Context: Adrenal failure secondary to hypothalamo-pituitary disease is a common clinical problem which has serious repercussions. It is essential to perform validated diagnostic procedures and manage such patients with clear objectives and based on well-established replacement programs.
Evidence acquisition: PubMed was searched for all data reflecting pituitary hypoadrenalism dating back to 1960 in order to establish a published database.
Evidence synthesis: The results from published studies were assessed in the light of the author's extensive personal experience dating back some 30 yr in clinical endocrinology, in an attempt to provide clear diagnostic and management advice.
Conclusions: While much of the physiology of the hypothalamo-pituitary-adrenal axis is well understood, its clinical assessment and diagnostic procedures to establish the need for replacement are still far from perfect, and to a certain extent clinical judgement is still vital. In terms of replacement therapies, these are still far from optimal in terms of quality of life and mortality, although they are increasingly being based on objective evidence rather than established practice. However, it is anticipated that newer replacement protocols will improve a situation that has previously changed little for many years.