Objective: Patients with adrenal insufficiency (AI) have impaired health-related quality of life (HRQoL), which is thought to be in part due to unphysiological glucocorticoid replacement therapy. The aim was to compare once-daily hydrocortisone (HC) dual-release tablet (modified-release) with conventional HC therapy regarding clinical data and HRQoL. Design and methods:We conducted an open, prospective trial at one endocrine center. There were 15 of 26 patients with primary AI, nine of 18 patients with secondary AI, and six congenital adrenal hyperplasia patients switched to modifiedrelease HC therapy by their own decision. We evaluated clinical outcome and disease-specific HRQoL by using AddiQoL questionnaire at baseline and at follow-up (median 202 days (85-498)). Results: Patients on modified-release HC (nZ30) showed significant decreases in BMI (26.0G0.75-25.6G0.71, P for changeZ0.006) and HbA1c (6.04G0.29-5.86G0.28, P for changeZ0.005), whereas patients remaining on conventional HC (nZ20) showed no change in these parameters (P for interactionZ0.029 and 0.017 respectively). No significant change in AddiQoL score were found in the modified-release HC group (83.8 baseline and 84.9 at follow-up; P for changeZ0.629). In the conventional HC group, there was a significant decrease in scores (84.0 baseline and 80.9 at follow-up; P for changeZ0.016), with a between-treatment P for interaction of 0.066. The fatigue subscore of AddiQoL showed the same pattern with a significant decrease (P for changeZ0.024) in patients on conventional HC therapy (P for interactionZ0.116). Conclusions: Modified-release HC decreases BMI and HbA1c compared with conventional HC treatment. In addition, it seems to stabilize HRQoL over time.

CSHI safely brought ACTH and cortisol toward normal circadian levels without adversely affecting glucocorticoid metabolism in the way that OHC did. Positive effects on HRQoL were noted with CSHI, indicating that physiological glucocorticoid replacement therapy may be beneficial and that CSHI might become a treatment option for patients poorly controlled on conventional therapy.

The validation process resulted in a revised 30-item AddiQoL questionnaire and an eight-item AddiQoL short version with good psychometric properties and high reliability.