The essential role of IGF-I: lessons from the long-term study and treatment of children and adults with Laron syndrome.
Fifty patients with primary GH resistance (Laron syndrome) due to molecular defects of the GH receptor or post-receptor pathways were followed from infancy through adulthood. This condition leading to long-term insulin-like growth factor-I (IGF-I) deprivation caused marked growth retardation (-4 to 8 height SD), acromicia, organomicria, retarded development of the skeletal and muscular systems, a small cranium, slow motor development, and impairment of intellectual development in some of the patients. In addition, there was progressive obesity, insulin resistance, a tendency for hypoglycemia, followed later in life by hypercholesterolemia and by glucose intolerance and even diabetes. IGF-I treatment of children with Laron syndrome, by our and other groups (150-240 microg/day sc), stimulated growth (8 cm in the first year and 4-5 cm in the following years) and normalized the biochemical abnormalities. Overdosage led to adverse effects such as hypoglycemia, edema, swelling of soft tissues, and hyperandrogenism. It is concluded that primary IGF-I deprivation induces severe auxological, biochemical, and hormonal changes, the only treatment being biosynthetic IGF-I administration.
Laron
Z
Z
Endocrine and Diabetes Research Unit, Schneider Children's Medical Center of Israel, Petah Tikva.
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D005260:Female; D019382:Human Growth Hormone; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000172:deficiency* / Q000502:physiology* / Q000627:therapeutic use; D008297:Male; D009154:Mutation; D011986:Receptors, Somatotropin / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use
D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I