title: Continuous subcutaneous hydrocortisone infusion versus oral hydrocortisone replacement for treatment of addison's disease: a randomized clinical trial.
abstract: BACKGROUND
  Conventional glucocorticoid replacement therapy fails to mimic the physiological cortisol rhythm, which may have implications for morbidity and mortality in patients with Addison's disease.
  
  
  OBJECTIVE
  The objective of the study was to compare the effects of continuous sc hydrocortisone infusion (CSHI) with conventional oral hydrocortisone (OHC) replacement therapy.
  
  
  METHODS
  This was a prospective crossover, randomized, multicenter clinical trial comparing 3 months of treatment with thrice-daily OHC vs CSHI. From Norway and Sweden, 33 patients were enrolled from registries and clinics. All patients were assessed at baseline and after 8 and 12 weeks in each treatment arm.
  
  
  METHODS
  The morning ACTH level was the primary outcome measure. Secondary outcome measures were effects on metabolism, health-related quality of life (HRQoL), sleep, and safety.
  
  
  RESULTS
  CSHI yielded normalization of morning ACTH and cortisol levels, and 24-hour salivary cortisol curves resembled the normal circadian variation. Urinary concentrations of glucocorticoid metabolites displayed a normal pattern with CSHI but were clearly altered with OHC. Several HRQoL indices in the vitality domain improved over time with CSHI. No benefit was found for either treatments for any subjective (Pittsburgh Sleep Quality Index questionnaire) or objective (actigraphy) sleep parameters.
  
  
  CONCLUSIONS
  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.
authors: Department of Clinical Science (M.Ø., P.M., K.T., K.L., E.S.H.), University of Bergen, N-5009 Bergen, Norway; Department of Medicine (M.Ø., K.L., E.S.H.) and Centre for Clinical Research, Haukeland University Hospital, N-5021 Bergen, Norway (R.M.N.); Department of Molecular Medicine and Surgery (S.Bj., A.-L.H., S.Be.), Karolinska Institutet, SE-171 77 Stockholm, Sweden; Departments of Medical Sciences (M.I., S.B., O.K.) and Neuroscience and Psychiatry (J.-E.B.), Uppsala University, SE-751 05 Uppsala, Sweden; and Department of Medicine (S.C.), Stavanger University Hospital, N-4068 Stavanger, Norway.
authors: Marianne
authors: M
authors: Oksnes
authors: Sigridur
authors: S
authors: Björnsdottir
authors: Magnus
authors: M
authors: Isaksson
authors: Paal
authors: P
authors: Methlie
authors: Siri
authors: S
authors: Carlsen
authors: Roy M
authors: RM
authors: Nilsen
authors: Jan-Erik
authors: JE
authors: Broman
authors: Kai
authors: K
authors: Triebner
authors: Olle
authors: O
authors: Kämpe
authors: Anna-Lena
authors: AL
authors: Hulting
authors: Sophie
authors: S
authors: Bensing
authors: Eystein S
authors: ES
authors: Husebye
authors: Kristian
authors: K
authors: Løvås
mesh_terms: D056044:Actigraphy; D000224:Addison Disease / Q000097:blood / Q000188:drug therapy*; D000284:Administration, Oral; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D018592:Cross-Over Studies; D005260:Female; 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; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone