title: A randomized, double-blind, crossover study comparing two- and four-dose hydrocortisone regimen with regard to quality of life, cortisol and ACTH profiles in patients with primary adrenal insufficiency.
abstract: BACKGROUND
  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 (HRQoL).
  
  
  METHODS
  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 HRQoL.
  
  
  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 < 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 HRQoL scores tended to be higher (high score indicates better HRQoL) 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 HRQoL remains inconclusive.
authors.affiliation: Department of Medical and Health Sciences, Section of Endocrinology, Faculty of Health Sciences, Linköping University, Linköping, Sweden. Bertil.Ekman@lio.se
authors.forename: Bertil
authors.initials: B
authors.lastname: Ekman
authors.forename: Margareta
authors.initials: M
authors.lastname: Bachrach-Lindström
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Lindström
authors.forename: Jeanette
authors.initials: J
authors.lastname: Wahlberg
authors.forename: Johan
authors.initials: J
authors.lastname: Blomgren
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Arnqvist
mesh_terms: D000224:Addison Disease / Q000097:blood* / Q000188:drug therapy*; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000097:blood*; D008875:Middle Aged; D010919:Placebos; D011788:Quality of Life; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D010919:Placebos; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone