Vet Clin Small Anim 38 (2008) 449–453

VETERINARY CLINICS
SMALL ANIMAL PRACTICE
Hypercalcemia: A Quick Reference
Patricia A. Schenck, DVM, PhDa,*, Dennis J. Chew, DVMb
a
Endocrine Diagnostic Section, Diagnostic Center for Population and Animal Health,
Department of Pathobiology and Diagnostic Investigation, Michigan State University,
4125 Beaumont Road, Lansing, MI 48910, USA
b
Department of Veterinary Clinical Sciences, College of Veterinary Medicine,
The Ohio State University, 601 Vernon L. Tharp Street, Columbus, OH 43210, USA

 Total calcium (tCa) is composed of ionized calcium (iCa), protein-bound

calcium (pCa), and complexed calcium (cCa).
 iCa is the biologically active fraction.
 Major hormones involved in calcium metabolism are parathyroid hormone
(PTH), calcitriol (1,25-dihydroxyvitamin D), and calcitonin.
 Major organs involved in calcium metabolism are bone, kidney, and small
intestine.

ANALYSIS
 Indications: Serum tCa is measured routinely in systemic diseases. Serum iCa
should be measured if tCa is elevated and in any patient that has renal dis-
ease. The simultaneous measurement of PTH along with iCa is often helpful
diagnostically. The typical reference range for serum tCa and iCa in pre-
sented in Table 1.
 To convert mmol/L to mg/dL, multiply mmol/L by 4.
 Caution
 Do not use adjustment formulas to ‘‘correct’’ the tCa to serum total pro-
tein or albumin concentration. These formulas do not accurately predict
iCa concentration.
 Do not directly compare serum iCa results with heparinized plasma or
whole blood iCa results (obtained by means of a blood gas analyzer or
point-of-care analyzer). The iCa concentration in heparinized plasma
or whole blood is typically lower than the serum iCa concentration.
 Do not use ethylenediaminetetraacetic acid (EDTA) plasma for iCa mea-
surement. EDTA chelates calcium, resulting in an extremely low iCa
concentration.
 Danger values
 Interaction with phosphorus is important. If tCa (mg/dL) times the phos-
phorus concentration is greater than 70, tissue mineralization is likely.

*Corresponding author. E-mail address: schenck5@msu.edu (P.A. Schenck).

0195-5616/08/$ – see front matter ª 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.cvsm.2008.01.020 vetsmall.theclinics.com
450 SCHENCK & CHEW

Table 1
Typical reference range (serum)
Canine Feline
tCa 9.0–11.5 mg/dL (2.2–3.8 mmol/L) 8.0–10.5 mg/dL (2.0–2.6 mmol/L)
iCa 5.0–6.0 mg/dL (1.2–1.5 mmol/L) 4.5–5.5 mg/dL (1.1–1.4 mmol/L)

Box 1: Causes of hypercalcemia

Nonpathologic
Nonfasting (minimal increase)
Physiologic growth of young
Laboratory error
Spurious
Lipemia
Detergent contamination of sample or tube
Transient or inconsequential
Hemoconcentration
Hyperproteinemia
Hypoadrenocorticism
Severe environmental hypothermia (rare)
Pathologic or consequential: persistent
Parathyroid dependent
Primary hyperparathyroidism
Adenoma (common)
Adenocarcinoma (rare)
Hyperplasia (uncommon)
Parathyroid independent
Malignancy-associated (most common cause in dogs)
Humoral hypercalcemia of malignancy
Lymphoma (common)
Anal sac apocrine gland adenocarcinoma (common)
Carcinoma (sporadic): lung, pancreas, skin, nasal cavity, thyroid,
mammary gland, adrenal medulla
Thymoma (rare)
Hematologic malignancies (bone marrow osteolysis, local osteolytic
hypercalcemia)
Lymphoma
Multiple myeloma
(continued on next page)
HYPERCALCEMIA: A QUICK REFERENCE 451

Myeloproliferative disease (rare)

Leukemia (rare)
Metastatic or primary bone neoplasia (uncommon)
Idiopathic hypercalcemia (most common association in cats)
Chronic renal failure (with and without ionized hypercalcemia)
Hypervitaminosis D
Iatrogenic
Plants (calcitriol glycosides)
Rodenticide (cholecalciferol)
Antipsoriasis creams (calcipotriol or calcipotriene)
Granulomatous disease
Blastomycosis
Dermatitis
Panniculitis
Injection reaction
Acute renal failure (diuretic phase)
Skeletal lesions (nonmalignant) (uncommon)
Osteomyelitis (bacterial or mycotic)
Hypertrophic osteodystrophy
Disuse osteoporosis (immobilization)
Excessive calcium-containing intestinal phosphate binders
Excessive calcium supplementation (calcium carbonate)
Hypervitaminosis A
Raisin/grape toxicity
Hypercalcemic conditions in human medicine
Milk-alkali syndrome (rare in dogs)
Thiazide diuretics
Acromegaly
Thyrotoxicosis (rare in cats)
Postrenal transplantation
Aluminum exposure (intestinal phosphate binders in dogs and cats?)

