People with Primary Adrenal Insufficiency (PAI) are dependent on different steroid hormone replacement for survival. Those with a confirmed diagnosis of PAI require daily replacement of their missing adrenal hormones, cortisol, and aldosterone. In current practice, glucocorticoid replacement therapy is usually given as either oral hydrocortisone or prednisolone. Hydrocortisone is typically administered in two to four divided doses, with a higher dose often administered in the morning in an attempt to mimic the natural circadian rhythm. Novel formulations of modified-release hydrocortisone allow for less frequent dosing, although their place in standard therapy is still not clear. Prednisolone has a longer duration of action and may be given once daily. There is considerable variation in the use of glucocorticoids in clinical practice and no current consensus on the optimum replacement therapy.

Both under and over-replacement of glucocorticoids may contribute to comorbidities and long-term complications. Appropriate glucocorticoid replacement therapy is therefore required to reduce these risks, maintain well-being, and improve outcomes.

People with Congenital Adrenal Hyperplasia CAH may also have dose adjustment of glucocorticoids to manage control of excess androgen production. The majority of people with primary adrenal insufficiency, also require the replacement of mineralocorticoids and this is given in the form of daily fludrocortisone. Sodium chloride supplements may also be necessary.

Babies, children, and young people with PAI go through a period of rapid growth and change requiring different doses and dosing schedules for adult patients and frequent adjustment to their doses to optimise growth and well-being.

In this chapter, we review the different glucocorticoid regimens to establish which is the most clinically and cost-effective pharmacological treatment for patients, and optimum management of mineralocorticoid replacement for patients with a diagnosis of primary adrenal insufficiency.