is known to directly suppress PTH secretion and release. We evaluated the effect of four months of treatment with low-dose intravenous calcitriol on PTH levels in 83 hemodialysis patients. The criteria for including patients in the study were a serum PTH levels at least four times the normal limit, a serum total calcium less than 10 mg/dl and good control of the serum phosphorus level. All patients underwent standard bicarbonate or acetate dialysis; dialysate calcium level was maintained at the usual 3.5 mEq/liter concentration. Initial calcitriol dose was 0.87 +/- 0.02 (SEM) micrograms (0.015 micrograms/kg body wt) thrice weekly at the end of dialysis, and it was reduced in case of hypercalcemia or elevated calcium-phosphate product. Seven out of 83 patients dropped out during treatment. Among the 76 patients who completed the study, 58 (76%) showed a highly significant decrease of intact PTH levels (average reduction 48%) and of alkaline phosphatase levels after four months of therapy. Total serum calcium increased slightly but significantly in the responder group but remained unchanged in the non-responders. No significant changes in ionized calcium levels could be detected, even in responders. Treatment was well tolerated by patients, but 60% of them had transient episodes of hyperphosphatemia. Mean serum phosphate was 4.95 mg/dl at the beginning of the study. It increased significantly after four months of treatment in patients who showed a decrease of PTH levels, although it remained within acceptable limits, below 5.5 mg/dl. Twenty-eight of 76 patients (37%) reduced the dose of calcitriol because their calcium-phosphate products exceeded 60.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low-dose intravenous calcitriol treatment of secondary hyperparathyroidism in hemodialysis patients. Italian Group for the Study of Intravenous Calcitriol. 145 3

Pamidronate (aminopropylidene diphosphonate, APD) is known to be an effective agent in lowering plasma calcium in cancer associated hypercalcaemia and in primary hyperparathyroidism. Combined therapy with pamidronate and calcitonin has proved efficient in the treatment of severe cancer-associated hypercalcaemia. A 66-year-old woman in hypercalcaemic crisis caused by primary hypreparathyroidism was successfully treated with this combined therapy. Albumin corrected plasma calcium was 5.26 mmol/l on arrival and the PTH level was very high. The combined therapy lowered the plasma calcium to normal and made it possible to perform elective parathyreoidectomy. A 5.8 g parathyroid adenoma was removed. It is recommended to consider combined therapy with pamidronate and calcitonin in the emergency management of hypercalcaemic crisis.
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PMID:[Combination therapy with pamidronate and calcitonin in hypercalcemic crisis caused by primary hyperparathyroidism]. 146 41

We describe an adult patient who developed persistent hypercalcemia while bedridden for more than three months with pancreatitis and sepsis. On the basis of hypercalciuria, suppressed serum intact PTH, suppressed serum 1,25-dihydroxy vitamin D3 and no clinical evidence of malignancy, the diagnosis of immobilization hypercalcemia was established His hypercalcemia improved during treatment with saline, calcitonin and/or etidronate. With active mobilization and weight-bearing exercises, serum calcium finally normalized. We discuss clinical and laboratory features as well as current modalities of treatment of this rare form of hypercalcemia in adults.
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PMID:Immobilization hypercalcemia in an adult patient with pancreatitis and sepsis: case report. 148 89

The effect of intravenous 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] on circulating levels of intact parathyroid hormone (PTH 1-84) and COOH-terminal immunoreactive PTH(PTH 53-84) was examined in 13 patients on chronic hemodialysis. Thirteen patients were treated for 300 days (10 months), 9 patients for 520 days (14 months) and 6 patients for 720 days (2 years) with increasing doses of 1 alpha(OH)D3 intravenously under careful control of plasma Ca2+. Blood samples were obtained 1 week before start of treatment and then at every 2nd week. None of the patients had previously been treated with oral vitamin D metabolites. Intact PTH levels were maximally suppressed after 27-33 weeks of treatment by approximately 73%. At the end of the study periods, PTH 1-84 was still suppressed by 78 +/- 4.3% after 300 days, 78 +/- 8.8% after 520 days and 85 +/- 6.5% after 720 days. Plasma Ca2+ was kept within normal levels, but showed an initial increase from 1.14 +/- 0.03 to 1.27 +/- 0.15 mmol/l, and an adjustment of the doses of 1 alpha(OH)D3 was necessary. The present investigation demonstrated (1) that intravenous administration of the 1-hydroxylated vitamin D metabolite 1 alpha(OH)D3 induced a significant decrease in circulating levels of biologically active intact PTH, and (2) that it was possible to maintain the marked suppression of PTH secretion by intravenous treatment of 1 alpha (OH)D3 for up to 2 years. Hypercalcemia could be avoided by careful monitoring of plasma Ca2+ and adjustment of the doses of 1 alpha(OH)D3.
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PMID:Long-term suppression of secondary hyperparathyroidism by intravenous 1 alpha-hydroxyvitamin D3 in patients on chronic hemodialysis. 148 99

