The essential role of IGF-I: lessons from the long-term study and treatment of children and adults with Laron syndrome

J Clin Endocrinol Metab. 1999 Dec;84(12):4397-404. doi: 10.1210/jcem.84.12.6255.


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.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Drug Resistance*
  • Female
  • Human Growth Hormone*
  • Humans
  • Insulin-Like Growth Factor I / deficiency*
  • Insulin-Like Growth Factor I / physiology*
  • Insulin-Like Growth Factor I / therapeutic use
  • Male
  • Mutation
  • Receptors, Somatotropin / genetics
  • Recombinant Proteins / therapeutic use


  • Receptors, Somatotropin
  • Recombinant Proteins
  • Human Growth Hormone
  • Insulin-Like Growth Factor I