Felis ISSN 2398-2950

Hypercalcemia: overview

Contributor(s): Audrey K Cook, Philip K Nicholls, Marion O'Leary

Introduction

  • Persistently raised ionized calcium concentrations.
  • Cause: multiple causes including neoplasia, renal failure, granulomatous disease, hypoadrenocorticism, hypervitaminosis D and others.
  • Diagnosis: defined by measurement of ionized calcium concentrations, but other tests may be required to identify the underlying cause.
  • Signs: may include anorexia, lethargy, weight loss, sometimes polyuria/polydipsia, and other signs dependent upon cause.
  • Treatment: fluid therapy, frusemide diuresis, glucocorticoids, or bisphosphonates may be used palliatively; other treatments will depend on underlying cause.
  • Prognosis: variable according to cause, but persistent untreated hypercalcemia may lead to renal failure, urolithiasis and organ mineralization.

Pathogenesis

Etiology

  • Osteolysis: from neoplasia or bone infection.
  • Neoplasia (hypercalcemia of malignancy): various tumors release parathyroid hormone (PTH) mimetics, such as PTH-related peptide (PTH-rp):
  • Primary hyperparathyroidism Primary hyperparathyroidism: inappropriate secretion of parathyroid hormone (PTH) by a functional parathyroid tumor, usually an ademoma Adenoma / adenocarcinoma.
  • Hypervitaminosis D (dietary over-supplemetation; rodenticide ingestion Vitamin D poisoning (cholecalciferol)).
  • Advanced chronic renal disease Kidney: chronic kidney disease may result in tertiary hyperparathyroidism, characterized by sustained hyperplasia of the parathyroid resulting in loss of sensitivity to calcium and autonomous release of PTH.
  • Granulomatous diseases, eg mycobacteriosis and fungal infections may cause hypercalcemia.
  • Large proportion of cases are idiopathic.

Pathophysiology

  • Hypercalcemia is the result of increased uptake from gastrointestinal system, excessive release of from bone, or decreased renal excretion.
  • PTH and PT-rp activate osteoclasts, with release of calcium from bone. These agents also promote renal conservation of calcium and stimulate the synthesis of active Vitamin D Vitamin D by the kidneys.
  • Vitamin D and its analogues increase gastrointestinal uptake of calcium. At high levels, calcium is also released from bone.
  • Osteolytic processes result in release of calcium and phosphorus from bone.
  • Hypercalcemia impairs renal responsiveness to anti-diuretic hormone (ADH), resulting in compromised renal concentrating ability, and compensatory polydipsia.
  • Excessive circulating calcium, on exceeding a critical Ca x P solubility product, leads to calcium deposition in tissues such as lungs, kidney, gastric mucosa, blood vessel walls, and myocardium (metastatic calcification).
  • Kidney and lung damage from such metastatic calcification can prove fatal.
  • Excess extracellular calcium reduces membrane excitability, resulting in dysrhythmias and muscle weakness.

Timecourse

  • Very variable according to cause and severity of hypercalcemia:
    • Vitamin D intoxication can be very rapid, with rapid tissue mineralization.
    • Renal failure typically has a more chronic course.

Diagnosis

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Treatment

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Hostutler R A, Chew D J, Jaeger J Q et al (2005) Uses and effectiveness of pamidronate disodium for treatment of dogs and cats with hypercalcemia. JVIM 19 (1), 29-33 PubMed.
  • Bolliger A P, Graham P A, Richard V et al (2002) Detection of parathyroid hormone-related protein in cats with humoral hypercalcemia of malignancy. Vet Clin Pathol 31 (1), 3-8 PubMed.
  • Smith S A, Freeman L C, & Bagladi-Swanson M (2002) Hypercalcemia due to latrogenic secondary hypoadrenocorticism and diabetes mellitus in a cat. J Am Anim Hosp Assoc 38 (1), 41-44 PubMed.
  • Midkiff A M, Chew D J, Randolph J F et al (2000) Idiopathic hypercalcemia in cats. J Vet Intern Med 14 (6), 619-626 PubMed.
  • Savary K C, Price G S & Vaden S L (2000) Hypercalcemia in cats: a retrospective study of 71 cases (1991-1997). J Vet Intern Med 14 (2), 184-189 PubMed.
  • Sueda M T & Stefanacci J D (2000) Ultrasound evaluation of the parathyroid glands in two hypercalcemic cats. Vet Radiol Ultrasound 41 (5) 448-451 PubMed.
  • McClain H M, Barsanti J A & Bartges J W (1999) Hypercalcemia and calcium oxalate urolithiasis in cats: a report of five cases. J Am Anim Hosp Assoc 35 (4), 297-301 PubMed.
  • Mealey K L, Willard M D, Nagode L A et al (1999) Hypercalcemia associated with granulomatous disease in a cat. J Am Vet Med Assoc 215 (7), 959-962 PubMed.
  • Kallet A J, Richter K P, Feldman E C et al (1991) Primary hyperparathyroidism in cats: seven cases (1984-1989). J Am Vet Med Assoc 199 (12), 1767-1771 PubMed.

Other sources of information

  • Schenick P A & Chew D J (2012) Investigation of hypercalcemia and hypocalcemia.In: BSAVA Manual of Canine and Feline Endocrinology. 4th edn. C T Mooney & M E Peterson (eds), BSAVA, England, pp 221-233.


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