Other Causes of Hypercalcemia - The Merck Veterinary Manual

Other Causes of Hypercalcemia

Hypervitaminosis D

Granulomatous Disease

Idiopathic Hypercalcemia of Cats

Houseplants

Osteolytic Lesions

Hypervitaminosis D:

Vitamin D toxicity refers to the effects of excessive intake of bioactive metabolites of vitamin D. Toxicity caused by ergocalciferol (vitamin D₂) or cholecalciferol (vitamin D₃) can occur from excessive dietary supplementation (most common in young growing dogs) for treatment of primary hypoparathyroidism. Both of these forms of vitamin D have a slow onset of action and prolonged duration, making correct dosing difficult. Treatment is directed at discontinuing the supplement or decreasing the dose of vitamin D. Toxicity caused by calcitriol (1,25-dihydroxyvitamin D), the most active form of vitamin D, most commonly occurs following treatment of primary hypoparathyroidism. Calcitriol is also the active ingredient in some rodenticides, but these products are no longer widely available, at least in the USA.

In dogs, a newly emerging cause of vitamin D toxicity is ingestion of the calcitriol analog, calcipotriene (also called tacalcitol), which is a topical preparation used to treat psoriasis in people. Calcipotriene toxicity in dogs can result in severe metastatic calcification in the GI tract, kidney, and other tissues; the condition is commonly fatal.

Granulomatous Disease:

Hypercalcemia associated with granulomatous disease arises from an alteration of endogenous vitamin D metabolism. Macrophages activated in response to granulomatous inflammation can develop the capability to convert vitamin D precursors to the active form of vitamin D (ie, calcitriol) in an unregulated manner. A similar alteration of vitamin D metabolism in humans may explain hypercalcemia in non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, and lymphomatoid granulomatosis.

In companion animals, hypercalcemia related to granulomatous disease has been reported in disseminated histoplasmosis, blastomycosis, coccidiomycosis, tuberculosis, and schistosomiasis. Animals with hypercalcemia related to granulomatous disease are expected to have high serum concentrations of ionized calcium and low values for PTH. Serum calcium concentrations return to normal with treatment (ie, antifungal drugs and surgical removal).

Idiopathic Hypercalcemia of Cats:

In recent years, a hypercalcemic syndrome in cats has emerged. Affected cats range in age from 2-13 yr, with no gender predilection. Clinical signs are nonspecific and may include vomiting, weight loss, anorexia, lethargy, and evidence of lower urinary tract disease. Crystalluria or calcium oxalate urolithiasis is often an underlying cause of the urinary tract signs. Many affected cats have received urine-acidifying diets.

The most consistent laboratory abnormality is hypercalcemia (high total and ionized calcium concentration), usually accompanied by normal serum phosphorus and normal renal function. In cats with idiopathic hypercalcemia, diagnostic evaluation does not identify malignancy, primary hyperparathyroidism, or vitamin D excess.

Treatment options include dietary modification, glucocorticoids, or both. A high-fiber diet is thought to be beneficial because the fiber content may decrease availability of dietary calcium for absorption. If dietary modification is unsuccessful, some cats respond to treatment with prednisone, administered at an initial dose of 5 mg bid and increased to 10 mg bid, if needed. If a response occurs, the prednisone dose can be tapered to the minimum daily dosage required to maintain normocalcemia.

Houseplants:

Certain house plants (eg, Cestrum diurnum [the day-blooming jessamine], Solanum malacoxylon , Triestum flavescens ) may contain a substance similar to vitamin D that may cause hypercalcemia when ingested.

Osteolytic Lesions:

Hypercalcemia resulting from tumor invasion or metastasis to bone develops very rarely in animals. Primary bone tumors (eg, osteosarcoma) and neoplastic cells within the bone marrow (eg, multiple myeloma) may occasionally produce hypercalcemia. The mechanisms whereby bony neoplasia may produce hypercalcemia include mechanical destruction by the infiltrating cells (as occurs with metastatic tumors and osteosarcoma) and local production of osteoclast-activating factor (as occurs with multiple myeloma). Bacterial and mycotic osteomyelitis can also occasionally produce hypercalcemia. The hypercalcemia may result from direct bone lysis or may be mediated by bone-resorbing factors (eg, prostaglandins, osteoclast-activating factor).