A-080 Morning Cortisol for Rule-in and Rule-out of Adrenal Insufficiency in an Asian Population

Background Short ACTH stimulation (Synacthen) tests are performed to investigate for adrenal insufficiency. Previous work suggests that morning cortisol concentrations can be used to rule in or out adrenal insufficiency to avoid performance of a Synacthen test. This study aimed to determine the optimal cortisol concentration for rule-in or rule-out adrenal insufficiency based on 30-minute cortisol (COR30) for adequate response using the assay-specific cut-off from The Endocrine Society of Australia/The Australasian Association for Clinical Biochemistry and Laboratory Medicine/The Royal College of Pathologists of Australasia (ESA/AACB/RCPA) Harmonization of Endocrine Dynamic Testing - Adult (HEDTA), in an Asian population. Methods Synacthen tests performed at our institution from 2012-2024, with a baseline cortisol between 6 and 10 am (COR0(6-10)), were extracted from the laboratory database. Plasma cortisol concentrations were measured by Beckman Coulter DxI 800. Synacthen tests were classified as adequate or inadequate based on the Beckman Coulter specific HEDTA cut-off for COR30 of 420 nmol/L. Performance characteristics (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under receiver operator characteristic (AUROC) curve) of COR0(6-10) concentrations to predict adequate or inadequate response were calculated using Microsoft Excel. Results 4609 Synacthen tests were included, 77% of which had adequate Synacthen response. COR0(6-10) >300 nmol/L could exclude inadequate COR30 response with sensitivity 95%, specificity 48%, PPV 35%, NPV 97%; and COR0(6-10) >364 nmol/L had sensitivity 99%, specificity 29%, PPV 29%, NPV 99%. COR0(6-10) <155 nmol/L could rule-in inadequate COR30 response with sensitivity 53%, specificity 95%, PPV 76%, NPV 87%; and COR0(6-10) <97 nmol/L had sensitivity 35%, specificity 99%, PPV 91%, NPV 84%. AUROC of COR0(6-10) for adequate COR30 response was 0.86. If patients with COR0(6-10) <97 nmol/L and >300 nmol/L did not proceed to Synacthen testing, up to 46% of tests could be avoided, while keeping misclassification under 5%. Conclusions Morning cortisol cut-offs were determined for rule-in and rule-out of adrenal insufficiency in an Asian population. Patients with morning cortisol >300 nmol/L or <97 nmol/L may be able to avoid Synacthen testing unless there is a strong suspicion of clinical discordance. Such a testing strategy could significantly decrease the number of Synacthen tests while keeping misclassification to a minimum.