How do malignancies cause hypercalcemia?
• Humoral hypercalcemia of malignancy refers to hypercalcemia from secretion of PTH-related peptide (PTH-rP) by tumors including squamous cell carcinomas of the lung, head, or neck and renal cell carcinoma. PTH-rP mimics the actions of PTH by binding to the same receptor (∼80% of cases).
• Local osteolytic hypercalcemia. Secretion of bone-resorbing cytokines (such as interleukin-1, interleukin-6, and macrophage inflammatory protein-α) has been reported with some solid tumors metastatic to the bone and multiple myeloma (∼20% of cases).
• Extra-renal 1,25D production. Certain lymphomas, ovarian dysgerminoma, will convert 25 OH vitamin D to the active 1,25 form (less than 1% of cases).
• Authentic ectopic hyperparathyroidism. Rare occurrence with ovarian, lung, thyroid carcinomas, etc.
