Differential Diagnosis: Hypercalcemia
Julie Allen, BVMS, MS, MRCVS, DACVIM (SAIM), DACVP (Clinical), Durham, North Carolina
Most (≈99%) calcium in the body is stored in the bones. The remaining calcium is stored in extracellular fluid and is composed of 3 parts: protein-bound, complexed, and unbound/ionized (active form) calcium. As a result, protein concentrations can affect total calcium; however, formulas to correct for albumin concentration should not be used, as they are often inaccurate. Any increase in total calcium should be rechecked and an ionized calcium test performed if calcium is still increased. Some conditions can cause hypercalcemia via multiple mechanisms.
Following are differential diagnoses for patients presented with hypercalcemia.*
Artifactual hypercalcemia
Severe lipemia or icterus
Physiologic hypercalcemia (mild hypercalcemia due to bone growth in young animals)
Increased protein binding
Hemoconcentration (ie, hyperalbuminemia)
Hyperproteinemia (ie, paraproteinemia)
Malignant hypercalcemia (most common cause in dogs)
Lymphoma
Anal sac apocrine gland adenocarcinoma
Other carcinomas (eg, mammary, thyroid, lung, clitoral), particularly if metastatic to bone
Thymoma
Multiple myeloma
Osteosarcoma or other primary bone tumor
Melanoma
Hypoadrenocorticism
Idiopathic hypercalcemia (most common cause in cats)
Primary hyperparathyroidism
Chronic kidney disease (less commonly, acute kidney injury)
Raisin/grape toxicity
Hypervitaminosis D
Cholecalciferol toxicity
Calcipotriene/calcipotriol (eg, antipsoriasis creams) ingestion
Calcitriol or vitamin D overdose (eg, due to inappropriate dietary supplementation)
Plant (eg, day-blooming jessamine) ingestion
Drug-induced effect
Thiazide diuretics
Excessive calcium (eg, calcium carbonate) supplementation
Aluminum-based phosphate binders
Dimethyl sulfoxide when used extra-label in the treatment of calcinosis cutis
Localized osteolysis
Osteomyelitis
Hypertrophic osteodystrophy
Disuse osteoporosis
Granulomatous disease
Blastomycosis
Histoplasmosis
Hepatozoonosis
Schistosomiasis
Pythiosis
Angiostrongylus vasorum infection
Heterobilharzia americana infection
Secondary to biologic implants
Benign humoral hypercalcemia
Benign mixed mammary tumors
Benign renal angiomyxoma
Benign esophageal/vaginal leiomyoma
Hypervitaminosis A
Retained fetus (dogs)
*Differential diagnoses for hypercalcemia do not have a determined order of likelihood and are listed in no particular order.