What Is the Best Treatment of an Adult Patient with Hypercalcemia of Malignancy?

The Hospitalist. 2011 January;2011(01):

January 1, 2011|The Hospitalist

Sarah Hartley, MD;William Repaskey, MD;Jeffrey Rohde, MD;University Of Michigan Health System

Case

A 63-year-old man with hypertension, diabetes, and recently diagnosed squamous-cell lung cancer presents with diffuse abdominal pain and confusion of two-day duration. He weighs 105 Kg, his blood pressure is 105/65 mm/Hg, heart rate is 105 beats per minute, and temperature is 99.0 degrees Fahrenheit. His respirations are 18 breaths per minute, oxygen saturation is 95% on room air, and his orthostatics are positive. Dry mucus membranes with decreased skin turgor are noted on physical examination. Laboratory evaluation reveals a calcium level of 15.5 mg/dL, creatinine level of 1.2 mg/dL, albumin level of 4.3 g/dL, and a phosphorous level of 2.9 mg/dL.

What is the best treatment of this condition?

KEY Points

Hypercalcemia of malignancy is the most common cause of hypercalcemia in hospitalized patients.
Volume repletion with IV isotonic fluids is an important initial intervention.
Furosemide use should generally be used only to correct volume overload from IV fluids.
Bisphosphonates are the best-studied and most efficacious treatment for hypercalcemia.
Attention must be paid to the underlying malignancy and its concomitant high mortality rate.

Additional Reading

Stewart A. Hypercalcemia associated with cancer. N Engl J Med. 2005;542(4):373- 379.
Assadi F. Hypercalcemia: an evidence-based approach to clinical cases. Iran J Kidney Dis. 2009;3:(2):71-79.
LeGrand SB, Leskuski D, Zama I. Narrative review: furosemide for hypercalcemia: an unproven yet common practice. Ann Intern Med. 2008;149:259-263

Overview

Calcium homeostasis involves complex interactions between the kidney, gastrointestinal (GI) tract, and the skeletal system via hormonal influences. Although 99% of the body’s calcium is stored in the bones, 50% of serum calcium is in the active ionized form, 40% is bound to albumin, and 10% is complexed with anions.¹ It’s important to remember these percentages when evaluating a patient’s serum calcium; elevated serum calcium can be validated by using either a correction formula (corrected calcium=measured total calcium + [0.8 x (4.5-albumin)]) or by direct measurement of the ionized calcium, which is the physiologically active form.

Hypercalcemia of malignancy is the most common cause of hypercalcemia in the hospitalized patient. Twenty to 30% of patients with cancer will develop hypercalcemia at some point in their disease course.² Overall, this portends a poor prognosis with a median survival of three to four months.³

Four general mechanisms are involved in the pathogenesis of malignant hypercalcemia; these mechanisms form the basis for available treatment strategies available:

Osteolytic tumors, such as multiple myeloma, can directly act on bone, leading to osteoclast activation and release of calcium;
Humoral mediators elaborated by malignant cells, such as parathyroid hormone-related peptide (PTH-RP), can effect activation of osteoclasts and decrease renal elimination of calcium, causing humoral hypercalcemia of malignancy;
Some malignancies (most commonly lymphomas) can directly synthesize 1,25 (OH)2 vitamin D, leading to increased luminal absorption of both calcium and phosphorus from the GI tract; and
Direct production of parathyroid hormone (PTH) by the malignant cells is rare, but has been reported.²

Other factors, including impaired mobility, might lead to further bone resorption and a worsening of the hypercalcemic state.

A patient with hypercalcemia must have a systematic workup, with knowledge of other causes of hypercalcemia that could be present, irrespective of malignancy. Examples include primary hyperparathyroidism, medications effect, and genetic etiologies. Although further discussion is beyond the scope of this article, a broad diagnostic approach is represented in Figure 1 (at right).