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Basics ⬇

Basics

Definition

  • Serum total calcium >11.5 mg/dL (dogs).
  • Serum total calcium >10.5 mg/dL (cats).
  • Serum ionized calcium >1.45 mmol/L (dogs).
  • Serun ionized calcium >1.4 mmol/L (cats).
  • Hypercalcemia must be confirmed by demonstration of increased concentrations of ionized calcium.
  • Total calcium concentrations and correction formulas do not accurately predict ionized calcium.

Pathophysiology

  • Control of calcium is complex and is influenced by the actions of PTH and vitamin D and the interaction of these hormones with the gut, bone, kidneys, and parathyroid glands.
  • Derangement in the function of these can lead to hypercalcemia.
  • Secretory products of some neoplastic cells can also disturb calcium homeostasis.

Systems Affected

  • Cardiovascular-hypertension and altered cardiac contractility.
  • Gastrointestinal-reduces excitability of smooth muscle and can alter gastrointestinal function.
  • Neuromuscular-depressed skeletal muscle contractility causes weakness.
  • Renal/Urologic-high levels of calcium are toxic to the renal tubules and can cause polyuria and polydipsia (PU/PD) and renal failure; can also lead to urolithiasis and associated lower urinary tract disease.

Signalment

  • Dog and cat
  • Primary hyperparathyroidism in the Keeshond and Siamese cat

Signs

General Comments

  • Depend on the cause of hypercalcemia.
  • Patients with underlying neoplasia, renal failure, or hypoadrenocorticism generally appear ill.
  • Patients with primary hyperparathyroidism show mild clinical signs, if any, due solely to the effects of hypercalcemia.
  • Signs become apparent when hypercalcemia is severe and chronic.

Historical Findings

  • Many animals have no clinical signs.
  • PU/PD-most common in dogs.
  • Anorexia.
  • Lethargy-most common in cats.
  • Vomiting.
  • Constipation.
  • Weakness.
  • Stupor and coma-severe cases.
  • Lower urinary tract signs in animals with secondary calcium-containing uroliths.

Physical Examination Findings

  • Lymphadenomegaly or abdominal organomegaly in patients with lymphoma.
  • Usually unremarkable in dogs with primary hyperparathyroidism.
  • Parathyroid gland adenoma-rarely palpable in dogs; often palpable in cats with primary hyperparathyroidism but can be confused with the thyroid gland.

Causes

  • Neoplasia-lymphoma (most common in dogs, less common in cats), anal sac apocrine gland adenocarcinoma (dogs), multiple myeloma, lymphocytic leukemia, metastatic bone tumor, fibrosarcoma (cats), various types of carcinoma.
  • Primary hyperparathyroidism.
  • Renal failure-acute or chronic.
  • Granulomatous diseases.
  • Hypoadrenocorticism.
  • Vitamin D rodenticide intoxication-no longer marketed in the United States.
  • Vitamin D intoxication from plant or food sources.
  • Osteolytic diseases.
  • Aluminum toxicosis.
  • Idiopathic hypercalcemia in cats.

Risk Factors

  • Keeshond breed-hyperparathyroidism
  • Renal failure
  • Neoplasia
  • Use of calcium supplements or calcium-containing intestinal phosphate binders
  • Use of calcitriol or other vitamin D preparations

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

  • History should include exposure to exogenous vitamin D sources and any previous response to steroids.
  • History of waxing/waning illness suggests hypoadrenocorticism.
  • Complete lymph node, rectal, and abdominal palpation may raise index of suspicion for lymphoma and other neoplasia.
  • Assessment of hydration status, renal palpation, and urinary history points toward lower urinary tract disease or renal failure.

Laboratory Findings

Drugs That May Alter Laboratory Results

  • Oxalate, citrate, and EDTA anticoagulants bind calcium and falsely lower calcium measurement.
  • Vitamin D preparations and thiazide diuretics can raise serum calcium concentrations.

Disorders That May Alter Laboratory Results

  • Hemolysis and lipemia can falsely raise calcium concentrations.
  • Hypoalbuminemia can falsely lower total calcium concentration.

Valid if Run in Human Laboratory?

Yes

CBC/Biochemistry/Urinalysis

  • Serum calcium-total calcium concentration depends on binding proteins; adjusted (corrected) calcium can be estimated by the following formulas:
CorrectedCa=Ca(mg/dL)-albumin(g/dL)+3.5

or CorrectedCa=Ca(mg/dL)-[0.4×totalprotein(g/dL)+3.3

  • (These formulas are not always indicative of true ionized calcium status in the dog, and have not been well evaluated in the cat.)
  • Azotemia and isosthenuria help define degree of renal impairment.
  • Serum phosphorus is usually low or low-normal in patients with primary hyperparathyroidism or hypercalcemia associated with malignancy.
  • Hyperphosphatemia in the absence of azotemia suggests a non-parathyroid cause of hypercalcemia.
  • Combination of hyperphosphatemia and azotemia is difficult to interpret because renal failure can be the cause or effect of hypercalcemia.
  • Hyperkalemia and hyponatremia suggest hypoadrenocorticism.
  • Hyperglobulinemia is associated with multiple myeloma.
  • Cytopenias are seen in patients with myelophthisic disease.

