A randomized, double‐blind, crossover study comparing two‐ and four‐dose hydrocortisone regimen with regard to quality of life, cortisol and <scp>ACTH</scp> profiles in patients with primary adrenal insufficiency

Abstract

Summary Context Current guidelines on how to divide the daily cortisol substitution dose in patients with primary adrenal insufficiency ( PAI ) are controversial and mainly based on empirical data. Objective To assess how an equal dose of hydrocortisone ( HC ) given either four times daily or twice daily influence diurnal profiles of cortisol and ACTH , patient preferences and health‐related quality of life ( HRQ o L ). Design Double blind, crossover. Methods Fifteen patients with PAI (six women) were included. Capsules of HC or placebo were given at 07:00, 12:00, 16:00 and 22:00 h in 4‐week treatment periods: either one period with four doses (10 + 10 + 5 + 5 mg) or one period with two doses (20 + 0 + 10 + 0 mg). Diurnal profiles of cortisol and ACTH were collected, and area under the curve ( AUC ) was calculated. Questionnaires were used to evaluate patient preferences and HRQ o L . Results The four‐dose regimen gave a higher serum cortisol before tablet intake in the morning ( P = 0·027) and a higher 24‐h cortisol AUC ( P &lt; 0·0001) compared with the two‐dose period. In contrast, a lower median plasma ACTH in the morning before tablet intake ( P = 0·003) and a lower 24‐h ln( ACTH AUC ) were found during the four‐dose period. The patients preferred the four‐dose regimen ( P = 0·03), and the HRQ o L scores tended to be higher (high score indicates better HRQ o L ) for the four‐dose period. In summary, a four‐dose regimen gives increased availability of cortisol and an enhanced effect with a less elevated ACTH in the morning in comparison with a two‐dose regimen but the effect on HRQ o L remains inconclusive.