ACTH

ACTH (short for adrenocorticotropic hormone) is made by the pituitary gland, a small organ in the brain. Its job is to tell your adrenal glands (which sit on top of your kidneys) to make cortisol, a hormone essential for managing stress, energy, blood sugar, blood pressure, and inflammation.

This whole system is called the hypothalamic-pituitary-adrenal (HPA) axis. When cortisol drops, the brain signals the pituitary to release more ACTH. When cortisol is high, ACTH shuts down. This cycle is known as negative feedback, and it helps the body stay balanced.

The ACTH plasma test measures how much ACTH is in your blood, usually in the early morning when levels are naturally highest. It’s most often used to figure out why cortisol is low, whether the problem lies in the adrenal glands themselves (called primary adrenal insufficiency, or Addison’s disease), or in the brain’s signaling system (called central adrenal insufficiency, which includes both pituitary and hypothalamus problems).

Here’s how results are typically interpreted:

• High ACTH + low cortisol → The adrenal glands aren’t responding → Primary adrenal insufficiency
• Low or normal ACTH + low cortisol → The brain isn’t sending enough signal → Central adrenal insufficiency
• In-between ACTH → May need further testing (like aldosterone, renin, or electrolyte levels)

This test should be done before starting steroids, because glucocorticoids (like prednisone) can artificially lower ACTH levels. If steroids are already being used, the blood should be drawn before the morning dose.

ACTH is also involved in other body functions. It can increase skin pigmentation (which is why people with Addison’s may get darker skin), and it may affect brain areas linked to stress and emotion, like the amygdala.

Several other hormones regulate ACTH, including:

• CRH (corticotropin-releasing hormone) and AVP (arginine vasopressin), which boost ACTH release
• ANF (atrial natriuretic factor), which can reduce it

By measuring ACTH, you can determine not only whether there’s adrenal failure, but where the problem starts. This distinction guides treatment—whether to replace just cortisol, or both cortisol and other adrenal hormones like aldosterone.