Hydrocortisone Versus Methylprednisolone for the Treatment of Glucocorticoid-Induced Adrenal Insufficiency

This study aims to compare the use of methylprednisolone and hydrocortisone as replacement therapies in patients with glucocorticoid-induced adrenal insufficiency. The primary goal is to evaluate and compare the recovery of the hypothalamic-pituitary-adrenal (HPA) axis.

Inclusion Criteria: * Age over 18 years. * Suspected adrenal insufficiency due to receiving supraphysiological doses of methylprednisolone for more than 4 weeks. * Receiving methylprednisolone 4 mg for at least the last 4 weeks. * Morning cortisol lower than 300 nmol/L. * Inadequate result of a short ACTH test performed on a physiological dose of methylprednisolone (cortisol rise after 30 min under 470 nmol/L AND after 60 min under 500 nmol/L). * No further indication for treating the underlying disease, and retreatment with glucocorticoids is not expected in the next 2 years. * Consent to participate in the research. Exclusion Criteria: * Known organic disease of the pituitary-adrenal axis. * Body mass over 130 kg. * Advanced comorbidities. * Advanced heart failure (NYHA IV). * Chronic kidney disease IV, eGFR under 30 ml/min. * Liver cirrhosis. * Active malignant disease. * Immune deficiencies. * Planned major surgery during the study duration. * Receiving drugs affecting cortisol metabolism or interfering with cortisol measurements (e.g., systemic estrogens, strong inducers or inhibitors of CYP3A4). * Conditions affecting cortisol metabolism (pregnancy, liver disease, nephrotic syndrome). * Alcohol dependence syndrome (consuming more than 21 units of alcohol per week). * Shift (night) work. * Presence of comorbidities with an expected life expectancy of less than 3 years.