Variability in cortisol assays creates an additional problem with setting criteria for a normal response to ACTH that apply to all centers. Two studies comparing cortisol results obtained with different assays showed a positive bias of radioimmunoassays and immunofluorometric enzyme assays of 10 to 50 percent compared with a reference value obtained using isotope dilution gas chromatography-mass spectrometry. As a result, in one study, depending on the combination of assay and criterion used, between 0 and 100 percent of healthy volunteers would be considered to have a normal response to ACTH. This illustrates the difficulty of interpreting cortisol responses that are close to the cutoff point. (3)
Side effects are minimized by taking the lowest doses possible (that still yields positive results) and following doctor's orders. It is important to avoid self-regulation of the dosage, either by adding more or stopping the drug without a schedule. After prolonged use, steroids must be gradually reduced to permit the adrenal glands to resume natural cortisol production. Eliminating doses too quickly can result in glucocorticoid withdrawal symptoms, worsening of underlying inflammatory disease (rebound effect), or rarely, adrenal crisis (a life-threatening state caused by insufficient levels of adrenal steroids).