• • Credits
    • Section Writer: Dr. Om J Lakhani
    • Section Editor: Dr. Om J Lakhani

• Q. Give the Recommended daily allowance of vitamin D?

  • infants- 400 IU
  • Children- 600 IU
  • Adults (<70 years)- 600 IU
  • Elderly (>70)- 800 IU
  • Pregnant and Lactating- 600 IU

• Q. What is the tolerable upper limit of vitamin D?

  • Infant 0-6 months- 1500 IU
  • Infant 6-12 months- 2500 IU
  • Child 1-5 years – 3000 IU
  • Child >5 years and adults – 4000 IU
  • However, short term ingestion of 10,000 IU / day poses no risk
    • Dose >10,000 IU/day – toxicity can occur

• Q. What are symptoms of vitamin D toxicity?

  • Acute or Subacute toxicity
    • Neurological symptoms- confusion, coma, muscle weakness
    • Nephrogenic Diabetes insipidus
      • polyuria
      • polydipsia
    • GI symptoms
      • anorexia
      • vomiting
  • Chronic toxicity
    • nephrocalcinosis
    • nephrolithiasis
    • bone demineralization

• Q. Does excess vitamin D increase the risk of falls?

  • Yes
  • Some recent studies have shown that excess vitamin D increases the risk of falls.

• Q. How is calcium reabsorbed in the thick ascending loop of Henle?

  • The Na-K ATPase pump on the basolateral membrane drives 3 Na molecules out of the cell while two potassium molecules come in.
  • Na-K-2Cl (furosemide sensitive Na channel) allows Na, K, and 2 Cl reabsorption – which is an electrically neutral process.
  • Now cell has extra potassium, which is leaks out into the lumen
  • Since Na is being pumped out and K is leaking out, there is a net negative charge inside the cell
  • This allows Ca to enter the cell

• Q. How does the Calcium sensing receptor receptor (CaSR) act in this area?

  • Increase calcium → activation of CaSR → generation of arachidonic acid metabolite → suppress the Na-K ATPase pump → blocks the leaking potassium channel
  • This disrupts the entire process, and hence calcium cannot be reabsorbed.

• Q. What are the lab findings of vitamin D toxicity?

  • Increase calcium
  • Increase Phosphate
  • Increase creatinine
  • Dilute urine
  • Hypercalciuria
  • Reduce PTH
  • Short QTc on ECG

• Q. What level of 25-hydroxyvitamin D predisposes to toxicity?

• Guidelines say >150 ng/ml leads to toxicity.

  • However, current evidence says >80 ng/ml can predispose to toxicity
  • However, toxicity depends on the amount of calcium intake, and hence all people with this level of vitamin D don’t develop toxicity
  • This has to be kept in mind

• Q. What produces hypercalcemia in hypervitaminosis of D ?

  • Increase intestinal absorption
  • Increased bone resorption

• Q. Which vitamin D analogs can cause vitamin D toxicity?

  • All of them can cause
    • Calcitriol- highest risk
    • Paracalcitol- lowest risk

• Q. What is the difference in toxicity due to 25 hydroxyvitamin D and Calcitriol?

  • The duration of toxicity
  • Since calcitriol has a short half-life- the duration of toxicity is shorter but produces more acute symptoms

• Q. What is the duration of toxicity of various vitamin D compounds?

  • 25 hydroxyvitamin D- 15 days
  • Alpha D3- 5 days
  • Calcitriol- 2-5 days

• Q. What is the management of patients with Vitamin D toxicity?

  • Patients without renal failure
    • Stop vitamin D and analogs
    • Isotonic fluids +/- furosemide
    • Glucocorticoids
  • Patients with renal failure
    • Stop offending drug
    • Fluids +/- diuretics if required
    • Glucocorticoids
    • Hemodialysis with low calcium bath (if required)

• Q. How does Glucocorticoid help?

  • Reduces intestinal absorption of calcium
  • Reduce 1 alpha-hydroxylase – reduce activation of vitamin D

• #Real-life-cases

  • An elderly female had pain in her joints secondary to osteoarthitis
  • She was prescribed a plethora of Vitamin D compounds in inappopriate doses including Calcitriol and calcium
  • Presented to the emergency in coma with hypercalcemia and vitamin D toxicity
  • The PTH value was 8 pg/ml suggesting PTH independent hypercalcemia
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