Humoral hypercalcemia of malignancy

PTHrP binds the PTH receptor and mimics PTH action, increasing bone resorption and renal calcium reabsorption while decreasing phosphate reabsorption. The most classic association is squamous cell carcinoma of the lung; other causes include head/neck SCC, renal cell carcinoma, bladder, breast, and ovarian carcinoma. Distinguish from primary hyperparathyroidism (PTH high) and from local osteolytic hypercalcemia (e.g., multiple myeloma, breast mets), which is mediated by cytokines like IL-1, IL-6, and RANKL rather than PTHrP. Patients present with 'stones, bones, groans, psychiatric overtones,' polyuria, and shortened QT interval. Treatment: aggressive IV saline, bisphosphonates, calcitonin, and treatment of the underlying malignancy.