ACTH, Plasma

Adrenocorticotropic hormone (ACTH), or corticotropin, is a peptide hormone consisting of 39 amino acids. It is produced in the anterior pituitary of the brain as part of the precursor molecule pro-opiomelanocortin (POMC). Tissue-specific cleavage results in ACTH and a range of related peptides.

ACTH stimulates formation and secretion of glucocorticoids (especially cortisol) by the adrenal cortex. The glucocorticoid production is regulated by various factors. After stimulation (eg, by physical effort or by the internal body clock), the hypothalamus secretes CRH (corticotropin-releasing hormone). CRH acts on the pituitary, which in turn synthesizes and secretes ACTH. Finally, ACTH stimulates secretion of the glucocorticoids by the adrenals. High concentrations of glucocorticoids in the blood inhibit secretion of CRH and ACTH via a negative feedback mechanism.

ACTH concentrations show a diurnal variation with high levels in the morning and low levels in the evening; therefore, as with cortisol, it is important to know the collection time of the plasma sample for interpretation of the results.

Plasma ACTH measurements are useful in the differential diagnosis of pituitary Cushing's disease (ACTH hypersecretion), autonomous ACTH-producing pituitary tumors (eg, Nelson's syndrome), hypopituitarism with ACTH deficiency, and ectopic ACTH syndrome. In addition to cortisol measurements, ACTH determinations can be used together with functional or stimulation tests to diagnose the origin of glucocorticoid overproduction. Similarly, ACTH measurements can be employed to facilitate differential diagnosis of adrenocortical insufficiency (Addison's disease).

ACTH not produced by the pituitary gland is known as ectopic ACTH; this is often associated with small cell carcinoma of the lung. In rare cases, ectopic ACTH can be caused by thymic tumors, pancreatic adenocarcinomas, or bronchial carcinoids. These tumors often secrete ACTH precursors (POMC and pro-ACTH).