What are the symptoms and treatment options for hypercalcemia?

Symptoms of Hypercalcemia

Hypercalcemia presents with a spectrum of symptoms ranging from mild constitutional symptoms to severe life-threatening manifestations, with the most common symptoms including fatigue, weakness, confusion, nausea, vomiting, constipation, polyuria, and polydipsia. 1

Clinical Presentation

Neurological Symptoms

• Altered mental status (confusion, irritability)
• Fatigue and weakness
• Somnolence
• Coma (in severe cases) 1, 2

Gastrointestinal Symptoms

• Nausea and vomiting
• Constipation
• Abdominal pain 1, 2

Renal Symptoms

• Polyuria (excessive urination)
• Polydipsia (excessive thirst)
• Renal injury
• Kidney stones (more common in primary hyperparathyroidism) 1, 2, 3

Cardiovascular Symptoms

• Hypertension
• Arrhythmias
• Shortened QT interval 2

Severity of Symptoms Based on Calcium Levels

• Mild hypercalcemia (total calcium <12 mg/dL or ionized calcium 5.6-8.0 mg/dL):

  • Often asymptomatic
  • May have constitutional symptoms like fatigue and constipation in approximately 20% of cases 2

• Severe hypercalcemia (total calcium ≥14 mg/dL or ionized calcium ≥10 mg/dL):

  • More pronounced symptoms
  • Dehydration
  • Confusion
  • Somnolence
  • Coma 2

Treatment of Hypercalcemia

Initial Management

1. Aggressive IV fluid resuscitation with normal saline

   • Corrects hypercalcemia-associated hypovolemia
   • Promotes calciuresis
   • Target urine output >2 L/day 1

2. Avoid medications that can worsen hypercalcemia

   • NSAIDs (especially in renal impairment)
   • Thiazide diuretics
   • Excessive vitamin D or calcium supplements 1

Pharmacological Management

For Moderate to Severe Hypercalcemia

1. Bisphosphonates

   • Zoledronic acid 4 mg IV over 15 minutes is the first choice due to superior efficacy and longer duration of action (30-40 days) 1, 4
   • Dose adjustments needed for patients with renal impairment:
     • CrCl 50-60 mL/min: 3.5 mg
     • CrCl 40-49 mL/min: 3.3 mg
     • CrCl 30-39 mL/min: 3 mg 4

2. Denosumab

   • For hypercalcemia refractory to bisphosphonates
   • For patients with severe renal impairment 1

3. Calcitonin

   • For immediate short-term management of severe symptomatic hypercalcemia 1, 3

4. Glucocorticoids

   • For hypercalcemia due to vitamin D toxicity, granulomatous disorders, or some lymphomas 1, 3

5. Loop diuretics

   • To enhance calcium excretion, but only after adequate hydration
   • May be required in individuals with renal insufficiency or heart failure 1, 3

Special Considerations

• Dental examination before starting bisphosphonate therapy due to risk of osteonecrosis of the jaw 1
• Regular monitoring of serum calcium, phosphate, magnesium, and renal function 1
• Watch for hypocalcemia after treatment, especially with denosumab 1
• Consider hemodialysis for patients with severe hypercalcemia complicated by kidney failure 5

Common Pitfalls to Avoid

• Using diuretics before correcting hypovolemia
• Inadequate hydration before bisphosphonate administration
• Administering bisphosphonates too rapidly
• Treating laboratory values without addressing the underlying cause
• Delaying treatment of severe hypercalcemia
• Failing to monitor for hypocalcemia after treatment 1

Underlying Causes

• Primary hyperparathyroidism and malignancy account for approximately 90% of hypercalcemia cases 1, 2
• Other causes include granulomatous diseases, endocrinopathies, medications, and supplements 2

Remember that the diagnosis should include measurement of serum intact parathyroid hormone (PTH) to distinguish PTH-dependent from PTH-independent causes of hypercalcemia 2.