A Single, Post-ACTH Cortisol Measurement to Screen for Adrenal Insufficiency in the Hospitalized Patient
BACKGROUND: Cosyntropin stimulation testing (CST) is used to screen patients for adrenal insufficiency (AI). Traditionally, CST includes baseline cortisol concentration, the administration of cosyntropin, and cortisol concentration at 30 and 60 minutes poststimulation. There is debate surrounding the utility of testing and cut-off points for concentrations at each time point.
OBJECTIVE: To determine if a single cortisol measurement at 30 or 60 minutes could replace the traditional approach.
DESIGN: We looked retrospectively at inpatients who underwent standard, high-dose CST (n = 702) and evaluated the number of patients who would screen positive for AI by using a single time point (30 or 60 minutes) compared with the traditional CST.
SETTING: A tertiary-care, academic medical center.
PATIENTS: Hospital inpatients present between January 2012 and September 2013.
RESULTS: Of tests, 84.3% were normal, which was defined as at least 1 cortisol concentration of 18 mcg/dL or higher at any time after stimulation. The average 60-minute concentration was higher than the average 30-minute concentration (P < .001). A single 60-minute concentration is 100% concordant with the full CST in the intensive care unit (ICU) subgroup and 99.6% concordant in floor patients. A single 30-minute concentration is significantly less concordant, 91.9% and 86.9%, in the ICU and floor subgroups, respectively.
CONCLUSIONS: Overall, a single 60-minute cortisol concentration to screen for AI was 99.7% concordant with the traditional CST, and the positive percent agreement was 98%. Fewer false-positive screens would occur with a single 60-minute cortisol concentration compared with a single 30-minute concentration (P < .001). High-dose CST screening may safely be interpreted with single 60-minute poststimulation cortisol serum concentrations.
© 2018 Society of Hospital Medicine
Zueger et al.18 evaluated the results of high-dose CST in 73 patients and found 13.7% of patients with inadequate cortisol response (<18 mcg/dL) at 30 minutes had normal concentrations at 60 minutes (>18 mcg/dL). Their study did not identify a single case of normal cortisol concentration at 30 minutes that would have inappropriately screened positive for AI if cortisol concentrations were only checked at 60 minutes. Similarly, they suggested that the 30-minute test did not add any additional diagnostic value; however, no confirmatory testing was performed.
Higher cortisol concentrations at 60 minutes poststimulation may result in improved specificity for AI without reducing sensitivity, but it may also indicate that the cutoff value may need to be raised from 18 mcg/dL at 60 minutes to maintain an appropriate clinical sensitivity. Continued research should resolve this clinical question with gold-standard confirmatory testing. Furthermore, there is debate about an appropriate screening cortisol concentration threshold for critically ill patients. Researchers have compared concentrations of 25 mcg/dL to the traditional 18 mcg/dL to improve sensitivity for AI, but these studies do not involve comparisons to confirmatory testing and often result in reduced specificity.23,24
In our study, only a small fraction of testing was performed in the early-morning hours, when basal cortisol results are of value. There may be indications to perform traditional CSTs with a basal concentration, such as for suspected secondary AI, but testing must be performed in the early morning for interpretable results per current recommendations. However, poststimulation cortisol concentrations may be interpreted regardless of the time of day at which the test was initiated.3
Our study is limited by its scope because it is a retrospective analysis. It is also limited by a lack of gold-standard, clinical confirmatory testing or analysis of other clinical data. Our method of testing and interpretation is considered the screening standard and is often used to plan treatment for AI without confirmatory testing, as ITT is not routinely available for hospitalized patients. The validation of the traditional CST to the ITT has been performed extensively, but a randomized trial comparing a single 60-minute concentration to the ITT may be useful. The exact timing of blood draws may have introduced error in the concentration measurements, and this is critical to screening accuracy. Total serum cortisol is 10% bound to albumin,25 and medications such as steroids or opioids and medical conditions such as obesity or liver disease can affect cortisol concentrations.26 Albumin and free cortisol concentrations that may be used to adjust for these variables were not available.
CONCLUSION
We recommend changes to the standard CST to exclude a basal cortisol concentration unless it is indicated for the evaluation of secondary AI or obtained at the appropriate early-morning hour. A single 60-minute poststimulation cortisol concentration may be an appropriate screening test for AI and demonstrates high concordance with the traditional CST. The use of a 30-minute poststimulation concentration alone may lead to a significantly higher number of false-positive results. Alternatively, the stimulated cortisol threshold used to define a normal test may need to be higher at 60 minutes to maintain the appropriate sensitivity. Further study and comparison with confirmatory testing are needed.
Disclosure
The authors have no relevant conflicts of interest to disclose.
