Angiotensin-Converting Enzyme (ACE)

The angiotensin-converting enzyme (ACE) test 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 are possibly due to sarcoidosis.

Sarcoidosis is a disorder in which small nodules called granulomas may form under the skin and in organs throughout the body. The cells surrounding granulomas can produce increased amounts of ACE and the blood level of ACE may increase when sarcoidosis is present. (See the “What is being tested?” section for more on this.)

The blood level of ACE tends to rise and fall with disease activity. If ACE is initially elevated in someone with sarcoidosis, the ACE test can be used to monitor the course of the disease and the effectiveness of corticosteroid treatment.

A health practitioner may order ACE along with other tests, such as AFB tests that detect mycobacterial infections or fungal tests. This may help to differentiate between sarcoidosis and another condition causing granuloma formation.

An ACE test is ordered when someone has signs or symptoms that may be due to sarcoidosis, such as:

• Granulomas
• A chronic cough or shortness of breath
• Red, watery eyes
• Joint pain

This is especially true if the person is between 20 and 40 years of age, when sarcoidosis is most frequently seen.

When someone has been diagnosed with sarcoidosis and initial ACE levels were elevated, a health practitioner may order ACE testing at regular intervals to monitor the change in ACE over time as a reflection of disease activity.

An increased ACE level in a person who has clinical findings consistent with sarcoidosis means that it is likely that the person has an active case of sarcoidosis, if other diseases have been ruled out. ACE will be elevated in 50% to 80% of those with active sarcoidosis. The finding of a high ACE level helps to confirm the diagnosis.

A normal ACE level cannot be used to rule out sarcoidosis because sarcoidosis can be present without an elevated ACE level. Findings of normal ACE levels in sarcoidosis may occur if the disease is in an inactive state, may reflect early detection of sarcoidosis, or may be a case where the cells do not produce increased amounts of ACE. ACE levels are also less likely to be elevated in cases of chronic sarcoidosis.

When monitoring the course of the disease, an ACE level that is initially high and then decreases over time usually indicates spontaneous or therapy-induced remission and a favorable prognosis. A rising level of ACE, on the other hand, may indicate either an early disease process that is progressing or disease activity that is not responding to therapy.

ACE assists in 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. This conversion is a normal regulatory process in the body. The 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.

High and low levels of ACE may be seen in a variety of conditions other than sarcoidosis. The ACE test, however, is not routinely used to diagnose or monitor these conditions; it has not been shown to be clinically useful.

Decreased ACE levels may also be seen in people with:

• Chronic obstructive pulmonary disease (COPD)
• Lung diseases such as emphysema, lung cancer, cystic fibrosis
• Starvation
• Steroid drug therapy
• Hypothyroidism

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

• HIV
• Histoplasmosis (fungal respiratory infection)
• Diabetes mellitus
• Hyperthyroidism
• Lymphoma
• Alcoholic cirrhosis
• Gaucher disease (a rare inherited lipid metabolism disorder)
• Tuberculosis
• Leprosy

A variety of tests may be ordered, both to help diagnose sarcoidosis and to determine the degree of organ involvement. Laboratory tests may include a liver panel, complete blood count (CBC), and calcium (both blood and urine levels may be elevated). Other tests may include a physical exam for skin lesions, pulmonary function tests as about 90% of the time there will be some degree of lung involvement, bronchoscopy (a procedure that uses a flexible tube to look at the lining of the airway and to biopsy the lung), chest x-ray, and gallium screening (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 exam. A test called a slit-lamp examination may be used.

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. Up to 40 people per 100,000 are affected in the U.S., the majority of them between 20 and 40 years old. In the U.S. and in the Caribbean, sarcoidosis is more common in those of African descent, but worldwide about 80% of those with sarcoidosis are white. It is relatively common in Scandinavia and Northern Ireland, but rare in China, Japan, and Africa. 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.