Cortisol as a stress biomarker: analytical perspectives and challenges

Clinical Snapshot

Key Findings

• Effect Size: Not applicable — no primary data generated; no pooled effect size reported

• Primary Outcome: Narrative synthesis of cortisol detection methodologies across biological matrices, tracing evolution from conventional immunoassays to electrochemical biosensors, wearable devices, and microfluidic POCT systems

• Nnt Or Sensitivity: Individual platform analytical performance metrics (limits of detection, linear ranges, sensitivity) likely reported in full text but not synthesised with precision estimates; specific values not available from abstract alone

• Confidence Interval: Not reported — narrative review without meta-analytic synthesis

Clinical Application

Currently limited for most advanced platforms reviewed. Conventional immunoassays (ELISA, CLIA, LC-MS/MS) remain the clinical standard and are widely available. Electrochemical biosensors and wearable cortisol monitors are largely at research or early commercialisation stages. Microfluidic POCT systems show promise for decentralised testing but require regulatory validation, standardisation, and cost-effectiveness demonstration before routine clinical adoption. In Australia, cortisol testing is primarily conducted via serum or salivary immunoassay through accredited NATA laboratories. Late-night salivary cortisol and 24-hour urinary free cortisol are endorsed by the Endocrine Society and used in Australian endocrinology practice for Cushing's syndrome screening. LC-MS/MS is increasingly available at major referral centres (e.g., Royal Prince Alfred, Austin Health) and is considered the gold standard for accuracy. The TGA has not yet approved wearable cortisol biosensors for clinical use in Australia. PBS does not currently subsidise POCT cortisol devices. RACGP guidelines do not yet incorporate biosensor-based cortisol monitoring. The review's findings are most relevant to Australian researchers and technology developers rather than frontline clinicians at this stage. Remote and rural healthcare settings in Australia could theoretically benefit from validated POCT cortisol platforms, particularly for monitoring patients with adrenal insufficiency on replacement therapy or for occupational stress surveillance in high-risk industries. Adults and potentially paediatric populations requiring cortisol monitoring for stress-related disorders, HPA axis dysfunction (Cushing's syndrome, adrenal insufficiency, congenital adrenal hyperplasia), psychiatric conditions with neuroendocrine components, and occupational health surveillance

Abstract

Point-of-care testing (POCT) has emerged as a transformative approach in modern healthcare for the rapid detection of physiological abnormalities through minimally or non-invasively collected samples. Biological matrices such as saliva, urine, hair, blood, and interstitial fluid contain clinically significant biomarkers that may serve as indicators of physiological disorders. Among these, cortisol is the key stress biomarker and exerts substantial effects on body metabolism, acting on both peripheral tissues and the CNS. This review comprehensively outlines the evolution of cortisol detection strategies, progressing from conventional laboratory-based immunoassays to advanced analytical platforms, including electrochemical biosensors, wearable devices, and microfluidic systems. Accurate and reliable detection of elevated cortisol levels is crucial for improving diagnostic, therapeutic, and preventive strategies for stress-related disorders. By tracing the analytical window, the work describes the detection of cortisol from traditional immunoassays to innovative biosensing platforms. Moreover, recent advances in nanomaterials, sensor design, and data integration have enabled continuous, on-site monitoring of cortisol levels, thereby enhancing their applicability across diverse clinical and non-clinical settings. This integration of physiological insight with technological advancement provides a comprehensive overview of developments in cortisol assessment, connecting fundamental endocrine science with practical diagnostic applications. The review underscores the potential of next-generation POCT systems to improve early diagnosis, therapeutic monitoring, and personalized healthcare through real-time biomarker analysis.

References

1. 1.Suryawanshi, R., & Sharma, S. (2026). Cortisol as a stress biomarker: analytical perspectives and challenges. Clinica Chimica Acta; International Journal of Clinical Chemistry. https://doi.org/10.1016/j.cca.2026.121008