Growth hormone insensitivity: Physiologic and genetic basis, phenotype, and treatment

Abstract

Primary growth hormone insensitivity is the absence of an appropriate growth or metabolic response to endogenous or exogenous growth hormone at physiologic concentrations, which is due to GH receptor deficiency or defective GH-GHR signal transduction. Numerous catabolic states and chronic conditions may demonstrate acquired GHI, but only that due to growth-inhibiting antibodies developing in patients with GH gene deletion who have been treated with GH has been considered, along with primary GHI, as appropriate for treatment with recombinant human insulin-like growth factor I. This review examines the physiology of the GH-IGF-I axis, noting the importance and varied actions of IGF binding proteins. Also considered is the classification and clinical and biochemical description of the conditions resulting in primary and acquired GHI and their similarity and differences from other IGF-I–deficient states. The molecular heterogeneity of primary GHI and the functional information certain mutations provide is discussed. A diagnostic sequence for these rare conditions is proposed, and the experience with rhIGF-I therapy in GHI is examined.