Glucocorticoid treatment: clinical consequences and effects on the HPA axis

This thesis comprehends a wide variety of angles on the hypothalamic-pituitary-adrenal (HPA) axis, our central stress response system. The studies described evaluate the residual function of the HPA axis when this has been lost due to disease or when the patient receives medication that suppresses the function of the HPA axis.
Cortisol is a vital hormone and is of great importance in almost all bodily processes. Cortisol is produced by the adrenal gland. The adrenal gland is controlled by hormones produced in the hypothalamus and pituitary gland. Once cortisol is in the bloodstream, it has effects on a variety of tissues. For example, cortisol plays a role in regulating blood pressure or inhibiting immune function. Cortisol can be inactivated by an enzyme. Inactivated cortisol is called cortisone. Cortisol and cortisone are metabolized in the liver. Cortisol, cortisone and the metabolites are excreted in urine. The amount of cortisol, cortisone and metabolites in urine is a good reflection of the HPA axis activity. Cortisol, cortisone and metabolites are therefore the main outcome parameters in this thesis.
In this thesis, the residual function of the HPA axis was investigated in patients with primary and secondary adrenal insufficiency, in patients who chronically use prednisolone and thereby suppress their HPA axis, and in patients who are tapering their prednisolone, thereby gradually recovering their own HPA axis activity. Finally, this thesis describes the CORE study, where we investigate the effects of prednisolone and dexamethasone in healthy subjects.