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Interpretations: IGFI
  1. Catherine J Peters1,
  2. Mehul T Dattani2
  1. 1Department of Endocrinology, Great Ormond St Hospital, London, UK
  2. 2Developmental Endocrinolgy Research Group, Clinical and Molecular Genetics Group, Institute of Child Health, London, UK
  1. Correspondence to Catherine J Peters, Department of Endocrinology, Great Ormond St Hospital, Great Ormond St, London, London WC1N 3JH, UK; peterc1{at}gosh.nhs.uk

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Introduction

Insulin-like growth factor 1 (IGFI) is produced in the liver and peripheral tissues including the growth plate, in response to growth hormone (GH) and is commonly used as a diagnostic marker of growth hormone deficiency (GHD) and to monitor GH replacement therapy, as recommended by an international GH consensus.1 However, while it is a useful biochemical tool, there are limitations to its use and results should be interpreted with care.

Physiological background

Production of IGFI

IGFI and IGF2 are named after their structural similarity to proinsulin. IGFI is a 70 amino acid polypeptide, and it circulates in the plasma bound to one of six IGF binding proteins (IGFBP). Up to 75% of IGFI is bound in a ternary complex with IGF-BP32 and the glycoprotein, acid-labile subunit (ALS). The stability of this ternary complex increases the half-life of IGFI and leads to relatively stable plasma concentrations. This is in contrast to GH, which is secreted in a pulsatile pattern. Other IGFBPs bind to IGFI with a lower affinity and form complexes with shorter half-lives.2 They have the ability to either potentiate or inhibit the actions of IGFI in different tissues.2

GH stimulates IGFI gene transcription in the liver and peripheral tissues. Production of IGFBP-3 and ALS proteins is also GH dependent. Circulating IGFI is thought to be produced mainly from the liver and exerts a negative feedback effect on the pituitary production of GH. Local production of IGFI in peripheral tissues makes up around 20% of circulating concentrations but stimulates growth in a paracrine fashion.

The effects of IGFI are also mediated by nutritional status, insulin, thyroxine, cortisol, oestrogen and androgens. The IGFI receptor (IGFIR) can be found in most tissues of the body and binds IGFI with high affinity. The structural homology between the IGF receptors and insulin receptors means that …

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