The low-dose corticotropin-stimulation test revisited: the less, the better?

In the standard corticotropin-stimulation test, which is used to assess the function of the hypothalamo-pituitary-adrenal axis, synthetic corticotropin is administered at a dose of 250 mu g. Previous studies suggested that tests that use lower corticotropin doses had better discrimination than standard-dose tests possibly by avoiding supraphysiological concentrations of corticotropin. Here, we discuss a meta-analysis by Kazluaskaite et al. that compared standard-dose and low-dose corticotropin-stimulation tests and concluded that the low-dose test has a superior sensitivity and specificity. Superiority over the standard-dose test, however, was only found following a series of internal corrections and adjustments conducted by the investigators that might be inappropriate. Unadjusted meta-analyses demonstrated no advantage of the low-dose test over the standard-dose test. As data on the long-term follow-up of patients with borderline results are only available for the standard 250 mu g dose test, this test should continue to be advocated, with assay-specific cut-off levels.