Clinical Significance

Cortisol is the major glucocorticoid produced and secreted by the adrenal cortex. It affects (a) the metabolism of protein, fat, and carbohydrates, (b) the maintenance of muscle and myocardial integrity, and (c) the suppression of inflammatory and allergic activities.

Corticosteroid-binding globulin and albumin bind approximately 90% of the cortisol secreted by the adrenal cortex. Bound cortisol circulates in an available, but temporarily inactive state. The physiological activity of cortisol depends upon levels of the small fraction of circulating unbound cortisol.

Adrenocorticotropic hormone (ACTH) activates the synthesis and release of cortisol from the adrenal cortex. The pituitary produces and releases ACTH upon stimulation by corticotropin-releasing hormone (CRH) secreted from the hypothalamus. Unbound cortisol acts in a negative feedback mechanism upon the hypothalamus-pituitary-adrenal cortex (HPA) axis at the levels of the pituitary and hypothalamus. In addition, diurnal variation and stress such as pyrogenically induced fever, severe psychosis, or trauma influence the neuroendocrine regulation of the adrenal cortex.

Abnormal changes in cortisol levels occur due to hypothalamic, pituitary, or adrenal malfunction. If undiagnosed and untreated, these disorders can lead to severe metabolic imbalance which may be life-threatening. The measurement of serum or plasma cortisol - utilizing morning and evening levels and/or stress tests such as ACTH stimulation or dexamethasone suppression - aids in the diagnosis of adrenal related disease. The cortisol stimulation test involves a pre dose blood sample and a 30, 60, and 90 minute post dose blood tests. The pre dose sample is drawn right before (within 15 minutes) cosyntropin (a synthetic ACTH) is given. The next blood samples are drawn 30, 60, and 90 minutes after the administration of the drug. There is an expected increase to greater than 20.0 ug/dL cortisol level following ACTH administration in normal patients.

Excess cortisol levels are found in Cushing's syndrome (adrenal cortical hyperfunction) while decreased levels are found in Addison's disease (adrenal cortical insufficiency). Cortisol bound to protein is protected from metabolism by the liver. Unbound (free) cortisol in serum is metabolized by the liver resulting in a wide variety of forms or metabolites. Many of these metabolites (conjugated, glucuronide and sulfate forms) are water-soluble and rapidly voided in the urine. A small amount (<100 ug/24 hours) of cortisol and other extractable metabolites are also excreted in the urine.

_{Source: Access Cort IFU #33600, 12/7/16}