 Clinical signs are usually present when serum tCa is greater than 15 mg/dL
or iCa is greater than 1.8 mmol/L.
 The patient is usually critically ill whenever serum tCa is greater than
18 mg/dL or iCa is greater than 2.2 mmol/L.
 Artifacts
 Serum iCa may be falsely elevated when stored in serum separator tubes.
 Severe lipemia of the serum may cause a false elevation in serum tCa
concentration.
452 SCHENCK & CHEW

Increased SerumTotal Calcium

(Repeatable)

Do NOT Use
"Correction" Formulas

Ionized Calcium Ionized Calcium

Minimum Database
Normal or Low Increased
(MDB) ; CBC, Serum
Biochemistry, UA,
± Imaging No Obvious Diagnosis
After History(Drug, Diet
Lipemia
Environment) Physical
Increased Binding Examination, & MDB
to Proteins

Increased Binding
to Complexes (renal failure) PTH Below Normal PTH High
or Lower Third or Upper Two Thirds
Dehydration: Reference Range Reference Range
Subacute to Chronic (Parathyroid (Parathyroid
Independent) Dependent)
Alkalosis:
Metabolic and Respiratory
Primary Hyperparathyroidism
(or tertiary in CRF)

Measure Measure
Vitamin D Metabolites PTH-rP High:
Neoplasia Likely

High 25(OH)-Vitamin D
with Low,Normal or High
1,25 (OH)2 Vitamin D
Ergo or Cholecalciferol
Toxicity
Normal:
Normal 25(OH)-Vitamin D Does NOT Exclude
Neoplasia
Idiopathic (Cats)
Malignancy Associated
Calcipotriene Toxicity Abdominal ULS
Day-Blooming Jessamine Chest Radiograph
Rectal Exam

Low to Normal
1,25(OH)2-Vitamin D
Idiopathic (Cats)
Malignancy Associated
Calcipotriene Toxicity
Day-Blooming Jessamine
R/O:
High 1,25(OH)2-Vitamin D LSA
Anal Sac Adenocarcinoma
Calcitriol Overdose Carcinoma
Malignancy Associated Bone Marrow Neoplasia
Hypercalcemia
Granulomatous Disease
Team Calcium- 2008
The Ohio State University
Michigan State University
College of Veterinary Medicine

Fig. 1. Algorithm for clinical approach to disorders initially characterized by high serum tCA.
CBC, complete blood cell count; CRF, corticotropin-releasing factor; LSA, lymphosarcoma;
PTH-rP, parathyroid hormone related protein; R/O, rule out; UA, urinalysis; ULS, ultrasound.
HYPERCALCEMIA: A QUICK REFERENCE 453

CAUSES OF HYPERCALCEMIA
 In dogs, neoplasia is the most common cause of hypercalcemia, followed by
hypoadrenocorticism, primary hyperparathyroidism, and renal failure (eleva-
tion of tCa but not iCa) (Box 1).
 In cats, idiopathic hypercalcemia and neoplasia are the most common
causes, followed by renal failure (elevation of tCa but not iCa).

CLINICAL SIGNS
 Polyuria, polydipsia, and anorexia are most common in dogs.
 Vomiting, depression, weakness, and constipation can occur.
 Uncommon signs include cardiac arrhythmias, seizures, muscle twitching,
and death.
 Cats do not exhibit polyuria, polydipsia, or vomiting as often as dogs.
 Cats with idiopathic hypercalcemia may have no clinical signs.

STEPWISE APPROACH
 An algorithm describing the clinical approach to disorders initially character-
ized by high total serum calcium is presented in Fig. 1.

Further Readings
Schenck PA, Chew DJ. Diseases of the parathyroid gland and calcium metabolism. In:
Birchard SJ, Sherding RG, editors. Manual of small animal practice. 3rd edition. St. Louis
(MO): Elsevier; 2006. p. 343–56.
Schenck PA, Chew DJ, Behrend EN. Updates on hypercalcemic disorders. In: August J, editor.
Consultations in feline internal medicine. St. Louis (MO): Elsevier; 2005. p. 157–68.
Schenck PA, Chew DJ, Nagode LA, et al. Disorders of calcium: hypercalcemia and hypocalce-
mia. In: Dibartola S, editor. Fluid therapy in small animal practice. 3rd edition. St. Louis
(MO): Elsevier; 2006. p. 122–94.