There has been debate regarding the appropriate cortisol cutoff during the cosyntropin stimulation test (CST) when newer cortisol assays are used. We aimed to evaluate the proper cortisol values during the standard dose CST in patients with normal hypothalamic-pituitary-adrenal (HPA) axis when the Elecsys Cortisol II assay from Roche Diagnostics is used.

We retrospectively reviewed the medical records of patients evaluated for possible adrenal insufficiency using the standard-dose (250 mcg) CST from January 2018 to December 2020 and eventually judged to have a normal HPA axis. All the CSTs were done in the outpatient setting. Evaluation by an endocrinologist, restrictive exclusion criteria including prior glucocorticoid and opioid use, and lack of glucocorticoid treatment for at least 6 months after the CST was used to define normal HPA axis. The results are reported in the median (range).

We identified 63 patients who met the inclusion criteria and were considered to have a normal HPA axis. The median age was 54.7 (27.6-89.1) years; 32 (51%) were female, and 27 (43%) were white. The duration of follow-up after the CST without any glucocorticoid replacement was 13.9 (6.3-43.9) months. Cortisol levels were 21.7 (15.7-29.1) µg/dl and 24.4 (17.9-35.8) µg/dl at 30- and 60-minutes after cosyntropin administration, respectively. The lowest cortisol levels at 30 and 60 minutes for patients with either normal TSH or gonadal axis (n=47) or in whom both axes were normal (n=18) were similar to the ones of the entire cohort.

Our study supports using a lower than previously recommended cortisol cutoff value at 30 minutes after Cosyntropin using the Roche Elecsys Cortisol II assay. The lowest cortisol levels in our cohort were 15.7 and 17.9 µg/dL at 30 and 60 minutes after the CST, respectively. Therefore, it is essential to consider the time of cortisol draw after cosyntropin administration.