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1
Question:

A 69-year-old man is brought to the emergency department by his family for increasing confusion over the last 2 days.  He also has had nausea, vomiting, and back and abdominal pain.  At baseline, the patient is interactive and pleasant.  His medical history is notable for type 2 diabetes mellitus controlled with metformin and hypertension treated with amlodipine.  Temperature is 37.2 C (99 F), blood pressure is 112/70 mm Hg, and pulse is 102/min and regular.  The patient appears disheveled and confused.  Examination shows clear lung fields and normal heart sounds.  There are no neck masses or enlarged lymph nodes.  Neurologic examination shows no focal muscle weakness.  Laboratory results are as follows:

Leukocytes3200/mm3
Hematocrit32%
Platelets87,000/mm3
Sodium139 mEq/dL
Potassium4.2 mEq/dL
Chloride111 mEq/dL
Bicarbonate26 mEq/dL
Calcium14.1 mg/dL
Blood urea nitrogen36 mg/dL
Creatinine1.8 mg/dL
Glucose190 mg/dL

Which of the following is the most appropriate next step for this patient?

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Explanation:

Management of hypercalcemia

Severe
(calcium >14 mg/dL)
or symptomatic

Short-term (immediate) treatment

  • Normal saline hydration plus calcitonin
  • Avoid loop diuretics unless volume overload (heart failure) exists

Long-term treatment

  • Bisphosphonate (zoledronic acid)

Moderate
(calcium 12-14 mg/dL)

  • Usually no immediate treatment required unless symptomatic
  • Treatment is similar to that for severe hypercalcemia

Asymptomatic or mild
(calcium <12 mg/dL)

  • No immediate treatment required
  • Avoid thiazide diuretics, lithium, volume depletion & prolonged bed rest

This patient has severe, symptomatic hypercalcemia, likely due to an undiagnosed malignancy.  Severe hypercalcemia (ie, serum calcium >14 mg/dL) can cause weakness, gastrointestinal distress, and neuropsychiatric symptoms (eg, confusion, stupor, coma), especially with a rapid rise in serum calcium.  Patients are typically volume-depleted due to polyuria and decreased oral intake.

Patients with severe hypercalcemia require aggressive saline hydration to restore intravascular volume and promote urinary calcium excretion.  Calcitonin, by inhibiting osteoclast-mediated bone resorption, quickly reduces serum calcium concentrations and can be administered concurrently with saline.  Bisphosphonates (eg, pamidronate, zoledronic acid) also inhibit bone resorption and provide a sustained reduction in calcium levels.  However, the calcium-lowering effect of bisphosphonates is delayed, usually occurring over 2-4 days, and they are typically given after initial administration of saline and calcitonin (Choice G).

(Choice A)  Severe hypercalcemia with pancytopenia is a typical presentation of multiple myeloma, which can be confirmed with bone marrow biopsy.  However, this patient's acute hypercalcemia should first be corrected with saline hydration.

(Choice B)  Routine use of loop diuretics (eg, furosemide) is not recommended in hypercalcemic patients as it can worsen the associated volume depletion.

(Choice C)  Hemodialysis is an effective treatment for hypercalcemia, but is typically reserved for patients with renal insufficiency or heart failure in whom aggressive hydration cannot be administered safely.  This patient likely has confusion due to hypercalcemia not uremia.

(Choice D)  Insulin can be used to drive potassium (and glucose) into cells and is an effective treatment for hyperkalemia.  It does not have a significant effect on acute hypercalcemia.

(Choice E)  Glucocorticoids (eg, methylprednisolone) inhibit the formation of 1,25-dihydroxyvitamin D by activated mononuclear cells in the lungs and lymph nodes.  They can be used to treat hypercalcemia due to excessive vitamin D intake, granulomatous diseases (eg, sarcoidosis), and certain lymphomas.  However, their calcium-lowering effects can take 2-5 days to occur.

Educational objective:
Severe hypercalcemia can cause weakness, gastrointestinal distress, and neuropsychiatric symptoms.  Patients are typically volume-depleted due to polyuria and decreased oral intake.  Initial treatment includes saline hydration to restore intravascular volume and calcitonin to inhibit bone resorption.  Bisphosphonates further reduce calcium levels and are given after initial administration of saline.