Accuracy of the Low-Dose ACTH Stimulation Test for Adrenal Insufficiency Diagnosis: A Re-Assessment of the Cut-Off Value

Background: The clinical practice shows that many low-dose ACTH-stimulation tests have a false positive result. The aim of the study was to determine the diagnostic accuracy of a low-dose ACTH-stimulation test in the diagnosis of adrenal insufficiency and to define its optimal cut-off. Methods: We analyzed data from 103 patients undergoing 1 µg ACTH-stimulation test. Four patients had adrenal insufficiency (AI) upon follow up: Two primary, and two secondary AI. Cortisol serum levels were evaluated at time 0, 20’, and 30’ after the injection of 1 µg i.v. of ACTH. The sensitivity, specificity, accuracy, and positive and negative predictive values of the test were calculated for both 20’ and 30’ sampling. The receiver operating characteristic (ROC) curve was obtained to assess the sensitivity and specificity of low-dose ACTH-stimulation test in the diagnosis of adrenal insufficiency at different cut-off values. Results: Considering 500 nmol/L as the standard cut-off value, low-dose ACTH stimulation test showed a 100% sensitivity and a 67.3% specificity, with a high rate of false positive results. ROC curve analysis showed that the cut-off of 401.5 nmol/L is the best compromise between sensitivity (100%) and specificity (93.9%). Conclusions: By using a cut-off value of 401.5 nmol/L for the low-dose ACTH stimulation test, the number of false positive patients decreased significantly, but the sensitivity remained high.