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SOURCE

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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, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=146061894. Accessed August 10, 2017.

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DEFINITION

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

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ETIOLOGY

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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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PATHOPHYSIOLOGY

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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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EPIDEMIOLOGY

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  • Incidence of primary hyperparathyroidism in United States ranges 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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PREVENTION

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  • Maintain hydration.

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RISK FACTORS

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  • Cancer.

  • Immobilization.

  • Medications.

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CLINICAL PRESENTATION

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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 (eg, hypercalcemia of malignancy)

      • Anorexia.

      • Nausea and vomiting.

      • Constipation.

      • Polyuria.

      • Polydipsia.

      • Nocturia.

    • 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 (eg, 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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DIAGNOSIS

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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 × (40 g/dL – measured albumin (g/dL))]  or Corrected Sca (mmol/dL) = measured Sca (mmol/dL) + [0.02 × (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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DESIRED OUTCOMES

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  • Reverse signs and symptoms.

  • Restore normocalcemia.

  • Correct or manage underlying cause.

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TREATMENT: GENERAL APPROACH

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  • Treatment depends on degree of hypercalcemia, acuity ...

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