Increased frequency of glucose intolerance, dyslipidaemia, and obesity has been reported in subjects treated for adrenocortical failure (Addison's disease, AD). Glucocorticoid substitution is difficult to adjust and patients display variable responses to steroid dosage. Since local regeneration markedly contributes to the available cortisol pool, the activity of 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1 gene) may be involved in adverse metabolic profile. Our aim was to explore if HSD11B1 polymorphisms might impact on individual requirements for glucocorticoid replacement and its metabolic effects.