Guide to Hypercalcemia

Causes

  • Primary hyperparathyroidism (main outpatient cause)
  • Malignancy: PTHrP, osteolytic, calcitriol (main inpatient cause)
  • Granulomatous diseases
  • Drugs: milk-alkali, vitamin D, thiazides, lithium
  • Endocrine: hyperthyroidism, adrenal insufficiency
  • Paget’s Disease
  • Immobilization
  • Familial hypocalciuric hypercalcemia
  • ESRD and tertiary hyperparathyroidism

Clinical Manifestations:

  • GI: constipation, PUD, pancreatitis
  • Renal: stones, DI, RTA (type I), tubular toxicity (nephrocalcinosis)
  • Cardiovascular: QT short, HTN
  • Neurologic: Myalgias, weakness, confusion, coma

Helpful Hints:

  • Level: higher with malignancy, rarely >11 or 12 with primary hyperparathyroidism
  • Serum PO4: low with humeral hypercalcemia of malignancy (PTHrP) or hyperparathyroidism
  • Urine calcium:
    • High or high normal with hyperparathyroidism and malignancy
    • Low with milk alkali (due to metabolic alkalosis), thiazides, and FHH
  • Serum Cl: high in hyperparathyroidism

Workup:

Hypercalcemia

Management:

  • Normal saline: 2 to 4 L IV daily for 1 to 3 days. Enhances filtration and excretion of calcium. Lowers calcium by 1 to 3 mg per dL. Caution in HF patients.
  • Furosemide: Inhibits calcium resorption in the distal renal tubule. Use following aggressive rehydration. Watch for hypokalemia and volume depletion.
  • Bisphosphonates: Pamidronate (Aredia) 60 to 90 mg IV over 4 hours or Zoledronic acid (Zometa), 4 mg IV over 15 minutes. Inhibits osteoclast action and bone resorption; maximal effect at 72 hours. Often used for hypercalcemia of malignancy. Watch for nephrotoxicity, rebound hypercalcemia in hyperparathyroidism, and hypophosphatemia.
  • Calcitonin: 4 to 8 IU per kg IM or SQ every 6 hours for 24 hours. Inhibits bone resorption and augments calcium excretion. Initial treatment (after rehydration) in severe hypercalcemia. Watch for rebound hypercalcemia, vomiting, cramps, flushing, etc.
  • Steroids: Hydrocortisone, 200 mg IV total daily dose for 3 days. Inhibits vitamin D conversion to calcitriol. Useful in vitamin D intoxication, hematologic malignancies, granulomatous disease.

Am Fam Physician. 2003 May 1;67(9):1959-1966.

Nature Clinical Practice Nephrology (2007) 3, 397-404