What is being tested?

Angiotensin converting enzyme (ACE) is an enzyme produced by vascular endothelial cells to help regulate blood pressure. It catalyses the conversion of angiotensin I (an inactive protein) to angiotensin II. Angiotensin II functions as a strong vasopressor - it causes arteries to contract, making them temporarily narrower and increasing the pressure of the blood flowing through them. ACE is produced throughout the body, but is especially concentrated in the lungs. It is normally found in high levels in the blood in those less than 20 years of age, but then drops to a relatively stable lower level in healthy adults.

Increased amounts of ACE are sometimes secreted by cells found at the margins (outside borders) of granulomas. Granulomas are small tumour-like masses of immune and inflammatory cells and fibrous tissue that create bumps under the skin and throughout the body. They are a classic feature of sarcoidosis, a systemic disorder of unknown cause that often affects the lungs but may also affect many other body organs including the eyes, skin, nerves, liver and heart. ACE levels often increase when granulomas develop. About 50-80% of patients with active sarcoidosis will have elevated levels of ACE; levels that will rise and fall with disease activity.

Granulomas, fibrosis and elevated ACE levels may also be seen with infectious disorders, such as leprosy and tuberculosis (the granulomas form around the invading mycobacteria) and with exposure to irritant particle poisons such as beryllium, asbestos, and silicon (with current worker protection, these causes are relatively rare).

How is it used?

ACE is primarily ordered to help diagnose and monitor sarcoidosis. It is often ordered as part of an investigation into the cause of a group of troubling chronic symptoms that may or may not be due to sarcoidosis. ACE will be elevated in 50% to 80% of patients with active sarcoidosis. If it is initially elevated in someone with sarcoidosis, ACE can be ordered at regular intervals to monitor the course of the disease and the effectiveness of corticosteroid treatment.

When is it requested?

ACE is ordered when you have signs or symptoms such as granulomas, a chronic cough or shortness of breath, red watery eyes, and/or joint pain that may be due to sarcoidosis or to another disorder. This is especially true if you are between 20 and 40 years of age, when sarcoidosis is most frequently seen. Your doctor may order ACE, along with other tests such as an Acid fast bacilli (AFB) culture or sputum culture (tests that can detect mycobacterial and fungal infections), when it is necessary to differentiate between sarcoidosis and another granulomatous condition.

If you have been diagnosed with sarcoidosis and your initial ACE levels were elevated, your doctor may order ACE testing at regular intervals to monitor their change over time.

What does the result mean?

Serum ACE levels are a nonspecific indicator of granulomatous disease. They do not tell you why the levels are elevated, what organs and/or body systems are involved, or to what degree. ACE does not cause granulomas, but it often reflects their presence.

If ACE levels are high, other diseases have been ruled out, and you have clinical findings consistent with sarcoidosis, then it is likely that you have an active case of sarcoidosis. About 20-50% of the time, however, sarcoidosis can be present without elevated ACE levels. This may be due to the disease being in an inactive state, due to early detection of sarcoidosis (before the levels have risen), or due to the granuloma cells not secreting increased amounts of ACE. ACE levels are also less likely to be elevated in those with chronic sarcoidosis.

High levels of ACE which then fall generally indicate improvement in the disease, either due to treatment or to the spontaneous remission of the sarcoidosis. Rising levels of ACE on the other hand, may indicate either an early disease process, or disease activity that is not responding to therapy.

ACE levels are often higher in healthy children and young adolescents than in adults, and do not, generally, indicate sarcoidosis.

Is there anything else I should know?

Conversion of angiotensin I to angiotensin II by ACE is a normal regulatory process in the body. This process has been targeted by the development of drugs called ACE inhibitors that are commonly used in treating hypertension and diabetes. These drugs inhibit the conversion process, keeping the blood vessels more dilated and the blood pressure lower. ACE inhibitors are useful in managing hypertension, but they are not monitored with ACE blood tests. They may, however, interfere with ACE measurements ordered for other reasons.

Haemolysis and hyperlipidaemia in the blood sample may falsely decrease ACE levels. Decreased ACE levels may also be seen in patients with:

• Chronic obstructive pulmonary disease (COPD)
• Emphysema
• Lung cancer
• Starvation
• Steroid drug therapy
• Hypothyroidism

ACE has been found in moderately increased levels in a variety of diseases and disorders such as:

• HIV
• Certain fungal diseases
• Diabetes mellitus
• Hyperthyroidism
• Lymphoma
• Alcoholic cirrhosis
• Gaucher’s disease (a rare inherited lipid metabolism disorder)
• Tuberculosis
• Leprosy
  The ACE test, however, is not routinely used to diagnose or monitor these conditions as it has not been shown to be clinically useful.

Common questions

• What other tests are used to diagnose sarcoidosis?

A variety of tests may be ordered, both to help diagnose sarcoidosis and to determine the degree of organ involvement. Laboratory tests may include liver function tests, FBC, and calcium (blood and urine levels tend to be elevated). Other tests may include a physical examination (for skin lesions) pulmonary function tests (about 90% of the time there will be some amount of lung involvement with sarcoidosis), bronchoscopy (passing a flexible tube that is used to look at the lining of the airway and to biopsy the lung), chest x-ray, and gallium scan (radioactive gallium is used to evaluate inflammation). Biopsies of the skin, lungs, lymph nodes and sometimes liver may also be needed, as may a thorough eye examination (a test called a slit-lamp examination may be used).

• What causes sarcoidosis?

The cause is not well understood. It is not contagious. It is inflammatory and involves the immune system. It appears to have a genetic component as well as an environmental one. It has been reported both in related and unrelated individuals living in the same area. About 20-40 people per 100,000 are affected in the population, the majority of them between 20 and 40 years old. In the U.S.A. sarcoidosis is more common in those of African descent. It is not uncommon in Scandinavia and Ireland, but unusual in Asians and Australian aborigines. For some reason, those who have moved from a part of the world where the prevalence is low to a part of the world where it is high tend to take on the risk of the higher prevalence area.

• What is the long-term prognosis for sarcoidosis?

The majority of those with sarcoidosis recover from this disease over a period of several months to a couple of years, but some may suffer permanent scarring in their lungs. Early detection can help better manage the disease although many cases resolve themselves without any treatment.

More information

RCPA Manual: Angiotensin converting enzyme