Clinical chemistry
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Vitamin D


Topic Completed: 18 May 2020

Minor changes: 18 May 2020

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PubMed Search: chemical chemistry vitamin d pathology free full text [SB]

Zhicheng Jin, Ph.D.
Xin Yi, Ph.D.
Page views in 2020 to date: 54
Cite this page: Jin Z, Bertholf RL, Yi X. Vitamin D. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/chemistryvitamind.html. Accessed May 24th, 2020.
Definition / general
  • Vitamin D plays an important role in the maintenance of calcium and phosphate homeostasis by regulating calcium absorption and osteoclastic / osteoblastic activity
  • Plasma concentrations of vitamin D should be interpreted in context with other measures of calcium and phosphate homeostasis, such as parathyroid hormone, calcium, phosphate and alkaline phosphatase
Essential features
  • Vitamin D3 is endogenously synthesized in skin exposed to sunlight, whereas vitamin D2 is the dietary form of the vitamin
  • Vitamin D2 and D3 are converted in the liver to 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, respectively
  • 25-hydroxyvitamin D has a long biological half life (2 - 3 weeks) and is the primary form of vitamin D in the body
    • Therefore, it is the best biomarker to assess vitamin D deficiency (see Diagrams / tables)
    • 1, 25-dihydroxyvitamin D (1α, 25-(OH)2VitD) is the biologically active form of the vitamin but has a short half life (approximately 4 hours) and it is present in significantly lower concentrations than 25-hydroxyvitamin D
Terminology
  • 25-hydroxyvitamin D3: calcidiol, cholecalciferol, vitamin D3, 25-hydroxycholecalciferol
  • 25-hydroxyvitamin D2: ergocalciferol, vitamin D2, 25-hydroxyergocalciferol
ICD coding
  • ICD-10: E55 - Vitamin D deficiency
Diagrams / tables

Contributed by Zhicheng Jin, Ph.D.

Structure and biological activation

Pathophysiology
  • Vitamin D3 is synthesized in the skin exposed to UV light
  • Vitamin D2 originates from dietary sources
  • In the liver, vitamin D is converted to 25-hydroxyvitamin D by 25-hydroxylase
  • 25-hydroxyvitamin D is a prohormone that represents the main reservoir and transport form of vitamin D, being bound by a transport protein while in circulation (Am J Clin Nutr 2012;95:1357)
  • In renal tubular cells, 25-hydroxyvitamin D is converted to the active form 1,25-dihydroxyvitamin D by 1-α-hydroxylase, which is tightly regulated by calcium, phosphate and PTH concentrations in the body (Nat Rev Endocrinol 2020;16:234)
  • The overall effect of vitamin D in the body is to increase calcium and phosphate levels in the blood
    • 1,25-dihydroxyvitamin D is transported in the bloodstream to the intestine via binding to vitamin D binding protein (DBP) and promotes absorption of calcium and phosphate in the small intestine
    • 1,25-dihydroxyvitamin D also increases osteoclastic activity in bones
    • In the kidney, 1,25-dihydroxyvitamin D increases calcium reabsorption by the distal renal tubules and inhibits phosphate reabsorption by the proximal tubules through its synergy with PTH (McPherson: Henry’s Clinical Diagnosis and Management by Laboratory Methods, 23rd Edition, 2017)
  • 24,25-dihydroxyvitamin D is an inactive vitamin D metabolite produced in the kidney by 24-α-hydroxylase
  • Laboratory
    • Methodology to measure levels:
      • Because of its relatively stable plasma concentration and longer half life, 25-hydroxyvitamin D is the best measure of overall vitamin D status
        • Chemiluminescent immunoassay (CLIA) is commonly used on automated instruments for high throughput vitamin D assays in clinical settings
        • Vitamin D binding protein concentration and binding kinetics may affect the accuracy of 25-hydroxyvitamin D measured by immunoassay
        • Antibodies used in many immunoassays often have lower cross reactivity with 25-hydroxyvitamin D2 and therefore may underestimate total vitamin D activity (Hormones (Athens) 2020 Mar 27 [Epub ahead of print])
      • Liquid chromatography tandem mass spectrometry (LC-MS/MS) method is the reference method for the quantification of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and can accurately quantitate both vitamin D2 and D3 (Mass Spectrom Rev 2015;34:2)

    Test limitations
    Reference ranges
    Test indications
    • Vitamin D deficiency causes rickets and may be due to inadequate dietary intake, intestine malabsorption, decreased synthesis or defective vitamin D receptors (McPherson: Henry’s Clinical Diagnosis and Management by Laboratory Methods, 23rd Edition, 2017)
    • Vitamin D deficiency may cause hypocalcemia, which is followed by increased secretion of parathyroid hormone (secondary hyperparathyroidism)
    • 1-α-Hydroxylase deficiency is caused by a mutation in CYP27B1 (chromosome 12q14.1), leading to vitamin D dependent rickets type I
    • Hypercalcemia is commonly associated with primary hyperparathyroidism
    Board review style question #1

      Which of the following conditions is likely to cause decreased 25-hydroxyvitamin D?

    1. Addison disease
    2. Cushing disease
    3. Iron deficiency anemia
    4. Kidney disease
    5. Liver disease
    Board review answer #1
    E. Liver disease. The liver is the major, if not sole, source of 25-hydroxyvitamin D production from vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol).

    Reference: Vitamin D

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    Board review style question #2
      Elevated 1,25-dihydroxyvitamin D is associated with which of the following conditions?

    1. Hyperparathyrodism
    2. Kidney disease
    3. Liver disease
    4. Rickets
    5. Sarcoidosis
    Board review answer #2
    E. Sarcoidosis. Increased level of 1,25-dihydroxyvitamin D and hypercalcemia may be associated with granulomatous diseases such as sarcoidosis, tuberculosis and granulomas.

    Reference: Vitamin D

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