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.

DESIGN:

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.

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 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: K Tordjman, A Jaffe, Y Trostanetsky, Y Greenman, R Limor, N Stern
• Journal: Clinical endocrinology (Clin Endocrinol (Oxf)) Vol. 52 Issue 5 Pg. 633-40 (May 2000) ISSN: 0300-0664 [Print] England
• PMID: 10792344 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Adrenocorticotropic Hormone
• Hydrocortisone

Topics

• Adrenal Insufficiency (diagnosis)
• Adrenocorticotropic Hormone (administration & dosage)
• Adult
• Case-Control Studies
• Drug Administration Schedule
• Female
• Humans
• Hydrocortisone (blood)
• Hypothalamo-Hypophyseal System (physiopathology)
• Male
• Middle Aged
• Pituitary Diseases (diagnosis)
• Pituitary Function Tests
• Pituitary-Adrenal System (physiopathology)
• Predictive Value of Tests
• ROC Curve
• Sensitivity and Specificity
• Stimulation, Chemical