The adrenal cortex has three distinct zones which secrete various hormones under the direct control of specific feedback mechanisms 1. Cortisol secretion from the adrenal glands’ zona fasciculata is primarily regulated by corticotropin, also known as adrenocorticotropic hormone, or ACTH. ACTH is released from the anterior pituitary in response to hypothalamic neuropeptides and stress 1, 2 .
ACTH and cortisol measurements are frequently used in the assessment of adrenocortical function and other disturbances of the hypothalamic-pituitary-adrenal (HPA) axis.
These include the differential diagnosis of Cushing’s syndrome (CS), a large group of signs and symptoms due to prolonged and inappropriately high exposure to glucocorticoids, mainly cortisol 3. Many common signs of Cushing’s such as obesity, high blood pressure, and increased blood glucose are frequently observed today 4. In general, normal or high ACTH concentrations indicate pituitary or ectopic sources of ACTH, while low concentrations indicate an adrenal tumour secreting glucocorticoids 5. In addition to measurement of late night Salivary Cortisol levels, the Endocrine Society recommends the overnight dexamethasone suppression test as one of the screening tests for diagnosing CS 6, with a cut-off at <1.8 µg/dL cortisol as an indication of suppressed serum levels.
ACTH and cortisol levels also play a role in the diagnosis of Addison’s disease, a failure of the adrenal gland to produce cortisol. Patients with primary adrenal insufficiency (AI) can be diagnosed based on a combined measurement of early morning serum cortisol and plasma ACTH levels. The Endocrine Society recommends that a peak cortisol <18 µg/dL following a standard-dose corticotropin stimulation test is indicative of adrenal insufficiency 1, 6. Secondary AI most commonly requires dynamic testing such as the insulin tolerance test or the overnight metyrapone test 1, 7, 8.