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Vitamin D poisoning (cholecalciferol)

icanis

Synonym(s): Cholecalciferol (colecalciferol, vitamin D3) poisoning; calcipotriol (calcipotriene), calciferol (ergocalciferol, vitamin D2), calcitriol or tacalcitol


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 (with calciferol and cholecalciferol) and from 6 hours (with calcipotriol, calcitriol and tacalcitol): polydipsia, anorexia, vomiting.
  • Diagnosis: signs, hypercalcemia, polydipsia.
  • Treatment: detoxification, calcitonin or pamidronate, fluid diuresis, corticosteroids.
  • Prognosis: guarded to poor.

Pathogenesis

Pathophysiology

  • Excess vitamin D Vitamin D → hypercalcemia → clinical signs.
  • Calciferol and cholecalciferol are rapidly absorbed and metabolized 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 (1,25-dihydroxycholecalciferol), 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.
    • 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.
  • Calcipotriol produces similar effects by the same mechanism.
  • As a generalization, recently synthesized vitamin D3 analogues, such as those in human medications, are more potent and therefore more toxic.
  • 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.
  • Cholecalciferol (colecalciferol):
    • Supplements can vary hugely in dose from 10 µg (400 IU) to 1.25 mg (50,000 IU).
    • Rodenticide baits are usually 0.075%.
    • The oral LD50 of cholecalciferol in dogs is 10-88 mg/kg and signs of poisoning can occur after ingestion of 0.5 mg (20,000 IU) of cholecalciferol per kilogram body weight.
    • Fatalities in dogs are reported after 2-13 mg/kg.
    • Weekly administration of 15 µg cholecalciferol may be toxic after 2 months in puppies.
  • Calcipotriol (calcipotriene):
    • A single oral dose as low as 10 µg/kg body weight can cause toxic effects and as little as 67 µg/kg can be fatal.
    • Psoriasis creams are generally 50 µg/g and a dose of 10 µg/kg is equivalent to 0.2 g of cream/kg.
  • The risk of secondary exposure to cholecalciferol from ingestion of animals that have died from poisoning is low.
  • Conversions:
    • 1 mg = 41000 IU approximately
    • 1 mcg = 41 IU approximately
    • 1 IU = 0.025 mcg approximately.

Timecourse

  • Latency varies between toxicants.
  • Clinical signs generally become apparent within 12-36 hours with calciferol and cholecalciferol and from 6 hours with calcipotriol, calcitriol and tacalcitol.

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.
  • Ho B, Ellison J, Edwards N, Bates N (2020) Prevalence of vitamin D analogue toxicity in dogs. Clin Exp Dermatol doi: 10.1111/ced.14499. Epub ahead of print PubMed.
  • Bates N (2017) Vitamin D toxicosis. Companion Animal 22, (12), 700-706 doi.org/10.12968/coan.2017.22.12.700.
  • Nakamura K, Tohyama N, Yamasaki M, Ohta H, Morishita K, Takiguchi M (2016) Hypercalcemia in a dog with chronic ingestion of maxacalcitol ointment. J Am Anim Hosp Assoc 52, (4), 256-258 PubMed.
  • Peterson M E, Fluegeman K (2013) Cholecalciferol. Topics Companion Anim Med 28, 24-37.
  • Dee T, Hovda LR (2012) Cholecalciferol rodenticide toxicosis. Vet Technician 33 (1), uhills.org/wp-content/uploads/2020/08/cholecalciferol-toxocosis.pdf.
  • Ulutas B, Voyvoda H, Pasa S, Alingan M K (2006) Clodronate treatment of vitamin D-induced hypercalcemia in dogs. J Vet Emerg Crit Care 16, (2), 141-145 doi.org/10.1111/j.1476-4431.2006.00190.x.
  • 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 hypercalcemia. J Vet Intern Med 19 (1), 29-33 PubMed.
  • Mellanby R J, Mee A P, Berry J L, Herrtage M E (2005) Hypercalcaemia in two dogs caused by excessive dietary supplementation of vitamin D. J Small Anim Pract 46, (7), 334-348 PubMed.
  • Morrow C K, Volmer P A (2002) Hypercalcaemia, hyperphosphataemia, and soft tissue mineralization. Compend Contin Educ Vet 24, (5), 380-388.
  • 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.
  • Eason C T, Wickstrom M, Henderson R, Milne R, Arthur D (2000) Non-target and secondary poisoning risks associated with cholecalciferol. NZ Plant Protect 53, 299-304 PubMed.
  • 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.
  • Talcott P A, Mather G, Kowitz E H (1991) Accidental ingestion of a cholecalciferol containing rodent bait in a dog. Vet Hum Toxicol 33, (3), 252-256 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) Hypercalcemia 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.
  • Ross L A (1988) Comments on toxicity of a vitamin D3 rodenticide. J Am Vet Med Assoc 193 (7), 757 PubMed.

Other sources of information

  • Adams CA (2016) Cholecalciferol. In: Blackwell’s Five-Minute Veterinary Consult Clinical Companion Small Animal Toxicology, Wiley Blackwell, Ames, Iowa. pp 850-855.
  • Rumbeiha W K (2013) Cholecalciferol. In: Small Animal Toxicology. 3rd edition. Editors M E Peterson and P A Talcott. Elsevier Inc., St Louis, MO. pp 489-498.

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