Hypercalcemia: A Practical Diagnostic Approach in Dogs and Cats
Barbara Davis, DVM, DACVIM
Hypercalcemia in dogs and cats can be caused by many different disease processes. It is helpful to focus on the most common causes first and then move toward less common causes once these have been ruled out. There are few non-pathologic causes such as spurious/lab error or growth in a young animal that do not require further evaluation.
Causes of Hypercalcemia
Common Causes
- Hypercalcemia of malignancy. In dogs it is most commonly caused by T-cell lymphoma. T-cell lymphoma accounts for almost 60% of dogs with hypercalcemia. Less common neoplasms include apocrine gland anal sac adenocarcinoma and multiple myeloma. It has also been reported in many other carcinomas (lung, mammary, nasal, thyroid, vaginal, etc) and melanoma. In cats, the most common neoplasms leading to hypercalcemia are squamous cell carcinoma, lymphoma, and multiple myeloma. Primary bone tumors do not typically cause hypercalcemia.
- Primary hyperparathyroidism
- Hypoadrenocortism (ionized calcium usually remains normal)
- Renal disease (typically ionized calcium is normal or low in these patients)
- Idiopathic (only in cats)
Less Common Causes
- Hypervitaminosis D: Over-supplementation with dietary supplements, food manufacturing error, certain psoriasis cream ingestion, ingestion of house plants (lilies and day blooming jessamine), acute toxicity with cholecalciferol rodenticide.
Uncommon/Rare Causes
- Secondary nutritional hyperparathyroidism
- Granulomatous disease (fungal infections, schistosomiasis)
- Acute kidney injury
Once it has been established that a patient truly is hypercalcemic a diagnostic investigation into the cause will be needed. Even in cats who commonly have idiopathic hypercalcemia, other causes need to be ruled out prior to coming to this diagnosis. All patients should have a thorough physical examination with particular attention to peripheral lymph nodes, mammary glands and rectal examination to evaluate anal sacs (dogs).
A logical approach is to start with first tier testing and if this does not yield a diagnosis, then move on to second tier testing. The author’s approach is as follows:
First Tier Testing
First thing to be done when total calcium is elevated is make sure it is repeatable, and if it is, an ionized calcium should be run. Next steps would be to complete CBC, chemistry panel, urinalysis, PTH/PTHrP/iCa panel, three view thoracic radiographs, and abdominal ultrasound. Consider ACTH stimulation testing if there is an index of suspicion for hypoadrenocorticism. Consider serum protein electrophoresis if hyperglobulinemia is present.
Important Tidbits
- PTHrP is defined as parathyroid hormone related protein. Some cancers secrete a protein that mimicks the action of endogenous PTH. A positive result is indicative of a malignancy. A negative result does not rule out a malignancy as some cancers increase calcium through other mechanisms.
- A normal PTHrP does not rule out neoplasia as there are different mechanisms of action that can also lead to hypercalcemia of malignancy.
- A PTH in the normal reference range in the face of an elevated iCa is abnormal and is consistent with primary hyperparathyroidism in a non-azotemic patient.
- Note that in cats, if first tier testing is normal, consider them to have idiopathic hypercalcemia and begin treatment. In dogs there is always an underlying etiology so move on to second tier testing.
Second Tier Testing
If the first tier of testing does not yield a diagnosis, next steps include vitamin D level, aspirate of peripheral lymph nodes even if palpate normally, aspirate organs (spleen/liver) even if sonographically normal, and bone marrow aspirate and core biopsy even if CBC is normal. The following algorithm demonstrates this authors approach:
References
Feldman DVM DACVIM, Edward C., Nelson DVM, Richard W., Reusch, Claudia, Scott-Moncrieff, J. Catharine. Canine and Feline Endocrinology, 4th Edition. 2015.