From the Guidelines
Elevated Angiotensin-Converting Enzyme (ACE) levels are most commonly associated with sarcoidosis, a complex disease characterized by the formation of non-caseating granulomas, which produce excess ACE, as noted in the 2020 European position paper on rhinosinusitis and nasal polyps 1.
Causes of Elevated ACE Levels
The causes of elevated ACE levels can be multifaceted, including:
- Sarcoidosis, which is the most well-known association, with ACE levels typically increased in about 60-80% of patients with active sarcoidosis, as the granulomas produce excess ACE.
- Other conditions such as tuberculosis, silicosis, asbestosis, berylliosis, hyperthyroidism, Gaucher's disease, leprosy, diabetes mellitus, and certain liver diseases like primary biliary cirrhosis.
- Medications, particularly ACE inhibitors, which can artificially lower levels, potentially masking elevations.
Clinical Considerations
It's essential to consider that ACE levels can vary with age and genetic factors, with children typically having higher levels than adults. While elevated ACE levels can suggest certain conditions, they are not specific enough for definitive diagnosis and should be interpreted alongside clinical presentation and other diagnostic tests, as outlined in the 2020 American Thoracic Society clinical practice guideline for the diagnosis and detection of sarcoidosis 1.
Diagnostic Approach
For example, in suspected sarcoidosis, ACE levels may be used to monitor disease activity and treatment response rather than as a standalone diagnostic tool. The diagnosis of sarcoidosis requires a combination of clinical, radiological, and histological evidence of non-caseating granulomas, as well as the consideration of other conditions that may mimic sarcoidosis, such as Erdheim-Chester disease, granulomatosis with polyangiitis, and IgG4-related disease 1.
From the Research
Causes of Elevated Angiotensin-Converting Enzyme (ACE) Levels
Elevated ACE levels can be caused by various factors, including:
- Sarcoidosis: a condition characterized by the growth of granulomas in various parts of the body, which can lead to elevated ACE levels 2, 3, 4, 5, 6
- Non-Hodgkin's lymphoma: a type of cancer that can cause elevated ACE levels 3
- Cirrhosis: a condition characterized by scarring of the liver, which can lead to elevated ACE levels 3
- Interstitial lung disease: a condition characterized by inflammation and scarring of the lungs, which can cause elevated ACE levels 3
- Familial ACE hyperactivity: a rare genetic condition that can cause extremely elevated ACE levels 4
- Cardiac sarcoidosis: a condition characterized by the growth of granulomas in the heart, which can cause elevated ACE levels, although this is not a sensitive marker for the disease 5
- Hypercalcemic disorders: conditions characterized by elevated calcium levels in the blood, such as primary hyperparathyroidism and oncogenic hypercalcemia, which can also cause elevated ACE levels 6
Disease-Specific ACE Level Elevations
- Sarcoidosis: ACE levels are elevated in 60-70% of patients with sarcoidosis, and extremely elevated ACE activity is suggestive of familial ACE hyperactivity 2, 4
- Cardiac sarcoidosis: ACE levels are elevated in only approximately 6.7% of patients with biopsy-proven cardiac sarcoidosis, making it an insensitive serological tool for diagnosis 5
- Hypercalcemic disorders: ACE activity is not a specific test for the differential diagnosis of hypercalcemia, but it remains useful as a chemical marker of successful treatment of sarcoidosis 6