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Insulin- like growth factor binding protein 3 (IGFBP-3)

Synonyms

  • IGFBP-3
  • Insulin-like growth factor binding protein-3
  • Somatomedin-binding protein
  • IGF-binding protein 3
  • BP-3

Units of Measurement

  • µg/mL
  • µg/dL
  • µg/100mL
  • µg%
  • µg/L
  • mg/L

Key Conversions

1 µg/mL = 100 µg/dL = 100 µg% = 100 µg/100 mL
 1 µg/mL = 1 mg/L = 1000 µg/L
 1 µg/dL = 0.01 µg/mL
 1 mg/L = 1 µg/mL

Description

IGFBP-3 is the most abundant IGF-binding protein, carrying ~80% of circulating IGF-1 and IGF-2.
It forms a ternary complex with:

  • IGF-1 / IGF-2, and
  • Acid-labile subunit (ALS)

This complex:

  • Prolongs IGF-1 half-life
  • Controls IGF-1 bioavailability
  • Reflects growth hormone (GH) activity

IGFBP-3 is GH-dependent, making it a stable surrogate marker of GH secretion-especially useful in children.

Physiological Role

1. Transport & Stabilization of IGF-1

Extends IGF-1 half-life from minutes → hours.

2. Regulation of IGF Bioavailability

Controls how much IGF-1 is free to bind receptors.

3. Growth & Development

Correlates strongly with:

  • Linear growth
  • GH–IGF axis function
  • Pubertal stage

4. Cellular Effects

Modulates:

  • Cell survival
  • Apoptosis
  • Tissue regeneration

Clinical Significance

LOW IGFBP-3

Most clinically relevant.

1. Growth Hormone Deficiency (GHD)

Low IGFBP-3 + low IGF-1 → strong indicators of:

  • Pediatric GHD
  • Adult GHD
  • Hypopituitarism

Markedly low levels occur in:

  • Congenital pituitary defects
  • Acquired pituitary tumors

2. Malnutrition

Caloric or protein deficiency significantly lowers IGFBP-3.

3. Chronic Systemic Illness

Including:

  • Chronic kidney disease
  • Chronic liver disease
  • Inflammatory disease
  • Celiac disease
  • Severe chronic infections

4. Hypothyroidism

Reduces GH–IGF axis activity.

5. Small for Gestational Age (SGA)

Some infants show low IGFBP-3.

HIGH IGFBP-3

1. GH Excess (Acromegaly / Gigantism)

Often elevated along with IGF-1.

2. Puberty

Physiologic peak during mid-puberty.

3. High GH States

  • Hyperthyroidism
  • Pregnancy
  • High protein intake

4. Rare Tumors

Extremely rare IGFBP-producing tumors.

Reference Intervals

Adults

  • 3.3 – 7.0 µg/mL
     (= 3.3 – 7.0 mg/L)

Children

IGFBP-3 rises with age and puberty.

AgeIGFBP-3 (µg/mL)
1–5 y1.0 – 2.5
6–10 y2.0 – 4.0
11–13 y2.5 – 5.8
14–17 y3.0 – 6.5
Adults3.3 – 7.0

Clinical Cutoffs

  • Low IGFBP-3 + low IGF-1 → high likelihood of GHD
  • High IGFBP-3 → consider GH excess (acromegaly/gigantism)

Diagnostic Uses

1. Growth Hormone Deficiency Screening (Children & Adults)

Best combined with IGF-1.
Low IGFBP-3 especially useful in:

  • Very young children (<3 yrs)
  • Malnutrition-controlled assessment
  • Differentiating constitutional delay vs GHD

2. Acromegaly / GH Excess

Elevated IGFBP-3 supports diagnosis alongside IGF-1.

3. Growth Disorders

  • Short stature
  • Delayed puberty
  • SGA follow-up
  • Chronic disease impact on growth

4. Malnutrition Evaluation

Falls proportionally with protein-energy deficiency.

5. Monitoring GH Therapy

IGFBP-3 used (less commonly than IGF-1) to:

  • Adjust GH dose
  • Assess safety
  • Monitor over-replacement

Analytical Notes

  • Serum preferred
  • Fasting not strictly required
  • Biotin interference possible with immunoassays
  • More stable and less variable than GH
  • Should be interpreted using age- and sex-specific reference ranges

Clinical Pearls

  • IGFBP-3 is very useful in toddlers, where IGF-1 is often low and less reliable.
  • Low IGFBP-3 is not specific to GHD-also falls in malnutrition and systemic illness.
  • In acromegaly, both IGF-1 and IGFBP-3 rise, improving diagnostic confidence.
  • IGFBP-3 has a longer half-life than IGF-1, making it a stable marker.
  • Always assess IGFBP-3 together with IGF-1 for best interpretation.

Interesting Fact

IGFBP-3 carries nearly 80–90% of circulating IGF-1, forming the large ternary complex that dramatically prolongs IGF-1 half-life and modulates growth physiology.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - GH–IGF Axis.
  2. Endocrine Society Guidelines - GH Deficiency & Acromegaly.
  3. Pediatric Endocrine Society - Growth Disorders.
  4. Mayo Clinic Laboratories - IGFBP-3.
  5. ARUP Consult - IGF Axis Interpretation.
  6. NIH / MedlinePlus - IGFBP-3 Test.

Last updated: January 26, 2026

Reviewed by : Medical Review Board

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