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)

The typical manifestations of severe hypercalcemia with osteitis fibrosa cystica have become exceedingly rare. We describe the case of a woman hospitalized for a tibial tumor with functional impotence, leading to a diagnosis of primary hyperparathyroidism (HPT I) associated with profound vitamin D deficiency. This 31-year-old woman was admitted, after two pregnancies complicated by the HELLP syndrome. Preoperative laboratory values were as follows: calcemia 4.05 mmol/l (2.2-2.6); urinary calcium 30 mmol/24 h (1.25-7.5); parathormone (PTH) 1 195 pg/ml (10-60); and 25 OH-vitamin D 13 nmol/l (22-120). Specific MIBI uptake by the tibial lesion oriented the diagnosis towards a brown tumor. After surgical excision of a parathyroid adenoma and the brown tumor (associated with tibial fracture), calcemia fell to 1.55 mmol/l and normalized after three months. Urinary calcium fell to 0.1 mmol/24 h and remained low during the 2 years following surgery. Vitamin D levels rapidly normalized on supplementation (87 nmol/l). PTH levels fell markedly after surgery but remained higher than normal till 2 years after surgery despite normalization of calcemia three months after. Bone repair, estimated by means of bone densitometry, improved from preoperative Z-score values of - 6.54, - 5.20 and - 3.50 in the left femoral neck, right femoral neck and lumbar spine, respectively, to - 0.20, - 1.55 and - 0.28, respectively, one year after surgery. In conclusion, this case illustrates: 1) the severe osseous expression of HPT probably related to vitamin D deficiency; 2) specific MIBI uptake by the bone lesion, orientating the diagnosis towards a brown tumor; 3) the consequences of vitamin D deficiency on postoperative outcome, with transient severe initial hypocalcemia related to bone calcium avidity; 4) a possible link between HPT and the HELLP syndrome.
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PMID:Vitamin D deficiency and severe hyperparathyroidism. 1252 57

Vitamin D-elicited hypercalcemia/hypercalciuria is associated with polyuria in humans and in animal models. In rats, dihydrotachysterol (DHT) induces AQP2 water channel downregulation despite unaltered AQP2 mRNA expression and thus we investigated the mechanism of AQP2 degradation. Incubation of AQP2-containing inner medullary collecting duct (IMCD) endosomes with Ca(2+) or calpain elicited AQP2 proteolysis, an effect abolished by leupeptin. This endogenous, Ca(2+)-sensitive protease activity exhibited a different proteolytic digest pattern from trypsin, which also degraded AQP2 in vitro. IMCDs contain abundant micro-calpain protein and functional calpain proteolytic activity as demonstrated by immunohistochemistry, immunoblotting, and gel zymography. Furthermore, by small particle flow cytometry we demonstrated that micro-calpain colocalizes with apical IMCD endosomes. DHT does not appear to elicit general proteolysis, however, in addition to AQP2 degradation, DHT treatment also diminished micro-calpain and calpastatin expression although whether these changes contributed to the AQP2 instability remains unclear. Together, these data show for the first time that AQP2 is a substrate for calpain-mediated proteolysis and that furthermore, micro-calpain, like AQP2, is both highly expressed in renal inner medulla and localized to apical IMCD endosomes.
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PMID:Calpain-mediated AQP2 proteolysis in inner medullary collecting duct. 1264 65

Vitamin D intoxication in infancy has serious consequences attributable to acute hypercalcemia and subsequent hypercalcuria/nephrocalcinosis. Current treatments of patients with vitamin D intoxication are unsatisfactory and associated with prolonged hypercalcemia. We now report the use of oral alendronate sodium in a 3-month-old infant with vitamin D intoxication. Short-term oral alendronate sodium treatment effectively corrected hypercalcemia/hypercalciuria, decreased the duration of hospitalization, and appears safe in 15 months of observation.
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PMID:Oral bisphosphonate therapy for vitamin D intoxication of the infant. 1664 27

