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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the study was to investigate the interrelation between induced hypercalcaemia and serum intact parathyroid hormone (S-PTH(1-84)) in normal man and in patients with primary hyperparathyroidism (PHPT) by measuring blood ionized calcium (B-Ca++) and S-PTH(1-84) before and during a controlled calcium infusion. Guided by frequent measurements of B-Ca++, we adjusted the calcium infusion rate continuously, thereby keeping B-Ca++ in a steady state at a pre-determined level approximately 0.25 mmol l-1 above baseline values. This calcium clamp technique (CCT) applied to 14 normal volunteers for 120 min established a standardized reference for parathyroid suppression and the renal physiological PTH response. The reproducibility of the method and the results obtained by the CCT were satisfactorily assessed in six of the 14 normal subjects. In normal subjects B-Ca++ was raised from 1.25 +/- 0.3 mmol l-1 (mean +/- SD) to 1.49 +/- 0.02 mmol l-1 suppressing S-PTH(1-84) to 264 +/- 9.9% of pre-infusion levels. We applied the CCT to 10 patients with PHPT for 120 min raising B-Ca++ from 1.41 +/- 0.09 mmol l-1 to 1.69 +/- 0.08 mmol l-1, thereby suppressing S-PTH(1-84) to 47.9 +/- 16.3% of pre-infusion levels. The renal handling of calcium and phosphate during CCT demonstrates the biological effects of suppressed activity of PTH on the renal tubules showing increments in the maximal tubular phosphate reabsorption in relation to the glomerular filtration rate (TmP/GFR) and decreased tubular reabsorption fraction of calcium. The described CCT is a safe and reliable dynamic test.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium clamp technique: suppression of serum intact PTH by induced hypercalcaemia in normal man and primary hyperparathyroidism. 141 Dec 58

This investigation was carried out to evaluate the clinical utility and diagnostic value of serum intact PTH measurement using a recently introduced immunochemiluminometric assay (ICMA). Studies were carried out in 42 normal subjects, 24 patients with primary hyperparathyroidism, 21 patients on chronic maintenance hemodialysis, 8 patients with postsurgical hypoparathyroidism, 7 patients with cancer hypercalcemia and 6 patients with osteomalacia. A good correlation was found in normal subjects between serum ICMA PTH levels and both intact PTH measured by a two-site immunoradiometric assay (n = 42, r = 0.67, p less than 0.001) and a widely used midmolecule radioimmunoassay (n = 21, r = 0.78; p less than 0.001). Similar good correlations were found in primary hyperparathyroidism patients (IC-MA vs immunoradiometric assay r = 0.74; p less than 0.001; ICMA vs midmolecule assay r = 0.77; p less than 0.001). As far as the hypercalcemic conditions were concerned, in 5 patients with mild primary hyperparathyroidism, ICMA PTH levels were in the upper range of those found in normal subjects, even though they were inappropriately high in respect to serum calcium values. However, serum ICMA PTH levels were clearly suppressed or undetectable in the majority of patients with cancer hypercalcemia or postsurgical hypoparathyroidism. Following calcium and EDTA infusions in patients with primary hyperparathyroidism, the behaviour of ICMA PTH levels in general parallelled that of immunoradiometric PTH assay, thus indirectly suggesting the ability of the method to measure the intact molecule.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Conventional and new diagnostic applications of a two-site immunochemiluminometric assay for parathyroid hormone. 144 86

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


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