Primary hyperparathyroidism: Most common cause of hypercalcemia; Isolated parathyroid adenoma (80-85%);4 gland parathyroid hyperplasia (10-15%)
Malignancy: PTHrP production (e.g. squamous cell); direct invasion of bone/osteolytic lesions (e.g. myeloma, breast); increased conversion 25-oh to 1, 25-Oh vitamin D (lymphoma)
Vitamin D intoxication
Granulomatous disease (e.g. Sarcoid) increased conversion 25-oh to 1, 25-Oh vitamin D
Meds→ e.g. HCTZ, lithium, antacids→ milk alkali synd
Immobility - Ca2+ elevation usually mild
Other endocrinopathy related (rare): hyperthyroidism, pheochromocytoma, hyper or hypoadrenal states
Paget's disease; Familial hypocalcuric hypercalcemia (often + family hx; low 24h urine calcium)

Confusion, weakness, fatigue, abdominal pain (hyper Ca2+ induced pancreatitis, PUD, constipation, other), fractures, renal stones, polyuria
Higher calcium levels are associated w/symptoms (e.g. as reach 12 or greater)
Cancer tends to cause higher levels hypercalcemia; also symptoms related to bone pain (mets) and/or primary cancer (e.g. mass effect, f, c, sweats, etc)

If mild and from hyperparathyroidism then may have no findings
Confusion, hypovolemia w/higher levels
Mass or other abnormal exam findings based on primary cancer if malignancy related

Malignancy

Medications

Immobility

Other Causes

Hypercalcemia = Ca2+> 10.5; Adjust for low albumin by adding .8x(4-albumin) to Ca2+
Mild hypercalcemia 10.5-12; Moderate 12-14; Severe > 14
Primary hyperparathyroidism: Elevated PTH (> 65ng/dl)
Hypercalcemia of malignancy (e.g. squamous cell): PTHrP elevated, PTH low
Hypercalcemia from bony invasion: lytic lesions on imaging of affected bones: + SPEP, FLC w/Myeloma; low PTH, PTHrP
Hypercalcemia from lymphoma, granulomatous disease: 1, 25 Vitamin D elevated
Vitamin D intoxicattion: 25-Oh Vitamin D elevated

Hypercalcemia