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

Chronic hypercalcemia (HC) is accompanied by urinary concentration defects, and functional studies indicate defects in the thick ascending limb (TAL). We hypothesize that dysregulation of renal sodium transporters may play an important role in this. Vitamin D-induced HC in rats resulted in polyuria, natriuresis, and phosphaturia. Immunoblotting revealed a marked reduction in the abundance of rat type 1 bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1) in inner stripe of the outer medullary (ISOM; 36 +/- 5%) and whole kidney (51 +/- 11%) in HC. Consistent with this finding, immunocytochemistry and immunoelectron microscopy demonstrated reduced BSC-1 labeling of the apical plasma membrane. Immunoblotting and immunohistochemical labeling of the K channel Kir 1.1 (ROMK) was also reduced in HC. In contrast, there were no reductions in the expression of Na/H exchanger (NHE)3 and Na,K-ATPase in ISOM. The abundance of the proximal tubule type II Na-P(i) cotransporter (NaPi-2) (but not Na,K-ATPase and NHE3) was significantly reduced (25 +/- 4%), consistent with a dramatic increase in urinary phosphate excretion. In conclusion, 1) the reduced abundance of BSC-1 and ROMK in TAL is likely to play a major role in the urinary concentration defects associated with HC and 2) the reduced abundance of NaPi-2 is likely to play a role in the increased urinary phosphate excretion.
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PMID:Reduced expression of Na-K-2Cl cotransporter in medullary TAL in vitamin D-induced hypercalcemia in rats. 1173 10

A 48-year-old woman presented with a history of premature menopause, polyuria, polydipsia, fever, and diffuse bony tenderness. Her evaluation revealed central diabetes insipidus, hypothalamic amenorrhea, an elevated free calcium on multiple occasions with an elevated 1,25 dihydroxyvitamin D level, and osteoporosis by densitometry. Skeletal series revealed multiple lytic lesions involving the long bones. The diagnosis of Langerhans' cell granulomatosis was made. She was treated with hormone replacement therapy, radiotherapy, and vinblastine, with a dramatic improvement in her pain and a near normalization of her free calcium. Whereas hypercalcemia has been described in several granulomatous disorders and is secondary to unregulated extrarenal production of 1,25 dihydroxyvitamin D, it is, however, extremely rare in Langerhans' cell granulomatosis. This is the first case report of Langerhans' cell granulomatosis with hypercalcemia and documented elevated increased 1,25 dihydroxyvitamin D level that responded to the treatment of her primary disease.
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PMID:Hypercalcemia in Langerhans' cell granulomatosis with elevated 1,25 dihydroxyvitamin D (calcitriol) level. 1179 6

A 9-year-old, spayed female domestic shorthair cat presented for polyphagia, polydipsia, and polyuria following chronic methylprednisolone acetate therapy for pruritus. Initial diagnostics were consistent with uncomplicated diabetes mellitus. Serum calcium was within reference range. Within 12 hours the cat developed depression, anorexia, vomiting, and severe dehydration. Laboratory analysis indicated marked hypercalcemia as measured by both ionized and total calcium concentration. No underlying neoplastic or inflammatory process was identified. An adrenocorticotropic hormone stimulation test was indicative of adrenocortical insufficiency. The hypercalcemia resolved with glucocorticoid supplementation and correction of the dehydration. The diabetes mellitus and adrenal insufficiency both resolved within 9 weeks.
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PMID:Hypercalcemia due to latrogenic secondary hypoadrenocorticism and diabetes mellitus in a cat. 1180 13

A retrospective study of 43 dogs with anal sac adenocarcinoma (ASAC) was performed to characterize the clinical presentation and response to treatment. Clinical signs at presentation varied considerably, with signs related either to sublumbar nodal metastasis (tenesmus or constipation) or hypercalcemia (polyuria-polydipsia and anorexia) being the most frequent findings. At the time of presentation, 23 (53%) dogs had hypercalcemia and 34 (79%) had metastases, with the regional lymph nodes (31 dogs, 72%) being the most common site of metastasis. A variety of chemotherapeutic agents were administered, with partial remission (PR) recorded in 4 of 13 (31%) dogs treated with cisplatin and in 1 of 3 (33%) dogs treated with carboplatin. The median survival for all dogs was 6 months (range, 2 days-41 months). There was no statistical association between the presence of hypercalcemia and survival, although the power of the study to detect an increase in survival of 3 months was low (.33). We conclude that platinum chemotherapy has antitumor activity in canine apocrine gland carcinoma and that further study of these agents is warranted.
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PMID:Canine anal sac adenocarcinomas: clinical presentation and response to therapy. 1182 97

A middle-aged woman presented with a history of constipation, easy fatigue, depressive mood, lassitude, polydipsia, and polyuria. The patient posed a challenging diagnostic dilemma due to the presence of persistent severe hypercalcemia and relative lack of clinically manifested symptoms. Clinical, biochemical, and genetic examinations confirmed the diagnosis of familial hypocalciuric hypercalcemia as a result of C562Y calcium-sensing receptor mutation, and a coexisting parathyroid adenoma. After adenectomy, the patient's clinical situation improved markedly, and a modest equilibrium hypercalcemia persisted. This case presents an unusual combination of two relatively common endocrine disorders.
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PMID:Parathyroid adenoma in a subject with familial hypocalciuric hypercalcemia: coincidence or causality? 1188 54

