Medical Treatment of Malignancy-Associated Hypercalcemia

Abstract

Malignancy-associated hypercalcemia (MAH) is the commonest cause of hypercalcemia in hospitalized patients. Its incidence is 15 cases per 100,000 person-year. Such complication develops in almost 10% of patients with advanced cancer representing, ultimately, the most frequent cause of death in several patients with cancer. Parathyroid hormone related protein (PTHrP), which has strong homology to parathyroid hormone, is the commonest hormonal mediator of MAH. Overall, about 80% of patients with MAH have increased PTHrP serum levels. Bisphosphonates are synthetic analogues of pyrophosphate, and represent the principal support of treatment. Several bisphosphonates have shown to decrease serum calcium levels by inhibiting PTH-dependent osteoclast activation. They are potent and effective inhibitors of osteoclast-mediated bone resorption, and have shown antiangiogenic properties in some experimental models. At present, pamidronate, zoledronate and ibandronate should be considered the drugs of choice in the treatment of MAH. Old agents such as mithramycin, calcitonine, and gallium nitrate have practically been abandoned due to their limited activity and huge side effects, especially for the kidney. A new experimental approach to MAH involves the blockade of receptor activator of nuclear factor-kappa B ligand, usually abbreviated as RANKL. RANKL is a key element in the differentiation, function, and survival of osteoclasts, which plays an essential role in removing Ca(++) from the bone in response to PTH stimulation. This review provides information about the actual medical treatment of MAH.

Paraneoplastic Syndromes: An Approach to Diagnosis and Treatment

“…4 The clinical features, associated malignancies, diagnostic studies, and treatment options of paraneoplastic endocrine syndromes are listed in Table 1. 4,[7][8][9][10][11][12][13][14][15][16][17][18][19][20] Syndrome of InapproprIate antIdIuretIc Hormone SecretIon The syndrome of inappropriate antidiuretic hormone secretion (SIADH), which is characterized by hypo-osmotic, euvolemic hyponatremia, affects 1% to 2% of all patients with cancer. Small cell lung cancer accounts for most of these cases, with approximately 10% to 45% of all patients with small cell lung cancer developing SIADH.…”

“…8 Indeed, the 30-day mortality rate for cancer patients with hypercalcemia is approximately 50%. 23 There are 4 principal mechanisms of hypercalcemia in cancer patients.…”

“…9 On binding to PTH receptors in bone and kidney, PTHrP regulates bone resorption and renal handling of calcium and phosphate. 8 Another 20% of cases arise directly from osteolytic activity at sites of skeletal metastases. Breast cancer, multiple myeloma, and lymphomas commonly cause hypercalcemia via this mechanism.…”

“…In patients with malignancy-associated hypercalcemia, typical laboratory findings include an elevated calcium level, a low-to-normal PTH level, and often a high PTHrP level. 8 In the absence of an ionized calcium level, total calcium, which represents both bound and unbound calcium, should be corrected for the albumin concentration using the following formula: Corrected Ca (mg/dL) = Measured Ca (mg/dL) + [0.8 × (4.0 -Albumin (mg/dL)].…”

“…It is mostly seen in patients with cancer (especially those with multiple myeloma) who have been treated with IV bisphosphonates for prolonged periods or in patients who have had recent invasive dental procedures. 8 Corticosteroids may also be used in the management of hypercalcemia. Their main effect is via direct antitumor properties against lymphoma and myeloma cells, but they may also reduce gastrointestinal calcium absorption.…”