Adrenocorticotropic Hormone (ACTH)

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

• Cushing disease: excess cortisol that is due to an ACTH-producing tumor in the pituitary gland (usually a benign tumor)
• Cushing syndrome: refers to the symptoms and signs associated with excess cortisol; in addition to Cushing disease, Cushing syndrome may be due to an adrenal tumor, adrenal hyperplasia, the use of steroid medications, or due to an ACTH-producing tumor located outside the pituitary (ectopic), such as in the lungs.
• Addison disease (primary adrenal insufficiency): decreased cortisol production due to adrenal gland damage
• Secondary adrenal insufficiency: decreased cortisol production because of pituitary dysfunction
• Hypopituitarism: 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.

If abnormal levels are detected, a healthcare practitioner will do additional testing to help confirm the findings and help determine the cause.

An ACTH test may be ordered after a cortisol test reveals abnormal results and when someone has signs or symptoms associated with excess or deficient cortisol.

Too much cortisol can cause symptoms that include:

• Obesity, with majority of the weight on the trunk of the body and not the arms and legs
• Fat collection between the shoulders
• Rounded, red face
• Fragile and thin skin
• Purple lines on the abdomen
• Muscle weakness
• Acne
• Skin infections
• Increased body hair
• Fatigue

These are often accompanied by findings such as high blood pressure, low potassium, high bicarbonate, high glucose levels, and sometimes diabetes.

People 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
• Loss of appetite
• Diarrhea, nausea and vomiting
• Dizziness
• Salt cravings

These are often accompanied by findings such as low blood pressure, low blood glucose, low sodium, high potassium, and high calcium.

Symptoms suggestive of hypopituitarism typically include several of the following:

• Loss of appetite
• Fatigue
• Irregular menstrual cycle
• Dysfunction of sex organs (hypogonadism)
• Decreased sex drive
• Frequent nighttime urination
• Unexplained weight loss
• Hot flashes
• Cold sensitivity

When the condition is due to a pituitary tumor (usually benign), the affected person may also have symptoms associated with the compression of nearby cells and nerves. For example, the tumor can cause a change in a pattern of headaches. It can also 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, or double vision.

In many cases, the interpretation of the results can be complex. Levels 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 daily 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.

Results of ACTH and cortisol tests are often evaluated together. The table below indicates the common patterns of ACTH and cortisol seen with different diseases involving the adrenal and pituitary glands.

An increased ACTH result can mean that a person has Cushing disease, Addison disease, overactive, tumor-forming endocrine glands (multiple endocrine neoplasia), or ectopic ACTH-producing tumors.

A decreased ACTH result can be due to an adrenal tumor, steroid medication, or hypopituitarism.

It is impossible to reliably distinguish Cushing disease and ectopic ACTH from cortisol and ACTH measurement alone. A variety of other tests are often used to assist health care practitioners in making this distinction. Testing the change in the level of cortisol when certain drugs are given to stimulate or suppress hormone production often helps the health care practitioner make the right diagnosis.

While ACTH is still used to diagnose adrenal insufficiency (Addison disease), the ACTH stimulation test is the preferred diagnostic test, when available.

Taking certain medications such as any steroid, oral, inhaled, topical or eye drop may cause abnormal results. Megestrol acetate can also cause abnormal results. Mifepristone (RU486) is a glucocorticoid receptor antagonist and, as such, likely causes changes to ACTH levels.

Stress may increase ACTH secretion.

ACTH has also been used therapeutically as a drug to treat multiple sclerosis and infantile spasms.

Cushing disease is caused by a pituitary gland tumor (usually benign) that over-secretes the hormone ACTH, thus overstimulating the adrenal glands’ cortisol production. Cushing syndrome refers to the signs and symptoms associated with excess cortisol in the body, regardless of the cause. In addition to a pituitary tumor, taking steroid hormones (often used to treat cancer or autoimmune diseases), adrenal gland tumors, and ACTH-producing tumors outside the pituitary gland can cause Cushing syndrome.

Addison disease is a condition caused by damage or destruction of the adrenal cortex. This damage leads to lack of cortisol and other adrenal steroids. It is typically felt to be an autoimmune condition.

In addition to an excess of ACTH from the pituitary gland, it can also come from elsewhere in the body. This is known as ectopic production of ACTH, which comes from tumors elsewhere in the body, usually (but not always) in the lungs. This causes Cushing syndrome and may alert your health care practitioner to the presence of a non-cancerous tumor.