Congenital mesoblastic nephroma (CMN) can present with atypical clinical and imaging findings. A premature male neonate was born to an 18-year-old woman after 33 weeks' gestation, which was complicated by polyhydramnios and placenta abruptio. A right abdominal mass was diagnosed antenatally. From the 1st day of life, the newborn had hypercalcemia with initially normal parathormone levels and polyuria for the first hours of life and normal urine output afterwards. Ultrasonographic study and magnetic resonance imaging of the abdomen showed at the upper pole of the right kidney a heterogeneous, solid, poorly defined mass, partially surrounded by a subcapsular fluid collection mimicking malignant rhabdoid tumor of the kidney. Surgical resection revealed a CMN of mixed, classic, and in areas, cellular type. One year after the resection, the patient is asymptomatic and normocalcemic. In conclusion, CMN may present with atypical clinical and imaging findings, necessitating an extensive work-up in order to exclude highly malignant renal tumors of the neonatal period.
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PMID:Congenital mesoblastic nephroma associated with polyhydramnios and hypercalcemia. 1195 58

The purpose of this study was to evaluate whether hypercalcemia is associated with downregulation of renal aquaporins (AQPs), including AQP1, AQP2, phosphorylated AQP2 (p-AQP2), AQP3, and AQP4, and if this is the case, to test whether cAMP-phosphodiesterase (PDE) inhibitor treatment can prevent AQP downregulation and prevent the development of polyuria. Vitamin D-induced hypercalcemia in rats was associated with increased urine output and reduced urine osmolality, consistent with previous findings (Levi M, Peterson L, and Berl T. Kidney Int 23: 489-497, 1983). Semiquantitative immunoblotting revealed a significant reduction in the abundance of inner medullary AQP2 (52 +/- 6% of control levels), consistent with previous studies, and of AQP2, which is phosphorylated at the PKA phosphorylation consensus site serine 256 (p-AQP2; 36 +/- 8%). Moreover, AQP3 abundance was also significantly decreased (45 +/- 7 and 61 +/- 6% of control levels in inner medulla and whole kidney, respectively). Consistent with this, immunohistochemistry demonstrated reduced AQP3 immunolabeling along the entire collecting duct. AQP4 expression was not reduced. Surprisingly, total kidney AQP1 abundance was also reduced (60 +/- 6%). AQP1 expression was reduced in the cortex and outer stripe of the outer medulla (48 +/- 7%; i.e., in proximal tubules). In contrast, AQP1 levels were not changed in the inner stripe of the outer medulla or in the inner medulla (i.e., descending thin limbs and vasa recta). Treatment with the cAMP-PDE inhibitors rolipram and milrinone in combination (inhibiting PDE IV and PDE III isoenzymes) at day 2 and onward completely prevented the hypercalcemia-induced downregulation of AQP2 and AQP3 (but not AQP1) and completely prevented the development of polyuria. In conclusion, AQP3, AQP2, and p-AQP2 are downregulated and are likely to play critical roles in the development of polyuria associated with vitamin D-induced hypercalcemia. Moreover, PDE inhibitor treatment significantly prevented the reduced expression of collecting duct AQPs and prevented the development of polyuria.
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PMID:AQP3, p-AQP2, and AQP2 expression is reduced in polyuric rats with hypercalcemia: prevention by cAMP-PDE inhibitors. 1238 9

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

We report a case of severe nephrocalcinosis related to hypercalcaemia in a newborn with glucose-galactose malabsorption. He presented with poor growth and was noted to have polyuria, which was later recognised to be severe watery diarrhoea. We discuss the possible aetiological factors for nephrocalcinosis in this condition.
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PMID:Neonatal nephrocalcinosis in association with glucose-galactose malabsorption. 1273 49

Hypercalcemia is a common, life-threatening metabolic disorder that can be associated with cancer. Its pathophysiology includes enhanced osteoclastic bone resorption and decreased renal excretion of extracellular calcium. Symptoms of hypercalcemia include nausea, vomiting, bone pain, polyuria, renal insufficiency, bradycardia, and arrhythmia. The goals of medical therapy are to inhibit bone resorption and promote renal calcium excretion. Hydration is the first step in management. Treatments for hypercalcemia include phosphates, calcitonin, bisphosphonates, and gallium nitrate. Although intravenous phosphates prevent intestinal calcium absorption and inhibit mineral and bone matrix resorption, serious adverse events include renal failure, hypotension, extraskeletal calcification, and severe hypocalcemia. Calcitonin has a rapid onset of action and can lower serum calcium concentrations within hours, but its usefulness is limited by its short duration of effect and the development of tachyphylaxis. Bisphosphonates are effective inhibitors of bone resorption but appear to have decreased response rates in hypercalcemic patients with high levels of parathyroid-related protein. Gallium nitrate, an antitumor agent noncytotoxic to osteoclasts and bone cells, appears to be more effective than pamidronate, etidronate, and calcitonin in the treatment of cancer-related hypercalcemia. Importantly, unlike bisphosphonates, gallium nitrate is effective in both parathyroid-related protein-mediated and non-parathyroid-related protein-mediated hypercalcemia.
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PMID:Treatment of cancer-related hypercalcemia: the role of gallium nitrate. 1277 55


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