title: GLUCOCORTICOID REPLACEMENT REGIMENS IN CHRONIC ADRENAL INSUFFICIENCY: A SYSTEMATIC REVIEW AND META-ANALYSIS.
abstract: OBJECTIVE
  Various glucocorticoid (GC) regimens have been used in the treatment of patients with adrenal insufficiency, yet the differences between such regimens on health outcomes are unclear. We performed a systematic review and meta-analysis to compare the effects of GC regimens on quality of life (QoL), bone density, incidence of adrenal crisis, and death. In pediatric studies, we also searched for final adult height.
  
  
  METHODS
  We searched 6 databases through July 2016. Studies were selected and appraised by independent reviewers. Data were pooled using the profile likelihood random-effects model.
  
  
  RESULTS
  We included 34 studies. We found no difference in QoL scores between higher (≥30 mg/day of hydrocortisone [HC] equivalence) vs. lower daily doses (<30 mg/day of HC equivalence) (P = .15) or based on frequency of daily dosing (once, twice or thrice daily). Extended-release (1 study), dual-/modified-release (3 studies), and continuous subcutaneous (3 studies) forms of GCs were associated with higher QoL scores. There was no significant association between dose and type of GC and the incidence of adrenal crises. The effect on bone mineral density was heterogeneous. No data were available on mortality or final adult height in children. The quality of evidence was low due to increased risk of bias, imprecision, and heterogeneity.
  
  
  CONCLUSIONS
  Extended-/dual-release, and continuous subcutaneous forms of GC may be associated with higher QoL scores. However, this is derived from short-term and imprecise evidence, warranting low confidence.
  
  
  BACKGROUND
  AI = adrenal insufficiency BMD = bone mineral density GC = glucocorticoids HC = hydrocortisone QoL = quality of life RCT = randomized controlled trial.
authors.forename: Alaa
authors.initials: A
authors.lastname: Al Nofal
authors.forename: Irina
authors.initials: I
authors.lastname: Bancos
authors.forename: Khalid
authors.initials: K
authors.lastname: Benkhadra
authors.forename: Naykky Maruquel Singh
authors.initials: NM
authors.lastname: Ospina
authors.forename: Asma
authors.initials: A
authors.lastname: Javed
authors.forename: Ekta
authors.initials: E
authors.lastname: Kapoor
authors.forename: Kalpana
authors.initials: K
authors.lastname: Muthusamy
authors.forename: Juan P
authors.initials: JP
authors.lastname: Brito
authors.forename: Adina F
authors.initials: AF
authors.lastname: Turcu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Larry
authors.initials: L
authors.lastname: Prokop
authors.forename: Dana Z
authors.initials: DZ
authors.lastname: Erickson
authors.forename: Aida N
authors.initials: AN
authors.lastname: Lteif
authors.forename: Neena
authors.initials: N
authors.lastname: Natt
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Murad
mesh_terms: D000284:Administration, Oral; D000309:Adrenal Insufficiency / Q000188:drug therapy*; D000328:Adult; D001827:Body Height; D015519:Bone Density; D002648:Child; D002908:Chronic Disease; D003692:Delayed-Action Preparations; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000627:therapeutic use; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000627:therapeutic use; D055104:Infusions, Subcutaneous; D009026:Mortality; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D005938:Glucocorticoids; D006854:Hydrocortisone