Genetic defects of the growth-hormone-IGF axis associated with growth hormone insensitivity

The central feature of growth hormone (GH) insensitivity is deficiency of insulin-like growth factor-1 (IGF-1) in association with elevated GH secretion. This condition is also known as primary IGF deficiency. There are currently four known genetic causes of GH insensitivity/primary IGF deficiency: GH receptor deficiency (also known as Laron syndrome or GH insensitivity syndrome), IGF-1 deficiency, signal transducer and activator of transcription 5b (STAT5b) deficiency and acid labile subunit (ALS) deficiency. Despite sharing the classical biochemical features of GH insensitivity, the phenotype in each of these conditions is quite distinct. This review will discuss each of these causes in turn, highlighting the insights these rare causes of growth failure afford into the functioning of the human GH-IGF-1 axis.