Aetiology and pathogenesis of growth hormone deficiency

Growth hormone deficiency (GHD) represents an aetiologically non-uniform disorder: it can have multiple causes. Three main groups can be differentiated: (1) GHD due to manifest organic alterations of the hypothalamo-hypophyseal system; (2) so-called idiopathic cases; and (3) genetically determined forms. The first group comprises the congenital malformations, affecting the midline structures of the brain more often than the pituitary itself, and the acquired lesions, mainly tumours, which are generally suprasellar rather than intrasellar. The large majority of the so-called idiopathic cases result from perinatal damage which affects the hypothalamus more often than the pituitary proper. Births in non-cephalic positions, in particular breech deliveries, play a significant role, but other difficult parturitions of prolonged duration also lead to such damage. With improved obstetric techniques, particularly the more frequent use of caesarean section, such lesions now occur far less frequently than 30 years ago. In the last 20 years, several genetically determined disorders associated with GHD have been described, four of them with isolated GHD, three with multiple deficiencies of pituitary hormones. Most cases are inherited by autosomal recessive transmission.