Corrected serum calcium greater than 11.0 mg/dL.

A. Normal serum calcium is 8.6 to 10.5, and normal ionized calcium is 1.13 to 1.32 mmol/L.

B. Calcium distribution within the body: 99% of body’s calcium is stored in the bone, and 1% of the total body calcium is located in the serum.

1. Of the 1% located in the serum, half is bound to protein and the other half is considered active and is ionized.

2. Most of the calcium bound to protein is bound to albumin.

3. Cancer patients often have preexisting hypoalbuminemia that will influence the amount of active calcium that is present in the serum. A formula to calculate corrected calcium is shown in Box 34-1.

4. When interpreting laboratory values, it is important to note that a decrease in albumin results in an increase in unbound or ionized calcium.

C. Calcium is necessary for the formation and maintenance of bones and teeth, transmission of nerve impulses, maintenance of normal clotting mechanisms, and contractility of cardiac, smooth, and skeletal muscle.

D. Normal levels of plasma calcium are maintained in the body by three major hormones: parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, and calcitonin. These individual hormones respond when necessary to maintain a steady normal level of calcium in the body.

A. Cancer is the most common cause of hypercalcemia in hospitalized patients and occurs in 10% to 20% of cancer patients in the United States. Eighty percent of cases are with solid tumor cancers, such as breast, lung, head and neck, bladder, thyroid, and renal. Twenty percent
are hematologic cancers, such as multiple myeloma, leukemia, and lymphoma.

B. Common nonmalignant causes of hypercalcemia include hyperparathyroidism, and hyperthyroidism.

C. The two primary mechanisms associated with hypercalcemia in cancer are humoral and osteolytic.

1. Humoral mechanisms are responsible for about 80% of all hypercalcemia of malignancy (Kaplan, 1994). Humoral hypercalcemia of malignancy has been defined as an increase in calcium levels above normal with absence of skeletal metastasis (Grill & Martin, 2000). Research is continuing to determine whether humoral and osteolytic hypercalcemia can coexist in patients, and the impact of multiple mechanisms on the clinical course of the complication (Grill & Martin, 2000). Tumor production of a parathyroid hormonelike substance (PTH), increased production of 1,25-dihydroxyvitamin D, or increased secretion of certain growth factors such as tumor necrosis factor, interleukin 6, and interleukin-1 are humoral mechanisms that have been identified.

a. The body can be tricked into believing that the calcium levels are low when tumors secrete a PTH-like substance. PTH typically functions to bring calcium levels back to normal when low. PTH does this by affecting three organs: bone, intestines, and kidneys. PTH stimulates osteoclast activity, which breaks down bone, causing the release of stored calcium into the bloodstream. PTH also stimulates the kidneys to increase excretion of phosphorus, causing serum calcium levels to rise to maintain its inverse relationship with phosphorus. The kidneys are unable to excrete the large amounts of calcium being released from bone. Intestinal reabsorption of calcium also occurs as a result of PTH secretion, thereby raising the calcium.

b. Intestinal stimulation to increase the production of 1,25-dihydroxyvitamin D, consumption of vitamin D-enriched foods, and exposure to natural sunlight all serve to increase calcium levels in the blood. Increased production of 1,25-dihydroxyvitamin D is a common cause of hypercalcemia in lymphoma and leukemia.

c. Growth factors and cytokines (eg, tumor necrosis factor, interleukins, interferons) stimulate osteoclast resorption of bone, resulting in elevated serum calcium levels.

2. Osteolytic causes include tumors that result in skeletal metastases or arise in the bone.

D. Other Medical Causes

1. Immobilization causes increased release of calcium into the bloodstream, which can potentiate hypercalcemia.

2. Dehydration causes the body to retain water and decrease calcium excretion through the kidneys.

3. In the presence of renal insufficiency, patients are unable to excrete excess calcium from the body.

4. Medications such as thiazide diuretics, calcium carbonate, hypervitaminosis D and A, theophylline toxicity, lithium, estrogen, and antiestrogen, and progestin therapies may cause or potentiate hypercalcemia.

A. Assessment: The following signs and symptoms are related to the actual calcium level, the general health of the patient, and the rapidity of onset of hypercalcemia. Elderly patients tend to have more symptoms with less severe increases in calcium (Table 34-1).

1. Neuromuscular: Fatigue, weakness, lethargy, confusion, apathy, and hyporeflexia are secondary to decreased neuromuscular excitability.

a. In severe cases, psychotic behaviors, visual changes, and seizures can occur.

b. Stupor, coma, and death can occur in severe cases left untreated.

c. Bone pain or achiness, skeletal fractures, and deformities can result from the increased osteoclast activity causing bone destruction.

2. Cardiovascular: Bradycardia or heart block can occur due to depressed cardiac contractility. Waveform changes may include shortened QT interval, prolonged PR interval, and flat, widened, or inverted T waves. Increased digitalis sensitivity may also be present. Hypercalcemia can also cause hypertension, related to renal dysfunction or direct vasoconstriction.

3. Gastrointestinal (GI): Anorexia, constipation, nausea, and vomiting are the result of decreased smooth muscle contractility and decreased motility of the GI tract. Development of a paralytic ileus is not an uncommon complication.

4. Genitourinary: Glomerular filtration of high calcium levels causes disruption of tubular filtering mechanisms, leading to increased fluid excretion and polyuria. Excess calcium salt precipitation in the renal tubules may lead to renal calculi that present as abdominal or flank pain. Renal insufficiency or renal failure may occur in extreme cases.