ACTH

Where it comes from

Made in

Corticotroph cells of the anterior pituitary

Sent out by

CRH and vasopressin from the hypothalamus, in a morning peak and under stress; cortisol feeds back to stop it

Acts on

• Adrenal cortex (cortisol, and some aldosterone and adrenal androgens)
• Melanocytes, weakly, through MC1R

What it does

• Drives cortisol release within minutes and keeps the adrenal cortex from shrinking
• Darkens the skin when very high, which is why Addison’s disease tans
• Rises with any stress, surgery, illness or hypoglycaemia

In medicine

• Measured with cortisol to sort out adrenal failure (high in Addison’s, low in pituitary failure) and Cushing’s syndrome (high from a pituitary or ectopic tumour, suppressed from an adrenal one) ¹
• Tetracosactide (ACTH 1-24, the Synacthen test) is the standard test of adrenal reserve ⁴
• Repository corticotropin gel is approved for infantile spasms and multiple sclerosis relapses, and its label also carries a list of older inflammatory indications, for which it is used at great cost ²

Beyond the body’s own use

• Whether corticotropin gel does more for inflammatory disease than an equivalent dose of a corticosteroid has never been settled by a head-to-head trial, and that is the open question about the drug
• Its infantile-spasms approval came only in October 2010, decades after the gel itself, and that is the indication with modern randomised evidence behind it ²
• Corticotropins and their releasing factors, corticorelin and tetracosactide among them, are banned in sport at all times under section S2 of the Prohibited List ³