title: Hydrocortisone Dose Influences Pain, Depressive Symptoms and Perceived Health in Adrenal Insufficiency: A Randomized Controlled Trial.
abstract: BACKGROUND
  There is a major lack of randomized controlled trials (RCTs) evaluating the effects of hydrocortisone (HC) substitution therapy in patients with secondary adrenal insufficiency. Therefore, we evaluated the effects of two different replacement doses of HC on health-related quality of life (HRQoL) in a RCT.
  
  
  METHODS
  This RCT with a double-blind cross-over design was performed at the University Medical Center Groningen. Forty-seven patients (29 men, age 51 ± 14 years, range 19-73 years) with secondary adrenal insufficiency participated. Patients received both a lower and a higher dose of HC (0.2-0.3 and 0.4-0.6 mg/kg body weight/day) for 10 weeks in random order. HRQoL was assessed with a daily mood and symptom checklist (Patient Health Questionnaire-15 [PHQ-15], Generalized Anxiety Disorder-7 [GAD-7], Patient Health Questionnaire-9 [PHQ-9]) and with questionnaires assessing general well-being (RAND 36-Item Health Survey [RAND-36]), mood (Hospital Anxiety and Depression Scale [HADS]) and fatigue (Multidimensional Fatigue Inventory-20 [MFI-20]). ClinicalTrials.gov identifier: NCT01546922.
  
  
  RESULTS
  Patients receiving the higher dose of HC reported significantly fewer symptoms of depression (p = 0.016 and p = 0.045 for HADS and PHQ-9, respectively), less general and mental fatigue (p = 0.004 and p = 0.003, respectively, both MFI-20), increased motivation (p = 0.021, MFI-20), better physical functioning (p = 0.041), better general health (p = 0.013) and more vitality (p = 0.025) (all RAND-36). In addition, while on the higher dose, fewer somatic symptoms (p = 0.022) and less pain (p < 0.001) (both PHQ-15) were experienced.
  
  
  CONCLUSIONS
  On the higher dose of HC, patients reported a better HRQoL on various domains as compared to the lower dose of HC. The fact that a higher dose of HC may improve patient well-being should be taken into consideration when individualizing the HC substitution dose.
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jorien
authors.initials: J
authors.lastname: Werumeus Buning
authors.forename: Pauline
authors.initials: P
authors.lastname: Brummelman
authors.forename: Janneke
authors.initials: J
authors.lastname: Koerts
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
authors.forename: Gerrit
authors.initials: G
authors.lastname: van den Berg
authors.forename: Melanie M
authors.initials: MM
authors.lastname: van der Klauw
authors.forename: Wim J
authors.initials: WJ
authors.lastname: Sluiter
authors.forename: Oliver
authors.initials: O
authors.lastname: Tucha
authors.forename: Bruce H R
authors.initials: BH
authors.lastname: Wolffenbuttel
authors.forename: André P
authors.initials: AP
authors.lastname: van Beek
mesh_terms: D000309:Adrenal Insufficiency / Q000150:complications* / Q000188:drug therapy / Q000523:psychology; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003866:Depressive Disorder / Q000188:drug therapy* / Q000209:etiology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D011788:Quality of Life / Q000523:psychology*; D018709:Statistics, Nonparametric
chemical_list: D000893:Anti-Inflammatory Agents; D006854:Hydrocortisone