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Disease
Symptom
Drug
Enzyme
Compound
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Target Concepts:
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Query: UMLS:C0020438 (
hypercalciuria
)
2,502
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Hypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)
2
D], and impaired degradation of 1,25(OH)
2
D. The ingestion of excessive amounts of vitamin D
3
(or vitamin D
2
) results in hypercalcemia and
hypercalciuria
due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)
2
D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D. In patients with granulomatous disease such as sarcoidosis or tuberculosis and tumors such as lymphomas, hypercalcemia occurs as a result of the activity of ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages or tumor cells and the formation of excessive amounts of 1,25(OH)
2
D. Recent work has identified a novel cause of non-PTH-mediated hypercalcemia that occurs when the degradation of 1,25(OH)
2
D is impaired as a result of mutations of the 1,25(OH)
2
D-24-hydroxylase
cytochrome P450
(CYP24A1). Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1,25(OH)
2
D, suppressed PTH concentrations,
hypercalciuria
, nephrocalcinosis, nephrolithiasis, and on occasion, reduced bone density. Of interest, first-time calcium renal stone formers have elevated 1,25(OH)
2
D and evidence of impaired 24-hydroxylase-mediated 1,25(OH)
2
D degradation. We will describe the biochemical processes associated with the synthesis and degradation of various vitamin D metabolites, the clinical features of the vitamin D-mediated hypercalcemia, their biochemical diagnosis, and treatment.
...
PMID:Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment. 2758 37
