Endocrine assessment, molecular characterization and treatment of growth hormone insensitivity disorders

This Review describes the many clinical, endocrine and genetic abnormalities that cause growth hormone (GH) insensitivity disorders, listing all the known GH-receptor mutations and describing the current therapy with insulin-like growth factor 1 (IGF1) and a novel therapy using complexes of IGF1 and IGF-binding protein 3. Advances in the diagnosis and treatment of growth hormone insensitivity disorders have occurred in the past 15 years. We discuss the current status of endocrine and molecular evaluation, focusing on the pediatric age range. All the identified mutations of the growth hormone receptor are included. Treatment with recombinant human insulin-like growth factor (rhIGF) 1 in classical cases is summarized and new targets for treatment are discussed, together with therapy using the complex formed between rhIGF1 and rhIGF-binding protein 3. Key Points Growth hormone insensitivity disorders represent a broad category of clinical, endocrine and genetic abnormalities A definitive list of the known mutations in the growth hormone receptor that occur in patients with growth hormone insensitivity is included in this article Recombinant human insulin-like growth factor 1, or the complex of recombinant human insulin-like growth factor 1 plus insulin-like growth-factor-binding protein 3, is effective as growth-promoting therapy for children with growth hormone insensitivity disorders, and offers hope of long-term benefits