The determination of cortisol is used for the recognition and treatment of functional disorders of the adrenal gland.
Cortisol (hydrocortisone) is the most prominent glucocorticosteroid, and it is essential for the maintenance of several body functions. Like other glucocorticosteroids, cortisol is synthesized from the common precursor cholesterol in the zona fasciculata of the cortex of the adrenal gland. For the transport of cortisol in blood, about 90 % of cortisol is bound to corticosteroid binding globulin (CBG) and to albumin. Only a small amount of cortisol circulates unbound in blood and is free to interact with its receptors.
The most important physiological effects of cortisol are the increase of blood glucose levels (enhancement of gluconeogenesis, catabolic action), and its anti‑inflammatory and immunosuppressive action.
Synthesis and secretion of cortisol by the adrenal gland are controlled by a negative feedback mechanism within the hypothalamus-pituitary-adrenal cortex-axis. If the cortisol level is low, corticotropin releasing hormone (CRH) is secreted by the hypothalamus, which causes the pituitary to release adrenocorticotropic hormone (ACTH). This stimulates the synthesis and secretion of cortisol by the adrenal gland. Cortisol itself acts in a negative feedback mechanism on the pituitary gland and the hypothalamus. In addition, stress is followed by increased cortisol secretion.
Serum cortisol concentrations normally show a diurnal variation. Maximum concentrations (700 nmol/L or 25.4 μg/dL) are usually reached early in the morning and then concentrations decline throughout the day to an evening level that is about half of the morning concentration. Therefore, for interpretation of results, it is important to know the collection time of the serum sample.
The cortisol status of a patient is used to diagnose the function or malfunction of the adrenal gland, the pituitary, and the hypothalamus. Thereby cortisol serum concentrations are used for monitoring of several diseases with an overproduction (e.g. Cushing's syndrome) or underproduction (e.g. Addison's disease) of cortisol and for the monitoring of several therapeutic approaches (e.g. dexamethasone suppression therapy in Cushing's syndrome and hormone replacement therapy in Addison's disease).
The determination of cortisol in 24‑hour urine is the method of choice for the detection of Cushing's syndrome since cortisol excretion in urine is not subject to the diurnal rhythm of cortisol secretion. This allows a more exact differentiation between healthy individuals and patients with Cushing's syndrome. Cortisol which is excreted into urine without alteration is referred to as urinary free cortisol (UFC). Usually there is a direct proportional relationship between urinary free cortisol and the unbound and hence biologically active cortisol in the blood.
Recent studies have demonstrated that several night-time salivary cortisol measurements are superior to the measurement of urinary free cortisol in establishing the diagnosis of Cushing syndrome. Determination of night-time salivary cortisol is particularly helpful in children, psychiatric patients, and subjects where a variety of stress factors might affect the adrenal cortex, causing increased adrenal steroid concentrations.