Optimizing the Diagnostic Criteria for Standard (250-μg) and low Dose (1-μg) Adrenocorticotropin Tests in the Assessment of Adrenal Function

Abstract

ACTH stimulation is the standard test for assessment of adrenal function. It was suggested that the low dose (1 microg) would be more sensitive for detecting mild secondary adrenal insufficiency than the usual dose of 250 microg. The aim of this study was to find the optimal diagnostic criteria and to compare standard dose test (SDT) with the low dose test (LDT). A group of patients treated with corticosteroids for the 6 months was considered to have hypothalamo-pituitary-adrenal impairment. Studies were performed in 14 corticosteroid-treated and 28 control subjects in random order on 2 consecutive days. Tests were analyzed using the receiver operating characteristic curve method. The best test was cortisol increment at 15 min of the LDT. It was significantly better than the cortisol concentration at 15 min of the SDT, the best test during the SDT (receiver operating characteristic curve area and 95% confidence interval: LDT, 0.997 and 0.956-0.999; SDT, 0.827 and 0.662-0.929; P = 0.0113). For the cortisol increment at 15 min of the LDT at 100% sensitivity, the diagnostic value was 100 mmol/L, and the specificity was 96%. Therefore, the LDT is superior to the standard dose test in the assessment of secondary adrenal insufficiency.

Changes in Serum Cortisol with Age in Critically Ill Patients

“…This finding is similar to that of Zarcovic et al [5] who reported that in non-critically ill patients the most sensitive parameter for the detection of hypothalamic-pituitary-adrenal dysfunction on the ACTH stimulation test is a small response to 1 Ìg ACTH at 15 min. It is speculated that a diminished early response might be the first sign of decreasing adrenal function analogous to the loss of early insulin response to glucose stimulation in non-insulin-dependent diabetes mellitus.…”

“…The significance of this finding lies in reports that in the critically ill patient, a high baseline serum cortisol and a small response to ACTH stimulation (often taken as !249 nmol/l) are markers of a poor prognosis [3][4][5]. Furthermore it is now recognized that subtle alterations in adrenal function may be a cause and not only a consequence of morbidity in the ICU [3].…”

“…It has been shown in severely ill patients with multiple medical problems that the addition of partial adrenocortical insufficiency can significantly increase mortality [3]. Recent studies in non-ICU patients have shown that the more physiologic low-dose (1 Ìg) ACTH stimulation test is a more sensitive detector of hypothalamic-pituitary-adrenal dysfunction than the pharmacological standard-dose (250 Ìg) test [5], but its role in detecting adrenal insufficiency in critically ill patients is still unclear.…”

Assessment of central adrenal insufficiency in children and adolescents with Prader–Willi syndrome

“…A baseline blood sample for ACTH was also taken. For the LDTST, a 250 μg vial of ACTH was diluted in a normal saline solution to a concentration of 0·5 μg/ml 25 . The solution was used immediately after preparation.…”

“…As ACTH is heat labile and proteolysis reduces its plasma concentration, tubes were collected and preserved on ice until separated and frozen. To diagnose CAI, in this study we elected the commonly accepted cut‐off value of ≤500 n m (corresponding to <18·1 μg/dl) as employed in most studies and currently used at our institutions 12,17,25,26 . Patients with peak cortisol response ≤500 n m were asked to undergo a second CAI test by standard 250 μg ACTH test or, alternatively, repeat a LDTST.…”