Hypercalcemia Associated with Malignancy
Medicine Central™ is a quick-consult mobile and web resource that includes diagnosis, treatment, medications, and follow-up information on over 700 diseases and disorders, providing fast answers—anytime, anywhere. Explore these free sample topics:
-- The first section of this topic is shown below --
- Hypercalcemia associated with malignancy is the most common cause of severe hypercalcemia diagnosed in a hospital setting.
- Often a very poor prognostic sign
- Occurs with both solid tumors and hematologic malignancies; most commonly associated with multiple myeloma and breast and lung cancer; also associated with metastases to bone
Hypercalcemia is diagnosed in 10–30% of all cancer patients during the course of illness, with an in-hospital mortality rate of 6.8%.
Etiology and Pathophysiology
- Increased bone resorption is involved in most cases, caused by either extensive local bone destruction or humoral factors.
- Nephrogenic diabetes insipidus induced by the hypercalcemia (1)
- Osteolytic metastases-induced hypercalcemia: most commonly in breast cancer, multiple myeloma, lymphoma, and leukemia
- Humoral hypercalcemia is most commonly associated with cancer, due to tumor secretion of parathyroid hormone (PTH)–related protein (rP), calcitriol, and prostaglandins, transforming growth factors, tumor necrosis factor (TNF), colony-stimulating factors, and interleukins.
- PTH-rP increases expression of receptor activator of nuclear factor κB ligand (RANKL) in bone. RANKL binds to RANK on the surfaces of osteoclast precursors, resulting in differentiation into osteoclasts and leading to bone resorption and the development of hypercalcemia.
- Ectopic PTH secretion is very rare but reported in ovarian carcinoma, neuroectodermal tumor, thyroid papillary carcinoma, lung cancer, rhabdomyosarcoma, and pancreatic cancer.
- Calcitriol production: mostly reported in lymphoma and ovarian dysgerminomas
- In multiple myeloma, the elevated serum calcium may be due to the binding of the monoclonal protein with calcium. Multiple myeloma also may cause impaired renal function that decreases calcium excretion.
- In patients with active disease, ~20% have another cause of hypercalcemia than cancer itself.
- Encourage adequate hydration and activity, especially in patients with multiple myeloma.
- In advanced cancer patients with bone metastasis, denosumab 120 mg subcutaneously every 4 weeks is more efficacious than zoledronic acid 4 mg IV every 4 weeks in delaying or preventing hypercalcemia of malignancy (2)[A].