The development of drugs that are highly selective and yet produce minimal toxicity to host tissue remains one of the most difficult challenges in cancer therapeutics. Since the majority of malignancies are treated with drugs in combination rather than single agents, one practical approach to circumvent this problem is to develop new therapeutic agents that will potentiate the effectiveness of current clinical protocols. This strategy would accelerate the acceptance of new drugs as adjunct therapies since these agents could be used at concentrations well below their maximal tolerated doses. Tumor cells derived from a variety of different sources have been shown to express the Vitamin D(3)receptor and to be susceptible to growth arrest and/or cell death in response to Vitamin D(3)and its analogues. The hypercalcemia that generally accompanies the utilization of pharmacological concentrations of Vitamin D(3) has been ameliorated in part through the development of Vitamin D(3) analogues. Studies in cell culture and in animal model systems as well as clinical trials have established the potential utility of Vitamin D(3) and Vitamin D(3) analogues as agents which can enhance the antiproliferative and/or cytotoxic effects of conventional chemotherapeutic drugs as well as ionizing radiation. Consequently, Vitamin D(3) and Vitamin D(3) analogues, utilized at concentrations which produce limited hypercalcemia, are likely to prove effective as adjuncts to conventional chemotherapy and radiotherapy.
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PMID:Vitamin D3 and vitamin D3 analogues as an adjunct to cancer chemo-therapy and radiotherapy. 1267 20

Severe Vitamin D(dihydrotachysterol)-intoxication with temporary anemia and hypercalcemia responsive to bisphosphonates. HISTORY AND FINDINGS: A 31-year old female patient presented with pain of her skeletal system. 6 months prior to her presentation, she underwent thyroid surgery for Graves disease. She also suffered from endocrine orbitopathy. Afterwards, she expirienced surgical hypoparathyroidism and received dihydrotachy-sterol (A.T.10 (R)) in a dose of up to 4 mg per day. The physical examination was unremarkable except for the presence of Graves' ophthalmopathy and a swelling at the left ancle. INVESTIGATIONS: Upon admittance, she had severe hypercalcemia (serum calcium: 4.1 mmol/l) with plasma intact PTH levels below the limit of detection, renal failure (serum creatinine: 5.5 mg/dl) and normocytic anemia (initial hemoglobin: 8.3 g/dl, upon rehydration: 6.6 g/dl). TREATMENT AND COURSE: Upon rehydration and induced diuresis, the renal function improved and the serum calcium came down rapidly in the early treatment phase. However, serum calcium remained elevated at around 3.0 mmol/l after 4 weeks. Only after the use of the bisphosphonate pamidronate (15 mg), serum calcium returned into the normal range and remained there. Treatment for hypoparathyroidism had to be reinstituted only 20 weeks after dihydrotachysterol had been discontinued. The anemia had resolved without any treatment at that time. CONCLUSIONS: Treatment with dihydrotachysterol and other long-acting Vitamin D preparations has to be monitored closely because of the risk of severe hypercalcemia, which may be difficult to treat. In our case, dihydrotachysterol was still active until week 20 after the drug was discontinued. Anemia should be considered as a side effect of dihydrotachysterol intoxication and does not warrant elaborate differential diagnosis in this context. A single administration of a bisphosphonate turned out to be of major therapeutic benefit and resulted in a lasting correction of hypercalcemia. Therefore, bisphosphonates should become part of the treatment regimen for vitamin D intoxication.
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PMID:[Severe Vitamin D(dihydrotachysterol)-intoxication with temporary anemia and hypercalcemia responsive to bisphosphonates] 1275 Oct 20

Breast cancer is the most frequent malignancy of women in the Western world. Vitamin D compounds constitute a novel alternative to the conventional use of antiestrogens for chemoprevention and chemotherapy. The biologically active form of vitamin D, 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], not only plays an essential role in the control of calcium homeostasis, but also acts on cells of a variety of tissues to promote inhibition of cellular proliferation and induction of differentiation. The potential use of 1,25(OH)2D3 in the treatment of cancer is limited by its propensity to cause hypercalcemia at pharmacologically active doses. This has led to the synthesis of analogs of vitamin D that exhibit potent anticancer effects, but have low calcemic activity. Evidence from both in vitro and in vivo studies has demonstrated that vitamin D compounds can inhibit the growth of breast cancer cells, suggesting their therapeutic value in the treatment or prevention of this disease.
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PMID:Vitamin D analogs and breast cancer. 1289 32

