A-335 Pediatric Cortisol Reference Intervals (RI): Impact of Age-Specific RI on the Rate of Abnormal “Low” Cortisol Results
Authors: Andress B D , Block D R , Baumann N A 
Published: September 2023

Abstract

Background
Serum cortisol, measured by automated immunoassay, is a rapid test used for the initial assessment of adrenal dysfunction. Physiologic serum cortisol concentrations are influenced by many factors including diurnal variation, stress, and patient age. In the absence of established pediatric reference intervals (RIs), our laboratory has utilized adult RIs to flag pediatric cortisol results as abnormally high or low in the electronic health record. However, pediatric cortisol RIs recently defined by the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) are considerably lower than the adult RIs currently in use. This could cause pediatric cortisol results to be incorrectly flagged as “low” when they are within the age-specific RI and lead to unnecessary follow-up testing. The aim of this study was to determine the impact of implementing CALIPER pediatric cortisol RIs on the rate of “low” result flagging for pediatric patients.

Methods
AM cortisol results for patients age &lt;18 years reported between 10/2012- 09/2022 were obtained from the Mayo Clinic data repository. These results contained values measured by both Beckman Access (n = 3 818) and Roche Cobas (n = 625) immunoassays. Results classified as abnormal “low” by current adult RIs (Beckman: 7–25 mcg/dL, Roche: 4.8–20 mcg/dL) were compared to results which would flag low according to the appropriate method- and age-specific RIs defined by CALIPER (Beckman: 1-&lt;13 yrs 2.19–12.8 mcg/dL, 13-&lt;16 yrs 3.03–17.1 mcg/dL, 16-&lt;19 yrs 3.78–19.4 mcg/dL; Roche: &lt;1 yr 0.58–17.2 mcg/dL, 1-&lt;12 yrs 2.39–14.9 mcg/dL, 12-&lt;19 yrs 3.63–17.4 mcg/dL). The proportion of results flagging low by adult versus pediatric RI were compared by chi-squared test, with P &lt; 0.05 considered significant.

Results
For Beckman, the percentages of pediatric patient cortisol results flagging low using the adult RI versus (vs) the pediatric age-specific RI were: 35% vs 7% for 1–12 years of age (P &lt; 0.001, n = 1866), 22% vs 5% for 13–15 years (P &lt; 0.001, n = 966), and 16% vs 5% for 16–18 years (P &lt; 0.001, n = 986). For Roche, the same analysis yielded: 52% vs 9% for 0–1 years (P = 0.001, n = 23), 14% vs 8% for 1–11 years (P = 0.03, n = 238), and 9% vs 6% for 12–18 years (P = 0.16, n = 364).

Conclusion
The implementation of pediatric RIs for serum cortisol will have a significant impact on the number of “low” result flags for patient results on both Beckman and Roche platforms. Statistically significant decreases in the percentage of low result flags were observed on both platforms for all age ranges except for the age bracket of 12–18 years by Roche. Furthermore, pediatric RIs appeared to produce more consistent rates of abnormal results across methods and age ranges, with all groups flagging low at a rate of 5–9%, whereas the same age ranges with adult RIs flagged at rates ranging from 9–52%. Lowering the RIs for pediatric cortisol to more appropriate ranges as identified by CALIPER will decrease the number of “low” flag results. This has the potential to decrease unnecessary follow-up, including repeat testing and further diagnostic procedures such as ACTH stimulation testing. Implementation of pediatric RIs has potential benefits regarding stress and cost for patients and parents, alarm fatigue for physicians, and utilization of laboratory resources.