Commentary - The essential role of IGF-I: Lessons from the long-term studyand 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 in fancy through adulthood. This condition leading to long-term insulin-like g rowth factor-I (IGF-II 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 impairm ent 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 a nd even diabetes. IGF-I treatment of children with Laron syndrome, by our a nd other groups (150-240 mu g/day sc), stimulated growth (8 cm in the first year and 4-5 cm in the following years) and normalized the biochemical abn ormalities. Overdosage led to adverse effects such as hypoglycemia, edema, swelling of soft tissues, and hyperandrogenism. It is concluded that primar y IGF-I deprivation induces severe auxological, biochemical, and hormonal c hanges, the only treatment being biosynthetic IGF-I administration.