Hypercalcemia

Key Features

Essentials of Diagnosis

• Serum calcium level > 10.5 mg/dL (> 2.6 mmol/L)

• Serum ionized calcium > 5.3 mg/dL (> 1.32 mmol/L)

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

• Asymptomatic, mild hypercalcemia (≥ 10.5 mg/dL [or 2.6 mmol/L]) is usually due to primary hyperparathyroidism; symptomatic, severe hypercalcemia (≥ 13 mg/dL [or 3.2 mmol/L]) is due to hypercalcemia of malignancy

General Considerations

• Primary hyperparathyroidism and malignancy account for 90% of cases

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

• Tumor production of parathyroid hormone–related proteins (PTHrP) is the most common paraneoplastic endocrine syndrome, accounting for most cases of hypercalcemia in inpatients

• Granulomatous diseases, such as sarcoidosis and tuberculosis, cause hypercalcemia from production of active vitamin D₃ (1,25 dihydroxyvitamin D₃) by the granulomas

• Patients with mild hypercalcemia and normal to slightly elevated PTH levels should be assessed for familial hypocalciuric hypercalcemia

• Milk-alkali syndrome has had a resurgence related to calcium ingestion for prevention of osteoporosis and treatment of dyspepsia

• Hypercalcemia can cause nephrogenic diabetes insipidus and volume depletion, which further worsen hypercalcemia

Etiology

• Increased intake or absorption (Table 21–7)

  • Milk-alkali syndrome

  • Vitamin D or A excess

• Endocrine disorders

  • Primary and secondary hyperparathyroidism

  • Acromegaly

  • Adrenal insufficiency

  • Pheochromocytoma

  • Thyrotoxicosis

• Neoplastic diseases

  • Tumor production of PTHrP (ovary, kidney, lung)

  • Plasma cell myeloma

  • Lymphoma

• Miscellaneous causes

  • Thiazide diuretics

  • Granulomatous diseases

  • Paget bone disease

  • Hypophosphatasia

  • Immobilization

  • Familial hypocalciuric hypercalcemia

  • Complications of kidney transplantation

  • Lithium intake

Clinical Findings

Symptoms and Signs

• History and physical examination should focus on the duration of hypercalcemia and evidence for a neoplasm

• May affect gastrointestinal, kidney, and neurologic function

• Mild hypercalcemia (< 12 mg/dL) is often asymptomatic

• Moderate hypercalcemia (12–14 mg/dL) may be tolerated if longstanding yet tends to be symptomatic if acute

• Severe hypercalcemia (> 14 mg/dL) is frequently symptomatic, including

  • Anxiety

  • Lethargy

  • Constipation

  • Anorexia

  • Cognitive changes

  • Lethargy

  • Stupor

• Polyuria and dehydration may occur from impaired renal concentrating ability

• Renal colic and hematuria may result from nephrolithiasis

• Acute hypercalcemia can shorten the QT interval, though clinically relevant arrhythmias are rare

Diagnosis