From the Guidelines
Elevated angiotensin-converting enzyme (ACE) levels are most commonly associated with sarcoidosis, as stated 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, where serum ACE is the most widely used laboratory test for investigation, and elevated levels are usually associated with more aggressive disease and multiple-organ involvement 1
- Other conditions such as tuberculosis, silicosis, asbestosis, berylliosis, hyperthyroidism, Gaucher's disease, leprosy, and certain fungal infections like histoplasmosis and coccidioidomycosis
- Liver diseases like cirrhosis, hepatitis, and alcoholic liver disease, which may elevate ACE levels due to impaired clearance
- Certain malignancies, particularly lymphomas and lung cancer
- Diabetes mellitus, especially with microvascular complications, associated with higher ACE levels
- Medications like corticosteroids that can affect ACE levels, while ACE inhibitors decrease measured ACE activity
Clinical Considerations
It's crucial to consider these various causes alongside clinical presentation and other diagnostic findings when interpreting ACE levels. Additionally, ACE levels can be elevated in healthy individuals due to genetic polymorphisms, and levels tend to be higher in children and young adults compared to older adults. The 2017 ACC/AHA/HFSA focused update on the management of heart failure provides insights into the role of ACE inhibitors in reducing morbidity and mortality in heart failure with reduced ejection fraction (HFrEF) 1, but this does not directly relate to the causes of elevated ACE levels.
Diagnostic Approach
When evaluating elevated ACE levels, a comprehensive diagnostic approach should be taken, considering the patient's clinical history, physical examination, and other laboratory and imaging findings to determine the underlying cause. This approach will help guide appropriate management and treatment.
From the Research
Causes of Elevated ACE Levels
Elevated Angiotensin-Converting Enzyme (ACE) levels can be caused by various factors, including:
- Sarcoidosis: a disease characterized by the formation of granulomas in various organs, particularly the lungs and lymph nodes 2, 3, 4.
- Familial ACE hyperactivity: a rare, benign condition that can cause extremely elevated ACE activity 3.
- Other diseases: such as tuberculosis and histoplasmosis, which can manifest similarly to sarcoidosis and may be related to the development of sarcoidosis 5, 6.
Disease Associations
The following diseases have been associated with elevated ACE levels:
- Sarcoidosis: elevated ACE levels are found in 60-70% of patients with sarcoidosis 3.
- Tuberculosis: may be related to the development of sarcoidosis, particularly in countries with high tuberculosis burden 5.
- Histoplasmosis: may be associated with sarcoidosis, and fibrosing mediastinitis is a common feature of both diseases 6.
Clinical Implications
Elevated ACE levels can have significant clinical implications, including:
- Diagnosis of sarcoidosis: ACE levels can be used as a diagnostic aid, but have limited sensitivity and specificity 4.
- Differential diagnosis: elevated ACE levels can be seen in other diseases, such as tuberculosis and histoplasmosis, making differential diagnosis challenging 5, 6.
- Treatment: ACE levels can be used to monitor treatment response in sarcoidosis, but may not be affected by steroid therapy 2.