Clinical assays for quantitation of insulin-like-growth-factor-1 (IGF1)

Insulin-like growth factor 1 (IGF1), a 70 amino acid peptide hormone is the principal mediator of effects of growth hormone (GH). Since GH secretion is pulsatile in nature and is affected by many factors including sleep, feeding and exercise it is not a reliable marker for diagnosis of GH related disorders. On the other hand, IGF1 levels does not undergo short-term fluctuations in the manner that GH does making it the preferred IGF1 biomarker for the diagnosis of growth related disorders. There are several immunoassays available for IGF1 determination. Since majority (>90%) of IGF1 circulates as a ternary complex bound to its principal carrier/binding protein, IGF binding protein 3 (IGFBP3) and acid labile subunit (ALS), the assay methodology used to quantitate IGF1 has to dissociate IGF1 from IGFBPs prior to quantitation. IGFBPs are known to be a source of interference in immunoassays and many techniques have been employed to circumvent this issue. Immunoassays rely on antibody specificity towards IGF1 and differential cross reactivity towards IGFBPs. Mass spectrometry (MS) has also been employed for quantitation of IGF1. Liquid chromatography tandem mass spectrometry (LC-MS/MS) assays for IGF1 rely on generating tryptic peptides followed by selective reaction monitoring (SRM) while LC high resolution accurate-mass mass spectrometry (LC-HRAMS) approaches for intact IGF1 rely on mass accuracy for reliable, robust and accurate quantitation. This review article will focus on the clinical assays available and the clinical utility of quantitative assessment of IGF1. IGF1 quantitation using diverse assay platforms including immunoassay, LC-MS/MS and LC-HRAMS are discussed in detail.