ACTH levels in the blood are tested to help diagnose Cushing's syndrome (see below), Addison's disease (see below), and tumours of the pituitary and adrenal glands. 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. For example, if your cortisol level is high and your ACTH level is also increased, that would indicate that there is a pituitary disease that causes production of too much ACTH.

The table below indicates the common patterns of ACTH and cortisol in different diseases involving the adrenal and pituitary glands.
 

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

This test is requested when a person has signs or symptoms of certain diseases, including Cushing's syndrome or Addison's disease and has abnormal blood cortisol levels.

Cushing's syndrome, caused by too much cortisol, can cause symptoms such as obesity, a rounded face, fragile and thin skin, purple lines on the abdomen, muscle weakness, acne, and increased body hair. It is often accompanied by physical and laboratory signs, including high blood pressure, low potassium, high bicarbonate, and high glucose (or even diabetes). Cushing's disease refers to Cushing's syndrome due to a tumour in the pituitary gland that makes ACTH. Other causes of Cushing's syndrome include adrenal tumours that make cortisol, tumours in other parts of the body (usually the lungs) that make ACTH, and taking high dose steroids prescribed by your doctor.

Addison's disease is due to a lack of cortisol, and presents with symptoms such as muscle weakness, tiredness, weight loss, increased skin pigmentation (even in areas not exposed to the sun) and loss of appetite, often accompanied by laboratory and physical signs such as low blood pressure, low blood glucose, low sodium, high potassium, and high calcium.

Congenital Adrenal Hyperplasia (CAH) is due to an inherited defect in producing cortisol. ACTH may be measured in children suspected of having this condition.

Findings suggestive of hypopituitarism (usually due to a benign tumour that reduces pituitary gland secretion) include loss of appetite, tiredness, irregular menstrual cycle, hypogonadism (lower levels of sex hormones), decreased sex drive, frequent night time urination, and weight loss. The tumours can also block the nerves controlling vision, causing symptoms such as "tunnel vision" (inability to see things off to the side), loss of vision to some localised areas, and double vision and headaches.

ACTH is usually requested if you are found to have low cortisol or have signs or symptoms that suggest adrenal or pituitary disease. 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 an ectopic ACTH-producing tumour. A decreased ACTH result can mean an adrenal tumour that is making cortisol or hypopituitarism.

In some cases, the test results are not clear enough to interpret. Testing the change in ACTH and/or 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 tetracosactide (trade name Synacthen, a drug form of ACTH) and dexamethasone.

• Tetracosactide, like ACTH, should normally tell the adrenal glands to make cortisol. If cortisol levels don't rise after tetracosactide 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.

About Reference Intervals

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

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

The concentration of ACTH varies greatly at different times of the day, with the highest amount at about 8 am and the lowest about midnight, therefore the sample will normally be collected first thing in the morning.

Secretion of ACTH may be increased by stress.

Cushing's syndrome is caused by having too much cortisol. Cushing's disease is when Cushing's syndrome is due to a tumour in the pituitary gland that makes ACTH. Other causes of Cushing's syndrome include adrenal tumours that make cortisol, tumours in other parts of the body (usually the lungs) that make ACTH, and after taking high dose steroids prescribed by your doctor.

Addison's disease is caused by the destruction of the part of the adrenal gland that makes the hormones cortisol and aldosterone. This is often due to autoimmune disease. The lack of cortisol and aldosterone produces symptoms such as weight loss, muscle weakness, tiredness and low blood pressure.

Another way your body can make ACTH is called 'ectopic production'. This means that ACTH is made from tumours elsewhere in the body, usually (but not always) in the lungs. This causes Cushing's syndrome and may alert your doctor to the presence of a tumour.