ACTH levels in the blood are measured to help detect, diagnose, and monitor conditions associated with excessive or deficient cortisol in the body. These conditions include:

Cushing’s disease: excess cortisol that is due to an ACTH-producing tumor in the pituitary gland (usually a benign tumor)

Cushing's syndrome: refers to the symptoms and signs associated with excess exposure to cortisol. In addition to Cushing’s disease, Cushing’s syndrome may be due to an adrenal tumor, adrenal hyperplasia, the use of steroid medications, or due to an ACTH-producing tumor that is located outside the pituitary (such as in the lungs).

Addison's disease, primary adrenal insufficiency: decreased cortisol production due to adrenal gland damage

Secondary adrenal insufficiency: decreased cortisol production because of pituitary dysfunction

Hypotituitarism: pituitary dysfunction or damage that leads to decreased (or no) hormone production by the pituitary – including ACTH production

Measuring both ACTH and cortisol can help to differentiate among some of these conditions. Because the level of ACTH normally changes in the opposite direction to the level of cortisol, your doctor can learn much by identifying an imbalance in this relationship and the direction in which the imbalance occurs. The table below indicates the common patterns of ACTH and cortisol seen with different diseases involving the adrenal and pituitary glands.

Disease	Cortisol	ACTH
Cushing's disease (pituitary tumor making ACTH)	High	High
Adrenal tumor	High	Low
"Ectopic" ACTH (ACTH made by a tumor outside the pituitary, usually in the lung)	High	High
Addison's disease (adrenal damage)	Low	High
Hypopituitarism	Low	Low

This test is ordered when a patient has signs or symptoms associated with excess or deficient cortisol.

Too much cortisol often causes symptoms such as obesity (especially if it spares the arms and legs), a rounded face, fragile and thin skin, purple lines on the abdomen, muscle weakness, acne, and increased body hair. It is often accompanied by findings such as high blood pressure, low potassium, high bicarbonate, and high glucose (or even diabetes).

Patients with insufficient cortisol production may exhibit symptoms such as muscle weakness, fatigue, weight loss, increased skin pigmentation (even in areas not exposed to the sun), and loss of appetite. This is often accompanied by findings such as low blood pressure, low blood glucose, low sodium, high potassium, and high calcium.

Symptoms suggestive of hypopituitarism include loss of appetite, fatigue, irregular menstrual cycle, hypogonadism, decreased sex drive, frequent nighttime urination, and weight loss. When the condition is due to a pituitary tumor (usually benign), the patient may also have symptoms associated with the compression of nearby cells and nerves. The tumor can affect the nerves controlling vision, causing symptoms such as "tunnel vision" (inability to see things off to the side), loss of vision to some localized areas, and double vision, and can cause a change in a pattern of headaches.

Changes in ACTH and cortisol are usually evaluated together, as shown in the table above.

An increased ACTH result can mean that a patient has Cushing's disease, Addison's disease, or ectopic ACTH-producing tumors. A decreased ACTH result can be due to an adrenal tumor, steroid medication, or hypopituitarism.

In some cases, the interpretation of the results can be complex. Concentrations of both ACTH and cortisol vary throughout the day. Normally, ACTH will be at its highest level in the morning and lowest at night. It will stimulate cortisol production, which will follow the same pattern but will rise after ACTH does and fall to its lowest level very late in the evening. Conditions that affect the production of ACTH and cortisol often disrupt this diurnal variation (daily pattern).

Testing the change in cortisol when certain drugs are given often helps to clarify the picture and allows the doctor to make the right diagnosis. The most commonly used drugs are cortrosyn (cosyntropin, a drug form of ACTH) for an ACTH stimulation test and dexamethasone for a dexamethasone suppression test.

Cortrosyn, like ACTH, stimulates the adrenal glands to make cortisol. If cortisol levels don't rise after cortrosyn is given, this indicates adrenal failure as can occur in Addison's disease or hypopituitarism.

Dexamethasone is a very potent drug that acts like cortisol. In normal people, it should stop ACTH production. By testing the ability of different doses of dexamethasone to stop ACTH production, it is often possible to tell if the patient has Cushing's syndrome and help determine its cause.

A number of other drugs are sometimes used, including insulin, corticotropin releasing hormone, and metyrapone (metapyrone).

Some drugs and conditions can cause ACTH levels to rise, including amphetamines, insulin, levodopa, metoclopramide, and RU 486.

Drugs that cause ACTH to fall include dexamethasone and other drugs that act like cortisol (including prednisone, hydrocortisone, prednisolone, and methylprednisolone), and megestrol acetate.

Secretion of ACTH may be increased by stress.

ACTH has also been used as a drug to treat Multiple Sclerosis.