Growth Failure due to JAK Inhibition Overcome by Recombinant IGF-I

Abstract

Introduction: Normal linear growth requires an intact GH/IGF-I axis, wherein GH from the pituitary induces the synthesis and release of IGF-I from the hepatocyte followed by IGF-I-mediated chondrocyte division at the growth plate. At the hepatocyte, GH binding to its cognate receptor results in a conformational change in the intracellular portion of the receptor that recruits and activates the tyrosine kinase JAK2. JAK2 then phosphorylates the transcription factor Stat5b which allows it to bind to the IGF-I promotor and increase IGF-I production. JAK kinase inhibitors are used for the treatment of inflammatory disorders such as rheumatoid arthritis, and theoretically would be expected to interfere with linear growth by impairing IGF-I production. We present a case of growth failure due to JAK2 inhibition and successful treatment with recombinant IGF-I therapy.