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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.

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

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  • 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

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  • 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.

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  • 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.

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  • Maintain hydration.

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  • Cancer
  • Immobilization
  • Medications

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Signs and Symptoms

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  • 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.

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Means of Confirmation and Diagnosis

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  • 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)

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Laboratory Tests

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  • 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

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Imaging

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  • Chest radiograph

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Diagnostic Procedures

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  • ECG

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Differential Diagnosis

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  • Hyperparathyroidism
  • Sarcoidosis
  • Renal tubular acidosis

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

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

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Figure 1.
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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.

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  • 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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