Cortisol (hydrocortisone) is the most prominent glucocorticosteroid, and it is essential for the maintenance of several body functions. The most important physiological effects of cortisol are the increase in blood glucose levels (enhancement of gluconeogenesis, catabolic action) and its anti-inflammatory and immunosuppressive action.
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 in 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.3
Serum cortisol concentrations normally show a diurnal variation.3 Maximum concentrations 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.4,5 Thereby, cortisol serum concentrations are used for monitoring several diseases with an overproduction (eg, Cushing syndrome)6,7 or underproduction (eg, Addison disease) of cortisol and for monitoring several therapeutic approaches (eg, dexamethasone suppression therapy in Cushing syndrome and hormone replacement therapy in Addison disease).
Pregnancy, contraceptives, and estrogen therapy give rise to elevated cortisol concentrations. In samples from patients who have been treated with prednisolone, methylprednisolone, or prednisone, falsely elevated concentrations of cortisol may be determined. During metyrapone tests, 11-deoxycortisol levels are elevated. Falsely-elevated cortisol values may be determined due to cross-reactions. Patients suffering from 21-hydroxylase-deficiency exhibit elevated 21-deoxycortisol levels and this can also give rise to elevated cortisol levels.
The time of sample collection must be taken into account when interpreting results due to the cortisol secretion circadian rhythm. Severe stress can also give rise to elevated cortisol levels.
As with all tests containing monoclonal mouse antibodies, erroneous findings may be obtained from samples taken from patients who have been treated with monoclonal mouse antibodies or who have received them for diagnostic purposes. In rare cases, interference due to extremely high titers of antibodies to streptavidin and ruthenium can occur. The test contains additives, which minimize these effects.
The determination of cortisol in 24-hour urine is the method of choice for the detection of Cushing syndrome since cortisol excretion in urine is not subject to the diurnal rhythm of cortisol secretion.
This test may exhibit interference when sample is collected from a person who is consuming a supplement with a high dose of biotin (also termed as vitamin B7 or B8, vitamin H, or coenzyme R). It is recommended to ask all patients who may be indicated for this test about biotin supplementation. Patients should be cautioned to stop biotin consumption at least 72 hours prior to the collection of a sample.