Hypercalcemia

Definition

Hypercalcemia is defined as an elevated level of calcium in the blood, typically >10.5 mg/dL (2.62 mmol/L). It can result from increased bone resorption, increased intestinal absorption, or decreased renal excretion of calcium, and can have significant systemic effects.

Epidemiology

• Most common in hospitalized patients: ~1–2% have mild hypercalcemia
• Primary hyperparathyroidism and malignancy are leading causes in adults
• Prevalence increases with age, especially in postmenopausal women
• Rare in children except in familial or endocrine disorders

Etiology

• Primary hyperparathyroidism (adenoma, hyperplasia, carcinoma)
• Malignancy-associated hypercalcemia (PTHrP-secreting tumors, bone metastases, multiple myeloma)
• Vitamin D intoxication or granulomatous disease (sarcoidosis, TB)
• Medications: thiazide diuretics, lithium, vitamin A
• Endocrine disorders: thyrotoxicosis, adrenal insufficiency, pheochromocytoma
• Familial or genetic disorders (familial hypocalciuric hypercalcemia)

Pathophysiology

• Excess PTH → increased bone resorption, increased renal calcium reabsorption, increased intestinal absorption via vitamin D activation
• Malignancy: PTHrP mimics PTH effects, osteolytic metastases release calcium
• Vitamin D excess → increased intestinal absorption of calcium
• Renal failure → impaired calcium excretion
• Hypercalcemia affects neuromuscular, gastrointestinal, renal, and cardiovascular systems