Hypercalcemia in Dogs

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Hypercalcemia refers to an abnormally high blood concentration of calcium. Blood calcium concentrations are measured in milligrams (mg) per deciliter (dl). One hundred milliliters equals one deciliter. Normal values for blood calcium concentration vary slightly from one laboratory to another but approximately 9.0 to 11.6 mg/dl is considered normal in adult dogs. Normal blood calcium concentration can be slightly higher in puppies less than six months of age. Blood calcium concentrations above 13.0 mg/dl are abnormal and warrant diagnostic evaluation and treatment.

Some relatively common (and benign) situations can cause erroneously high blood calcium concentrations to be reported by the laboratory depending on the analyzer used. Examples include blood samples with high fat content (lipemia) due, for example, to collection of blood soon after a meal or release of hemoglobin from the red blood cells during processing of the blood (hemolysis). Certain anticoagulants and detergents used to clean laboratory glassware also may cause erroneously high blood calcium concentrations to be reported. In these situations, the blood calcium concentration should be determined again using a properly collected blood sample that is free of lipemia and hemolysis.

Dehydration is a common clinical situation that can result in mildly increased blood calcium concentration. Blood calcium concentration should be re-evaluated after the patient has been rehydrated by intravenous or subcutaneous (under the skin) administration of fluids.

What to Watch For

  • Loss of appetite
  • Increased urine production
  • Increased water consumption
  • Vomiting
  • Weakness
  • Lethargy
  • Dehydration

    Diagnosis

    A thorough diagnostic evaluation of the dog is necessary if hypercalcemia persists after correction of lipemia, hemolysis and dehydration, because high blood calcium concentration can be a marker of some serious underlying disease processes including several different types of cancer. Routine laboratory testing provides information about the total concentration of calcium in the blood. It also may be necessary, however, for your veterinarian to have the laboratory measure the active component of blood calcium (ionized calcium). This component contributes to many of the clinical symptoms and physiologic consequences of hypercalcemia.

    The symptoms of hypercalcemia are nonspecific. Diagnostic tests are needed to recognize hypercalcemia and exclude other diseases causing similar symptoms. Tests may include:

  • A complete medical history and physical examination. The medical history will include questions about changes in water consumption and urination, change in appetite, weight loss, previous illnesses, medications being given, and exposure to toxins such as vitamin D-containing rat poison, vitamin D-containing topical ointments or toxic plants. Physical examination may include palpation of the abdomen to evaluate for enlargement of the liver or spleen, palpation of lymph nodes located under the skin to detect enlargement, palpation of the anal sacs to detect masses because one important cause of hypercalcemia is cancer of anal sac glands, and listening to the chest with a stethoscope.

  • A complete blood count (CBC) to evaluate red blood cell count and rule out anemia and blood protein concentration

  • Serum biochemistry tests to evaluate your dog's general health and determine the effects of hypercalcemia on other body systems, especially the kidneys

  • Urinalysis to evaluate the effects of hypercalcemia on the ability of the kidneys to concentrate urine

  • Blood ionized calcium concentration to evaluate the biologically active form of calcium

    Treatment

    Treatment for hypercalcemia is determined by the underlying cause and the severity of your dog's hypercalcemia and its effects on kidney function. Emergency treatment may be necessary when blood calcium concentration is very high. This may include hospitalization for intravenous fluid therapy and drug treatment.

    Serious damage to the kidneys and mineralization of soft tissues can occur if very high blood calcium concentration is allowed to persist.

    Home Care and Prevention

    Administer any medications prescribed by your veterinarian. Follow-up with your veterinarian for physical examinations and repeated testing of blood calcium concentration.

    If the underlying cause of hypercalcemia is not identified on initial evaluation, or if your dog responds inadequately to treatment, further diagnostic evaluation and treatment will be necessary.

    Make sure your dog has free access to ample amounts of fresh drinking water. Avoid exposure of your dog to toxins known to cause hypercalcemia such as vitamin D-containing rat poisons, topical ointments containing vitamin D-like compounds like calcipotriene, and plants such as day-blooming Jessamine (Cestrum diurnum), Solanum malacoxylon and Trisetum flavescens.

