Chemistry, toxicology & urinalysis
General chemistry
Metabolism
Vitamin D
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Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Diagrams / tables | Pathophysiology | Laboratory | Test indications | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Jin Z, Bertholf RL, Yi X. Vitamin D. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/chemistryvitamind.html. Accessed March 24th, 2023.
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
Pathophysiology
- Vitamin D3 is synthesized in the skin exposed to UV light
- Vitamin D2 originates from dietary sources
- 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)
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)
- Because of its relatively stable plasma concentration and longer half life, 25-hydroxyvitamin D is the best measure of overall vitamin D status
Test limitations
- Antibodies used in immunoassays for vitamin D have variable reactivity toward 25-hydroxyvitamin D2 and D3, which may result in a bias between different vitamin D immunoassays (Rifai: Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 6th Edition, 2018)
- Presence of inactive vitamin D metabolites may introduce a positive bias for both immunoassays and LC-MS / MS methods (Mass Spectrom Rev 2015;34:2)
Reference ranges
- Plasma vitamin D concentration is considered insufficient if < 20 ng/mL and deficient if < 10 ng/mL
- Reference range of 25-hydroxyvitamin D is 10 - 65 ng/mL in serum or plasma
- Vitamin D toxicity may occur at concentrations > 100 ng/mL (Rifai: Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 6th Edition, 2018)
- Reference range of circulating 1,25-dihydroxyvitamin D is 15 - 60 pg/mL (McPherson: Henry’s Clinical Diagnosis and Management by Laboratory Methods, 23rd Edition, 2017)
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
- Elevated PTH increases the conversion of 25-hydroxyvitamin D to the active form 1,25-dihydroxyvitamin D in the kidney
- Increased 1,25-dihydroxyvitamin D and hypercalcemia may be associated with granulomatous diseases such as sarcoidosis, tuberculosis and granulomas (McPherson: Henry’s Clinical Diagnosis and Management by Laboratory Methods, 23rd Edition, 2017)
Board review style question #1
- Which of the following conditions is likely to cause decreased 25-hydroxyvitamin D?
- Addison disease
- Cushing disease
- Iron deficiency anemia
- Kidney disease
- Liver disease
Board review style 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).
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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?
- Hyperparathyrodism
- Kidney disease
- Liver disease
- Rickets
- Sarcoidosis
Board review style 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.
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Reference: Vitamin D
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