Animal knockout experiments have offered the opportunity to study genes that play a role in growth and development. In the last few years, reports of patients with genetic defects in GH-IGF-I axis have greatly increased our knowledge of genetically determined causes of short stature. We will present the animal data and human reports of genetic disorders in the GH-IGF-I axis in order to describe the role of the GH-IGF-I axis in intrauterine and postnatal growth. In addition, the effects of the GH-IGF-I axis on the development and function of different organ systems such as brain, inner ear, eye, skeleton, glucose homeostasis, gonadal function, and immune system will be discussed. The number of patients with genetic defects in the GH-IGF-I axis is small, and a systematic diagnostic approach and selective genetic analysis in a patient with short stature are essential to identify more patients. Finally, the implications of a genetic defect in the GH-IGF-I axis for the patient and the therapeutic options will be discussed.European Journal of Endocrinology 157 S15-S26

Four out of 10 children in two unrelated families presented with a total pituitary growth hormone (GH) and prolactin deficiency and a partial thyrotropin (TSH) deficiency. The GH gene was intact in family I. The pituitaries, visualized by magnetic resonance imaging, were normal. All children responded well to GH and L-thyroxine therapy. Baseline plasma somatostatin and its peak response to arginine infusion were elevated in family I and they had a milder TSH deficiency than family II. Plasma insulin showed a poor response to arginine infusion. This hereditary combination of pituitary deficiencies suggests a deficiency of a common positive transcription factor.

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