Hypercalcemia

SOURCE

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.

DEFINITION

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

ETIOLOGY

• 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.

PATHOPHYSIOLOGY

• 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.

EPIDEMIOLOGY

• 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.

PREVENTION

• Maintain hydration.

RISK FACTORS

• Cancer.

• Immobilization.

• Medications.

CLINICAL PRESENTATION

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 (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.

DIAGNOSIS

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 S_ca (mg/dL) = measured S_ca (mg/dL) + [0.8 × (40 g/dL – measured albumin (g/dL))]  or Corrected S_ca (mmol/dL) = measured S_ca (mmol/dL) + [0.02 × (40 g/L – measured albumin (g/L))]

  • Serum albumin.

IMAGING

• Chest radiograph.

DIAGNOSTIC PROCEDURES

• ECG

DIFFERENTIAL DIAGNOSIS

• Hyperparathyroidism.

• Sarcoidosis.

• Renal tubular acidosis.

DESIRED OUTCOMES

• Reverse signs and symptoms.

• Restore normocalcemia.

• Correct or manage underlying cause.

TREATMENT: GENERAL APPROACH

• Treatment ...