Hypercalcemia

Background

Pathophysiology

• Vitamin D is absorbed from GI tract
  • First hydroxylation to 25-OH vitamin D in liver
  • Second hydroxylation to 1,2-OH vitamin D in kidneys by alpha-1 hydroxylase
• PTH from parathyroid glands
• Calcitriol is involved somewhere

Differential Diagnosis

• High PTH
  • Primary hyperparathyroidism
    • Parathyroid adenoma (most common)
  • Tertiary hyperparathyroidism
  • Familial hypocalciuric hypercalcemia (FHH)
• Low PTH
  • Malignancy
    • Humoural hypercalcemia of malignancy (HHM): mediated by PTHrP, and most common in squamous cell carcinomas
    • alpha-1 hydroxylase: lymphoma
    • Local osteolysis: multiple myeloma
    • Bony metastases: breast cancer
  • Granulomatous disease (alpha-1 hydroxylase)
    • Tuberculosis
    • Sarcoidosis
  • Nutritional
    • Hypervitaminosis A
    • Hypervitaminosis D
    • Milk-alkali syndrome
    • Total parenteral nutrition
  • Endocrine
    • Thyrotoxicosis
    • Pheochromocytoma, including in MEN-2 or via production of PTH-RP
    • Adrenal insufficiency, rarely
  • Medication: thiazide diuretics, prolonged retinoic acid, calcium carbonate (causing milk-alkali syndrome)
  • Prolonged immobilization, rarely
  • Many other rare causes1