title: Low-dose (1 microgram) adrenocorticotrophin (ACTH) stimulation as a screening test for impaired hypothalamo-pituitary-adrenal axis function: sensitivity, specificity and accuracy in comparison with the high-dose (250 microgram) test.
abstract: OBJECTIVE
  We have shown previously that in contrast to the standard high-dose 250-microgram ACTH test, a low-dose 1-microgram ACTH stimulation test correctly identified all patients with pituitary disease who had impaired hypothalamo-pituitary-adrenal (HPA) function. In this study we further compared the performances of these two tests as screening procedures for possible HPA impairment.
  
  
  METHODS
  A comparison of the 1-microgram and the 250-microgram ACTH stimulation tests in healthy controls and in patients with pituitary disease whose HPA axis status was characterized formally by a gold standard test.
  
  
  METHODS
  A total of 89 subjects were investigated: 27 healthy normal controls, 43 patients with pituitary disease and normal HPA function, and 19 patients with various pituitary diseases and impaired HPA function.
  
  
  METHODS
  All 89 subjects underwent stimulation with 1 microgram ACTH; 80 also underwent the high-dose 250-microgram ACTH test. A receiver operating characteristic analysis (ROC) was performed to compare the tests.
  
  
  RESULTS
  Using a stimulated cortisol > 500 nmol/l as the criterion for a normal response, the 1-microgram ACTH stimulation identified 18 of the 19 subjects with impaired HPA function (94.7% sensitivity with a likelihood ratio of 0.0588 for a negative test). In contrast, 15/16 passed the high-dose test (a 6.2% sensitivity with a likelihood ratio of 0.875 for a negative test). All normal controls, and 36/43 patients with preserved HPA function, passed the 1-microgram ACTH test (90% specificity). This degree of accuracy was unrivalled by the high dose test at all the cut-off levels considered.
  
  
  CONCLUSIONS
  More sensitive and accurate, the low-dose 1-microgram ACTH test is as simple and safe as the standard 250-microgram test. We suggest it should replace it in screening for adrenal insufficiency.
authors.affiliation: Institute of Endocrinology, Tel Aviv-Sourasky Medical Center, Tel Aviv University Sackler Faculty of Medicine, Tel Aviv, Israel. ktordjma@im.wustl.edu
authors.forename: K
authors.initials: K
authors.lastname: Tordjman
authors.forename: A
authors.initials: A
authors.lastname: Jaffe
authors.forename: Y
authors.initials: Y
authors.lastname: Trostanetsky
authors.forename: Y
authors.initials: Y
authors.lastname: Greenman
authors.forename: R
authors.initials: R
authors.lastname: Limor
authors.forename: N
authors.initials: N
authors.lastname: Stern
mesh_terms: D000309:Adrenal Insufficiency / Q000175:diagnosis*; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage*; D000328:Adult; D016022:Case-Control Studies; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010900:Pituitary Diseases / Q000175:diagnosis; D010901:Pituitary Function Tests; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013268:Stimulation, Chemical
chemical_list: D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone