Growth Hormone Insensitivity

Growth hormone insensitivity (GHI) or resistance is the absence of 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 those due to mutations affecting genes of serum transducers and activators of transcription 5B (STAT5b), protein tyrosine phosphatase non-receptor type 11 (PTPN11), acid labile subunit (ALS), insulin-like growth factor-I (IGF-I), the IGF-I receptor, and pappalysin 2 (PAPP-A2). Mutation of cell surface GH binding protein, IGF-I, IGF-I binding protein, and other intracellular growth factors seldom occurs, whereas secondary GH insensitivity due to undernutrition, renal failure, and disease states is common. 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.