Cortisol is a steroid hormone that regulates energy metabolism, stress reactions, and immune response. Cortisol is produced in the kidneys’ adrenal cortex. Its levels in the circulatory system are regulated by the neuroendocrine system with a negative feedback loop of the hypothalamic–pituitary–adrenal axis (HPA-axis) following circadian rhythm. Conditions associated with HPA-axis disruption cause deteriorative effects on human life quality in numerous ways. Psychiatric, cardiovascular, and metabolic disorders as well as a variety of inflammatory processes accompanying age-related, orphan, and many other conditions are associated with altered cortisol secretion rates and inadequate responses. Laboratory measurements of cortisol are well-developed and based mainly on the enzyme linked immunosorbent assay (ELISA). There is a great demand for a continuous real-time cortisol sensor that is yet to be developed. Recent advances in approaches that will eventually culminate in such sensors have been summarized in several reviews. This review compares different platforms for direct cortisol measurements in biological fluids. The ways to achieve continuous cortisol measurements are discussed. A cortisol monitoring device will be essential for personified pharmacological correction of the HPA-axis toward normal cortisol levels through a 24-h cycle.
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