An increased serum calcium is typically first noted when total calcium (tCa) is measured as part of a biochemistry profile.
Abnormalities in tCa warrant further diagnostic investigation. First it should be verified that the abnormality is repeatable.
If the abnormality is repeatable, ionized calcium (iCa) should be measured for an accurate assessment of calcium status. Total
or adjusted tCa are not reliable measurements of calcium status as noted by a high degree of diagnostic discordance between
total, adjusted, and ionized calcium measurements.
Small increases in ionized serum calcium concentration can have adverse consequences in some animals whereas others with a
similar or greater degree of hypercalcemia may not manifest obvious clinical signs. A mild degree of hypercalcemia may not
be immediately dangerous and there is time to establish a definitive diagnosis before starting treatment. In those with severe
clinical signs associated with hypercalcemia, diagnostic and therapeutic efforts may need to proceed concurrently. Interaction
with serum phosphorus is important, as those with a tCa (mg/dL) times phosphorus concentration product greater than 70 are
most likely to have severe tissue changes associated with mineralization. Hypercalcemia can be toxic to all body tissues,
but major deleterious effects are on the kidneys, nervous system, and cardiovascular system. Most animals with tCa greater
than 15.0 mg/dL will show systemic signs, and those with tCa concentrations greater than 18.0 mg/dL are critically ill.
Polydipsia, polyuria, and anorexia are the most common clinical signs attributed to hypercalcemia, though depression, weakness,
vomiting, and constipation can also occur. Uncommonly, cardiac arrhythmias, seizures, and muscle twitching are observed. Severe
hypercalcemia that has developed rapidly (hypervitaminosis D) can result in death. Cats with hypercalcemia do not display
polyuria, polydipsia or vomiting as commonly as do dogs with a similar degree of hypercalcemia. Cats with idiopathic hypercalcemia
may have no obvious clinical signs.
Table 1. Anticipated changes in calcemic hormones and serum biochemistry associated with disorders of hypercalcemia
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Hypercalcemia is initially defined on results of serum total calcium from obviously sick animals, but also fortuitously during
wellness examinations, pre-anesthesia screenings, evaluation of urolithiasis, and from those evaluated for vague GI signs.
The initial finding of a mild increase in serum tCa should be repeated to see if the hypercalcemia is persistent. A transient
increase in serum tCa is documented in some cats with minor increases in serum tCa; further workup is not indicated in these
instances in which the serum tCa concentration is normal on subsequent analysis. Measurement of serum iCa is the next step
in the diagnostic evaluation of those with persistent or more substantial increases of serum tCa. Prediction of iCa status
from tCa measurement is not accurate, and iCa needs to be specifically measured. Increased iCa concentration is documented
in all cats with IHC, but may be normal or low in other conditions associated with increased serum tCa, especially chronic
renal failure (CRF). Serum iCa can be measured alone, or preferably at the same time that parathyroid hormone (PTH) concentration
is measured.
Differential Diagnoses for Hypercalcemia
There are many potential causes of hypercalcemia (See HARDIONS Eponym). Though cancer-associated hypercalcemia has traditionally
been noted to be the primary cause of elevated serum in both dogs and cats, IHC appears to be the most prominent cause in
cats followed by renal failure, and then malignancy in primary care practice. In some cases with persistent hypercalcemia,
the diagnosis of the cause of the hypercalcemia will be obvious after analysis of history (vitamin D exposure, drugs, ingestion
of houseplants), and findings from physical examination (masses, organomegaly, cancer or granulomatous disease). In other
cases, the cause will not be obvious and information from hematology, serum biochemistry, body cavity imaging, cytology, and
histopathology will be necessary.
Hypercalcemias can be classified as parathyroid-dependent (primary hyperparathyroidism), or parathyroid-independent (normal
parathyroid gland). In hypercalcemic dogs, neoplasia is the most common diagnosis, followed by hypoadrenocorticism, primary
hyperparathyroidism, and chronic renal failure. Approximately 70% of hypercalcemic dogs are also azotemic, with azotemia uncommon
only in dogs with hyperparathyroidism. In hypercalcemic cats, neoplasia is second to renal failure or idiopathic hypercalcemia.
H = Hyperparathyroidism (1°,3°, hyperplasia), Humoral Hypercalcemia of Malignancy, Houseplants, Hyperthyroid
A = Addison's Disease, Aluminum Toxicity, Vitamin A, Milk-Alkali
R = Renal Disease, Raisins(Grapes)- dogs
D = Vitamin D Toxicosis (Granulomatous Dz),
Drugs, Dovonex, Dehydration, DMSO (calcinosis cutis), Diet
I = Idiopathic (Cats), Infectious, Inflammatory,
Immobilization
O = Osteolytic (osteomyelitis, immobilization, Local Osteolytic Hypercalcemia, bone infarct)
N = Neoplasia (HHM and LOH), Nutritional
S = Spurious, Schistosomiasis, Salts of Calcium, Supplements
