Clinical meaning
Hypercalcemia (corrected calcium > 10.5 mg/dL or ionized calcium > 5.6 mg/dL) results from increased bone resorption, increased intestinal calcium absorption, or decreased renal calcium excretion. Primary hyperparathyroidism (PHPT) and malignancy account for > 90% of cases. PHPT: autonomous PTH secretion from a parathyroid adenoma (85%), hyperplasia (10-15%), or carcinoma (< 1%) increases bone resorption (osteoclast activation via RANKL), renal calcium reabsorption (DCT), and intestinal absorption (via 1,25-dihydroxyvitamin D production). Malignancy-related mechanisms are covered in hypercalcemia-malignancy-np. Other causes: vitamin D intoxication (25-OH-D levels > 150 ng/mL), granulomatous disease (sarcoidosis, TB — macrophage 1-alpha-hydroxylase producing calcitriol), milk-alkali syndrome (excess calcium + alkali intake), thyrotoxicosis, immobilization (increased bone resorption), lithium (shifts PTH set point), thiazide diuretics (increase renal calcium reabsorption). The PTH level is the pivotal branching point in workup: elevated/inappropriately normal PTH = PTH-dependent; suppressed PTH = PTH-independent.