Laboratory Assessment
        Laboratory studies
Patient assessment
Decision to Treat Hypercalcemia

Laboratory Assessment

Normal serum calcium levels are maintained within narrow and constant limits, approximately 9.0 to 10.3 mg/dL (= 4.5–5.2 mEq/L or 2.25–2.57 mmol/L) for men and 8.9 to 10.2 mg/dL (= 4.4–5.1 mEq/L or 2.22–2.54 mmol/L) for women. Symptoms of hypocalcemia or hypercalcemia are caused by abnormalities in the ionized fraction of the plasma calcium concentration; however, ionized calcium levels are rarely checked routinely in clinical laboratories. The total plasma calcium is used to infer the ionized calcium fraction and is usually accurate, except in the setting of hypoalbuminemia. Because hypoalbuminemia is not uncommon among patients with cancer, it is necessary to correct the total plasma calcium concentration for the percent of calcium that would have been measured if the albumin level were within normal range. The calculation is as follows:

total serum calcium corrected for albumin level: [(normal albumin – patient’s albumin) × 0.8] + patient’s measured total calcium

This calculated value is fairly accurate, except in the presence of elevated serum paraproteins, such as in multiple myeloma. In this case, laboratory measurement of the actual ionized calcium concentration may be necessary.[1]

Calcium also binds to globulins in blood. In contrast with hypoalbuminemia, hypogammaglobulinemia has a relatively small effect on calcium protein binding. Serum total calcium concentration can be corrected for changes in globulins as follows: total serum calcium concentration varies directly by 0.16 mg/dL, 0.08 mEq/L, or 0.04 mmol/L with each 1 g/dL change in globulin concentration. In clinical practice, changes in serum globulin concentrations rarely effect clinically significant changes in the ionized calcium fraction.

Acid-base status also affects the interpretation of serum calcium values. While acidosis decreases the protein-bound fraction (consequently increasing the ionized calcium fraction), alkalosis increases protein binding. Serum total calcium concentration can be corrected for changes in pH as follows: total serum calcium concentration varies inversely by 0.12 mg/dL, 0.06 mEq/L, or 0.03 mmol/L with each 0.1 unit change in pH. Unlike changes in serum albumin concentration, alterations in blood pH rarely effect clinically significant changes in the ionized calcium fraction.[2]

It is important to measure the serum calcium and albumin concentrations. Other selected tests (as shown below) may be useful in some instances:

• Blood urea nitrogen and creatinine concentrations (renal function).



• Immunoreactive parathormone (iPTH):
  • iPTH concentration is increased or rarely normal in hyperparathyroid disease.
  • iPTH is typically decreased or undetectable in hypercalcemia of malignancy.



• Parathyroid hormone–related peptide (if available).



• Serum 1,25-dihydroxy vitamin D concentration in patients with hematologic malignancies.



• Other serum electrolyte concentrations (phosphate, magnesium).

Primary assessment should include the following:[3,4]

• History:
  • How rapidly have symptoms developed? Symptoms of malignancy are usually present when hypercalcemia is caused by cancer. Rapid symptom onset is more typical of hypercalcemia of malignancy than hypercalcemia associated with hyperparathyroidism and other diseases.
  
  
  
  • Is there radiographic evidence of primary or metastatic bony disease?
  
  
  
  • Has the patient recently received treatment with tamoxifen or estrogenic or androgenic steroids?
  
  
  
  • Is the patient taking digoxin?
  
  
  
  • Is there an exogenous calcium source such as intravenous fluids or parenteral nutrition?
  
  
  
  • Is the patient receiving thiazide diuretics, vitamin A, vitamin D, or lithium?
  
  
  
  • Is there concurrent disease predisposing to dehydration or immobility?
  
  
  
  • Are there potentially effective treatments for the patient’s underlying malignancy?
  
  
  



• Clinical status (refer to the Manifestations section of this summary):
  • Neuromuscular (evaluate muscular strength, muscle tone, and decreased deep-tendon reflexes).
  
  
  
  • Neurologic (fatigue, apathy, depression, confusion, or restlessness).
  
  
  
  • Cardiovascular (hypertension, electrocardiogram changes, arrhythmias, or digitalis toxicity).
  
  
  
  • Renal (urine output polyuria, nocturia, glucosuria, or polydipsia).
  
  
  
  • Gastrointestinal (anorexia, nausea, abdominal pain, constipation, decreased bowel sounds, or abdominal distention).
  
  
  
  • Miscellaneous (musculoskeletal pain or pruritus).
  
  
  

The decision to correct clinical hypercalcemia must be considered within the context of therapeutic goals as determined by the patient, the caregivers, and the medical staff. The natural course of untreated hypercalcemia is well known to clinicians: As with hepatic or metabolic encephalopathy, untreated hypercalcemia will progress to loss of consciousness and coma. This clinical course may be desirable at the end of life in patients with intractable suffering and/or unmanageable symptoms when no further active treatment is available or desired for reversal of the primary disease process.

References

1. Beers MH, Berkow R, eds.: The Merck Manual of Diagnosis and Therapy. 17th ed. Whitehouse Station, NJ: Merck Research Laboratories, 1999. 
   
   
2. Bajorunas DR: Clinical manifestations of cancer-related hypercalcemia. Semin Oncol 17 (2 Suppl 5): 16-25, 1990.  [PUBMED Abstract]
   
   
3. Calafato A, Jessup AL: Body fluid composition, alteration in: hypercalcemia. In: McNally JC, Somerville ET, Miaskowski C, et al., eds.: Guidelines for Oncology Nursing Practice. 2nd ed. Philadelphia, Pa: WB Saunders Company, 1991, pp 397-401. 
   
   
4. Coward DD: Hypercalcemia knowledge assessment in patients at risk of developing cancer-induced hypercalcemia. Oncol Nurs Forum 15 (4): 471-6, 1988 Jul-Aug.  [PUBMED Abstract]
   
   

Back to Top

< Previous Section  |  Next Section >