Adrenocorticotrophic hormone (ACTH)

Adrenocorticotrophic hormone (ACTH) or corticotrophin is a polypeptide hormone secreted by the pituitary gland to regulate the production of steroid hormones by the adrenal cortex. Control of ACTH secretion from the anterior pituitary involves both a classical negative feedback mechanism and CNS-stress mediated control system. Two hypothalamic peptide hormones modulate this secretion; corticotrophin-releasing hormone (CRH) stimulates ACTH secretion synergistically with vasopressin (AVP). ACTH increases the synthesis and release of all adrenal steroids, aldosterone, cortisol and adrenal androgens. It is the principal modulator of cortisol and the primary glucocorticoid in man. As the effective concentration of cortisol in the circulation rises, release of ACTH is inhibited directly at a pituitary level. Through this same mechanism, falling cortisol concentrations lead to elevated ACTH concentrations. Like other pituitary hormones, ACTH is secreted in a pulsatile manner. These small pulses are superimposed on a characteristic, diurnal fluctuation of greater amplitude. In normal individuals, ACTH reaches a peak in the early morning (6-8am) and concentrations become lowest late in the day and near the beginning of the sleep period. Because of this diurnal rhythm, it is customary to draw plasma ACTH samples between 8-10am. However, discrimination of patients with Cushing syndrome from normal individuals may be best made on samples obtained in the evening (4-6pm). The diurnal pattern of ACTH secretion is usually absent in Cushing and ectopic ACTH syndromes.
Plasma ACTH determinations are useful in the differential diagnosis of pituitary Cushing syndrome, Addison disease, autonomous ACTH producing pituitary tumours, hypopituitarism with ACTH deficiency and ectopic ACTH syndromes. The most common cause of Cushing syndrome is bilateral adrenal hyperplasia, due to pituitary ACTH hypersecretion from a pituitary adenoma.