"Managing Hypercalcemia" TUMOR TIDBITS, A BIWEEKLY VETERINARY ONCOLOGY E-LETTER Volume 3; Number 12; March 29, 2002. Editor: Kevin A. Hahn, DVM, PhD, Dipl - ACVIM (Oncology) & Overall Nice Guy! www.gcvs.com ANNOUNCEMENTS * We had a PARTY at Gulf Coast Veterinary Oncology to Celebrate Life and Hope for pets with cancer. The turnout was wonderful and check our web site regularly for pictures from the event. * We hope to finalize plans to begin our newest clinical trials offering therapy for lymphoma in dogs at NO COST to the pet owner. Check our web site regularly for details. * Looking to join our team? Are you a registered veterinary technician? We offer a good salary, a 4 day work week, no weekends, and great benefits! Call Dr. Hahn for further information. * These are exciting times for us at Gulf Coast Veterinary Oncology - Please call us (Drs. King, Hahn, Cerraras, Freeman & Turner) at any time and check our web site regulary for more information! ====================================================== THIS WEEK'S TUMOR TIDBIT: MANAGING HYPERCALCEMIA DEFINITION * Serum total calcium > 11.5 mg/dl (dogs) * Serum total calcium > 10.5 mg/dl (cats) Pathophysiology * Control of calcium is complex and is influenced by the actions of PTH and vitamin D, and by the interaction of these hormones with the gut, bone, kidneys, and parathyroid glands. Derangement in the function of these can lead to hypercalcemia. Calcium homeostasis can also be disturbed by secretory products of neoplastic cells. Systems Affected * Renal/Urologic--high levels of calcium are toxic to the renal tubules and can cause polyuria and polydipsia (PU/PD) and renal failure. Hypercalcemia can also lead to urolithiasis and associated lower urinary tract disease. * Gastrointestinal--hypercalcemia reduces excitability of smooth muscle and can alter gastrointestinal function. * Neuromuscular--depressed skeletal muscle contractility causes weakness. * Cardiovascular--hypertension and altered cardiac contractility. SIGNS General Comments * Signs depend on the cause of hypercalcemia. Animals with neoplasia, renal failure, or hypoadrenocorticism as underlying causes generally appear ill. In animals with primary hyperparathyroidism, clinical signs are usually mild and due solely to the effects of hypercalcemia. Signs become apparent when hypercalcemia is severe and chronic. Historical Findings * PU/PD (most common in dogs) * Anorexia * Lethargy (most common in cats) * Vomiting * Constipation * Weakness * Stupor and coma (severe cases) Physical Examination Findings * Lymphadenopathy or abdominal organomegaly in patients with lymphosarcoma. * In dogs with primary hyperparathyroidism, results are usually unremarkable. * Parathyroid gland adenoma not palpable in dogs but sometimes palpable in cats with primary hyperparathyroidism. CAUSES * Neoplasia--lymphosarcoma (most common), anal sac apocrine gland adenocarcinoma, multiple myeloma, lymphocytic leukemia, and metastatic bone tumor * Primary hyperparathyroidism * Renal failure (acute and chronic) * Blastomycosis * Hypoadrenocorticism * Vitamin D rodenticide intoxication RISK FACTORS * Keeshond breed (hyperparathyroidism) * Renal failure * Neoplasia * Use of calcium supplements or intestinal phosphate binders DIFFERENTIAL DIAGNOSIS * History should include exposure to rat poison 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 lymphosarcoma or 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 Lab Results * Oxalate, citrate, and EDTA anticoagulants bind calcium and falsely lower calcium measurement. * Vitamin D preparations and thiazide diuretics can raise serum calcium concentration. Disorders That May Alter Lab Results * Hemolysis and lipemia can falsely raise calcium concentration. * Hypoalbuminemia can falsely lower total calcium concentration. CBC/BIOCHEMISTRY/URINALYSIS * Serum calcium--total calcium concentration depends on binding proteins. Adjusted (corrected) calcium can be estimated by the following formulas: Corrected Ca = Ca (mg/dl) - albumin (g/dl) + 3.5 or Corrected Ca = Ca (mg/dl) - [0.4 x total protein (g/dl)] + 3.3 * 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 absence of azotemia suggests a nonparathyroid cause of hypercalcemia. * Combination of hyperphosphatemia and azotemia is difficult to interpret, since 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. It is usually normal or low 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 concentrations suggests primary hyperparathyroidism; low concentration suggests neoplasia. * Serum PTH-rp measurement is often high in patients with hypercalcemia associated with malignancy. * Vitamin D assays are not readily available. IMAGING * Radiography useful to assess renal size and shape, urolithiasis, bone lysis, and occult neoplasia. * Ultrasonography valuable to assess renal architecture, abdominal lymphadenopathy, and urolithiasis. OTHER DIAGNOSTIC PROCEDURES * Perform a rectal examination to identify anal sac tumors, perinanal tumors, plasmacytomas, lymphomas. * Cytologic examination of fine needle aspirate of lymph nodes to confirm lymphosarcoma. * Examination of bone marrow aspirate to confirm occult hematopoietic neoplasia. * ACTH stimulation testing to confirm hypoadrenocorticism. TREATMENT * Because of the deleterious effects of hypercalcemia and the need for fluid therapy, inpatient care is necessary. Severe hypercalcemia should be considered a medical emergency. * Normal saline is the fluid of choice. * Calcium-containing fluids should be avoided. * Diuretics (furosemide) and corticosteroids can be useful in the treatment of hypercalcemia. * Until the diagnosis of lymphoma has been excluded, glucocorticoids should not be used since they can obfuscate the diagnosis. If hypoadrenocorticism is suspected, glucocorticoids should not be given until after ACTH stimulation testing has been performed. * Thiazide diuretics can cause calcium retention. * Avoid use of calcium or phosphorus-containing compounds since they can cause soft tissue mineralization in severely hypercalcemic and hyperphosphatemic patients. * Sodium bicarbonate (1-4 mEq/kg) may be useful in combination with other treatments. * Mithramycin has been used in severe hypercalcemic crises. Its use should be avoided if possible because of associated nephrotoxicity and hepatotoxicity. * Calcitonin may be useful in treatment of hypervitaminosis D. PATIENT MONITORING * Serum calcium every 12 hours * Renal function tests (the first sign of tubular damage may be casts in the urine sediment) * Urine output and hydration POSSIBLE COMPLICATIONS * Irreversible renal failure * Soft tissue calcification ASSOCIATED CONDITIONS Calcium-containing urolithiasis AGE RELATED FACTORS * Mild elevations in calcium and phosphorus may be normal in a growing dog. * Middle-aged to old patients are at a higher risk for cancer. MORE QUESTIONS ABOUT HYPERCALCEMIA? Check us out on the web at www.gcvs.com or call us any time (when in doubt, check it out)! ALL THE BEST, Kevin Hahn Kevin A. Hahn, DVM, PhD Diplomate ACVIM (Oncology) & Overall Nice Guy Gulf Coast Veterinary Specialists 1111 West Loop South, Suite 150 Houston, TX 77027 P: 713.693.1166 F: 713.693.1167 http://www.gcvs.com mailto:drhahn@gulfcoastvetspec.com