Hypercalcemia

Key Features

Essentials of Diagnosis

• Most common causes: primary hyperparathyroidism and malignancy-associated hypercalcemia

• Hypercalciuria usually precedes hypercalcemia

• Asymptomatic, mild hypercalcemia (≥ 10.5 mg/dL [or 2.6 mmol/L]) is usually due to primary hyperparathyroidism

• Symptomatic, severe hypercalcemia (≥ 14 mg/dL [or 3.5 mmol/L]) is due to hypercalcemia of malignancy

General Considerations

• Important causes of hypercalcemia are listed in Table 21–7

• Primary hyperparathyroidism and malignancy account for 90% of cases

• Primary hyperparathyroidism is the most common cause of hypercalcemia (usually mild) in ambulatory patients

• Chronic hypercalcemia (over 6 months) or some manifestation such as nephrolithiasis also suggests a benign cause

• Tumor production of PTH-related proteins (PTHrP)

  • Most common paraneoplastic endocrine syndrome, accounting for most cases of hypercalcemia in inpatients

  • The neoplasm is clinically apparent in nearly all cases when the hypercalcemia is detected

• Granulomatous diseases, such as sarcoidosis and tuberculosis, cause hypercalcemia via overproduction of active vitamin D₃ (1,25 dihydroxyvitamin D₃)

• Milk-alkali syndrome has had a resurgence due to calcium ingestion for prevention of osteoporosis

• Hypercalcemia causes nephrogenic DI through activation of calcium-sensing receptors in collecting ducts, which reduces ADH-induced water permeability

• Volume depletion further worsens hypercalcemia

Clinical Findings

History and physical examination

• Should focus on the duration of hypercalcemia and evidence for a neoplasm

Symptoms and Signs

• May affect gastrointestinal, kidney, and neurologic function

• Mild hypercalcemia is often asymptomatic

• Symptoms usually occur if the serum calcium is > 12 mg/dL (or > 3 mmol/L) and tend to be more severe if hypercalcemia develops acutely

• Constipation and polyuria

• Polyuria is absent in hypocalciuric hypercalcemia

• Polyuria from hypercalciuria-induced nephrogenic diabetes insipidus can result in volume depletion and acute kidney injury

• Other abdominal symptoms include

  • Nausea

  • Vomiting

  • Anorexia

  • Peptic ulcer disease

  • Renal colic

  • Hematuria from nephrolithiasis

• Neurologic manifestations may range from mild drowsiness to weakness, depression, lethargy, stupor, and coma in severe cases

• Ventricular ectopy and idioventricular rhythm occur and can be accentuated by digitalis

Diagnosis

Laboratory Tests

• The ionized calcium exceeds 1.32 mmol/L

• A high serum chloride concentration and a low serum phosphate concentration in a ratio ...