Hypercalcaemia

Section: Endocrine Sub-section: Parathyroid

Incidence

• 0.5% of general population
• 5% of hospital population
• Most common outpt cause: Primary hyperparathyroidism
• Most common inpt cause: Malignancy

Causes

Can be broken down into

• Increased intake

• Decrease output

• Redistributive

• Redistributive

  • Hyperparathyroidism
  • Malignancy
    • Associated hypercalcaemia
    • Three causes
      • Release of PTHrP
      • Release of Calcitriol
      • Lytic bone mets
  • Granulomatous Diseases
    • Extra-renal 1,25-dihydroxyvitamin D synthesis
      • Extra-renal 1-α-hydroxylase
      • PTH independent
    • Sarcoidosis
    • Tuberculosis
    • Histoplasmosis
    • Coccidioidomycosis
  • Endocrine disorders
    • Thyrotoxicosis, Acromegaly, Phaeochromocytomas, Adrenal insufficiency
  • Prolonged immobilization

• Increased intake

  • Vitamin D or calcium replacement.
  • TPN

• Decreased output

  • Thiazide diuretics
  • Lithium
  • Familial hypocalciuric hypercalcaemia – germline mutation resulting in reduction in urinary excretion of calcium

Signs and Symptoms

• Stones
  • Nephrolithiasis and Nephrocalcinosis
• Bones
  • Osteopenia and pathological fractures.
• Abdominal moans
  • Abdominal pain, constipation, peptic ulcers, pancreatitis.
• Psychotic groans
  • Neurocognitive symptoms – fatigue, malaise, depression, memory loss
• Other
  • Calciphylaxis
    • Serious but uncommon disease caused by calcium blocking the small vessels of the fat and skin.
    • Causes painful ulceration of the skin.
  • ECG changes
    • Prolonged PR interval
    • Shortened QT
    • Wide QRS
    • Bradycardia.

Cut offs

• Mild: < 3mmol/L
  • Can be asymptomatic
  • Non-specific constipation, fatigue, depression
• Moderate: 3-3.5mmol/L
  • Can tolerate chronically, if acute may get marked symptoms
  • Polyuria, polydipsia, dehydration, anorexia, nausea, muscle weakness, and changes in sensation
• Severe: > 3.5mmol/L
  • More severe manifestations of moderate symptoms

Treatment of hypercalcaemia

• Mild – treat risk factors, hydrate the patient
• Moderate – rehydrate with N saline, consider bisphosphonates

Management of Hypercalcaemic Crisis

• Fluid resuscitate aggressively
  • Aiming for a urine output above 100mls/hour.
• Loop diuretic (Frusemide)
  • Inhibits calcium reabsorption
  • Once intravascular volume has been restored
• Glucocorticoids (Hydrocort 100mg QID IV)
  • Decrease intestinal absorption of Ca2+, increase renal excretion of Ca2+, and inhibit osteoclast-activating factor
    • Not effective in cases of hypercalcaemia associated with malignancy
• For patients with renal failure of heart failur
  • Requires dialysis
• Calcitonin (4-8U/kg IV)
  • Lowers serum Ca2+ levels quickly (within 24 to 48 hours)
  • Synergistic effect with glucocorticoids
  • Diminishes osteoclastic activity and increased calciuresis within minutes
• IV Bisphosphonates - Pamidronate (60-90mg) or Zoledronic Acid
  • Good in malignancy-associated hypercalcaemia
  • Rapid reduction of serum Ca2+
  • Inhibit osteoclast activity, reducing serum Ca2+
  • Have long half-life of bisphosphonates
  • Can exacerbate severe post-op hypocalcaemia and complicate surgical management