SUN-067 The Reflex Dexamethasone Suppression Test: Development and Assessment of Reflexed Serum Dexamethasone Measurement for the Diagnosis of Cushing Syndrome

Abstract Disclosure: J. Klahr: None. T.B. Carroll: Corcept Therapeutics. R. Nerenz: None. H. Raff: None. The overnight 1 mg dexamethasone suppression test (oDST) is used to screen for Cushing Syndrome (CS). Serum dexamethasone (SerDex) measurement improves the specificity of the test by minimizing false positives (non-suppressed serum cortisol [SerCort] due to a failure to achieve diagnostic SerDex levels). To reduce the number of SerDex levels measured and reduce cost, we implemented a Reflex oDST protocol in which SerDex is only measured if post-oDST SerCort is ≥1.6 mcg/dL (conservative cutoff). We report the number of SerDex tests avoided and the diagnostic performance and impact of the Reflex oDST. This is a retrospective analysis of 261 oDSTs completed during 6 months before (Pre) and 281 oDSTs completed during 6 months after (Post) reflex SerDex measurement implementation. To show equivalency in performance of the Reflex oDST, we used ROC analysis of oDST SerCort. In the Pre-group with CS, there were 38 patients (25 ACTH-independent; 13 ACTH-dependent). In the Post-group with CS, there were 40 patients (29 ACTH-independent; 11 ACTH-dependent; Pre vs Post not different [p=0.52]). In the Post-group, 68% of oDSTs had a SerCort <1.6 mcg/dL and therefore avoided SerDex measurement. None with SerCort <1.6 mcg/dL had CS using Guidelines criteria. In oDSTs with SerCort >1.8 mcg/dL, there were 9% and 6% false positives in the Pre- vs Post-group, respectively. In the Pre-group, the median SerCort was 1.1 mcg/dL (95% CI: 0.8-1.5) in patients without CS and 3.9 mcg/dL (95% CI: 2.6-7.9) in those with CS (p< 0.001). The optimal ROC cutoff of SerCort in the Pre-group was 2.1 mcg/dL (sensitivity 92%, specificity 93%). In the Post-group oDSTs, the median SerCort was 1.8 mcg/dL (95% CI: 0.8-1.5) in patients without CS and 2.9 mcg/dL (95% CI: 2.6-7.9) in those with CS (p< 0.001). The optimal ROC cutoff of SerCort in the Post-group was 2.0 mcg/dL (sensitivity 93%, specificity 100%; not different from Pre-group). In the Pre-group without CS, partitioning the SerDex levels by <140 ng/dL (below the reference interval) vs >140 ng/dL had no effect on the oDST SerCort (median 1.2 vs. 1.1 mcg/dL, p=0.621). Detectable SerDex (>50 ng/dL) levels were sufficient to adequately suppress SerCort in non-CS patients. Implementation of reflex SerDex testing reduced the number of post-oDST SerDex measurements by ∼68% and resulted in a cost savings of $12.67 per ordered oDST using Medicare reimbursement rates. Reflex testing did not affect the performance of the oDST. Presentation: Sunday, July 13, 2025