Hypercalcemia is defined as a serum or plasma total calcium level exceeding the normal level. Reference ranges vary considerably among laboratories however a serum calcium concentration > 12mg/dl is considered to be a clinically important elevation and a repeated calcium elevation warrants clinical investigation. Routine calcium levels reported on chemistry profiles are Total calcium, of which 50% is ionized (the metabolically active form) , 40% is protein bound (to albumin) and 10% calcium complexes. In the dog serum calcium concentration is adjusted for albumin level by subtracting the albumin level from the total Ca++ level and adding 3.5.;this yields a corrected calcium level in mg/dl. This method is not accurate in cats. Recently, (2005) it has been suggested that ionized calcium must be measured directly in order to obtain the most accurate level and prevent misdiagnosis of disease especially in dogs with chronic renal failure.
It should be noted that lipemia or hemolysis MAY cause severe artifactual elevation of calcium concentration depending upon the method being used to measure calcium concentration.
The most common cause of hypercalcemia in the dog is cancer. In the cat, idiopathic hypercalcemia is rather common especially in those animals with upper urinary tract calculi but hypercalcemia may also be cancer caused in the cat. The differential diagnosis for hypercalcemia follows:
I. Causes of Hyperclacemia
Hypercalcemia of Malignancy
- Anal sac adenocarcinoma
- Mammary tumors
- Thyroid carcinoma
- Bone tumors
- Colonic carcinoma
- Testicular cancer
- Renal failure
- Hypervitmainosis D
- Idiopathic (Cats)
1. Neoplasia involving bone may produce osteoclast activating factor leading to Calcium mobilization.
2. Primary hyperparathyroidism = Excess PTH
3. Solid tumors including lymphoma produce PTH related protein PTHrP which is not measaured by assays that measure the intact PTH molecule.
4. Hypervitaminosis D= Absorption of excess calcium from the Gi tract
5. Renal failure= Decreased calcium excretion, hemoconcentration, secondary hyperparathyroidsism
6. Idiopathic= Cats= Unknown
III. Clinical and Diagnostic approach
1. Hypercalcemia often detected on routine blood work. What is a significant elevation? Repeat of the test often indicated. What is the ionized calcium level?
2. Are there clinical signs relative to hypercalcemia? Signs of hyperclacemia including PU/PD, anorexia or hyporexia, lethargy, and weakness, constipation, and calcium uroliths. Uncommonly, neurologic signs and muscle fasiculations may be seen. Cardiac arrythmias are also possible. Signs usually begin at 15 mg/dL.
3. Clinical signs related to the underlying disease process may be more apparent such as lymphadenopathy (LSA), bone pain with bone, lameness and possible neuro defects with myeloma, vomiting with Renal failure and Vit D intoxication.
1. Evaluate renal values and phosphorous levels. If azotemia and hyperphosphatemia are present with normal electrolytes then primary renal failure or Vit D intoxication are likely.
2. If Ca, Phosphorous, BUN and creatitnine are elevated with a normal sdium hypoadrenocorticism should be suspected and an ACTH response test performed.
3. If Ca is elevated and phosphorous is normal or low and no azotemia, the major DDX include malignancy caused hypercalcemia and Primary hyperparathyroidism.
4. Consider measuring PTH levels, PTHrP levels, and ionized calcium levels. We send this test package to Michican State University, Cost= $ 60.00, turn-around time is rather quick, 3-4 days. Depending upon results
- REEXAMINE (or examine) lymph nodes
- DO A RECTAL exam being careful to palpate anal sacs for abnormalities and more rostrally and dorsally for the sublumbar lymph nodes
- Palpate mammary glands and/or testicles
- Consider ultrasound examination of the neck looking for parathyroid/thyroid mass
- Consider search for occult neoplasia
- Thoracic radiographs (pulmonary mets or mediastinal masses)
- Abdominal ultrasound
- Lymph node aspirate and cytologic evaluation