- Hypercalcemia is defined as either an elevation of total serum calcium (tCa) or ionized calcium (iCa) above physiologically normal homeostatic levels.
- In dogs, tCa above 12.0 mg/dl or iCa above 1.5 mmol/L qualifies as hypercalcemia.
- In cats, tCa above 11.0 mg/dl or iCa above 1.4 mmol/L qualifies as hypercalcemia.
- Elevated iCa can affect multiple organs, resulting in altered cell membrane permeability and subsequent disturbances in biological functions of the nervous, gastrointestinal, cardiac, and renal systems.
- Causes of hypercalcemia are diverse, but may be categorized into several subgroups differentiated by severity and underlying cause.
- Nonpathologic increases in serum calcium are often incidental findings and do not result in clinical signs classically associated with severe elevations in calcium. Causes accounting for nonpathologic hypercalcemia include:
- Mobilization of calcium secondary to skeletal growth, most commonly observed in young large- to giant-breed dogs
- Lipemic serum samples resulting in spurious elevations in calcium.
- Increases in serum calcium may be transient, often resulting from significant but reversible dehydration or relative increases in intravascular protein concentrations, especially albumin. Hemoconcentration secondary to any of the following causes may result in transient hypercalcemia:
- Gastrointestinal fluid loss associated with excessive vomiting, diarrhea, and/or salivation
- Renal fluid loss related to primary or secondary polyuria with concurrent inadequate compensatory polydipsia
- Loss of intravascular volume into a body cavity such as the peritoneal, pleural, or pericardial space, resulting in a state of relative dehydration.
Although many causes of elevated calcium levels are benign, hypercalcemia is usually associated with some underlying disease process. Pathologic hypercalcemia may be categorized as parathyroid hormone (PTH)-dependent or independent as follows:
- PTH-dependent conditions-primary hyperparathyroidism results in excessive production of PTH, resulting in elevated iCa.
- Adenoma (common)
- Functional adenocarcinoma (rare)
- Hyperplasia (rare)
- PTH-independent conditions
- Many diseases that induce elevations in calcium are not dependent on the production and secretion of PTH per se, but cause hypercalcemia via alternative mechanisms.
- Humoral hypercalcemia of cancer occurs when cancer cells liberate a peptide that is structurally similar to endogenous PTH, called PTH-related peptide (PTH-rp).
- Lymphoma (most common form in dogs): anatomical location-mediastinal (common), immunophenotype-T cell (common)
- Anal sac apocrine gland adenocarcinoma (second most common form in dogs): tumors cause elevations in calcium through the secretion of PTH-rp.