GHRH and growth delay due to insulin-like growth factor type 1 deficiency: Mutation at any level of the GHRH–GH–IGF-1 axis can cause GHI or IGF-1 deficiency, which must be differentiated from GHD by the presence of normal or high serum GH levels.25 Consequently, primary IGF-1 deficiency includes: GHI syndrome, genetic anomalies of the GH signalling pathway, defects of IGF-1 bioavailability and deletions or mutations of the IGF-1 gene itself.