Treating paraneoplastic hypercalcemia in dogs and cats - Veterinary Medicine
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Treating paraneoplastic hypercalcemia in dogs and cats
Various tumor-related factors may lead to elevated calcium concentrations that can greatly contribute to a cancer patient's morbidity. Here's how to help alleviate the suffering associated with this common paraneoplastic syndrome.


1A & 1B. A ventrodorsal radiograph of the right humerus (1A) and a right lateral radiograph of the lumbar spine (1B) of an 11-year-old female spayed mixed-breed dog presenting with signs of pain. Hypercalcemia, hypoalbuminemia, and hyperglobulinemia were noted on the serum chemistry profile. Multifocal purely lytic lesions are seen. Bone marrow cytology and protein electrophoresis confirmed a diagnosis of multiple myeloma.
When the history, physical examination, standard imaging (thoracic radiography, abdominal ultrasonography), and CBC and serum chemistry profile results fail to identify a potential cause, further tests can be considered, such as PTH and PTH-related peptide (PTHrP) concentration measurement and an ultrasonographic examination of the ventral cervical area, ideally by an experienced radiologist. Generally, as with other disorders, the most common conditions are ruled out first by using the least invasive techniques initially.

2A & 2B. Bone scintigraphy (99-Tc-EDTMP) in a 12-year-old male neutered mixed-breed dog (the dogs head is to the left) with prostate carcinoma-a tumor type not reported to be associated with hypercalcemia in this species. Increased uptake represents abnormal bone turnover and can be observed in many ribs (2A-open arrows) , in the sternum (2A-solid arrow), in the thoracic spine (2A-arrowhead), and in the femoral diaphysis and ischium (2B-open arrows). Nonspecific uptake is also observed in the coxofemoral and stifle joints from osteoarthritis (2B-arrowheads). Cytologic examination confirmed that a target bone lesion (femur) was metastatic.
Routine tests to detect tumors ("tumor hunting") or complete staging procedures are recommended to better determine the histologic origin and extent of malignancy. Bone survey, via plain radiographs of the long bones and spine (Figures 1A & 1B), or bone scan, via nuclear scintigraphy (Figures 2A & 2B) generally with technetium 99m-ethylenediamine-tetramethylenephosphonic acid (99-Tc-EDTMP), may provide diagnostic clues in cases of occult or unexplained hypercalcemia.


Hypercalcemia of malignancy may arise through three main mechanisms. First, tumor cells may produce and liberate soluble mediators capable of acting on bone and kidneys through endocrine and paracrine pathways, a mechanism referred to as humoral hypercalcemia of malignancy.3-5,7,8,15,19 Second, cancer cells may subvert the enzymatic activity of 1 alpha-hydroxylase, thereby causing the unregulated conversion of calcidiol to active calcitriol, which enhances intestinal absorption of calcium.8,22-26 This mechanism is poorly described with tumors in companion animals. Finally, certain tumor histologies such as leukemias, lymphomas, myeloma, and certain carcinomas may directly cause osteolysis when they invade or metastasize to bones, resulting in the dissolution of hydroxyapatite crystals through an agonist effect on osteoclasts during tumor progression.9,27


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