The active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25(OH)D3), has been recognized for over 2 decades as a modulator of cell proliferation and differentiation in many cell types, including breast cancer. However, any potential anti-tumour properties displayed by 1,25(OH)D3 are limited by the tendency to cause hypercalcaemia when administered at high doses. Because of this, synthetic vitamin D analogues have been developed that retain the anti-tumour effects seen with 1,25(OH)D3 but which have reduced calcaemic activity. However, it is still unclear as to how 1,25(OH)D3 and its synthetic analogues act within breast cancer cells to elicit the effects on cellular proliferation and differentiation. In this chapter we review the advances that have been made in trying to answer this question. It has been found so far that 1,25(OH)D3 has an effect on the expression of certain cell cycle regulators and in this way can bring about G1 arrest. Evidence has also emerged that vitamin D compounds can also affect the growth-promoting pathways initiated by two important factors involved in breast cancer cell promotion; namely the insulin-like growth factor I (IGF-I) and oestrogen-receptor (ER) pathways. Vitamin D compounds have also been implicated in promotion of apoptosis in breast cancer cells and evidence suggests that 1,25(OH)D3 and its synthetic analogues may potentiate responsiveness of breast cancer cells to conventional cytotoxic agents. Although much remains to be learned about the associated underlying mechanisms, ongoing research suggests that vitamin D analogues are a new class of compounds with potential in breast cancer treatment and prevention.
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PMID:Mechanisms implicated in the growth regulatory effects of vitamin D compounds in breast cancer cells. 1290 48

The active metabolite of vitamin D, 1alpha, 25-dihydroxyvitamin D3 [1,25(OH)2D3]--a seco-steroid hormone is a pivotal regulator of cellular proliferation and differentiation those are independent of its classical function of calcium homeostasis and bone mineralization. The existence of the nuclear vitamin D receptor (VDR) has been found in numerous tissues in different organs, which are the so-called 'non-classical' targets of this seco-steroid hormone. Vitamin D has been documented as a potent antiproliferative agent in different tissues and cells. Epidemiological studies reveal a negative correlation between physiological level of vitamin and cancer risk. Studies using animal models clearly demonstrate protective role of vitamin D in different cancer types by the reduction in tumor progression and by monitoring biochemical parameters. Experiments with cultured human and animal cancer cell lines show similar antiproliferative role of vitamin D manifested by up or down regulations of crucial genes leading to inhibition of cellular growth. Hypercalcemia hinders broad-spectrum therapeutic uses of vitamin D in cancer chemotherapy. Application of vitamin D analogs having similar chemical structures or other compounds having vitamin D like actions but lacking calcemic adverse effects are getting significant attention towards rational therapeutics to treat cancer. The current review focuses on the application of vitamin D and its analogs in different forms of cancer and on the molecular mechanism involved in vitamin D mediated inhibition in cellular proliferation, cell cycle, induction of apoptosis and tumor suppression, which may eventually evolve as a meaningful cancer therapy.
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PMID:Antiproliferative role of vitamin D and its analogs--a brief overview. 1461 76

Vitamin D has been used for topical treatment of psoriasis, and 22-oxacalcitriol (OCT), shown to be less calcemic, was developed for the topical treatment of psoriasis in Japan. Recently, we treated a psoriatic patient with diabetic nephropathy who developed severe hypercalcemia with exacerbation of chronic renal failure by the use of topical OCT. Analysis of the reported cases demonstrated that both the severity of psoriasis and renal dysfunction are critical factors in the induction of hypercalcemia in the topical treatment of psoriasis. Therefore, we must pay attention to the severity of psoriasis, especially when complicated by renal function impairment. Regular monitoring of Ca and renal function is essential to avoid life-threatening hypercalcemia from the topical treatment with vitamin D analogues.
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PMID:Topical treatment with 22-oxacalcitriol (OCT), a new vitamin D analogue, caused severe hypercalcemia with exacerbation of chronic renal failure in a psoriatic patient with diabetic nephropathy; a case report and analysis of the potential for hypercalcemia. 1471 59

The goal of this study was to investigate the influence of experimentally induced hypercalcaemia (after 100000 UI Vigantol and CaCl2) on neuroendocrine cells (NECs) in the thyroid and airways in the rat. After 24 h, 7 days and 14 days the thyroid and lungs were collected. Paraffin sections were immunocytochemically stained with specific antibodies against CGRP, calcitonin (CT) and synaptophysin (SY) in the airway NECs and thyroid C cells. The largest hypercalcaemia were observed in experimental rats after 7 days. More significant changes in the number and size of neuroendocrine cells were observed in the thyroid gland as well as in the airways. In the airways only a slight increase in the number of neuroepithelial bodies (NEBs) was observed, some of which gave evidence of hypertrophy symptoms.
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PMID:A preliminary evaluation of thyroid and respiratory tract neuroendocrine cells in the rat after experimental hypercalcaemia. 1503 14


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