Page 163 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Disorders of Calcium: Hypercalcemia and Hypocalcemia 153

by hypercalcemia. Measurement of serum 25- been encountered when dosing errors have been made
hydroxyvitamin D concentration can provide conclusive (mg/kg amounts given as opposed to ng/kg amounts).
evidence for hypervitaminosis D after exposure to chole- High serum concentrations of calcitriol have been
calciferol or ergocalciferol. Serum concentrations of 25- observed in some dogs with lymphoma and hypercalce-
hydroxyvitamin D were increased to at least twice the mia, 489 but it is not clear whether the excess calcitriol
upper limit of normal, with a mean concentration approx- was synthesized by the tumor or by the kidneys under
imately 10 times the normal in dogs with hypervitamin- stimulation of PTHrP.
osis D 107 and were increased for weeks to months in some Topical ointments containing potent vitamin D
instances. 149 In ten episodes of cholecalciferol intoxica- analogues (calcipotriene) for treatment of human psoria-
tion, concentrations of cholecalciferol were increased sis can result in hypercalcemia when toxic quantities are
above the normal range for 10 to 61 days. 112 The half-life ingested by dogs.* Minimal toxic dose is 10 mg/kg; min-
for cholecalciferol was 29 days in experimental dogs. 500 imal lethal dose is 65 mg/kg; and the oral LD50 is
Serum calcitriol concentrations were also increased early between 100 and 150 mg/kg in dogs. 234 In 25 dogs with
in the syndrome, 107 but suppression of calcitriol synthesis calcipotriene ingestion, 28% died and 50% experienced
occurs later. AIRF. Phosphorus, tCa, and iCa are elevated with
Hypervitaminosis D with hypercalcemia, azotemia, calcipotriene toxicity. 230,234 The affinity of calcipotriene
high concentrations of 25-hydroxyvitamin D, and/or for vitamin D-binding protein is much lower than that
renal calcification has been described in cats from Japan of calcitriol; thus, free calcipotriene is readily available
fed fish-based commercial cat food. 236,391,509 Cholecal- for binding to VDRs. The rapid binding to VDRs
ciferol content of these diets exceeded the dietary accounts for the rapid onset of hypercalcemia and
requirements of vitamin D by more than 100 times. Renal hyperphosphatemia and also for the rapid catabolism of
disease and failure occurred within 4 to 14 months in a calcipotriene. Hypercalcemia decreases after several days
large number of cats fed a commercial cat food containing rather than being prolonged for weeks to months as seen
30 times the vitamin D requirement. 392 All commercial in cholecalciferol toxicity. Exposure to calcipotriene has
cat foods provide vitamin D in excess of the minimal not yet been reported in cats, although there are several
requirements, and there is no regulated upper limit on anecdotal reports of cats that developed hypercalcemia
the quantity of vitamin D that can be included. Other after licking calcipotriene from their owner’s skin. Tele-
factors may modulate the toxicity of hypervitaminosis phone calls to animal poison control centers indicate that
D, such as increased dietary calcium and phosphorus or exposure to this ointment has been increasing in dogs. 354
dietary reduction in magnesium. 534 Hypervitaminosis Whether calcipotriene cross-reacts with calcitriol in the
D with hypercalcemia, high concentrations of serum measurement of vitamin D metabolites has not yet been
25-hydroxyvitamin D and calcitriol concentrations have determined, but it is not detected by methods to measure
been described in two dogs that consumed a commercial 25-hydroxyvitamin D.
diet containing more than 100 times the manufacturer-
stated vitamin D concentration. 370 Accidental Granulomatous Disease
oversupplementation of commercial dog and cat foods Hypercalcemia can result from calcitriol synthesis by
with excessive vitamin D resulted in a large recall of activated macrophages during granulomatous inflamma-
products in 2006. tion. Normal macrophages express 1a-hydroxylase activ-
Hypercalcemia attributed to the effects of increased ity (which converts 25-hydroxyvitamin D to calcitriol)
calcitriol occasionally occurs during calcitriol treatment when stimulated by interferon or lipopolysaccharide.
in animals with hypoparathyroidism and rarely during Macrophages in granulomatous inflammation express
treatment of renal secondary hyperparathyroidism. When such activity without stimulation. 159 Blastomycosis is a
hypercalcemia is observed, it is usually in patients given granulomatous disease in dogs that is occasionally (5%
doses more than 3.5 ng/kg daily. Discontinuation of to 14% of cases) associated with hypercalcemia. Hypercal-
calcitriol should result in normocalcemia within 1 week. cemia is usually mild but can be severe. 15,150 In a study of
Dosing with calcitriol at twice the daily dosage every 38 dogs with blastomycosis, 5% had elevated serum iCa
other day up-regulates fewer intestinal epithelial cells but only 2.6% had elevated serum tCa. 132 In this study,
for calcium absorption and decreases the chance for fur- 61% of dogs with blastomycosis had low serum tCa,
ther development of hypercalcemia. No adverse effects but no dogs were hypocalcemic based on serum iCa con-
were noted when using this intermittent dosing protocol centration, showing an overestimation of hypocalcemia
in one study in 20 cats. 263 Formulation errors have also based on serum tCa measurement. Reports of granulo-
been encountered in which the concentration of calcitriol matous diseases associated with hypercalcemia include a
in a compounded product was too high. There are no vet- dog with gastric pythiosis, 323 a dog with granulomatous
erinary preparations of calcitriol; thus, the available
preparations of calcitriol must be diluted in pharmaceuti-
cal oils for appropriate dosing. Hypercalcemia has also *References 96, 172, 234, 246, 272, 274, 576.