Cortisol Axis Testing

Cortisol production runs along the hypothalamic-pituitary-adrenal (HPA) axis. Hypothalamic corticotropin-releasing hormone (CRH) stimulates pituitary adrenocorticotropic hormone (ACTH), and ACTH stimulates the adrenal cortex to release cortisol. Rising cortisol should then suppress CRH and ACTH production. Dexamethasone suppression testing asks whether this feedback brake works. Dexamethasone acts like cortisol at the hypothalamus and pituitary; a healthy axis responds by reducing ACTH drive, so endogenous cortisol falls. Failure to suppress raises concern for endogenous cortisol excess. ACTH stimulation testing asks a different question: can the adrenal cortex produce cortisol when directly stimulated? Synthetic ACTH, called cosyntropin or tetracosactide, should trigger an adequate cortisol rise if the adrenal cortex has sufficient reserve. This makes stimulation testing useful when adrenal insufficiency is suspected. The test direction is a useful memory aid: - Cortisol excess: suppress the axis. - Cortisol deficiency: stimulate the adrenal gland.