ACE (angiotensin-converting enzyme)

What is being tested? Angiotensin converting enzyme (ACE) is produced by endothelial cells to regulate blood pressure. It is an enzyme that catalyses the conversion of angiotensin I (an inactive protein) into angiotensin II, which acts as a vasopressor, causing the arteries to constrict, temporarily making them narrower and raising the pressure of the blood within them. ACE is produced throughout the body but is particularly concentrated in the lungs. It is found at high concentrations in people under 20; after the age of 20 levels fall and stabilise at a lower level. High levels of ACE are sometimes secreted by the cells at the outer edges of granulomas. Granulomas are small masses of tumour-like tissue made up of inflammatory, immune and fibrous cells that form swellings under the skin and in other parts of the body. They are a characteristic feature of sarcoidosis, a systemic disease of unknown origin that often affects the lungs but can affect any other organ, including the eyes, skin, nerves, liver and heart. ACE levels often rise when granulomas develop. About 50-80% of patients with active sarcoidosis have raised ACE levels, which rise and fall with the course of the disease. Granulomas, fibrosis and raised ACE levels can also be found in other diseases such as leprosy and tuberculosis (granulomas form around the site of bacterial infection) and after exposure to irritant poisons such as beryllium, asbestos and silicone (under current workplace regulations these causes are fairly rare). How is the sample collected for testing? A blood sample is taken from a vein in the arm.

How is it used? When is it requested? What does the result mean? Is there anything else I should know? How is it used? ACE is mainly used to diagnose and monitor sarcoidosis. It is often requested when certain chronic symptoms that could point to sarcoidosis are present. ACE is raised in 50-80% of patients with active sarcoidosis. If it is raised at the start of the disease, regular checks will be requested to monitor the course of the disease and the effectiveness of corticosteroid treatment. When is it requested? ACE is requested when there are signs or symptoms such as granulomas, chronic cough, shortness of breath, red eyes and/or joint pain that could be related to sarcoidosis or another disease. This is most common in people aged 20 to 40. Your doctor may request ACE together with other tests, such as a sputum culture for acid-fast bacilli (AFB) (a test for fungal and mycobacterial infections), to distinguish between sarcoidosis and other granulomatous diseases. If you have been diagnosed with sarcoidosis and your initial ACE levels are raised, your doctor may request ACE at regular intervals to assess how it changes and therefore how the disease is progressing. What does the result mean? If you are under 20, raised ACE values are common and not significant. If you are over 20, plasma ACE levels are not specific indicators: they do not show why they are raised, or which organ or system is involved and how severely. ACE does not cause granulomas but is often a sign that they are present. If ACE levels are raised, other diseases have been ruled out and you have the clinical signs of sarcoidosis, you are likely to have active sarcoidosis. In 20-50% of cases sarcoidosis occurs without a rise in ACE levels. This can happen when the disease is inactive, when sarcoidosis has been diagnosed early before plasma levels have risen, or when the cells do not secrete large amounts of ACE. ACE levels are rarely raised in chronic sarcoidosis. What matters in sarcoidosis is the initial ACE value and whether it falls spontaneously or in response to treatment. A fall in levels generally indicates a good prognosis. A rise in levels, on the other hand, may indicate either an early disease process or active disease that is not responding to treatment. Is there anything else I should know? ACE converts angiotensin I into angiotensin II, a normal physiological process in the body. It is the target of some medicines, ACE inhibitors, used to treat high blood pressure and diabetes. These medicines block the conversion so that the blood vessels stay more dilated and blood pressure stays lower. ACE inhibitors are useful to control blood pressure but are not taken into account in ACE testing: taking these medicines may interfere with the results of an ACE test requested for other reasons. Haemolysis (breakdown of red blood cells) and hyperlipidaemia (excess lipids) in the sample may falsely lower the results. Decreased ACE levels can also be found in the following patients:

• chronic obstructive pulmonary disease (COPD)
• cystic fibrosis
• emphysema
• lung cancer
• malnutrition
• steroid therapy
• hyperthyroidism

ACE levels have been found to be moderately raised in many diseases, such as:

• HIV infection
• some fungal infections
• diabetes mellitus
• hyperthyroidism
• lymphoma
• alcoholic cirrhosis
• Gaucher disease (a rare inherited disorder of lipid metabolism)

ACE testing is not used routinely to diagnose and monitor these diseases (its clinical usefulness has not been demonstrated

1. What other tests are used to diagnose sarcoidosis? 2. What causes sarcoidosis? 3. What is the long-term outlook? 1. What other tests are used to diagnose sarcoidosis? A number of tests may be requested, both for diagnosis and to determine how far the organ concerned is involved. Laboratory tests include liver enzymes, a full blood count and serum and urine calcium. Other tests include a clinical examination of skin lesions, lung function tests (the lungs are at least partly involved in 90% of cases of sarcoidosis), bronchoscopy (a thin, flexible endoscope is used to look deep into the lungs and take biopsies), a chest X-ray and a gallium scan (the radioactive element gives information on inflammation). Biopsies of the skin, lung, lymph nodes and sometimes the liver may be needed, as well as an eye examination. 2. What causes sarcoidosis? The cause of the disease is not well understood; it is not contagious and is an inflammatory disease involving the immune system. It also seems to have both a genetic and an environmental component. It is found in both blood relatives and unrelated people living in the same geographical area. In the United States the incidence is 10-40 people per 100,000, and most of them are aged between 20 and 40. In the United States and the Caribbean sarcoidosis is more common among African Americans, while worldwide about 80% of patients are white. It is relatively common in Scandinavia and Northern Ireland but rare in China, Africa and Japan. Because of migration, people who move from a low-prevalence area to a high-prevalence one tend to take on the risk of the latter. 3. What is the long-term outlook? Most patients with sarcoidosis recover over a period ranging from several months to a couple of years, but some will have permanent scarring in their lungs. Early diagnosis helps speed up treatment, although in many cases the disease resolves on its own.