  • Several serious medical conditions can result in hypercalcemia. It is important to identify the underlying cause of hypercalcemia in your dog so that effective treatment can be instituted. Disorders that can cause hypercalcemia include:

  • Lymphosarcoma, a type of cancer

  • Chronic kidney failure sometimes caused by hereditary kidney disease

  • Primary hyperparathyroidism, which is overactivity of the parathyroid gland usually due to a benign tumor called an adenoma

  • Hypoadrenocorticism, also known as Addison's disease, which is a hormonal disorder caused by insufficient production of steroid hormones by the adrenal glands

  • Apocrine gland adenocarcinoma of anal sac, or a cancer of the glands of the anal sacs

  • Vitamin D intoxication caused by consumption of vitamin D-containing rat poison

  • Vitamin D intoxication caused by consumption of vitamin D-containing plants such as day-blooming Jessamine (Cestrum diurnum)

  • Vitamin D intoxication caused by consumption of topical ointments containing calcipotriene used to treat psoriasis in people

  • Multiple myeloma, which is a cancer of antibody-producing cells called plasma cells

  • Other cancers including squamous cell carcinoma, thyroid adenosarcoma, nasal adenocarcinoma, mammary gland adenocarcinoma, and others

  • Acute kidney failure

  • Granulomatous diseases, which refer to a specific type of inflammation, such as blastomycosis (fungal infection). In these diseases, inflammatory cells (called macrophages) are thought to produce vitamin D-like chemicals.

  • Osteomyelitis, bacterial infection of bone

  • Overactivity of the parathyroid glands due to nutritional disturbances

  • Dehydration with increased blood concentrations of albumin, a major protein of the blood

  • Hypercalcemia can occur normally in young growing dogs.

  • Veterinary care should include diagnostic tests and subsequent treatment recommendations. Diagnostic tests must be performed to confirm the cause of hypercalcemia and exclude other diseases. The following diagnostic tests may be recommended:

  • A complete history and physical examination. The history will include questions about changes in water consumption, urination, appetite, and weight and questions about reproductive status – whether your pet is sexually intact or neutered. Your veterinarian will also ask about previous illnesses, previous medications, exposure to rat poison or toxic plants. Physical examination will include palpation of the abdomen to evaluate for enlargement of the liver or spleen, palpation of the peripheral lymph nodes lying under the skin in various locations, and listening with a stethoscope to the chest to evaluate the heart and lungs.

  • A complete blood count (CBC), serum chemistry tests and urinalysis. An ionized calcium blood test also may be useful because the free (or ionized) calcium in the blood has important biological effects that contribute to the damaging effects of hypercalcemia in the body.

    Your veterinarian may recommend additional diagnostic tests to exclude or diagnose other conditions or to better understand the impact of hypercalcemia. These tests insure optimal medical care and are selected on a case-by-case basis. Examples include:

  • Microscopic examination of lymph node samples collected by needle aspiration or biopsy

  • Microscopic examination of a bone marrow sample

  • Ionized calcium blood test to evaluate the biologically active form of calcium

  • Abdominal X-rays to evaluate for liver or spleen enlargement

  • Chest X-rays to evaluate for tumors or lymph node enlargement

  • Biopsy of any tumor masses found during physical examination

  • Ultrasound examination of the neck to evaluate the parathyroid glands and lymph nodes

  • Ultrasound examination of the chest to evaluate for tumors or enlarged lymph nodes

  • Ultrasound examination of the abdomen to evaluate for enlargement of lymph nodes, liver or spleen

  • X-rays of the skeleton to evaluate for tumors

  • Measurement of parathyroid hormone concentration in blood to evaluate for overactivity of the parathyroid glands

  • Adrenocorticotropic hormone (ACTH) stimulation test to evaluate the function of the adrenal glands and exclude the possibility of hypoadrenocorticism or Addison's disease

  • Measurement of the blood concentration of a substance called parthyroid hormone-related peptide (PTHrP) that serves as a marker of hypercalcemia caused by cancer

  • Blood concentration of vitamin D to evaluate for vitamin D intoxication

    The decision to perform some diagnostic tests will be made based on the likelihood of specific disease processes. Your veterinarian will make these decisions on the basis of your dog's medical history and physical examination results. Some underlying disorders that may cause hypercalcemia and prompt your veterinarian to run specific tests include:

  • Lymphosarcoma. This malignancy is the most common cause of hypercalcemia in dogs and diagnosis is based on a positive biopsy or cytology results obtained from enlarged lymph nodes, liver, spleen, kidney or bone marrow. X-rays of the chest and abdomen are often performed. Approximately 40 percent of dogs with hypercalcemia caused by lymphosarcoma have a mass or enlarged lymph nodes in the chest that can be identified on X-rays.

