Adrenocorticotropic Hormone (ACTH)

ACTH is a 39-residue peptide released by corticotroph cells of the anterior pituitary. It is not transcribed as itself: prohormone convertase 1 excises it from proopiomelanocortin, the precursor that also yields beta-endorphin and, in other tissues, alpha-MSH. Activity lives almost entirely in the first 24 residues, so the fragment ACTH 1-24 is fully active at the melanocortin-2 receptor of the adrenal zona fasciculata, raising cyclic AMP and driving cortisol synthesis.

Cosyntropin, or tetracosactide, is that synthetic ACTH 1-24 and the reagent in the short stimulation test: cortisol is measured at baseline and again at 30 and 60 minutes after a fixed injected dose, with a peak near 500 nmol/L the conventional pass mark, though the threshold moves with the assay. Endogenous ACTH is secreted in pulses that crest before waking and clears with a plasma half-life of about ten minutes.

ACTH is the measurement that localises the lesion. Low cortisol with a high ACTH is adrenal disease; low cortisol with a low or inappropriately normal ACTH points at the pituitary or hypothalamus, including suppression by exogenous glucocorticoid. The stimulation test does not interrogate the axis directly: it asks only whether the adrenal cortex can still respond, a proxy that gives falsely reassuring answers in acute pituitary loss, before the gland has atrophied.

ACTH is also preanalytically fragile. It adsorbs to glass, degrades in whole blood at room temperature, and needs chilled plasma separated promptly, so a surprising low result is often a transport artefact rather than a diagnosis. A second error runs POMC biology backwards: because ACTH shares its core heptapeptide with alpha-MSH, marketing for tanning peptides sometimes implies steroidogenic effects, when selectivity across the melanocortin receptors decides what happens.