Comparison of Intramuscular and Intravenous ACTH Stimulation Test in Normal Volunteers
Status:
Withdrawn
Trial end date:
2020-12-31
Target enrollment:
Participant gender:
Summary
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 centers use intramuscular cosyntropin injections given its convenience, and as
mentioned earlier, many institutions are now using the new Roche Cortisol II assay.
Investigators will conduct a study looking at healthy subjects to establish the expected
range of peak cosyntropin-stimulated cortisol levels with two different cosyntropin
administration modalities. The goal of this study is to compare intravenous (IV) and
intramuscular (IM) administration, and to generate a normal range of post-cosyntropin serum
cortisol measure with the new assay.
The two aims of the study are: (1) Compare the cortisol values at baseline, 30 minutes and 60
minutes after IV and IM cosyntropin stimulation testing in the same subjects. (2) Generate
assay-specific normal ACTH stimulation test results