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The Essential Role of IGF-I: Lessons from the Long-Term Study and Treatment of Children and Adults with Laron Syndrome

Endocrine and Diabetes Research Unit, Schneider Children’s Medical Center of Israel, Petah Tikva 49202; and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 49202, Israel

Address correspondence and requests for reprints to: Prof. Zvi Laron, M.D., Endocrine and Diabetes Research Unit, Schneider Children’s Medical Center of Israel, 14 Kaplan Street, Petah Tikva 49202, Israel.

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 µg/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.

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