title: Comparison of methods for evaluation of the suppressive effects of prednisolone on the HPA axis and bone turnover: changes in s-DHEAS are as sensitive as the ACTH test.
abstract: OBJECTIVE
  Different hypothalamic-pituitary-adrenal (HPA) axis function tests are used for diagnosing disease and evaluating suppressive effects of corticosteroid treatment. Our objectives were to evaluate sensitivity and precision of different HPA axis tests to be able to select one that combines good performance with good practicability, suitable for investigation of new corticosteroids in clinical trials.
  
  
  METHODS
  In this descriptive, double-blind, parallel-group study, 60 healthy male volunteers were treated with once-daily morning doses of prednisolone for 2 weeks. The volunteers were randomized to 1 of 5 treatment groups (prednisolone 2.5, 5, 7.5, 10, or 15 mg). We compared the plasma-cortisol (p-cortisol) 24-hour average concentration (Cav) with morning (08:00 hours) p-cortisol, daytime p-cortisol Cav, and 24-hour urinary cortisol excretion. Adrenocorticotrophic hormone (ACTH) stimulation tests and the metyrapone test were also performed. Furthermore, we analyzed levels of serum dehydroepiandrosterone sulfate (s-DHEAS), insulin, and markers of bone turnover.
  
  
  RESULTS
  Dose-related effects were shown, but the magnitude of effects and sensitivities varied greatly between the tests. P-cortisol measurements over the course of 24 hours were used as the reference method. Low- and standard-dose ACTH tests and morning s-DHEAS levels had similar sensitivity. Urinary cortisol excretion and the metyrapone stimulation test had low sensitivity. The effects of prednisolone on markers of bone turnover were, in general, less than those on the HPA axis. Only osteocalcin, procollagen Type 1 C-peptide and procollagen Type 3 N-peptide were significantly affected. Treatment with prednisolone was well tolerated.
  
  
  CONCLUSIONS
  Changes in s-DHEAS and the low-dose ACTH test combine good sensitivity and precision for evaluation of the suppressive effect of exogenous corticosteroids on the HPA axis, and they are easy to perform.
authors.forename: Eva
authors.initials: E
authors.lastname: Gruvstad
authors.forename: Lars Pavo
authors.initials: LP
authors.lastname: Hedner
authors.forename: Peter
authors.initials: P
authors.lastname: Höglund
authors.forename: Anders
authors.initials: A
authors.lastname: Luts
authors.forename: Ensio
authors.initials: E
authors.lastname: Norjavaara
mesh_terms: D000324:Adrenocorticotropic Hormone; D000328:Adult; D016723:Bone Remodeling / Q000187:drug effects*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood*; D004311:Double-Blind Method; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011239:Prednisolone / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D007328:Insulin; D019314:Dehydroepiandrosterone Sulfate; D000324:Adrenocorticotropic Hormone; D011239:Prednisolone; D006854:Hydrocortisone