To diagnose adrenal and pituitary diseases such as Cushing syndrome, Cushing disease, Addison disease, adrenal tumours, and pituitary tumours; usually done as a diagnostic test once an abnormal cortisol level is detected
ACTH Test
If your doctor has discovered that you have abnormal or inappropriate cortisol levels. ACTH will help to sort out the possible cause of the abnormal cortisol result.
A blood sample taken from a vein in your arm. Samples for ACTH were regarded as unstable but newer evidence has demonstrated that samples are stable for 24h. There may be local variations in collection protocols, so please follow any advice given by your healthcare professional or local laboratory. Samples cannot usually be collected at a GP surgery, and are usually collected in a hospital with a laboratory on site.
Samples for ACTH are typically taken in the morning, about 9 am There may be local variations in collection protocols, so please follow any advice given by your healthcare professional or local laboratory.
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How is it used?
ACTH levels in the blood are tested to help diagnose Cushing syndrome (see below), Addison disease (see below), and tumours of the pituitary and adrenal glands. Measuring both ACTH and cortisol can help sort out some of the causes of these conditions. Because the level of ACTH normally changes in the opposite direction to the level of cortisol, your doctor can learn a lot 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 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 disease (adrenal damage) Low High Hypopituitarism Low Low -
When is it requested?
ACTH test is requested when a patient has signs or symptoms of certain diseases, including Cushing syndrome or Addison disease and has abnormal or inappropriate blood cortisol levels.
Cushing syndrome is a group of disorders caused by too much cortisol. It can cause symptoms such as obesity, a rounded face, fragile and thin skin, purple lines on the tummy, muscle weakness, acne, and increased body hair. It is often seen with other physical and laboratory signs, including high blood pressure, low potassium, high bicarbonate, and high glucose (or even diabetes). When Cushing syndrome is due to a tumour in the pituitary gland that makes ACTH this is referred to as Cushing disease. Other causes of Cushing syndrome include adrenal tumours that make cortisol, tumours in other parts of the body (usually the lungs) that make ACTH (which then stimulates the adrenal glands to make cortisol), and taking high dose steroids prescribed by your doctor.
Addison disease is due to a lack of cortisol, and is found to have 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 nighttime urination, and weight loss. 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.
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What does the test result mean?
ACTH is usually measured 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 concentration in the blood can mean that a patient has Cushing's disease, Addison's disease, or an ectopic ACTH-producing tumour. A decreased ACTH result can suggest an adrenal tumour that is making cortisol or hypopituitarism.
In some cases, the test results do not identify a particular condition. Testing the change in ACTH and/or cortisol when certain drugs are given often may help to clarify the picture allowing 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 (synacthen), 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 strong 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 indentify its cause.
A number of other drugs are sometimes used to help clarify the diagnosis, including insulin, corticotropin releasing hormone (CRH), and metyrapone
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Is there anything else I should know?
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), in addition the progestational drug, megestrol acetate, used in various cancer treatments.
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 samples will normally be collected first thing in the morning.
Secretion of ACTH may be increased by stress, very considerably by severe stress such as childbirth or psychotic illness.
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What is the difference between Cushing's disease and Cushing's syndrome?
Cushing syndrome is caused by too much circulating cortisol. Cushing disease is one type of Cushing syndrome and is due to a tumour in the pituitary gland that makes ACTH. Other causes of Cushing 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.
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What is Addison's disease?
Addison 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. Tuberculosis (or TB) is uncommon in the UK but a common cause of Addison disease in countries where TB is endemic. The lack of cortisol and aldosterone produces symptoms such as weight loss, muscle weakness, tiredness and low blood pressure.
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My doctor told me that my extra ACTH is not produced in my pituitary gland. What is going on?
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When are ACTH precursors measured?
ACTH measurements do not always distinguish between pituitary and ectopic sources of ACTH in Cushing syndrome because of the overlap in ACTH concentrations in these two groups of patients. In these situations measurement of ACTH precursors may be helpful. These are compounds that are larger than ACTH from which the ACTH molecule is made.