Circulating N-terminal PTH-related protein (PTHrP), N-terminal PTH, and 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations were measured in normal dogs and dogs with cancer-associated hypercalcemia (CAH), parathyroid adenomas, and miscellaneous tumors. PTHrP was undetectable (less than 1.8 pM) in normal dogs and increased in dogs with CAH due to adenocarcinomas derived from apocrine glands of the anal sac (44.9 +/- 27 pM), lymphoma (8.3 +/- 4.4 pM), and miscellaneous carcinomas (13.3 +/- 11.4 pM). The PTHrP concentration decreased in dogs with lymphoma and anal sac adenocarcinomas after successful treatment of CAH. The PTHrP concentration had a significant linear correlation with total serum calcium in dogs with anal sac adenocarcinomas and hypercalcemia, but not in dogs with lymphoma and hypercalcemia. Serum N-terminal PTH concentrations were usually in the normal range (12-34 pg/ml) for all groups of dogs except dogs with parathyroid adenomas (83 +/- 38 pg/ml). The serum PTH concentration increased after successful treatment of CAH. Serum 1,25-(OH)2D concentrations were decreased, normal, or increased in dogs with CAH, and 1,25-(OH)2D levels decreased after treatment of CAH. In summary, circulating concentrations of PTHrP are consistently increased in dogs with CAH, and PTHrP appears to play an important role in the induction of hypercalcemia.
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PMID:Parathyroid hormone (PTH)-related protein, PTH, and 1,25-dihydroxyvitamin D in dogs with cancer-associated hypercalcemia. 150 57

Despite extensive study since the first report of familial benign hypercalcemia (FBH, or hypocalciuric hypercalcemia) in 1972, there is no evidence of the specific abnormal gene product. FBH is highly suitable for either a candidate gene or a reverse genetics approach to localizing the genetic abnormality, because it is inherited in an autosomal dominant pattern, is highly penetrant, does not affect survival, and can be diagnosed in families with readily available measurements. Importantly, several candidate genes have been cloned and mapped. Therefore, we collected blood samples and extracted leukocyte DNA from 94 members of 4 families with well documented FBH (44 affected, 45 unaffected, and 5 unclassifiable). We digested the DNA samples with various restriction endonucleases, conducted standard Southern blotting, and searched for restriction fragment length polymorphisms for the following candidate genes (probe names in parentheses): multiple endocrine neoplasia (MEN) type 1 (pMCMP.1, pHBI59, p3C7, and pTHH26), MEN 2a (MCK2 and cTB14.34), basic fibroblast growth factor (pHFL1-7), (Ca2+,Mg2+)ATPase isoform 4 (hPMCA4), membrane Na/Ca exchanger (cNC28 M-A), PTH (pPTH-LF), and calbindin-D28K (pSKCalb). In addition, we used the anonymous variable number tandem repeat marker pYNH24 to verify pedigree structures by excluding misinheritances. Data were analyzed using the Linkage program. For none of the genes was there significant linkage with the FBH trait; logarithm of odds scores ranged from -1.3 to -26.0 at a recombination fraction of 0.001, and from 0.6 to -5.6 at a recombination fraction of 0.10. We conclude that FBH is unrelated to the MEN syndromes and is not caused by mutations in any of the calcium-regulating or -binding proteins or growth factors studied thus far.
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PMID:Genetic linkage analysis in familial benign hypercalcemia using a candidate gene strategy. I. Studies in four families. 151 76

