Hypercalcemia of malignancy

Background

Causes

• PTHrP release
  • SCC (particularly of the head and neck), breast renal, endometrial cancer
• Local osteolysis
  • Associated primarily with bone mets
  • Multiple myeloma, lung, breast cancer
• Production of vitamin D analogues
  • Lymphoma (Hodgkin)

Clinical Features

Symptoms of hypercalcemia

Mnemonic: Stones, Bones, Groans, Moans, Thrones, Psychic Overtones

• "Stones"
  • Renal calculi
  • Renal failure
• "Bones"
  • Bone pain/destruction
• "Groans"
  • Abdominal pain, vomiting
  • Dehydration
  • Pancreatitis
• "Thrones"
  • Polyuria/polydipsia (Renal insufficiency)
  • Constipation
• "Psychic Overtones"
  • Lethargy/confusion/hallucinations

Differential Diagnosis

Causes of Hypercalcemia

• Addison's disease
• Calciphylaxis
• Excess vitamin D
• Hypercalcemia of malignancy
• Hyperparathyroidism
• Hyperthyroidism
• Hypothyroidism
• Lithium
• Milk-alkali syndrome
• Paget disease
• Sarcoidosis
• Thiazide diuretics

Oncologic Emergencies

Related to Local Tumor Effects

• Malignant airway obstruction
• Bone metastases and pathologic fractures
• Malignant spinal cord compression
• Malignant Pericardial Effusion and Tamponade
• Superior vena cava syndrome

Related to Biochemical Derangement

• Hypercalcemia of malignancy
• Hyponatremia due to SIADH
• Adrenal insufficiency
• Tumor lysis syndrome
• Carcinoid syndrome

Related to Hematologic Derangement

• Neutropenic fever
  • Neutropenic enterocolitis (typhlitis)
• Leukostasis and hyperleukocytosis
• Hyperviscosity syndrome
• Thromboembolism

Related to Therapy

• Chemotherapy-induced nausea and vomiting
• Cytokine release syndrome
• Chemotherapeutic drug extravasation
• Differentiation syndrome (retinoic acid syndrome) in APML
• Stem cell transplant complications
• Catheter-related complications
  • Tunnel infection
  • Exit site infection
  • CVC obstruction (intraluminal or catheter tip thrombosis)
  • Catheter-related venous thrombosis
  • Fracture of catheter lumen
  • Oncologic therapy related adverse events

Evaluation

• Chemistry
• Ionized Ca
• CBC
• LFTs (alk phos, albumin)
• ECG

Management

Asymptomatic or Ca <12 mg/dL

• Does not require immediate treatment
• Advise to avoid factors that can aggravate hypercalcemia (thiazide diuretics, Li, volume depletion, prolonged inactivity, high Ca diet)

Mildly symptomatic Ca 12-14 mg/dL

• May not require immediate therapy; however, an acute rise may cause symptoms necessitating treatment as described for severe hypercalcemia (see below)

Symptomatic or Severe hypercalcemia (Ca >14 mg/dL)

• Patients are likely dehydrated and require saline hydration as initial therapy

Hydration

• Isotonic saline at 200-300 mL/hour; adjust to maintain urine output at 100-150 mL/hour

Calcitonin

• Consider adding calcitonin 4 units/kg SC or IV q12hr in patients w/ Ca >14 mg/dL (3.5 mmol/L) who are also symptomatic (lowers Ca w/in 2-4hr)
• Tachyphylaxis limits use long term, but is a great choice for emergent cases

Bisphosphonates

Give for severe hypercalcemia due to excessive bone resorption (lowers Ca within 12-48hr)[≥12 mg/dL][≥3 mmol/L]

• Pamidronate 90mg IV over 24 hours OR
• Zoledronate 4mg IV over 15 minutes
• Caution in renal failure, though bisphosphonates have been safely used in pts with pre-existing renal failure

Electrolyte Repletion

• Correct hypokalemia
• Correct hypomagnesemia

Diuresis

• Furosemide is NOT routinely recommended
• Only consider in patients with renal insufficiency or heart failure and volume overload

Dialysis

Consider if patient:

• Anuric with renal failure
• Failing all other therapy
• Severe hypervolemia not amenable to diuresis
• Serum Calcium level >18mg/dL
• Neurologic symptoms
• Heart failure with reduced ejection fraction (unable to provide fluids)

Corticosteroids

Decrease Ca mobilization from bone and are helpful with steroid-sensitive tumors (e.g. lymphoma, MM)

• Prednisone 60mg PO daily

Disposition

• Ca <12
  • Home with follow up if oncology concurs
• Ca>12
  • Admit
• ECG changes
  • Admit with telemetry

See Also

• Hypercalcemia