The parathyroid glands play an integral role in maintaining calcium homeostasis through secretion of parathyroid hormone (PTH). PTH exerts direct effects on the bone and kidney and acts indirectly on the intestine, via calcitriol, which then regulates serum calcium levels on a minute to minute basis. In normal animals, release of PTH is regulated by negative feedback of serum calcium so, as calcium levels rise, release of PTH from the parathyroid glands is suppressed and vice versa.

Extracellular calcium exists in 3 forms: ionized, complexed (bound to phosphate, bicarbonate, etc.) and protein bound. The biologically active form of calcium is the ionized calcium (iCa) fraction, and it is this form of calcium that acts on the parathyroid glands to mediate PTH release. While it has been assumed that the total serum calcium measured on most routine serum chemistry panels is proportional to the iCa, this is not always the case, because iCa makes up only a portion of the total calcium. A recent study found 27% discordance between total serum calcium and iCa. In addition, equations that adjust the serum calcium relative to the albumin level in dogs have questionable accuracy.

For this reason, measurement of iCa is often important in the diagnostic workup of hypercalcemic patients.

Less common causes include fungal disease, vitamin D toxicosis, nutritional influences and spurious results from hemolysis or lipemia of the specimen.

As hyperparathyroidism is a relatively uncommon cause of hypercalcemia in dogs and cats, looking for other more common causes of hypercalcemia is important. However, certain factors such as age (> 6 years), breed (Keeshonds appear predisposed), and the fact that the patient is otherwise feeling well, may raise your index of suspicion for hyperparathyroidism.

History and physical examination findings should include: examination of the peripheral lymph nodes and mammary chain to check for any enlargements, plus a thorough rectal examination to look for any anal sac gland masses. Questions about any exposure to vitamin D, pain on physical exam that may indicate the presence of lytic lesions typical of malignancy, or waxing and waning signs that would raise the suspicion of Addison's disease, are all helpful in narrowing down the list of differentials.

Assessment of the CBC, serum chemistry and urinalysis results will be helpful in looking for underlying renal disease or electrolyte abnormalities consistent with hypoadrenocorticism. Phosphorus concentrations can help to narrow the differentials, with PHPTH and hypercalcemia of malignancy being typified by high Ca concentrations in the presence of low or low-normal phosphorus concentrations. If these patients are polydipsic as a result of their hypercalcemia, expect to find a urine specific gravity below 1.010

At this point, if the reason for the hypercalcemia remains elusive, measurement of an iCa and PTH level are indicated.