Clinical Significance

Cortisol (hydrocortisone) is quantitatively the major glucocorticoid product of the adrenal cortex. The main reason to measure cortisol is to diagnose human diseases which are caused by the overproduction of cortisol in Cushing’s syndrome (CS), deficiency of adrenal steroid excretion in Addison’s disease, and for therapy monitoring (e.g. dexamethasone suppression test in Cushing's syndrome and hormone replacement therapy in Addison's disease). Cortisol plays an important role in the regulation of many essential physiological processes, including energy metabolism, maintenance of electrolyte balance and blood pressure, immunomodulation and stress responses, cell proliferation as well as cognitive functions. The major fraction of cortisol circulates bound to plasma proteins as corticosteroid binding globulin and albumin. The biologically active free fraction comprises only 2‑5 % of the total hormone concentration. 

Elevated serum levels can be found in stress responses, psychiatric diseases, obesity, diabetes, alcoholism and pregnancy, which may cause diagnostic problems in patients with Cushing's syndrome. Low levels of cortisol are seen in patients with rare adrenal enzyme defects and after long-lasting stress. For diagnostic purposes the following analyses are used: Total and free cortisol in serum. 

The secretion of cortisol is mainly controlled by the hypothalamic-pituitaryadrenal axis (HPA). When cortisol levels in the blood are low, a group of cells in a region of the brain called the hypothalamus release corticotropin-releasing hormone (CRH) which causes the pituitary gland to secrete another hormone, adrenocorticotropic hormone (ACTH), into the bloodstream. High levels of ACTH are detected in the adrenal glands and stimulate the formation and secretion of cortisol, causing blood levels of cortisol to rise. As the cortisol levels rise, they start to block the release of CRH from the hypothalamus and ACTH from the pituitary. 

Normally, the highest cortisol secretion happens in the second half of the night with peak cortisol production occurring in the early morning. Following this, cortisol levels decline throughout the day with lowest levels during the first half of the night. Therefore, the circadian variations of cortisol secretion and the influence of stress have to be considered for the sampling conditions in serum and plasma.

_{Source: Roche cobas Elecsys Cortisol II method sheet, V 3.0 2022-10}