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.
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.
Tordjman
K
K
Institute of Endocrinology, Tel Aviv-Sourasky Medical Center, Tel Aviv University Sackler Faculty of Medicine, Tel Aviv, Israel. ktordjma@im.wustl.edu
Jaffe
A
A
Trostanetsky
Y
Y
Greenman
Y
Y
Limor
R
R
Stern
N
N
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
D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone