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Vitamin D3, 1,25-dihydroxyvitamin D (Calcitriol)

SI UNITS (recommended)

CONVENTIONAL UNITS

(1,25-OH₂ Vitamin D - Active Hormone; Regulates Calcium, Phosphate & Parathyroid Physiology)

Synonyms

  • 1,25-Dihydroxyvitamin D
  • 1,25-OH₂ D
  • Calcitriol
  • Active vitamin D
  • 1α,25-dihydroxycholecalciferol
  • 1,25-OH₂ D₃
  • Hormonal form of vitamin D
  • “Active D3”

Units of Measurement

  • pmol/L
  • ng/L
  • ng/dL
  • ng/100 mL
  • ng%
  • pg/mL

Unit Conversions

Molecular weight of 1,25-dihydroxyvitamin D₃ ≈ 416.65 g/mol

pmol/L ↔ pg/mL

1 pmol/L=0.416 pg/mL1\ \text{pmol/L} = 0.416\ \text{pg/mL}1 pmol/L=0.416 pg/mL 1 pg/mL=2.40 pmol/L1\ \text{pg/mL} = 2.40\ \text{pmol/L}1 pg/mL=2.40 pmol/L

ng/L ↔ pg/mL

1 ng/L=1 pg/mL1\ \text{ng/L} = 1\ \text{pg/mL}1 ng/L=1 pg/mL

ng/dL → pg/mL

1 ng/dL=10 pg/mL1\ \text{ng/dL} = 10\ \text{pg/mL}1 ng/dL=10 pg/mL

ng/100 mL = ng% = ng/dL

Description

1,25-Dihydroxyvitamin D (Calcitriol) is the active hormonal form of vitamin D.
It is produced from 25-OH Vitamin D (calcidiol) by 1-alpha hydroxylation in:

  • Kidneys (primary site)
  • Macrophages & extrarenal tissues (immune activation)

Calcitriol regulates:

  • Calcium absorption
  • Phosphate homeostasis
  • Bone turnover
  • PTH suppression

Important:

Calcitriol is NOT a good indicator of vitamin D stores.
It may remain normal or even elevated in vitamin D deficiency due to secondary hyperparathyroidism.

Physiological Role

1. Calcium Absorption

Upregulates TRPV6 channels, calbindin → increases Ca²⁺ absorption.

2. Phosphate Absorption

Increases Na/P co-transporter activity.

3. Bone Remodeling

Works with PTH:

  • Promotes osteoblast differentiation
  • Regulates osteoclastogenesis indirectly

4. Parathyroid Regulation

Suppresses PTH gene transcription.

5. Renal Mineral Homeostasis

Modulates calcium/phosphate reabsorption.

6. Immune Modulation

Extrarenal calcitriol production affects:

  • Antimicrobial response
  • Autoimmune modulation

Clinical Significance

LOW 1,25-OH₂ D (Calcitriol Deficiency)

Causes

  • Chronic Kidney Disease (CKD)
    (Reduced 1-α hydroxylase activity; hallmark of CKD–MBD)
  • Hypoparathyroidism (low PTH → low calcitriol)
  • Severe Vitamin D deficiency (also decreases substrate)
  • Hereditary vitamin D–dependent rickets (VDDR types 1 & 2)
  • Chronic liver disease
  • Tumor-induced osteomalacia (FGF23 excess → suppresses 1-α hydroxylase)
  • Medications: ketoconazole, anticonvulsants

Clinical Features

  • Hypocalcemia
  • Hypophosphatemia
  • Muscle cramps
  • Seizures (neonates)
  • Rickets / osteomalacia
  • Tetany

HIGH 1,25-OH₂ D (Calcitriol Excess)

Causes

  • Primary hyperparathyroidism
  • Granulomatous diseases:
    • Sarcoidosis
    • Tuberculosis
    • Crohn’s disease
      (macrophages produce calcitriol autonomously)
  • Lymphoma
  • Vitamin D intoxication (late finding)
  • CYP24A1 mutation (reduced degradation)

Clinical Features

  • Hypercalcemia
  • Suppressed PTH
  • Nephrocalcinosis
  • Kidney stones
  • Polyuria / polydipsia

Reference Intervals

(Tietz 8E + Mayo + ARUP + Endocrine Society)

1,25-OH₂ Vitamin D (Calcitriol)

Agepg/mLpmol/L
Adults18 – 72 pg/mL43 – 173 pmol/L
ChildrenSlightly higher physiological levels

Deficiency

  • <18 pg/mL (<43 pmol/L)

Excess

  • >72 pg/mL (>173 pmol/L)

Diagnostic Uses

1. Renal Osteodystrophy / CKD–MBD Evaluation

Primary test when CKD suspected.

2. Investigation of Hypercalcemia

Differentiate:

  • PTH-mediated
  • Non-PTH granulomatous causes

3. Workup of

Hypocalcemia

Determine PTH-vitamin D axis involvement.

4. Assessment of Rickets / Osteomalacia

Especially in:

  • Vitamin D-dependent rickets
  • Phosphate-wasting disorders (FGF23 excess)

5. Immunologic Diseases

Granulomatous disorders increase calcitriol.

Analytical Notes

  • Specimen: serum (preferred)
  • Timing: no fasting needed
  • Method: LC-MS/MS is most accurate
  • Calcitriol is present in picogram quantities - sensitive analytical methods required
  • Very sensitive to:
    • Assay interference
    • Renal function
    • PTH status

Do NOT use this test to assess general Vitamin D status.
Use 25-OH D for routine deficiency screening.

Clinical Pearls

  • In CKD, 25-OH D may be normal, but calcitriol is low → secondary hyperparathyroidism.
  • Granulomatous diseases cause hypercalcemia with high calcitriol and low PTH.
  • High calcitriol + high calcium + low PTH → think sarcoidosis or lymphoma.
  • In nutritional deficiency, calcitriol may be normal early but falls when 25-OH D substrate is extremely low.
  • Neonates with seizures may have calcitriol-dependent rickets.

Interesting Fact

Calcitriol acts like a steroid hormone, binding to nuclear vitamin D receptors (VDR) across >36 tissues and influencing over 200 genes.

References

NIH Office of Dietary Supplements - Vitamin D Pathways

Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Vitamin D Metabolites

Endocrine Society Clinical Practice Guidelines - Vitamin D, 2024

KDIGO CKD-MBD Guidelines

Mayo Clinic Laboratories - Calcitriol (1,25-OH₂ D)

ARUP Consult - Vitamin D Testing

Last updated: January 27, 2026

Reviewed by : Medical Review Board

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