Comparison of Intramuscular and Intravenous ACTH Stimulation Test in Normal Volunteers

Cosyntropin (synthetic ACTH) stimulation test is considered the optimal test for diagnosis of primary and long-standing secondary adrenal insufficiency. The standard cosyntropin stimulation test is performed by administering 250 µg cosyntropin intravenously. Serum cortisol is measured before, and at 30 and 60 minutes after the bolus injection. Peak cortisol levels below 500 nmol/L (18.1 µg/dL) at 30 or 60 minutes after cosyntropin administration indicate adrenal insufficiency per recent guidelines, without specification of how the cosyntropin is administered (intravenously or intramuscularly). However, the peak stimulated cortisol cutoff value is based on old, fluorometric or radio-immunological methods that are known to detect significant amounts of glucocorticoids other than cortisol. For this reason, peak cortisol levels, as determined by older assays, may set higher thresholds than what might be considered necessary using a newer, more specific assay. The widely-used old Elecsys® Cortisol Immunoassay from Roche Diagnostics (Cortisol I) is now replaced worldwide (including Johns Hopkins Hospital) by a new Elecsys® Cortisol assay from Roche Diagnostics (Cortisol II). The new Cortisol II assay employs a monoclonal as opposed to a polyclonal capturing antibody, which was used in the old Cortisol I assay. This results in greater specificity for cortisol. The new Cortisol II assay was shown to have strong correlation with cortisol levels measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) which is considered the gold standard for cortisol measurement. Previous studies addressing the cortisol cutoff levels for the diagnosis of adrenal insufficiency with different cortisol assays have been heterogeneous in terms of the dose and route of administration of cosyntropin used, and the wide variety of subjects being tested including healthy subjects that are occasionally on oral estrogen therapy and patients with adrenal insufficiency. Many clinical cent