Growth hormone--from molecule to mortality

Growth hormone (GH) acts predominantly via insulin-like growth factor-I (IGF-I) expression. Acromegaly is associated with an increased mortality which can be reversed by optimal treatment. Somatostatin analogues are effective adjunctive therapies in patients treated with surgery and/or radiotherapy and result in tumour shrinkage in many patients. Pegvisomant is a GH analogue which inhibits functional dimerization of GH receptors, inhibits GH activity and normalizes IGF-I in over 90% of subjects. Adult GH deficiency is associated with changes in body composition, insulin status, lipid profile and Quality of Life measures. Hypopituitarism is associated with an increased mortality. Replacement with GH has clinically beneficial effects but there are no data on effects on mortality. Taller individuals are at a 20-60 percent increased risk of a range of cancers, an effect that may be mediated via IGFs. These observations suggest that there is an optimal level of circulating GH and IGF-I required to maintain normal health.