  • Hypoadrenocorticism. Addison's disease may result in hypercalcemia in up to one-third of affected dogs. The diagnosis is based on failure of the adrenal glands to respond to stimulation by the hormone adrenocorticotropin (ACTH).

  • Kidney failure. Affected dogs also typically have high blood concentrations of phosphorus and waste products used to assess kidney function, including blood urea nitrogen (BUN) and serum creatinine. The kidneys can be damaged by persistent hypercalcemia, and sometimes it is difficult to determine if the kidney disease caused the hypercalcemia or the hypercalcemia caused the kidney disease.

  • Primary hyperparathyroidism. Overactivity of the parathyroid gland can cause marked hypercalcemia in dogs that may have no symptoms other than increased water consumption and urination. Such dogs usually have low or normal blood phosphorus concentrations, as opposed to those with kidney failure and hypercalcemia. The serum concentration of ionized calcium usually is high in affected dogs. A high serum parathyroid hormone (PTH) concentration in a hypercalcemic dog supports a diagnosis of primary hyperparathyroidism. Ultrasound examination may allow identification of enlarged parathyroid glands. In normal dogs, the parathyroid glands usually are not visible on ultrasound examination.

  • The parathyroid hormone-related peptide (PTHrP) test may identify cancer as the underlying cause of hypercalcemia.

  • Approximately 20 percent of dogs with multiple myeloma, which is cancer of the antibody-producing plasma cells, have hypercalcemia, which may arise from the bone destruction caused by these tumors. The diagnosis is made by abnormal results of bone X-rays that appear as lucent or black areas in the normally white-appearing bony structure, a very high concentration of one specific blood protein (monoclonal gammopathy) identified on a serum protein electrophoresis test, increased numbers of antibody-producing plasma cells in the bone marrow, and fragments of the antibody protein molecules in the urine (Bence Jones proteins).

  • Vitamin D intoxication and hypercalcemia can be caused by consumption of vitamin D-containing rat poisons, vitamin D-containing plants (Cestrum diurnum, Solanum malacoxylon, Trisetum flavescens), or topical ointments containing a vitamin D-like chemical called calcitpotriene. Diagnosis is based on history of exposure. Blood concentration of vitamin D can be measured if necessary.

  • Initial therapy should be aimed at the diagnosis and treatment of the underlying cause of the hypercalcemia. Treatment of hypercalcemia must be individualized based on the severity of the condition and its underlying cause.

    Moderate to severe hypercalcemia is a medical emergency because hypercalcemia has adverse effects on several organ systems, notably the kidneys, heart, nervous system, and intestinal tract. The decision to begin aggressive medical therapy is based on clinical symptoms, abnormalities of kidney function, abnormalities on the electrocardiogram (ECG), and nervous system abnormalities.

    Symptomatic dogs – those with increased water consumption and urination, loss of appetite, and lethargy – that have calcium concentrations greater than 15 milligrams per deciliter (mg/dl) of blood require immediate treatment. Such dogs are at risk for mineralization of their soft tissues, including their kidneys.
    Emergency Treatment

  • Intravenous administration of fluids, usually physiologic salt solution, facilitates the excretion of calcium in the urine.

  • Administration of the diuretic drug [furosemide (Lasix®) also facilitates excretion of sodium and calcium in the urine.

  • Cortisone-like drugs (prednisone) can limit bone release of calcium, decrease intestinal absorption of calcium, and increase excretion of calcium in the urine. These drugs can have a direct toxic effect on some cancer cells, specifically, malignant lymphocytes, and, if at all possible, they should not be given until a definitive diagnosis has been made.

  • A new class of drugs called diphosphonates can be given to decrease bone release of calcium.

  • Many other drugs (some with potentially serious adverse effects) may be required to treat dogs with refractory hypercalcemia. Examples include mithramycin, calcitonin, and ethylenediametetraacetic acid (EDTA).

  • Above all it is crucial to treat the underlying disease process that is causing the hypercalcemia.

    Optimal treatment for your dog requires a definitive diagnosis and a combination of home and professional veterinary care. Follow-up is crucial and may include the following:

  • Administer any veterinary prescribed medications.

  • Allow your dog unlimited access to fresh clean water.

  • Follow-up with your veterinarian for examinations and repeated measurements of blood calcium concentration.

  • Other recommendations will be determined by the underlying cause of the hypercalcemia.

  • Contact your veterinarian immediately if you experience difficulty treating your dog.

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