Top 10 Differentials for Hypercalcemia in the Dog

Hypercalcemia in the dog can have many etiologies, including malignancy (e.g., humoral hypercalcemia of malignancy, primary hyperparathyroidism, multiple myeloma, and neoplasia in bone), increased vitamin D activity (e.g., rodenticides containing cholecalciferol, anti-psoriasis creams containing calcipotriene or calcipotriol, plants containing calcitriol glycosides, excess dietary supplementation), granulomatous inflammation, adrenal insufficiency, or renal disease (1-10).

Two Helpful Mnemonics to Remember the Differential Diagnosis of Hypercalcemia

HARD IONS

• H—Hyperparathyroidism, Humoral hypercalcemia of malignancy, Houseplants
• A—Addison’s disease; Aluminum or vitamin A toxicity
• R—Renal disease, Raisins (Grapes)
• D—Vitamin D toxicosis
• I—Idiopathic (particularly in cats; very rare in dogs)
• O—Osteolytic
• N—Neoplasia (humoral hypercalcemia of malignancy)
• S—Spurious

GOSH DARN IT

• G—Granulomatous disease, Grapes
• O—Osteolytic
• S—Spurious
• H—Hyperparathyroidism, Humoral hypercalcemia of malignancy, House plants
• D—Vitamin D toxicity, Dehydration
• A—Addison’s, Vitamin A, or Aluminum toxicity
• R—Renal disease
• N—Neoplasia (humoral hypercalcemia of malignancy)
• I—Idiopathic
• T—Temperature (hypothermia)

My Top 10 Differential List for Canine Hypercalcemia

Even though these mnemonics can be helpful in recalling all of the various causes of hypercalcemia, I find my list below to be more helpful.

This is my top-10 list for potential rule outs for hypercalcemia in dogs, in an approximate incidence order as seen in practice, starting with the most common to least common problem:

1. Spurious (lab error, lipemic sample causing false elevation of calcium)
2. Lymphosarcoma  
3. Hypoadrenocorticism (Addison's disease)
4. Primary hyperparathyroidism (parathyroid tumor)
5. Renal failure
6. Vitamin D toxicosis
7. Apocrine gland carcinoma of the anal sac  
8. Multiple myeloma of bone (10-15% of cases have high calcium)
9. Other carcinomas (e.g., lung, mammary, nasal, pancreatic, thymic, thyroid, testicular)
10. Granulomatous diseases (e.g., blastomycosis, histoplasmosis, schistosomiasis)

Steps in Workup for the Dog with Hypercalemia

In some dogs with hypercalcemia, the primary diagnosis becomes obvious after analysis of history and findings from physical examination. In most dogs, however, the underlying cause for the hypercalcemia is not all that clear and further testing must be done.

In these dogs, a stepwise approach to diagnosis of the underlying cause of the hypercalcemia is recommended. I'll discuss my approach to diagnosis of these difficult cases in my next post.

References:

1. Schenck PA, Chew DJ, Nagode LA, et al.  Disorders of calcium: hypercalcemia and hypocalcemia. In: Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice, ed. DiBartola SP, 3rd ed., pp. 122–194. Saunders Elsevier, St. Louis, MO, 2006.
2. Schenck PA, Chew DJ. Hypercalcemia: a quick reference. Veterinary Clinics of North America Small Animal Practice 2008;38:449–453.
3. Schenck PA, Chew DJ. Investigation of hypercalcaemia and hypocalcaemia In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;221-233.
4. Schenck PA, Chew DJ. Prediction of serum ionized calcium concentration by use of serum total calcium concentration in dogs. American Journal of Veterinary Research 2005; 66:1330–1336.
5. Peterson ME, Fineman JM. Hypercalcemia associated with hypoadrenocorticism in sixteen dogs. Journal of the American Veterinary Medical Association 1982; 181:802-804.
6. Hare WR, Dobbs CE, Slayman KA, et al. Calcipotriene poisoning in dogs. Veterinary Medicine 2000; 95:770–778.
7. Gwaltney-Brant S, Holding JK, Donaldson CW, et al. Renal failure associated with ingestion of grapes or raisins in dogs. Journal of the American Veterinary Medical Association 2001; 218:1555–1556.
8. Feldman EC, Hoar B, Pollard R, et al. Pretreatment clinical and laboratory findings in dogs with primary hyperparathyroidism: 210 cases (1987-2004). Journal of the American Veterinary Medical Association  2005;227:756.
9. Gear RN, Neiger R, Skelly BJ, et al. Primary hyperparathyroidism in 29 dogs: diagnosis, treatment, outcome and associated renal failure. Journal of Small Animal Practice 2005;46:10-16.
10. Messinger JS, Windham WR, Ward CR. Ionized hypercalcemia in dogs: a retrospective study of 109 cases (1998–2003). Journal of Veterinary Internal Medicine 2009;23: 514–519.