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Whereas almost any kind of tumor may cause humoral hypercalcemia of malignancy (HHM), the most common types are squamous carcinoma of any origin (lung, esophagus, skin, and cervix are common sites) and breast and renal carcinomas. The continuous secretion of PTHrP by tumors leads to a dramatic uncoupling of bone resorption from formation, by activating osteoclastic bone resorption and suppressing bone formation. As a result, large net amounts of calcium of up to 700–1,000 mg/day leave the skeleton, causing hypercalcemia. In addition, the anticalciuric effect of PTHrP restricts effective renal calcium clearance. Finally, HHM is associated with a reduction of 1,25 dihydroxyvitamin D [1,25(OH)₂D₃] levels, which in turn limit intestinal calcium absorption but enhance skeletal resorption. HHM is also associated with a reduction in the renal phosphorous threshold with hyperphosphaturia and hypophosphatemia [7–9]. In very rare instances, benign neoplastic lesions may also lead to hypercalcemia by systemic overproduction of PTHrP [7].