The relationship between the growth hormone (GH)-insulin like growth factor (IGF)-I system and the hypothalamic-pituitary-adrenal (HPA) axis is complex and not univocal. Both a stimulatory and neutral effect of IGF-I on HPA axis has been demonstrated in in vitro models and in healthy subjects, respectively. The effect of GH on the 11beta-hydroxysteroid dehydrogenases (11beta-HSD) isozymes is always to be considered in patients affected by GHD both at diagnosis and during GH treatment. Indeed, in peripheral tissues, corticosteroid hormone action is partially determined by the activity of 11beta-HSD, two isozymes of which interconvert hormonally active cortisol and inactive cortisone. 11beta-HSD2 inactivates cortisol to cortisone in the kidney, whilst 11beta-HSD1 performs the reverse reaction activating cortisol from cortisone in the liver and adipose tissue.