ACTH

ACTH is the pituitary's order to the adrenal glands: “make cortisol.” It is the middle link in the body's main stress pathway, carrying the brain's command from the pituitary down to the adrenal cortex.

ACTH is a peptide hormone made by corticotroph cells in the anterior pituitary, which release it in response to CRH from the hypothalamus. Once in the blood, ACTH acts on the outer layers of the adrenal cortex, stimulating the production and release of cortisol and, to a lesser degree, adrenal androgens.

ACTH is cut from a much larger precursor protein called proopiomelanocortin (POMC). The same precursor also yields melanocyte-stimulating fragments, which is why very high ACTH levels can darken the skin — a clue seen in primary adrenal failure (Addison's disease), where low cortisol drives ACTH sky-high.

Like its partners, ACTH follows a daily rhythm peaking in the early morning and is restrained by cortisol feedback. Measuring ACTH alongside cortisol helps doctors tell whether a cortisol problem starts in the pituitary, the adrenal gland, or elsewhere.