title: Hypothalamic-pituitary-adrenal axis suppression in asthmatic children on inhaled and nasal corticosteroids: is the early-morning serum adrenocorticotropic hormone (ACTH) a useful screening test?
abstract: BACKGROUND
  Hypothalamic-pituitary-adrenal axis suppression (HPAS) in asthmatic children treated with inhaled corticosteroids (ICS), with or without nasal steroids (NS), may be more common than previously thought. Only dynamic testing will identify children at risk of adrenal crisis. It is impractical to test all asthmatic children for HPAS with a gold standard adrenal function test, i.e. the metyrapone or insulin tolerance test.
  
  
  OBJECTIVE
  To determine which clinical or biochemical parameter is the most useful screening test for HPAS in asthmatic children.
  
  
  METHODS
  Twenty-six asthmatic children, 5-18 yr old, on ICS ± NS, not treated with oral or topical steroids in the preceding year were recruited. Height, weight, height velocity, weight velocity and a change in systolic blood pressure from the recumbent to the standing position (ΔSBP) were recorded. Early-morning urine for urinary free cortisol (UFC) and urinary cortisol metabolites (UCM) was collected. UFC was analysed by both a chemiluminescent assay and gas chromatography/mass spectrometry (GC-MS). Morning serum cortisol and adrenocorticotropic hormone (ACTH) levels were measured. The overnight metyrapone test was performed if the fasting morning serum cortisol was >83 nmol/l. HPAS was diagnosed if the ACTH failed to rise >100 pg/ml after metyrapone. Spearman correlation coefficients (r) were calculated between the post-metyrapone ACTH and each variable. A receiver-operating characteristics (ROC) curve was drawn for the most promising test, and the diagnostic performance was calculated.
  
  
  RESULTS
  All clinical and biochemical parameters investigated were weakly and non-significantly correlated with the post-metyrapone ACTH, except for the morning serum ACTH (r = 0.68; p <0.001). The best discrimination between those who have and those who do not have HPAS is a morning serum ACTH level of 11.7 pg/ml. This corresponds to a sensitivity of 0.89 (0.57-0.98), a specificity of 0.77 (0.53-0.90), a positive predictive value of 0.67 (0.39-0.87), a negative predictive value of 0.93 (0.69-0.99), an accuracy of 0.81 (0.61-0.94), a positive likelihood ratio of 3.78 (1.68-9.49) and a negative likelihood ratio of 0.15 (0.03-0.60).
  
  
  CONCLUSIONS
  The morning serum ACTH level was found to be the most useful screening test to detect HPAS in this sample of children receiving ICS ± NS. A larger study should be undertaken to refine the diagnostic precision of the morning serum ACTH level.
authors.affiliation: Paediatric Endocrine Unit, Tygerberg Children's Hospital, University of Stellenbosch, Cape Town, South Africa. zollner@sun.ac.za
authors.forename: Ekkehard W
authors.initials: EW
authors.lastname: Zöllner
authors.forename: Carl
authors.initials: C
authors.lastname: Lombard
authors.forename: Ushma
authors.initials: U
authors.lastname: Galal
authors.forename: Stephen
authors.initials: S
authors.lastname: Hough
authors.forename: Elvis
authors.initials: E
authors.lastname: Irusen
authors.forename: Eugene
authors.initials: E
authors.lastname: Weinberg
mesh_terms: D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects*; D000307:Adrenal Gland Diseases / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis*; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001249:Asthma / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008797:Metyrapone; D010913:Pituitary-Adrenal System / Q000187:drug effects; D012680:Sensitivity and Specificity
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D000324:Adrenocorticotropic Hormone; D008797:Metyrapone