Effect of Supplemental Hydrocortisone During Stress in Prednisolone-induced Adrenal Insufficiency

Inclusion Criteria:

• Age ≥ 50 years

• Women must be postmenopausal (FSH is measured at the screening visit)

• A diagnosis of PMR/GCA, or both conditions combined.

• Treatment with prednisolone ≥12 weeks

• Ongoing prednisolone treatment, with current daily prednisolone dose > 0 mg and ≤5mg. The dose must have been ≤5 mg for minimum 2 weeks at the time of the screeningvisit.

Exclusion Criteria:

• Known primary or secondary adrenal insufficiency

• Known Cushing's Syndrome

• Known allergy towards study medication ingredients

• Severe comorbidity: Heart failure (New York Heart Association class IV); Kidneyfailure with an estimated glomerular filtration rate <30 mL/min (Chronic kidneydisease stage 4-5); Liver disease in the form of cirrhosis; Active cancer; Knownsevere immune deficiency; A history of psychiatric disease requiring treatment by apsychiatric department (for affective disorders only if within the last year beforestudy entry)

• Alcohol consumption >21 units per week

• Planned major surgery during the study period at study entry.

• Use of drugs that interfere with cortisol metabolism/measurements: Systemicoestrogen treatment (discontinued < 1 month before inclusion), Treatment with strongCYP3A4 inhibitors or inducers, Use of other glucocorticoid formulations (Inhaledcorticosteroids, intraarticular or intramuscular injections, steroid creams Europeansteroid group IV-V used in the genital area. Note: Permitted glucocorticoidformulations: Eye-drops, nasal spray, glucocorticoid creams European steroid groupI-III, and European steroid group IV-V used in the non-genital area only.)

• Inability to provide written informed consent.