Low dose (1 mu g) ACTH test in the evaluation of adrenal dysfunction in pre-clinical Addison's disease

OBJECTIVE The presence of al-hydroxylase autoantibodies (21OHAb) is a marke r of adrenal autoimmunity and can be used to identify subjects with preclin ical Addison's disease. The low-dose (1 mu g) ACTH test (LDT) is more sensi tive than the high-dose (250 mu g) test (HDT) for the diagnosis of pituitar y adrenal insufficiency, but no information is available on the use of a LD T in subjects with autoimmune adrenalitis and primary adrenal insufficiency . The aim of our study was to evaluate the clinical use of the LDT in the d iagnosis of early adrenocortical dysfunction in patients with adrenal autoa ntibodies. DESIGN AND METHODS Firstly, we evaluated the cortisol responses to both a L DT and a HDT in a group of 12 healthy volunteers. We then performed a LDI i n 11 subjects positive for 21OHAb, but without clinical signs of Addison's disease identified by screening 920 patients with one or more organ-specifi c autoimmune diseases. In all cases, the LDT was followed by a sequential H DT which was used as a control test of the sensitivity and specificity of t he LDT. RESULTS In healthy subjects, the peak cortisol levels after the LDT were si milar to those after the classical HDT. In 21OHAb-positive subjects, the LD T showed a pathological response in five out of 11 (45%) cases and the diag nostic concordance between the results of the LDT and those of the HDT was 100%, All the five cases with pathological LDT were also positive for adren al cortex autoantibodies (ACA) and 4/5 had high levels of basal ACTH. One s ubject with pathological LDT developed clinical Addison's disease 4 months after the test had been performed. CONCLUSIONS Our study demonstrates that the low dose ACTH test has a high d iagnostic sensitivity and specificity for primary adrenal insufficiency and suggests that it can accurately identify subjects with pre-clinical adrena l dysfunction.