Cortisol

General Information

Cortisol is the most significant glucocorticosteroid and is essential for the maintenance of several body functions. Like other glucocorticosteroids it is synthesised in the zona fasciculata of the cortex of the adrenal gland. Cortisol is secreted in response to adrenocorticotrophic hormone (ACTH) which is released from the anterior pituitary gland. Cortisol is bound to cortisol-binding globulin and albumin, with only the free (unbound) fraction being biologically active.

Blood and urine tests for cortisol may be used to help diagnose Cushing’s syndrome and Addison’s disease, two serious disorders affecting cortisol production. Cushing’s syndrome is caused by prolonged exposure to elevated levels of glucocorticoids, while Addison’s disease is associated with insufficient cortisol production due to adrenal dysfunction. A single random cortisol measurement is of limited diagnostic value, and interpretation should consider the timing of sampling and clinical context.

In the investigation of Cushing’s syndrome, further tests such as a dexamethasone suppression test or 24-hour urinary cortisol may be required.

In the investigation of suspected adrenal insufficiency, morning (08:00–09:00) cortisol measurements are most informative. Guidance from NICE (NG243) suggests that a cortisol <150 nmol/L is consistent with adrenal insufficiency, while >300 nmol/L makes it very unlikely. Values between 150–300 nmol/L are indeterminate and may require further assessment with a short synacthen test (SST), depending on the clinical context.