Phenotypes, investigation and treatment of primary IGF-1 deficiency.

GH insensitivity, also known as primary IGF-1 deficiency (PIGFD), presents as growth failure, and in its severe form is associated with dysmorphic and metabolic abnormalities. PIGFD is caused by genetic defects in the GH-IGF-1 axis. The field of PIGFD due to mutations affecting GH action has evolved since the original description of the extreme phenotype related to homozygous GH receptor mutations over 40 years ago. A continuum of genetic, phenotypic, and biochemical abnormalities can be defined associated with clinically relevant defects in linear growth. A systematic protocol of investigation assessing Gh secretion and the IGF system will lead to a diagnosis of PIGFD. PIGFD can be effectively treated with rhIGF-1, the optimal recommended maintenance dose being 120 µg/kg twice daily by SC injection. Most therapeutic experience is in severely affected patients with the Laron syndrome phenotype, who show growth acceleration and may reach normal adult height. Further controlled studies are needed in more mildly affected subjects.