Growth Hormone Therapy for Paediatric Growth Disorders: The Past, Present, and Future

Abnormal pituitary function was linked to excessive height and acromegaly in the late 19th century. Harvey Cushing proposed a pituitary substance that regulated human linear growth. Chemical characterization of the Growth Hormone (GH) molecule by Li led to a demonstration of its species specificity with only Human GH (hGH) stimulating growth in children. Extraction of hGH from cadaver pituitaries and its purification led to therapy by Raben in the 1950s, demonstrating growth acceleration in children with hypopituitarism. From the 1960s until 1985, pituitary-extracted hGH was used as therapy in GH-deficient children. In 1985, an epidemic of Creutzfeldt-Jakob disease, caused by contamination of pituitary-derived hGH with the prion protein, caused the deaths of more than 200 children worldwide. Cadaveric hGH was discontinued and replaced by Recombinant hGH (rhGH), which was licensed by the US Food and Drug Administration and European Medicines Agency for GH Deficiency (GHD), followed by non-GHD disorders, Turner syndrome, small for gestational age short stature, and idiopathic short stature. A mathematical model predicted human growth responses, but despite rhGH’s wide use and availability and good safety record, long-term responses remain variable. Poor adherence to rhGH has led to development of weekly or fortnightly hGH administration using different techniques to prolong activity. Data on tolerability efficacy, and long-term safety of long-acting rhGH preparations will make up the next stage of the development of this important hormone therapy.