The 40th Minute Cortisol Measurement is the Key Time-Point in the Low-Dose Synacthen Stimulation Test: A Large, Assay-Specific Pediatric Validation Study
Year: 2026
Type: article
Study design: Observational Study
Abstract: Objective: Low-dose Synacthen stimulation test (LDSST) is widely used to assess central adrenal insufficiency (CAI). With the adoption of monoclonal antibody (mAb) cortisol immunoassays, lower basal and peak cortisol concentration thresholds require external validation under real-world clinical conditions. To externally validate previously defined LDSST sampling strategies, basal cortisol thresholds, and gray-zone cut-offs in a large real-world cohort using mAb immunoassays. Methods: minute cortisol levels after administration of 1 μg of synthetic Adrenocorticotropic hormone. The diagnostic performance of single and combined sampling strategies and previously defined basal cortisol thresholds and grey-zone cut-offs were evaluated across different peak cortisol criteria. Results: minute (p<0.0001). At the basal cortisol threshold of ≥6.5 μg/dL identified in our previous prospective study, specificity decreased from 68% to 57.5% (p=0.21) and sensitivity remained comparable (73.8% vs. 75.1%, p=0.74), while negative predictive value declined significantly from 91% to 78.4% (p=0.02) and positive predictive value increased to 53% in this retrospective cohort. Validation of basal cortisol gray-zone thresholds confirmed high diagnostic accuracy across different peak cortisol cut-offs. Conclusion: minute, combined with assay-specific basal cortisol interpretation and a gray-zone framework, offers a practical approach for individualized clinical decision-making in suspected CAI.
Institution: Marmara University
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $100
OpenAlex ID: W7156017166
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