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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 <8.5 mg/dL (<2.13 mmol/L) with ionized calcium <4.4 mg/dL (<1.1 mmol/L)

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ETIOLOGY

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  • Primary causes:

    • Postoperative hypoparathyroidism secondary to surgical procedures involving thyroid, parathyroid, and neck.

    • Vitamin D deficiency.

  • Other causes:

    • Magnesium deficiency.

    • Medications.

      • Drug-induced hypocalcemia:

        • Furosemide.

        • Calcitonin.

        • Bisphosphonates.

        • Oral phosphorus agents.

      • Drug-induced hypomagnesemia.

        • Aminoglycosides.

        • Diuretics.

        • Cisplatin.

    • Hypoalbuminemia.

    • Chronic kidney disease.

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PATHOPHYSIOLOGY

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  • Vitamin D is necessary for optimal absorption of calcium and phosphorus.

    • Deficiency is most common cause of chronic hypocalcemia worldwide.

  • Hypomagnesemia impairs parathyroid hormone (PTH) secretion and induces resistance of target organs to PTH actions.

    • Associated with severe symptomatic hypocalcemia unresponsive to calcium replacement therapy.

    • Calcium normalization is dependent on magnesium replacement.

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EPIDEMIOLOGY

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  • Infrequent in outpatient setting.

    • Most common in elderly, malnourished patients and as a result of sodium phosphate bowel preparation agents.

  • Higher incidence in intensive care unit patients.

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PREVENTION

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  • Maintain adequate vitamin D intake.

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RISK FACTORS

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  • Vitamin D deficiency associated with:

    • Gastrointestinal disease including:

      • Gastric surgery.

      • Chronic pancreatitis.

      • Small-bowel disease.

  • Malnutrition.

  • Use of drugs known to induce hypocalcemia or hypomagnesemia (see Etiology)

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CLINICAL PRESENTATION

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  • Clinical manifestations are variable and depend on onset of hypocalcemia.

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SIGNS AND SYMPTOMS
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  • Acute decrease in serum calcium.

    • Tetany: hallmark sign manifested as:

      • Neuromuscular irritability with increased seizure potential and:

        • Paresthesia around mouth and in extremities.

        • Muscle spasms and cramps.

        • Hand and feet spasms.

    • Cardiovascular.

      • Electrocardiogram (ECG) changes include prolonged QT interval.

      • Arrhythmias.

      • Bradycardia.

  • Chronic hypocalcemia.

    • Depression.

    • Anxiety.

    • Memory loss.

    • Confusion.

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DIAGNOSIS

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MEANS OF CONFIRMATION AND DIAGNOSIS
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  • Total serum calcium <8.5 mg/dL (<2.13 mmol/L) with ionized calcium <4.4 mg/dL (<1.1 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.

    • Serum magnesium.

    • Serum phosphorus.

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DIAGNOSTIC PROCEDURES
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  • ECG

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DIFFERENTIAL DIAGNOSIS
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  • Acute renal failure.

  • Hyperparathyroidism.

  • Hypomagnesemia.

  • Hyperphosphatemia.

  • Metabolic alkalosis.

  • Acute pancreatitis.

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DESIRED OUTCOMES

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  • Resolution of signs and symptoms.

  • Restoration of normocalcemia.

  • Management of associated electrolyte abnormalities.

  • Treatment of underlying cause.

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TREATMENT: GENERAL APPROACH

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  • Emergent treatment rarely warranted unless life-threatening symptoms present (eg, frank tetany or seizures).

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TREATMENT: PHARMACOLOGIC THERAPY

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  • Acute, symptomatic ...

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