Differential Diagnoses of Hypercalcemia
Hypercalcemia in the dog can have many etiologies, including malignancy (e.g., primary hyperparathyroidism, humoral hypercalcemia of malignancy, multiple myeloma, and neoplasia in bone), renal failure, hypoadrenocorticism, and increased vitamin D activity (e.g. rodenticides containing cholecalciferol, compounds containing calcipotriene or calcipotriol, plants containing calcitriol glycosides, excess dietary supplementation, and granulomatous inflammation).
Hypercalcemia of malignancy is the most common cause of hypercalcemia in the dog and is most often due to lymphosarcoma or apocrine gland adenocarcinoma of the anal sac. It is less commonly present with other malignancies, including multiple myeloma and carcinomas.
In primary hyperparathyroidism, the most common tumor of the parathyroid glands is an adenoma, whereas hyperplasia and parathyroid carcinoma are more infrequently diagnosed.
Working Up a Case of Hypercalcemia
Diagnosing the source of hypercalcemia begins with a complete history that will indicate the likelihood of vitamin D toxicosis owing to supplementation, rodenticide, certain plants, or antipsoriasis creams. A complete physical examination will reveal the presence or absence of enlarged lymph nodes, rectal masses, or skeletal pain.
Diagnostic work-up for hypercalcemia should include a CBC, serum biochemistry profile, and urinalysis. All dogs with a high total calcium concentration should have true hypercalcemia confirmed by measuring an ionized calcium concentration. Specialized hormone analysis, including determination of PTH and parathyroid-related protein (PTH-rp) concentrations, can also be extremely helpful in determining the cause of a dog's hypercalcemic state.
The serum PTH concentration in dogs with malignancy-associated hypercalcemia is usually low, indicating an appropriate response of the parathyroid glands to the elevated serum calcium concentration. In some dogs with hypercalcemia of malignancy, the tumor secretes excessive amounts of PTH-rp; this tumor-secreted hormone acts to bind to PTH receptors, thereby inducing hypercalcemia.
Dogs with primary hyperparathyroidism will generally have serum PTH that are either clearly high or in the high-normal range. It's important to realize that the finding of a high-normal serum PTH value in a dog with ionized hypercalcemia is not normal — in these cases, the PTH secretion is inappropriate for the degree of hypercalcemia.
In dogs in which primary hyperparathyroidism is suspected, ultrasonography of the neck region can be very useful in detecting an enlarged parathyroid nodule. For definitive diagnosis, however, histopathological examination of an excised parathyroid nodule is required.
