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Source: Pai, AB. Disorders of Calcium and Phosphorus Homeostasis. In: DiPiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. http://www.accesspharmacy.com/content.aspx?aid=7983818. Accessed August 18, 2012.

  • Total serum calcium >10.5 mg/dL (>2.62 mmol/L)

  • Most commonly caused by cancer and primary hyperparathyroidism.
    • Hypercalcemia of malignancy common complication with:
      • Squamous cell carcinomas of the lung, head, and neck
      • Multiple myeloma
      • T-cell lymphomas
      • Ovarian cancer
      • Kidney cancer
      • Bladder cancer
      • Breast cancer
  • Chronic hypercalcemia caused by:
    • Medications
    • Endocrine and granulomatous disorders
    • Physical immobilization
    • High bone-turnover states (adolescence and Paget disease)
    • Rhabdomyolysis

  • Primary homeostatic mechanisms increased:
    • Bone resorption
    • Gastrointestinal (GI) absorption
    • Tubular reabsorption by kidneys
  • Parathyroid-related protein (PTHrP) secreted by tumors (especially breast and squamous cell lung cancers).
    • Binds to receptors, resulting in enhanced bone resorption.

  • Incidence of primary hyperparathyroidism in United States ranges from 10–30 cases per 100,000 people; primarily occurs in outpatients.
  • Hypercalcemia of cancer occurs in ~20–40% of patients at some time in course of disease and predominantly seen in inpatients.

  • Maintain hydration.

  • Cancer
  • Immobilization
  • Medications

Signs and Symptoms

  • Mild to moderate hypercalcemia (serum calcium <13 mg/dL [3.25 mmol/L]): often asymptomatic
  • Severe hypercalcemia (serum calcium >13 mg/dL [3.25 mmol/L]):
    • Rapid onset (e.g., hypercalcemia of malignancy)
    • Hypercalcemic crisis
      • Acute increase in serum calcium to >15 mg/dL [>3.75 mmol/L])
      • Acute renal insufficiency
      • Obtundation
      • If untreated, progresses to oliguric renal failure, coma, and life-threatening ventricular arrhythmias
    • Chronic hypercalcemia (e.g., hyperparathyroidism)
      • Metastatic calcification
      • Nephrolithiasis
      • Chronic renal insufficiency
  • Electrocardiogram (ECG) changes include shortening of QT interval and coving of ST-T wave.

Means of Confirmation and Diagnosis

  • Serum calcium concentration >10.5 mg/dL (>2.62 mmol/L)
    • Mild to moderate hypercalcemia: up to 13 mg/dL (3.25 mmol/L)
    • Severe hypercalcemia: >13 mg/dL (3.25 mmol/L)

Laboratory Tests

  • Metabolic panel
    • Serum calcium
      • Corrected total serum calcium calculated as follows:
        • Corrected Sca (mg/dL) = measured Sca (mg/dL) + [0.8 x (40 g/dL – measured albumin (g/dL))] or Corrected Sca (mmol/dL) = measured Sca (mmol/dL) + [0.02 x (40 g/L – measured albumin (g/L))]
    • Serum albumin

Imaging

  • Chest radiograph

Diagnostic Procedures

  • ECG

Differential Diagnosis

  • Hyperparathyroidism
  • Sarcoidosis
  • Renal tubular acidosis

  • Reverse signs and symptoms
  • Restore normocalcemia
  • Correct or manage underlying cause

  • Treatment depends on degree of hypercalcemia, acuity of onset, and presence of symptoms requiring emergent treatment (Figure 1).

Figure 1.

Pharmacotherapeutic options for acutely hypercalcemic patient. Serum calcium of 12 mg/dL equivalent to 3 mmol/L. (EKG, electrocardiogram.) Reprinted with permission from Wells BG, DiPiro JT, Schwinghammer TL, et al. Pharmacotherapy Handbook. 8th ed. New York: McGraw-Hill, 2012.

  • Management of moderate to severe hypercalcemia in absence of life-threatening symptoms begins with attention to underlying condition and correction of fluid and electrolyte abnormalities.
    • Initial step ...

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