Categorized as metabolic, cardiovascular, infectious, neurologic, hematologic, or respiratory.
Hypercalcemia is experienced by up to one third of patients with cancer at some point in their course.
Among patients hospitalized for hypercalcemia cancer is the most common cause.
Malignancies most commonly associated with hypercalcemia are breast, lung, renal, myeloma, adult T-cell leukemia/lymphoma.
The presence of hypercalcemia in a patient with a malignancy is associated with an adverse prognosis, indicating a shorter survivorship.
Mechanisms explaining hypercalcemia include excess parathyroid hormone-related peptide (PTHrP), paracrine stimulation of osteoclasts by bone metastases leading to osteolysis, and secretion of vitamin D analogues by the tumor.
There are three categories of mechanisms account for hypercalcemia of malignancy: humoral type usually results from tumor production of parathyroid hormone-related peptide and less commonly intact parathyroid hormone; bone destruction type with dissolution from extensive bone metastases; The third and least common category is the excess production of vitamin D analogues by the malignant cells.
Up to 80% of malignant hypercalcemia is caused by tumor released parathyroid hormone-related peptide into the systemic circulation.
PTHrP mimics the effects of parathormone on the kidneys and bones but does not influence intestinal absorption of calcium.
PTHrP represents a true paraneoplastic syndrome.
PTHrP hypercalcemia may be seen in squamous cell carcinomas of the aerodigestive, genitourinary tracts, and in breast cancer, kidney, cervical, endometrial, and ovarian cancer.
Paracrine effects are most commonly seen with hypercalcemia from metastatic breast cancer and multiple myeloma.
PTHrP is closely related to PTH and exerts many functions of PTH: it binds to receptors on osteoblasts and stimulates their activity through receptor activator of nuclear factor kB ligand (RANK) signaling.
PTHrP stimulates osteoclasts, increasing activation and proliferation and subsequently releases calcium into circulation.
Elevation of PTHrP in humoral hypercalcemia of malignancy, associated with poor prognosis and decreased response to treatment with bisphosphonates.