Treating paraneoplastic hypercalcemia in dogs and cats - Veterinary Medicine
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Treating paraneoplastic hypercalcemia in dogs and cats
Various tumor-related factors may lead to elevated calcium concentrations that can greatly contribute to a cancer patient's morbidity. Here's how to help alleviate the suffering associated with this common paraneoplastic syndrome.



Measured total serum calcium is composed of three organic forms: 1) It is bound to plasma proteins (40%); 2) it is complexed as citrates, acetates, and phosphates (10%); and 3) it is ionized or free (50%). Because only the latter form possesses biological activity, ionized calcium measurements are the most physiologically relevant values to obtain when hypercalcemia is suspected based on an elevated total serum calcium concentration.15,16 Depending on the reference laboratory, hypercalcemia is usually defined by a total serum calcium concentration of ≥ 12 mg/dl (3 mmol/L) in dogs and ≥ 11 mg/dl (2.75 mmol/L) in cats.10 True hypercalcemia is confirmed when the ionized calcium concentration is > 1.45 mmol/L in dogs or > 1.4 mmol/L in cats.7

Accurately determining the calcium concentration in critically ill patients is important. So being aware of certain factors' influence on the reliable and precise laboratory assessment of calcium is fundamental. Fasting blood samples are necessary for accurate quantification, as lipemia may falsely increase the measurement of serum calcium.17,18 Appropriate blood sampling technique is equally important to minimize laboratory errors secondary to hemolysis that may interfere with colorimetric analyzer readings.18

Furthermore, hypoproteinemia, especially from hypoalbuminemia, may lead to a relative or spurious decrease in total serum calcium. To compensate for albumin, an adjusted total calcium concentration (mg/dl) can be calculated in dogs by subtracting the measured serum albumin concentration (g/dl) from the measured total serum calcium concentration (mg/dl) and adding 3.5.15,19 However, in some disease conditions, total calcium concentrations corrected for protein may still poorly correlate with ionized calcium concentrations, so they should not be considered a substitute for assessing ionized calcium.20 Also, this formula is not valid in dogs younger than 1 year of age or in cats of any age.

In addition, although ionized calcium is physiologically active, interconversion among all three organic forms can occur and should be considered when managing a critically ill patient. Blood pH or the plasma hydrogen ion concentration may affect the protein binding of calcium, as a larger proportion of total serum calcium exists in a protein-bound form under alkalotic conditions, while acidosis favors calcium ionization.15 So samples collected and processed anaerobically ensure more accurate results, since the pH is less likely to increase from loss of carbon dioxide.15

Finally, ionized calcium and pH are more stable in serum than in whole or heparinized blood, and measured ionized calcium in serum is stable for seven days when collected anaerobically and stored at 39.2 F (4 C).15


Hypercalcemia of malignancy generally results in nonspecific signs that may be insidious and vary in severity. Regardless of the cause of the hypercalcemia, the urinary, neuromuscular, and gastrointestinal systems are most susceptible to the effects of a high calcium concentration. The clinical signs' severity correlates not only with the magnitude of the hypercalcemia but also with the rate of calcium concentration elevation.15 In addition, in cases of hypercalcemia of malignancy, certain clinical signs may be related to the underlying neoplastic disease rather than the secondary hypercalcemia. Thus, therapies should be aimed at treating the underlying cause in addition to the associated clinical consequences.

Urinary signs

The urinary system is severely affected by pathologic elevations in serum calcium concentrations, with primary polyuria and compensatory polydipsia being the most common clinical signs seen in hypercalcemic dogs. Elevated serum calcium concentrations lead to excessive production of dilute urine by inhibiting antidiuretic hormone receptors at the level of the distal renal tubules, causing a secondary nephrogenic diabetes insipidus.15,19 In addition to these functional changes, structural damage in the renal tubules such as mineralization of the basement membrane and secondary tubular degeneration with resulting interstitial fibrosis can exacerbate kidney dysfunction and predispose affected animals to progressive renal failure.


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