IGF-2 Test: Role, High/Low Levels, Functions & Complete Medical Guide
What Is Insulin-Like Growth Factor 2 (IGF-2)?
Insulin-Like Growth Factor 2 (IGF-2) is a protein hormone that closely resembles IGF-1 and insulin in structure. It plays a key role in fetal development, childhood growth, metabolism, and cellular repair. IGF-2 is one of the dominant growth-regulating hormones during early life, ensuring that organs, tissues, and bones form properly inside the womb.
Although IGF-2 is most active before birth, it continues to function throughout adulthood by supporting tissue repair, wound healing, and normal metabolic activity. Abnormal levels of IGF-2 can be linked to tumor growth, hypoglycemia, overgrowth syndromes, developmental abnormalities, and liver or endocrine disorders.
Doctors may measure IGF-2 to investigate unexplained hypoglycemia (especially tumor-related), evaluate abnormal growth patterns, diagnose rare cancers, or assess growth hormone–related disorders alongside IGF-1 and IGFBP-3.
Where Is IGF-2 Produced in the Body?
1. Liver (Primary Source)
The liver produces the majority of circulating IGF-2. Growth hormone and other growth signals regulate its production.
2. Placenta
During pregnancy, the placenta produces large amounts of IGF-2 to support fetal nourishment, tissue growth, and organ development.
3. Fetal Tissues
IGF-2 is highly active in:
- Developing muscles
- Kidneys
- Brain
- Bones
- Other organs
This early activity helps determine birth weight and overall fetal health.
4. Other Tissues in Adults
Smaller amounts of IGF-2 are produced in:
- Adrenal glands
- Gastrointestinal tract
- Bone and cartilage
- Immune cells
In these tissues, IGF-2 can act locally through paracrine (nearby cells) and autocrine (the same cell) signaling for repair and cell maintenance.
Main Functions and Importance of IGF-2
1. Promotes Fetal Growth and Development
IGF-2 is essential for normal fetal development. It supports:
- Organ formation
- Cell proliferation
- Placental growth
- Nutrient transfer
- Birth weight regulation
Problems with IGF-2 expression can contribute to conditions like Intrauterine Growth Restriction (IUGR) or overgrowth syndromes.
2. Helps Regulate Cell Growth and Survival
IGF-2 promotes:
- Cell division
- Cell maturation
- Protection from cell death
These processes are crucial during early development and also important later in life for tissue maintenance.
3. Supports Wound Healing and Tissue Repair
In adults, IGF-2 assists with:
- Muscle repair
- Skin wound healing
- Tissue regeneration after injury
Declining IGF-2 levels with age contribute to slower healing.
4. Works With IGF-1 to Regulate Metabolism
Together, IGF-1 and IGF-2 help regulate:
- Protein synthesis
- Glucose movement into cells
- Fat metabolism
- Cellular energy use
Because of these effects, abnormal IGF-2 levels can influence metabolism and energy balance.
5. Binds to IGF Receptors
IGF-2 acts through:
- IGF-1 receptor, which regulates growth and metabolism
- IGF-2 receptor, which helps clear IGF-2 and regulate cell survival
Imbalance in receptor activity can contribute to abnormal cell growth or tumor development.
6. Acts as a Tumor Marker in Certain Cancers
Elevated IGF-2 levels can signal tumors such as:
- Hepatocellular carcinoma
- Adrenocortical carcinoma
- Wilms’ tumor (a kidney cancer in children)
- Other rare IGF-secreting neoplasms
Some tumors also produce an abnormal form of IGF-2 that triggers severe hypoglycemia.
Causes of Low IGF-2 Levels
1. Genetic Disorders Affecting IGF-2 Expression
Abnormal imprinting or mutations in the IGF-2 gene may reduce production.
2. Growth Hormone Deficiency
When GH is low, both IGF-1 and IGF-2 production decrease.
3. Intrauterine Growth Restriction (IUGR)
Low IGF-2 contributes to:
- Poor fetal growth
- Low birth weight
- Delayed organ development
4. Malnutrition and Chronic Illness
Inadequate nutrition reduces IGF synthesis in both children and adults.
5. Liver Disease
Cirrhosis, hepatitis, or liver failure can reduce IGF-2 production significantly.
Symptoms of Low IGF-2 Levels
In Fetuses or Newborns
- Poor intrauterine growth
- Low birth weight
- Developmental delay
- Failure to thrive
In Children
- Short height
- Slower growth compared to peers
- Delayed physical milestones
In Adults
Low IGF-2 rarely causes direct symptoms, but may contribute to:
- Slow wound healing
- Reduced muscle recovery
- Weakness
- Poor tissue repair
In most adults, symptoms depend on the underlying cause such as liver disease, chronic illness, or hormonal imbalance.
Causes of High IGF-2 Levels
1. IGF-2–Producing Tumors
These tumors may release excess IGF-2 or abnormal forms of IGF-2.
Common examples include:
- Hepatocellular carcinoma
- Adrenocortical carcinoma
- Wilms’ tumor (children)
- Sarcomas
- Mesothelioma
2. Non-Islet Cell Tumor Hypoglycemia (NICTH)
High IGF-2 mimics insulin and lowers blood glucose, causing episodes of severe hypoglycemia.
3. Overgrowth Syndromes
Conditions such as Beckwith–Wiedemann syndrome involve excessive IGF-2 activity, causing:
- Large birth weight
- Rapid childhood growth
- Enlarged organs (organomegaly)
4. Genetic Imprinting Disorders
Errors in gene expression can increase IGF-2 levels and contribute to overgrowth or tumor risk.
Symptoms of High IGF-2 Levels
In Children
- Very large birth size
- Rapid growth in early years
- Enlarged organs
In Adults
High IGF-2 often results from tumors, and symptoms depend on the tumor type.
Hypoglycemia Symptoms
Excess IGF-2 lowers blood sugar, causing:
- Sweating
- Dizziness
- Tremors
- Blurred vision
- Confusion
- Weakness or fainting
These episodes can be recurrent and severe.
Tumor-Related Symptoms
Depending on the tumor’s location:
- Abdominal pain
- Distension or swelling
- Unexplained weight loss
- Loss of appetite
Reference Ranges
There is no universal reference range for IGF-2 because levels vary with:
- Age
- Sex
- Pregnancy
- Laboratory method
General patterns:
- Very high in fetal life
- High during pregnancy
- Moderate in childhood
- Stable but lower in adults
Doctors always interpret IGF-2 results relative to IGF-1, IGFBP-3, GH, and clinical findings.
Sample Type
- Blood sample (serum or plasma)
Test Preparation
- No fasting required
- Avoid high-protein meals before the test
- Inform your doctor about GH therapy
- Additional assessments may include: IGF-1, IGFBP-3, GH levels, liver tests, glucose levels
When to Consult a Doctor
In Pregnancy
- Poor fetal growth
- Abnormal ultrasound findings
- Low birth weight risk
In Children
- Rapid excessive growth
- Very tall stature
- Slow growth or developmental delay
In Adults
- Recurrent unexplained hypoglycemia
- Dizziness or fainting episodes
- Abdominal swelling or pain
- Unexplained weight loss
- Suspected adrenal or liver tumors
Any abnormal IGF-2 result should be discussed with an endocrinologist or oncologist.
Important Word Explanations
IGF-1 / IGF-2: Hormones regulating growth, metabolism, and cell survival
Paracrine: A hormone acting on nearby cells
Autocrine: A hormone acting on the same cell that releases it
IUGR: Poor fetal growth inside the womb
NICTH: Low blood sugar caused by tumors releasing IGF-2
Differentiation: Process where cells become specialized
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