Hypercalcemia of malignancy

Background

In the setting of cancer, hypercalcemia falls into the following 4 categories:

1. Local osteolysis associated primarily with bone metastasis (20%)
   1. breast, MM, lymphoma
2. Humoral hypercalcemia of malignancy (HHM) associated with PTHrP
   1. Squamous cell carcinoma (particularly of the head and neck); renal, endometrial, and breast cancers, HTLV-lymphoma
3. Lymphoma-associated secretion of calcitriol, which increases intestinal calcium absorption and bone resorption by osteoclasts (1%)
   1. Hodgkin-associated hypercalcemia and 30% to 40% of non-Hodgkin lymphoma–associated hypercalcemia
4. Ectopic secretion of PTH, which is extremely rare (usually with parathyroid carcinomas)
   1. ovary, lung, and primitive neuroectoderm

Diagnosis

Signs & Symptoms

1. Consistent with degree of hypercalcemia and rate of increase (see Hypercalcemia)
2. Polydipsia, polyuria
3. Bone pain
4. Gastrointestinal symptoms (anorexia, nausea, vomiting, and constipation)
5. Psychiatric symptoms (memory loss, apathy)
6. Lethargy, and fatigue
7. Bony tenderness over sites of osteolysis
8. Dehydration
9. Look for signs of CHF, renal failure to avoid vol overload

Work-Up

1. Chem10
2. ionized Ca
3. CBC
4. LFTs (alk phos, albumin)
5. PTH
6. PTH-rP (non emergent)
7. EKG (prolonged PR interval, widened QRS complex, shortened QT interval, bundle branch block, or bradydysrhythmia and even cardiac arrest (typically with calcium levels > 15 mg/dL)

Categorization

1. Mild (total calcium level, 10.5-11.9 mg/dL)
2. Moderate (total calcium level, 12.0-13.9 mg/dL)
3. Severe (total calcium level ≥ 14.0 mg/dL)

Treatment

Address volume losses and reduce bone resorption

Calcium level < 12 mg/dL (mild or chronic)

1. Oral hydration
2. High-salt diet
3. Avoid medications that cause hypercalcemia
4. No treatment at all may be an option

Calcium level ≥ 12 mg/dL (severe or symptomatic)

1. Normal saline
   1. initially 200-300 mL/h until patient is euvolemic
   2. then adjust to maintain urine output of 100-150 mL/h
2. IV Bisphosphonate (pyrophosphate analogues bind to hydroxyapatite and inhibit bone crystal dissolution and therefore osteoclastic resorption)
   1. Zoledronic acid: 4 mg over 15 minutes; 8 mg if second dose is required (not FDA approved)
   2. Pamidronate: given over 2-24 hours, either as 60 mg (calcium level, 12-13.5 mg/dL) or 90 mg (calcium level >13.5 mg/dL)
   3. Calcium levels begin to decrease 2 to 4 days after administration of IV bisphosphonates, reach a nadir between 4 and 7 days, and typically remain within the reference range for 1 to 4 weeks
   4. In a head-to-head comparison of zoledronate (4 mg) versus pamidronate (90 mg), zoledronate had the benefit of a shorter administration time (15 minutes vs 2 hours, respectively) and a statistically significant difference (p 0.001) of 0.7 mg/dL in the calcium level at its nadir (9.8 mg/dL vs 10.5 mg/dL, respectively)
3. Calcitonin 4 IU/kg SQ or IM; repeat every 6-12 hours only if patient is responsive
   1. Calcitonin exerts this effect by inhibiting osteoclastic resorption and inducing calciuresis
   2. peak activity within 12-24h
   3. lowers Ca ~1.0mg/dL
4. Loop diuretics only after volume repletion in patients with congestive heart failure or chronic kidney disease
5. Hemodialysis for patients with any of the following:
   1. Neurologic symptoms
   2. Calcium level ≥ 18 mg/dL
   3. Acute or chronic kidney disease (GFR < 10-20 mL/min)
   4. Congestive heart failure

Disposition

1. Ca <12: home with f/u after d/w onc
2. Ca>12: admit ward
3. EKG changes: tele

See Also

Hypercalcemia

Source

EM Practice 3/10