title: Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation.
abstract: BACKGROUND
  Patients with treated adrenal insufficiency (AI) have increased morbidity and mortality rate. Our goal was to improve outcome by developing a once-daily (OD) oral hydrocortisone dual-release tablet with a more physiological exposure-time cortisol profile.
  
  
  OBJECTIVE
  The aim was to compare pharmacokinetics and metabolic outcome between OD and the same daily dose of thrice-daily (TID) dose of conventional hydrocortisone tablets.
  
  
  METHODS
  We conducted an open, randomized, two-period, 12-wk crossover multicenter trial with a 24-wk extension at five university hospital centers.
  
  
  METHODS
  The trial enrolled 64 adults with primary AI; 11 had concomitant diabetes mellitus (DM).
  
  
  METHODS
  The same daily dose of hydrocortisone was administered as OD dual-release or TID.
  
  
  METHODS
  We evaluated cortisol pharmacokinetics.
  
  
  RESULTS
  Compared with conventional TID, OD provided a sustained serum cortisol profile 0-4 h after the morning intake and reduced the late afternoon and the 24-h cortisol exposure. The mean weight (difference = -0.7 kg, P = 0.005), systolic blood pressure (difference = -5.5 mm Hg, P = 0.0001) and diastolic blood pressure (difference: -2.3 mm Hg; P = 0.03), and glycated hemoglobin (absolute difference = -0.1%, P = 0.0006) were all reduced after OD compared with TID at 12 wk. Compared with TID, a reduction in glycated hemoglobin by 0.6% was observed in patients with concomitant DM during OD (P = 0.004).
  
  
  CONCLUSIONS
  The OD dual-release tablet provided a more circadian-based serum cortisol profile. Reduced body weight, reduced blood pressure, and improved glucose metabolism were observed during OD treatment. In particular, glucose metabolism improved in patients with concomitant DM.
authors: Department of Endocrinology, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden. Gudmundur.Johannsson@gu.se
authors: G
authors: G
authors: Johannsson
authors: A G
authors: AG
authors: Nilsson
authors: R
authors: R
authors: Bergthorsdottir
authors: P
authors: P
authors: Burman
authors: P
authors: P
authors: Dahlqvist
authors: B
authors: B
authors: Ekman
authors: B E
authors: BE
authors: Engström
authors: T
authors: T
authors: Olsson
authors: O
authors: O
authors: Ragnarsson
authors: M
authors: M
authors: Ryberg
authors: J
authors: J
authors: Wahlberg
authors: B M K
authors: BM
authors: Biller
authors: J P
authors: JP
authors: Monson
authors: P M
authors: PM
authors: Stewart
authors: H
authors: H
authors: Lennernäs
authors: S
authors: S
authors: Skrtic
mesh_terms: D000309:Adrenal Insufficiency / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D006854:Hydrocortisone