Other Laboratory Tests

  • Serum ionized calcium is high in patients with primary hyperparathyroidism or hypercalcemia associated with malignancy; usually normal in patients with hypercalcemia associated with renal failure.
  • Serum PTH measurement-intact molecule and two-site assay methods have the greatest specificity; high-normal or high concentration suggests primary hyperparathyroidism; can be high in patients with chronic renal failure; low concentration makes neoplasia more likely.
  • Serum PTH-rp measurement is often high in patients with hypercalcemia associated with malignancy.
  • Vitamin D assays are not widely available.

Imaging

  • Radiography is useful for assessing renal size and shape, urolithiasis, bone lysis, and occult neoplasia.
  • Ultrasonography valuable for assessing renal architecture, abdominal lymphadenomegaly, parathyroid tumors, and urolithiasis.

Diagnostic Procedures

  • Cytologic examination of fine-needle aspirate of lymph nodes to confirm lymphoma.
  • Examination of bone marrow aspirate to confirm occult hematopoietic neoplasia.
  • ACTH stimulation testing to confirm hypoadrenocorticism.

Treatment ⬆ ⬇

Treatment

Medications ⬆ ⬇

Medications

Drug(s) Of Choice

  • Normal saline-fluid of choice.
  • Avoid calcium-containing fluids.
  • Diuretics (furosemide) and corticosteroids can be useful.

Contraindications

  • Do not use glucocorticoids until the diagnosis of lymphoma is excluded; they can obfuscate the diagnosis; if hypoadrenocorticism is suspected, do not give glucocorticoids until after ACTH stimulation testing.
  • Thiazide diuretics can cause calcium retention.

Precautions

N/A

Possible Interactions

Avoid the use of calcium- or phosphorus-containing compounds; they can cause soft tissue mineralization in severely hypercalcemic and hyperphosphatemic patients.

Alternative Drug(s)

  • Sodium bicarbonate (1–4 mEq/kg) may be useful in combination with other treatments.
  • Mithramycin has been used in severe hypercalcemic crises; avoid its use if possible, because of associated nephrotoxicity and hepatotoxicity.
  • Calcitonin may be useful in the treatment of hypervitaminosis D.
  • Pamidronate has been used successfully for treatment of hypercalcemia of various causes in dogs and cats.

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

  • Serum calcium every 12 hours (ionized calcium if possible).
  • Renal function tests-the first sign of tubular damage may be casts in the urine sediment.
  • Must monitor urine output, particularly if oliguric renal failure is suspected, in which case urine output should be measured carefully; oliguria cannot be determined unless the patient is fully hydrated.
  • Hydration status must be monitored; indicators of overhydration include increased body weight, increased central venous pressure, and edema (pulmonary or subcutaneous).

Possible Complications

  • Irreversible renal failure
  • Soft tissue mineralization

Miscellaneous ⬆

Miscellaneous

Associated Conditions

Calcium-containing urolithiasis

Age-Relatedfactors

  • Mild elevations in calcium and phosphorus may be normal in growing animals.
  • Middle-aged and older dogs and cats are at increased risk for cancer.

Pregnancy/Fertility/Breeding

A fetus is at the same risk as the dam; do not alter treatment because of pregnancy.

Abbreviations

  • ACTH = adrenocorticotropic hormone
  • Ca = calcium
  • EDTA = ethylene diamine tetra-acetic acid
  • PTH = parathyroid hormone
  • PTH-rp = parathyroid hormone–related peptide
  • PU/PD = polyuria and polydipsia

Author Thomas K. Graves

Consulting Editor Deborah S. Greco

Client Education Handout Available Online

Suggested Reading

Greco DS.Endocrine causes of calcium disorders. Top Companion Anim Med 2012, 27(4):150–155.

Messinger JS, Windham WR, Ward CR. Ionized hypercalcemia in dogs: A retrospective study of 109 cases (1998–2003). J Vet Intern Med 2009, 23(3):514–519.

Midkiff AM, Chew DJ, Randolph JF, Center SA, DiBartola SP. Idiopathic hypercalcemia in cats. J Vet Intern Med 2000, 14(6):619–626.

Savary KC, Price GS, Vaden SL. Hypercalcemia in cats: A retrospective study of 71 cases (1991–1997). J Vet Intern Med 2000, 14(2):184–189.

Schenck PA, Chew DJ. Prediction of serum ionized calcium concentration by use of serum total calcium concentrations in dogs. Am J Vet Res 2005, 66(8):1330–1336.

Hostutler RA, Chew DJ, Jaeger JQ, et al. Uses and effectiveness of pamidronate disodium for treatment of dogs and cats with hypercalcemia. J Vet Intern Med 2005, 19(1):29–33.