Hypercalcemia of malignancy and new treatment options - 0 views
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Hypercalcemia of malignancy occurs as the result of direct bone metastasis and via humoral mechanisms such as parathyroid hormone-related protein (PTHrP) or 1,25-dihydroxyvitamin D mediated pathways
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Hypercalcemia due to osteolytic bone lesions is common in multiple myeloma, leukemia, and breast cancer
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Humoral hypercalcemia is predominant in squamous cell, renal cell and ovarian cancers, and lymphomas are associated with 1,25-dihydroxyvitamin D mediated hypercalcemia
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20% of cases of hypercalcemia of malignancy and is frequently encountered in multiple myeloma, metastatic breast cancer, and to a lesser extent in leukemia and lymphoma
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Physiologic bone turnover requires the complementary activity of osteoblasts – mesenchymal stem cell-derived bone-forming cells – and bone-resorbing cells of monocyte and macrophage lineage known as osteoclasts
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In local osteolytic hypercalcemia, the RANKL/RANK interaction results in excessive osteoclast activation leading to enhanced bone resorption and thus hypercalcemia
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In addition, osteoclast activation is also mediated by malignancy secreted cytokines, including interleukin-1, initially termed “osteoclast stimulating factor”
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increased production of 1,25-dihydroxyvitamin D occurs nearly exclusively in Hodgkin and non-Hodgkin lymphoma with case reports of the same in ovarian dysgerminoma
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in 1,25-dihydroxyvitamin D induced hypercalcemia, malignant cells likely recruit and induce adjacent macrophages to express 1-α-hydroxylase, converting endogenous calcidiol into calcitriol.31 Calcitriol then binds to receptors in the intestine leading to heightened enteric calcium reabsorption with resultant hypercalcemia
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Ectopic production of PTH by malignant cells has been described in a handful of cases involving cancer of the ovary and lung, as well as neuroendocrine tumors and sarcoma
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an initial panel consisting of PTH, PTHrP, phosphorus, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D should be obtained
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Lymphoma, a hypercalcemia due to 1,25-dihydroxyvitamin D mediated pathways, is implied by elevations in 1,25-dihydroxyvitamin D without concomitant elevations in 25-hydroxyvitamin D. In such cases, PTH is low and PTHrP undetectable
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Treatment of hypercalcemia of malignancy is aimed at lowering the serum calcium concentration by targeting the underlying disease, specifically by inhibiting bone resorption, increasing urinary calcium excretion, and to a lesser extent by decreasing intestinal calcium absorption
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hydration with isotonic fluid (if admitted), avoidance of thiazide diuretics, and a low-calcium diet