Clinically, azotemia with decreased urine specific gravity or isosthenuria is often detected, and signs of uremia may be present
when renal tubule damage is severe and prolonged. Hypercalcemic nephropathy may be partially reversible with appropriate therapy,
but progressive renal failure with oliguria and anuria can occur if the condition is left untreated. Overt polydipsia is a
compensatory response to the hypercalcemic-induced polyuria and is one of the most common clinical signs reported by pet owners.
Despite excessive water consumption, most patients are unable to replenish total body water stores, resulting in moderate
to severe dehydration. In an attempt to compensate for the loss of intravascular volume associated with dehydration, an increase
in sodium and calcium reabsorption occurs at the proximal tubules, further worsening the ongoing hypercalcemia.
In addition to renal tubular epithelium, neurons are also sensitive to abnormal serum calcium concentrations. High ionized
calcium concentrations decrease neuronal membrane permeability to sodium, which increases action potential thresholds and
reduces neuronal depolarization events.16 Lethargy and weakness are clinical signs often reported by pet owners because of this electrochemical impairment. The concomitant
use of narcotics or sedatives may worsen neurologic signs, and cancer patients with central nervous system involvement will
also be more severely affected by high serum calcium concentrations.15,19
Hypercalcemia also affects the gastrointestinal system, leading to nonspecific signs such as nausea, anorexia, vomiting, constipation,
diarrhea, and weight loss. Constipation may develop secondary to depressed contractility of the gastrointestinal smooth muscles,
resulting in prolonged intestinal transit times. Furthermore, hypercalcemia may increase gastrin secretion with subsequent
increases in hydrochloric acid secretion by parietal cells, leading to upper gastrointestinal irritation and mucosal ulceration.15,16,21 Gastrointestinal signs are among the most common presenting signs in cats with hypercalcemia.
Table 1: Differential Diagnoses in Pets with Hypercalcemia and Typical Diagnostic Test Findings*
DIAGNOSTIC APPROACH TO HYPERCALCEMIC PATIENTS
This review focuses on the common causes of paraneoplastic hypercalcemia. Other important differential diagnoses associated
with hypercalcemia in companion animals are presented in Table 1, using the acronym GOSH DARN IT. Once the list of differential diagnoses is understood, it is important to consider a stepwise
diagnostic approach in hypercalcemic patients. Table 2 lists diagnostic tests to help you determine the underlying cause of the hypercalcemia, along with the possible findings.
Table 2: Diagnostic Tests to Identify the Cause of Hypercalcemia in Dogs and Cats*
Obtaining a history and performing a complete and thorough physical examination, including rectal palpation in dogs, are always
the first steps in evaluating hypercalcemic patients. The CBC and serum chemistry profile results may help you narrow the
potential causes of hypercalcemia. For example, if hyperglobulinemia is present (with or without hypoalbuminemia), consider
performing serum and urine protein electrophoresis, as well as bone survey radiography and a bone marrow aspiration and cytology,
to rule out multiple myeloma.