What is insulin-like growth factor-1 (IGF-1)?

What is IGF-1?

IGF-1 (insulin-like growth factor-1) is a critical anabolic peptide hormone synthesized primarily in the liver in response to growth hormone stimulation, which mediates growth hormone's effects throughout the body by promoting cell growth, proliferation, and survival while also regulating glucose metabolism. 1, 2

Primary Physiological Role

• IGF-1 is the principal mediator of growth hormone (GH) action, serving as the anabolic effector hormone that translates GH signals into tissue-level growth and metabolic effects 2, 3
• The hormone acts through transmembrane IGF-1 receptors to initiate glucose uptake and stimulate cell growth and proliferation across multiple tissue types 1
• IGF-1 manages critical cellular processes including proliferation, differentiation, and apoptosis throughout the lifespan 2, 4

Synthesis and Circulation

• While the liver is the primary source of circulating IGF-1, it is also produced locally in an autocrine manner by target tissues such as bone, cardiac tissue, and growth plates 5, 1
• Approximately 98% of all circulating IGF-1 is bound to six insulin-like growth factor binding proteins (IGFBPs), which serve as carrier proteins and modulate IGF-1 bioavailability 2
• IGF-1 circulates either as binary complexes with IGFBPs or as ternary complexes with IGFBP-3 or IGFBP-5 and an acid-labile subunit (ALS) 6
• IGF-1 displays a longer half-life compared to GH and is less susceptible to acute fluctuations, making it more reliable for clinical assessment 4

Tissue-Specific Actions

• In bone: IGF-1 is a bone trophic factor that enhances proliferation of periodontal ligament cells and bone precursor cells, with different effects on cortical versus trabecular bone compartments 1, 6
• In cardiac tissue: IGF-1 is a major regulator of "adaptive" or "physiological" cardiac hypertrophy, promotes survival of cardiac myocytes, and is produced by cardiac fibroblasts 1
• In growth plates: Local IGF-1 production in response to GH stimulates longitudinal bone growth during childhood and adolescence 7

Clinical Diagnostic Applications

• IGF-1 measurement is the primary biochemical tool for diagnosing growth hormone deficiency (GHD) and monitoring GH replacement therapy, as it is more specific and sensitive than direct GH measurement 7, 4
• IGF-1 levels must be interpreted in the context of age, sex, pubertal stage, and clinical presentation, as normal ranges vary significantly across the lifespan 8
• The hormone serves as a critical marker of energy deficiency in conditions like the Female Athlete Triad, reflecting inadequate energy availability 8

Pathophysiological States

GH Insensitivity

• Advanced chronic kidney disease creates a state of GH insensitivity characterized by deficiency of functional IGF-1 due to reduced GH receptor expression and disturbed signaling pathways 9
• This insensitivity can be overcome by supraphysiological doses of recombinant human GH, which stimulates IGF-1 synthesis and normalizes somatomedin bioactivity 9

Secondary Causes of Low IGF-1

• Malnutrition and energy deficiency directly suppress hepatic IGF-1 production 8
• Severe hypothyroidism, liver disease, poorly controlled diabetes, renal failure, and severe infection all impair IGF-1 generation through various mechanisms 8
• Oral estrogen therapy suppresses hepatic IGF-1 production through first-pass liver metabolism, which is particularly problematic in amenorrheic athletes who already have low endogenous IGF-1 8

Excess IGF-1

• Chronic excess of GH and IGF-1 secretion in acromegaly results in biventricular cardiac hypertrophy and can progress to dilated cardiomyopathy 5
• People with acromegaly have a two- to threefold increase in mortality, primarily from vascular disease 1

Longevity and Aging Implications

• Reduced IGF-1 signaling is associated with increased lifespan and reduced risk of aging-related diseases 1
• Polymorphic variants causing reduced IGF-1 signaling confer health and lifespan benefits in humans, with female Ashkenazi Jewish centenarians showing overrepresentation of loss-of-function mutations in the IGF-1 receptor 1

Common Clinical Pitfalls

• IGF-1 assay results require careful interpretation because IGFBPs significantly reduce levels of immunoreactive IGF-1 in samples, requiring multiple pre-treatment steps that reduce reproducibility 2
• Age-matched, sex-matched, and Tanner stage-matched reference ranges specific to the laboratory's assay must be used to avoid misinterpretation 8
• Low IGF-1 does not always indicate GH deficiency—secondary causes must be systematically excluded before attributing low levels to primary GHD 8