Growth Hormone Insensitivity

Growth hormone insensitivity (GHI) or resistance is the absence of a growth or metabolic response to endogenous GH produced by the liver or to recombinant human (rh) GH administered in physiologic doses. Genetic disorders that result in GHI are rare and include GH receptor deficiency (GHRD, Laron syndrome), as well as mutations affecting genes of signal transducer and activator of transcription 5B (STAT5b), protein tyrosine phosphatase nonreceptor type 11 (PTPN11), acid labile subunit (ALS), insulin-like growth factor-I (IGF-I), the IGF-I receptor, and pappalysin 2 (PAPP-A2). Limited experience with rhIGF-I therapy in GHRD demonstrates restoration of growth that is less than seen with rhGH replacement in GH deficiency, probably due to the absence of direct effects of GH in bone and muscle.