A Single, Post-ACTH Cortisol Measurement to Screen for Adrenal Insufficiency in the Hospitalized Patient

Cortisol concentrations were assessed by the laboratory according to the manufacturer’s instructions by using the ADVIA Centaur Cortisol assay (Siemens Healthcare Diagnostics Inc, Tarrytown, NY), a competitive chemiluminescent immunoassay. For the traditional CST, a cortisol concentration ≥18 mcg/dL at any time point during the test was used to define normal (negative). Patients with a positive (no results >18 mcg/mL) CST were defined as “screen positives” for the purposes of this analysis. Patient location data were available that allowed for an ICU vs non-ICU comparison.

Statistical analyses were performed in SAS version 9.4 (SAS Institute Inc, Cary, North Carolina). Continuous variables were compared by using a 2-tailed Student t test. Percentiles and proportions were compared by using χ² tests or Fisher’s exact tests when appropriate. The concordance of screening at each time point compared with the traditional CST was calculated. Positive percent agreement (PPA) with the traditional CST in each subgroup (ICU and floor) and combined was also evaluated. A P value of .05 was used to determine significance.

RESULTS

A total of 702 complete cosyntropin tests on separate patients were included in the analysis. This included 198 ICU patients and 504 non-ICU (floor) patients. Fifty-one percent of patients were male in both the floor and ICU subgroups. The average age of ICU patients was 60.2 ± 13.2 years compared to 57.3 ± 17.3 years for patients on a general medicine floor (P = .02).

Cortisol concentrations obtained at 30 minutes were significantly higher than baseline cortisol concentrations (baseline: 12.8 mcg/dL; 30 minutes: 23.9 mcg/dL; P < .001) for all patients. The average cortisol concentrations obtained at 60 minutes (27.4 mcg/dL) were significantly higher than those at baseline and 30 minutes (P < .001). This trend was seen in each subgroup of patients in the ICU and on the floor (Figure). The average baseline cortisol concentration was higher for ICU patients compared to floor patients (17.6 mcg/dL vs 10.9 mcg/dL, respectively).

By using the traditional CST, there were 26 (13.1%) positive tests for AI in ICU patients and 84 (16.7%) positive tests in floor patients (Table).

The Table shows the number of patients who screened positive at each time point and compares the concordance of these results with the results of the overall CST in each subgroup (ICU and floor). The 60-minute concentration demonstrated higher concordance with the traditional CST than the 30-minute concentration overall (99.7% vs 88.0%, respectively), in ICU patients (100% vs 91.9%, respectively), and in floor patients (99.6% vs 86.9%, respectively). In the ICU subgroup, 60-minute concentrations were 100% concordant with the traditional CSTs. The PPA of a 60-minute–only screening compared to a traditional CST was better than a 30-minute–only screening overall (98% vs 57%, respectively), in ICU patients (100% vs 62%, respectively), and in floor patients (98% vs 56%, respectively). A 60-minute concentration was required to prevent false-positive screening in 11.7% of all screening tests, but the 30-minute concentration only prevented false-positive screening in 0.3% of screening tests. Of all 30-minute concentrations screening positive for AI alone, 42.7% were negative for AI at 60 minutes. Conversely, only 1.8% of all 60-minute concentrations screening positive for AI alone were negative for AI at 30 minutes. The likelihood of a false-positive screening test at 30 minutes was higher in floor patients (13.1%) than in ICU patients (8.1%). The difference between the false-positive screening rate of a single 30-minute cortisol concentration and a single 60-minute concentration was significant (P < .0001) for both floor and ICU patients. There were no instances of basal cortisol concentrations >18 mcg/dL that were subsequently <18 mcg/dL at 30 and 60 minutes after cosyntropin stimulation.

Only 13% of CSTs were started in the recommended 3-hour window from 6:00 am to 8:59 am. The remaining tests were begun outside this window.

DISCUSSION

Our investigation of 702 CSTs, the largest retrospective analysis to date, finds that the 60-minute cortisol concentration is significantly higher than the 30-minute concentration in a standard, high-dose CST. Sixty-minute cortisol concentrations are more concordant with traditional CST results than the 30-minute concentrations in both critically ill ICU and noncritically ill floor patients. This suggests that a single 60-minute measurement is sufficient for AI screening. The use of only 30-minute concentrations would lead to a significant increase in false-positive screening tests and significantly lower PPA (98% vs 57%). With peak cortisol concentrations occurring at 60-minutes poststimulation, measuring both 30- and 60-minute poststimulation concentrations does not appear to be of significant clinical benefit. The cost-saving from reduced phlebotomy and laboratory expenses would be significant, especially in locations with limited staff or financial resources. Our findings are similar to other recent results by Chitale et al.,¹⁷ Mansoor et al.,¹⁶ and Zueger et al.¹⁸