What Is Cortisol

Cortisol, a vital glucocorticoid, is synthesized in the zona fasciculata of the adrenal cortex. Its secretion is regulated by the hypothalamic hormone, CRH (corticotropin-releasing hormone), and the pituitary hormone, ACTH (adrenocorticotropic hormone), in the hypothalamus-pituitary-adrenal (HPA) axis. As a stress hormone, cortisol plays a critical role in responding to physical and emotional stressors. Moreover, cortisol is involved in maintaining homeostasis by influencing blood pressure, the immune system, anti-inflammatory processes, and the metabolism of proteins, carbohydrates, and adipose tissues.

Addison's disease, characterized by a decrease in cortisol production, occurs when the adrenal glands fail to produce sufficient amounts of cortisol. Conversely, Cushing's syndrome is associated with excessive cortisol production. These conditions highlight the importance of maintaining a balanced cortisol level for overall health and well-being.

Browse all Cortisol products

Metabolism of Cortisol

The metabolism of cortisol refers to the processes by which cortisol, a steroid hormone, is broken down and eliminated from the body. Cortisol metabolism primarily occurs in the liver, where it undergoes various enzymatic reactions.

• 11 beta-hydroxysteroid dehydrogenases
  Cortisol metabolism involves the action of enzymes such as 11-beta hydroxysteroid dehydrogenases (11-beta HSD). These enzymes convert cortisol to cortisone and vice versa. 11-beta HSD1 catalyzes the conversion of cortisone to cortisol, while 11-beta HSD2 converts cortisol to cortisone, regulating local cortisol concentrations in different tissues.

Figure 2. Recycle of cortisol and cortisone between placenta and fetal membranes in human pregnancy.
(Source: Wang, W. S. et al., 2020)

• A-ring reductases
  Cortisol undergoes metabolism by A-ring reductases, including 5-alpha reductase and 5-beta reductase, which convert cortisol into metabolites such as 5-alpha tetrahydrocortisol (5-alpha THF) and 5-beta tetrahydrocortisol (5-beta THF).
• Cytochrome P450, family 3, subfamily A monooxygenases
  Cytochrome P450 enzymes, particularly CYP3A4, also contribute to cortisol metabolism by converting it into 6β-hydroxycortisol. Drugs that induce CYP3A4 may accelerate cortisol clearance.

Measurement of Cortisol

• Blood Measurement
  Blood cortisol measurement is commonly performed using immunoassays, such as enzyme-linked immunosorbent assay (ELISA) or chemiluminescent assays. These assays detect and quantify cortisol levels based on the binding of cortisol-specific antibodies to cortisol molecules in the blood sample. Blood samples can be collected through venipuncture or by using dried blood spot (DBS) sampling, which involves collecting a small amount of blood on filter paper.
• Urine Measurement
  Urinary cortisol measurement provides information about the total cortisol output over a specific time period. It is often used to assess cortisol levels over a 24-hour period, known as urinary free cortisol (UFC) measurement. UFC reflects the amount of cortisol that is not bound to proteins and is excreted in the urine. UFC can be measured using immunoassays or liquid chromatography-mass spectrometry (LC-MS) techniques.
• Saliva Measurement
  Salivary cortisol measurement offers a non-invasive and convenient method to assess cortisol levels. Cortisol in saliva represents the biologically active, free fraction of cortisol. Salivary cortisol levels can be measured using immunoassays or more sensitive techniques like LC-MS. Saliva samples are collected using specialized collection devices or saliva collection tubes, and the cortisol levels are measured in the laboratory.
• Dynamic Tests
  In certain clinical scenarios, dynamic tests may be performed to evaluate cortisol levels under specific conditions. These tests involve administering synthetic hormones or substances that stimulate or suppress cortisol production. For example, the ACTH stimulation test measures how cortisol levels respond to the administration of synthetic ACTH, which should stimulate cortisol release. The dexamethasone suppression test assesses the ability of dexamethasone (a synthetic glucocorticoid) to suppress cortisol production.

Measuring cortisol levels aids in the diagnosis of conditions such as adrenal insufficiency, Cushing's syndrome, and stress-related disorders. It helps evaluate the effectiveness of treatments, monitor disease progression, and assess the function of the hypothalamic-pituitary-adrenal (HPA) axis. However, cortisol levels should be interpreted in conjunction with clinical symptoms and other diagnostic tests to obtain a comprehensive understanding of a patient's endocrine status.