Hypercalcemia may occur as a complication of haematological malignancies, in association with solid tumors with bone metastases, and with solid tumors in the absence of bone metastases. The latter syndrome, known as the humoral hypercalcemia of malignancy (HHM) shares many features with primary hyperparathyroidism. A parathyroid hormone-related protein (PTHrP) has been identified, isolated and cloned, which is most likely responsible for the calcium disturbances in HHM, PTHrP is a previously unrecognized hormone which has limited amino-terminal sequence homology with PTH and is the product of a separate gene. Tissue localization studies have identified PTHrP in squamous cell carcinomata, renal cortical carcinomata, in a proportion of breast cancers and in adult T-cell leukemia/lymphoma. In normal tissues, PTHrP has been immunohistochemically localized in keratinocytes, placenta and fetal parathyroid glands. In addition to its role in mediating hypercalcemia in cancer, PTHrP is likely to have an important endocrine role in the fetus, and perhaps a paracrine function in several organs.
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PMID:Hypercalcemia in cancer. 152 53

The purpose of this study is to evaluate the place of intravenous 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) in the prevention of radiologically obvious hyperparathyroidism (HPT) in patients on maintenance dialysis while excluding aluminium phosphate binder and using a dialysate calcium concentration of 1.62 mmol which keeps the intradialytic calcium balance neutral. Therefore, 47 patients without subperiosteal resorption and previously treated by oral CaCO3 and if necessary Mg(OH)2 as phosphate binder while their dialysate calcium had a Ca level of 1.62 and a Mg level of 0.2 mmol/l were randomized into a control group of 24 who were maintained on the same treatment and an experimental group of 23. This group discontinued CaCO3 and received intravenous 1 alpha-OH-D3 after each dialysis at increasing doses up to 4 micrograms and increased Mg(OH)2 as their sole phosphate binder. When plasma Ca increased above 2.7 mmol/l, the dose of 1 alpha-OH-D3 was decreased. When plasma PO4 increased above 2 mmol/l, the dose of Mg(OH)2 was increased to the highest dose not inducing diarrhea, hypermagnesemia (less than 2 mmol/l) or hyperkalemia (less than 6 mmol/l). In case of persistent hyperphosphatemia, the dose of 1 alpha-OH-D3 was decreased. Since mean plasma alkaline phosphatase was normal, HPT was monitored on the plasma concentration of 1-84 PTH for which a previous histological study showed that frank osteitis fibrosa was present only when they were above 70 pg/ml, i.e. (about twice the upper limit of the normal value). Before the study, plasma PTH was below this limit in 16 patients of the CaCO3 group and in 14 patients of the 1 alpha-OH-D3 group. After 6 months, they remained below this limit in all patients except 2 of each group. Plasma PTH was initially above 70 pg/ml in 8 of the CaCO3 and did not change significantly throughout the study, 2 patients having at 6 months a PTH level below 70 pg/ml. In contrast with intravenous 1 alpha-OH-D3, all the 9 patients with initial frank HPT decreased their PTH levels after 2 months, the levels being below 70 pg/ml in 6 cases. However, because of hypercalcemia and/or of hyperphosphatemia in spite of a highest tolerable dose of Mg(OH)2, 1 alpha-OH-D3 doses had to be decreased down to 0.4 microgram per dialysis at the 6th month so that at 6 months 6 of 9 patients had their PTH levels above 70 pg/ml, a number comparable to that of patients treated with CaCO3 (6 of 8).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prevention of hyperparathyroidism in patients on maintenance dialysis by intravenous 1-alpha-hydroxyvitamin D3 in association with Mg(OH)2 as sole phosphate binder. A randomized comparative study with the association CaCO3 +/- Mg(OH)2. 155 99

Parathyroid carcinoma is a rare tumor responsible for 0.5-5% of primary hyperparathyroidism. It is usually small (not more than 27 g) and the precise diagnosis of malignancy is made when local or distant metastases are found. We describe a case of a 37 yr old male presenting with a substernal goiter and no specific symptoms except hypertension. This mass had cysts and calcifications and it was in the anterior upper mediastinum. The patient had severe hypercalcemia (Ca greater than 14 mg/dl), high PTH levels and mild renal failure. Bone scanning showed signs of hyperparathyroidism. The patient was subjected to total thyroidectomy and removal of the mass en block. The tumor was circumscribed lobulated and mostly cystic. It weighed 1,200 g (380 g after evacuation of cysts) and measured 12 x 9 x 4.5 cm. Histologic examination showed a highly differentiated adenocarcinoma of parathyroid with metastasis in a regional lymph node. Almost 4 years later the patient is alive and well without hypercalcemia and without evidence of distant metastases.
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PMID:Large parathyroid functioning carcinoma (1,200 g) presenting as a substernal goiter. 156 Jan 89


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