Canis ISSN: 2398-2942

Vitamin D poisoning (cholecalciferol)

Synonym(s): Cholecalciferol poisoning

Contributor(s): Rosalind Dalefield

Introduction

  • Rare but increasingly common.
  • Cause: poisoning with vitamin D3 rodenticide or ingestion of poisoned wild life. Ingestion of human medications containing vitamin D which are prescribed for a variety of conditions including hypoparathyroidism, osteomalacia, osteoporosis, renal failure, psoriasis, and to prevent recurrence of cancer. Oversupplementation with Vitamin D via the diet can also cause toxicosis, and suckling puppies are particularly susceptible if the dam is oversupplemented.
  • Signs: usually develop within 12-36 hours: anorexia, vomiting.
  • Diagnosis: signs, hypercalcemia, polydipsia.
  • Treatment: detoxification, calcitonin, pamidronate, fluid diuresis, corticosteroids.
  • Prognosis: guarded to poor.

Pathogenesis

Pathophysiology

  • Calciferolandcholecalciferolare rapidly absorbed and metabolised by the liver and kidney. The parent compounds and the intermediate metabolites have some limited pharmacological action but the major toxic effects are due to the major metabolite,calcitriol, which enhances resorption of calcium from bone, absorption of calcium from the gut, intestinal calcium transport and proximal renal tubule reabsorption of calcium in the kidney. This gives rise to hypercalcemia Hypercalcemia: overview and toxicity.
  • Calcipotriolproduces similar effects by the same mechanism.
  • Excess vitamin D → hypercalcemia → clinical signs.
  • A dose as low as 2 mg/kg can be toxic as a single oral dose in the dog.
  • Calcipotriol may be toxic at a single oral dose as low as 50 µg/kg body weight.
  • Daily intake of 50-100 µg/kg causes toxicosis after 2-3 weeks in dogs.
  • Weekly administration of 15 mg cholecalciferol may be toxic after 2 months in puppies.
  • As a generalization, recently synthesized Vitamin D3 analogues, such as those in human medications, are more potent and therefore more toxic.
  • Vitamin D3 → 25-hydroxycholecalciferol in liver → 24, 25 dihydroxycholecalciferol in kidney which may be further hydroxylated to calcitriol (1, 25 dihydroxycholecalciferol - the most active form).
  • Calcitriol causes:
    • Calcium uptake from intestine.
    • Calcium resorption from renal tubules.
    • Bone resorption.
  • This results in hypercalcemia → calcium deposition in soft tissues including kidney → renal failure.
  • Animals with pre-existing renal failure or hyperparathyroidism have increased susceptibility.
  • Cholecalciferol is rapidly absorbed from the GI tract and transported to the liver by vitamin D binding protein.
  • Hepatic metabolism to the principal circulating metabolite, 25-hydroxycholecalciferol (25(OH)D3) is very rapid.
  • Within 24 hours of ingestion, serum 25(OH)D3 increases 15-20 times above the normal level of 3-4 µmol/l.
  • 25(OH)D3 is further metabolized to calcitriol (1,25 dihydroxycholecalciferol, 1,25(H)2D3) in the kidney.
  • Serum 1,25(OH)2D3 increases to approximately 3x normal, peaking at 48-96 hours after ingestion, but returns to normal levels within 7 days.

Timecourse

  • Latency varies between toxicants.
  • Clinical signs generally become apparent 36-48 hours after ingestion of cholecalciferol.
  • Clinical signs may appear 8-24 hours after ingestion of 25(OH)D3, 1,25(H)2D3 or their analogues.

Diagnosis

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Treatment

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Ulutas B, Voyvoda H, Pasa S et al (2006) Clodronate treatment of vitamin D-induced hypercalcaemia in dogs. J Vet Emerg Crit Care 16 (2), 141-145 VetMedResource.
  • Hostutler R A, Chew D J, Jaeger J Q et al (2005) Uses and effectiveness of pamidronate disodium for treatment of dogs and cats with hypercalcaemia. J Vet Intern Med 19 (1), 29-33 PubMed.
  • Pesillo S A, Khan S A, Rozanski E A et al (2002) Calcipotriene toxicosis in a dog successfully treated with pamidronate disodium. J Vet Emerg Crit Care 12 (3), 177-181 VetMedResource.
  • Morrow C (2001) Cholecalciferol poisoning. Vet Med 96 (12), 905-911 ASCPApro.
  • Hare W R, Dobbs C E, Slayman K A et al (2000) Calcipotriene poisoning in dogs. Vet Med 95 (10), 770-778 VetMedResource.
  • Hilbe M, Sydler T, Fischer L et al (2000) Metastatic calcification in a dog attributable to ingestion of a tacalcitol ointment. Vet Pathol 37 (5), 490-492 PubMed.
  • Rumbeiha W K, Fitzgerald S D, Kruger J M et al (2000) Use of pamidronate disodium to reduce cholecalciferol-induced toxicosis in dogs. Am J Vet Res 61 (1), 9-13 PubMed.
  • Durtnell R E (1999) Canine vitamin D toxicosis. JSAP 40 (11), 550 PubMed.
  • Rumbeiha W K, Kruger J M, Fitzgerald S D et al (1999) Use of pamidronate to reverse vitamin D3-induced toxicosis in dogs. Am J Vet Res 60 (9), 1092-1097 PubMed.
  • Fan T M, Simpson K W, Trasti S et al (1998) Calcipotriol toxicity in a dog. JSAP 39 (12), 581-586 PubMed.
  • Cumming C (1991) Suspected vitamin D rodenticide poisoning in a dog. Vet Rec 128 (25), 600 PubMed.
  • Dorman D C (1990) Anticoagulant, Cholecalciferol, and Bromethalin-based Rodenticides. Vet Clinic N Am Sm Anim Pract 20 (2), 339-352 PubMed.
  • Dougherty S A, Center S A & Dzanis D A (1990) Salmon calcitonin as adjunct treatment for vitamin D toxicosis in a dog. J Am Vet Med Assoc 196 (8), 1269-1272 PubMed.
  • El Bahri L et al (1990) Poisoning in dogs by vitamin D3 containing rodenticides. Compend Contin Educ 12 (10), 1414-1417 VetMedResource.
  • Fooshee S K & Forrester S D (1990) Hypercalcaemia secondary to cholecalciferol rodenticide toxicosis in two dogs. J Am Vet Med Assoc 196 (8), 1265-1268 PubMed.
  • Studdert V P (1990) Toxicity of Cholecalciferol-containing rodenticides for dogs and cats. Aust Vet J 67 (6), N218 PubMed.
  • Gunther R, Felice L J & Nelson R K et al (1988) Toxicity of a vitamin D3 rodenticide to dogs. J Am Vet Med Assoc 193 (2), 211-214 PubMed.
  • (1988) Comments on toxicity of a vitamin D3 rodenticide. J Am Vet Med Assoc 193 (7), 757 PubMed.

Other sources of information

  • Rumbeiha W K (2006) Cholecalciferol. In:Small Animal Toxicology. 2nd edition. Editors M E Peterson and P A Talcott. Elsevier Inc., St Louis, MO. pp 629-642.
  • Bahri L E (1990) Poisoning in dogs by vitamin D3-containing rodenticides. Comp Cont Ed Pract Vet 12, 1414-1417.

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