Glucocorticoid replacement therapies: past, present and future

Since the original description of adrenal insufficiency by Thomas Addison in 1855, there has been an exponential growth in the understanding of adrenal gland biology and its role in the hypothalamic-pituitary-adrenal axis. Despite this, the mainstay of therapeutic glucocorticoid replacement for most clinicians has remained unchanged for nearly 50 years. More recently, there has been better recognition of the morbidity and mortality associated with current approaches and the challenges to tackle in reducing this and improving clinical outcomes. In this review, we have summarised the history of glucocorticoid replacement therapy from its nascence in the 1930s, through common practice and culminating in more recent glucocorticoid replacement strategies plus the potential of stem cell therapy in the future.