The 40^th Minute Cortisol Measurement is the Key Time-Point in the Low-Dose Synacthen Stimulation Test: A Large,...

Area of Science:

• Endocrinology
• Clinical Diagnostics
• Hormone Assays

Background:

• Low-dose synacthen stimulation test (LDSST) is standard for assessing central adrenal insufficiency (CAI).
• Monoclonal antibody (mAb) cortisol immunoassays necessitate validation of existing LDSST thresholds in clinical practice.

Purpose of the Study:

• To externally validate LDSST sampling strategies, basal cortisol thresholds, and gray-zone cut-offs using mAb immunoassays in a large patient cohort.
• To assess the diagnostic performance of these parameters in a real-world clinical setting.

Main Methods:

• Retrospective analysis of 646 LDSSTs in patients with suspected CAI.
• Measurement of cortisol at baseline, 40th, and 60th minutes post-1 μg synthetic ACTH administration.
• Evaluation of diagnostic accuracy using various peak cortisol criteria and previously defined thresholds.

Main Results:

• Cortisol measurement at the 40th minute showed superior reliability over the 60th minute, with fewer false negatives (p<0.0001).
• At a basal cortisol threshold of ≥6.5 μg/dL, sensitivity decreased in this cohort, while specificity remained comparable.
• Validation confirmed high diagnostic accuracy of basal cortisol gray-zone thresholds across different peak cortisol cut-offs.

Conclusions:

• Real-world validation supports current LDSST sampling strategies and basal cortisol thresholds.
• A 40th-minute cortisol measurement, combined with assay-specific interpretation and a gray-zone framework, provides a practical approach for diagnosing CAI.