title: Optimizing glucocorticoid replacement therapy in severely adrenocorticotropin-deficient hypopituitary male patients.
abstract: BACKGROUND
  The optimal replacement regimen of hydrocortisone in adults with severe ACTH deficiency remains unknown. Management strategies vary from treatment with 15-30 mg or higher in daily divided doses, reflecting the paucity of prospective data on the adequacy of different glucocorticoid regimens.
  
  
  OBJECTIVE
  Primarily to define the hydrocortisone regimen which results in a 24 h cortisol profile that most closely resembles that of healthy controls and secondarily to assess the impact on quality of life (QoL).
  
  
  METHODS
  Ten male hypopituitary patients with severe ACTH deficiency (basal cortisol <100 nm and peak response to stimulation <400 nm) were enrolled in a prospective, randomized, crossover study of 3 hydrocortisone dose regimens. Following 6 weeks of each regimen patients underwent 24 h serum cortisol sampling and QoL assessment with the Short Form 36 (SF36) and the Nottingham Health Profile (NHP) questionnaires. Free cortisol was calculated using Coolen's equation. All results were compared to those of healthy, matched controls.
  
  
  RESULTS
  Corticosteroid binding globulin (CBG) was significantly lower across all dose regimens compared to controls (P < 0·05). The lower dose regimen C (10 mg mane/5 mg tarde) produced a 24 h free cortisol profile (FCP) which most closely resembled that of controls. Both regimen A(20 mg mane/10 mg tarde) and B(10 mg mane/10 mg tarde) produced supraphysiological post-absorption peaks. There was no significant difference in QoL in patients between the three regimens, however energy level was significantly lower across all dose regimens compared to controls (P < 0·001).
  
  
  CONCLUSIONS
  The lower dose of hydrocortisone (10 mg/5 mg) produces a more physiological cortisol profile, without compromising QoL, compared to higher doses still used in clinical practice. This may have important implications in these patients, known to have excess cardiovascular mortality.
authors.affiliation: Division of Endocrinology, Beaumont Hospital and RCSI Medical School, Dublin, Ireland.
authors.forename: Lucy-Ann
authors.initials: LA
authors.lastname: Behan
authors.forename: Bairbre
authors.initials: B
authors.lastname: Rogers
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Hannon
authors.forename: Patrick
authors.initials: P
authors.lastname: O'Kelly
authors.forename: William
authors.initials: W
authors.lastname: Tormey
authors.forename: Diarmuid
authors.initials: D
authors.lastname: Smith
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Thompson
authors.forename: Amar
authors.initials: A
authors.lastname: Agha
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000172:deficiency*; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use*; D007018:Hypopituitarism / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone