Adrenal insufficiency diagnosis: new approaches to indeterminate baseline cortisol

Adrenal insufficiency is a potentially life-threatening condition requiring timely diagnosis. Baseline morning cortisol remains the initial diagnostic test; however, indeterminate values (3-15 μg/dl) necessitate dynamic testing, which is costly and labor-intensive. This review summarizes recent advances in diagnostic approaches for patients with indeterminate baseline cortisol levels.

Studies support lowering morning cortisol cutoff values to reduce unnecessary cosyntropin testing. Dehydroepiandrosterone sulfate (DHEAS), when age-adjusted and sex-adjusted, may help rule out primary adrenal insufficiency in indeterminate cases. Salivary cortisone has emerged as a practical, home-based screening alternative that circumvents cortisol-binding globulin variability. The insulin tolerance test and overnight metyrapone test remain valuable for central adrenal insufficiency diagnosis, with recent data supporting revised cortisol thresholds.

Emerging evidence supports a multimodal diagnostic approach combining baseline cortisol with adjunctive markers such as DHEAS and salivary cortisone. These strategies may reduce reliance on dynamic testing while maintaining diagnostic accuracy, ultimately improving patient convenience and healthcare efficiency.