Insulin-Like Growth Factor I Biomarker

Overview

Insulin-like growth factor I (IGF‑1) is a peptide hormone produced mainly by the liver in response to growth hormone (GH) and reflects average GH secretion over time. IGF‑1 promotes linear growth in children and also supports protein synthesis, bone and muscle maintenance, and metabolic functions in adults. Low IGF‑1 levels, interpreted using age and sex specific reference intervals or Z‑scores, can suggest GH deficiency or GH insensitivity, while high levels may indicate GH excess such as gigantism in children or acromegaly in adults. Because IGF‑1 levels are relatively stable throughout the day compared with GH, IGF‑1 measurement is clinically useful for screening, diagnosing, and monitoring GH-related disorders. IGF‑1 results are often expressed as both an absolute concentration and a Z‑score, which indicates how far the value is above or below the age and sex adjusted population median and helps standardize interpretation across different ages.

Clinical Use Cases

Evaluation of suspected growth hormone deficiency in children with short stature or poor growth and in adults with features suggestive of GH deficiency.
Assessment for growth hormone insensitivity (for example Laron syndrome) in children with growth failure and low IGF‑1 despite normal or high GH.
Screening and diagnostic support for growth hormone excess, including gigantism in children and acromegaly in adults.
Monitoring disease activity and treatment response in acromegaly and gigantism (for example after surgery, medical therapy, or radiotherapy).
Monitoring recombinant human growth hormone therapy efficacy and safety in children and adults with GH deficiency.
Evaluation of pituitary function as part of broader endocrine workups, often in combination with GH stimulation or suppression tests.

Specimen Types

Serum (most common).
Plasma (used in some laboratories, depending on validated assay).

Measurement Methods

Immunoassays, including:
- Chemiluminescent immunoassays (CLIA or CMIA).
- Enzyme-linked immunosorbent assays (ELISA), where validated.
Liquid chromatography–tandem mass spectrometry (LC‑MS/MS), which can provide high specificity and allows detailed age and sex stratified reference ranges and Z‑scores.

Test Preparation and Influencing Factors

Fasting: Many laboratories do not require fasting, but some may request a fasting sample for consistency in endocrine testing; local instructions should be followed.
Age and sex: IGF‑1 levels are low in early childhood, peak during puberty, and decline with age; interpretation must use age and sex specific reference ranges or Z‑scores.
Pubertal stage: Tanner stage influences IGF‑1 concentrations in adolescents, and staging is often considered when interpreting results.
Time of day: Unlike GH, IGF‑1 shows relatively little diurnal variation, so timing is less critical; this stability is one reason IGF‑1 is used to assess GH status.
Nutritional status and chronic illness: Malnutrition, chronic systemic disease, liver disease, and poorly controlled diabetes can lower IGF‑1 independently of GH secretion and may confound interpretation.
Liver function: Because the liver is the primary source of circulating IGF‑1, liver dysfunction can reduce IGF‑1 levels.
Renal function: Chronic kidney disease may alter IGF‑1 metabolism and levels.
Medications and hormones:
- Exogenous growth hormone therapy increases IGF‑1; targets are often set using IGF‑1 Z‑scores.
- Oral estrogens, glucocorticoids, and other drugs can affect GH–IGF‑1 axis and may raise or lower IGF‑1.
Physiologic states: Pregnancy, acute stress, and severe systemic illness can modify IGF‑1 concentrations and should be considered when interpreting results.
Assay and reference method: Different assays have different calibration and reference intervals; results and Z‑scores are assay specific and should not be directly compared across methods.

Role of Z‑Score in IGF‑1 Interpretation

A Z‑score for IGF‑1 is the number of standard deviations that a patient’s IGF‑1 result is above (positive) or below (negative) the age and sex adjusted population median.
Z‑scores are calculated using the measured IGF‑1 concentration and assay specific reference data, allowing consistent interpretation across the lifespan where absolute ranges vary widely.
In many clinical protocols, IGF‑1 results within the reference interval correspond to Z‑scores between about −2.0 and +2.0, while results below a Z‑score of about −2 are considered below the 2.5th percentile and can support a diagnosis of GH deficiency or severe GH resistance in the appropriate clinical context.
For GH excess disorders such as acromegaly, diagnostic and monitoring criteria often use elevated IGF‑1 expressed as a Z‑score above the upper limit of normal (for example > +2 or > 1.3 times the age related upper limit), in combination with clinical features and GH testing.
During GH replacement therapy, clinicians frequently adjust GH dose to keep the IGF‑1 Z‑score within a target range (often between 0 and +2, depending on guidelines and patient factors) to balance efficacy and safety.