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Low‐dose (1 μg) 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 μg) test
Author(s) -
Tordjman Karen,
Jaffe Anat,
Trostanetsky Yana,
Greenman Yona,
Limor Rona,
Stern Naftali
Publication year - 2000
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1046/j.1365-2265.2000.00984.x
Subject(s) - medicine , endocrinology , stimulation , pituitary disease , acth stimulation test , adrenocorticotropic hormone , receiver operating characteristic , gold standard (test) , hormone
OBJECTIVE We have shown previously that in contrast to the standard high‐dose 250‐μg ACTH test, a low‐dose 1‐μg 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. DESIGN A comparison of the 1‐μg and the 250‐μg ACTH stimulation tests in healthy controls and in patients with pituitary disease whose HPA axis status was characterized formally by a gold standard test. SUBJECTS 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. MEASURES All 89 subjects underwent stimulation with 1 μg ACTH; 80 also underwent the high‐dose 250‐μg 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‐μg 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‐μg 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‐μg ACTH test is as simple and safe as the standard 250‐μg test. We suggest it should replace it in screening for adrenal insufficiency.