Angiotensin Converting Enzyme (ACE)

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Sarcoidosis is an inflammatory disease that leads to granuloma formation, especially in the lungs and lymph nodes. Granulomas release excess ACE, making it a useful biomarker.

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Angiotensin Converting Enzyme (ACE) Test Guide

Why is it done?
- Diagnosis and monitoring of sarcoidosis, a multisystem inflammatory disease characterized by granuloma formation
- Evaluation of pulmonary fibrosis and chronic lung diseases with suspected granulomatous involvement
- Assessment of disease activity and progression in sarcoidosis and related granulomatous conditions
- Monitoring response to treatment with corticosteroids and other immunosuppressive therapies
- Detection of complications including hypercalcemia, kidney involvement, and cardiac manifestations
- Investigation of unexplained fever, weight loss, and constitutional symptoms with suspected granulomatous disease
- Differential diagnosis between sarcoidosis and other granulomatous conditions such as tuberculosis or fungal infections
Normal Range
- Typical Normal Range: 8-52 units per liter (U/L) or 11-82 nanomoles per minute per milliliter (nmol/min/mL). Note: Reference ranges may vary by laboratory and testing method used
- Normal Result: ACE levels within the reference range suggest absence of significant granulomatous disease or sarcoidosis. The lungs, kidneys, and liver are functioning normally without evidence of inflammatory granuloma formation
- Elevated ACE (Above Upper Limit): Suggests active granulomatous inflammation, most commonly associated with sarcoidosis. Higher elevations may indicate more extensive disease or acute inflammatory activity
- Borderline/Mildly Elevated: May indicate early or low-burden granulomatous disease, or may be related to other conditions. Clinical correlation and additional testing are recommended
- Units of Measurement: U/L (units per liter) in most laboratories; some labs report in nmol/min/mL or international units
- Clinical Significance: ACE is produced by granulomas and activated macrophages; elevated levels correlate with granuloma burden but are not specific to sarcoidosis alone
Interpretation
- Moderately Elevated ACE (1-2 times upper limit of normal): Suggests possible sarcoidosis or other granulomatous conditions. Requires clinical correlation with symptoms, imaging findings, and tissue biopsy results for definitive diagnosis
- Significantly Elevated ACE (>2 times upper limit of normal): Strongly suggestive of active sarcoidosis or extensive granulomatous disease. Often associated with higher disease burden and multi-organ involvement
- Declining ACE Levels During Treatment: Indicates good response to corticosteroid or immunosuppressive therapy and decreasing granuloma burden and inflammatory activity
- Rising ACE Levels: May indicate disease progression, increased inflammatory activity, or inadequate response to current treatment. May warrant treatment adjustment or escalation
- Persistent Elevation Despite Treatment: Suggests either inadequate treatment response, ongoing granulomatous disease, or possible alternative diagnosis. May indicate need for treatment modification or further investigation
- Factors Affecting Interpretation: Age, race, sex, genetic factors, concurrent medications (especially ACE inhibitors and angiotensin II receptor blockers), liver disease, kidney disease, and laboratory methodology can all influence results
- Low Sensitivity and Specificity: Approximately 40-60% of sarcoidosis patients have elevated ACE. False positives can occur with tuberculosis, histoplasmosis, leprosy, berylliosis, and hypersensitivity pneumonitis. Therefore, ACE should never be used as sole diagnostic criterion
- Disease Stage Correlation: Higher elevations are more common in early-stage pulmonary sarcoidosis (stages I-II) compared to chronic or resolved disease (stage IV)
Associated Organs
- Primary Organ Systems Involved: Lungs (pulmonary system - most commonly affected), kidneys, liver, heart, nervous system, skin, and eyes. ACE is primarily produced by activated macrophages in granulomas
- Sarcoidosis: Most common condition associated with elevated ACE. Multi-system granulomatous disease of unknown etiology affecting up to 90% with pulmonary involvement and 30% with systemic manifestations
- Tuberculosis (TB): Granulomatous infection causing elevated ACE. Requires differentiation from sarcoidosis through culture, PCR testing, and clinical context
- Fungal Infections: Histoplasmosis, coccidioidomycosis, cryptococcosis, and blastomycosis cause granulomas and elevated ACE. Geographic exposure history and fungal serologies/cultures help differentiate
- Hypersensitivity Pneumonitis (HP): Allergic granulomatous lung inflammation from inhaled antigens causing elevated ACE. Requires exposure history and specific antigen testing for diagnosis
- Berylliosis: Occupational granulomatous lung disease from beryllium exposure causing elevated ACE. Beryllium lymphocyte proliferation test and occupational history are diagnostic
- Chronic Granulomatous Disease (CGD): Genetic immune disorder with abnormal phagocyte function causing persistent infections and granulomas with elevated ACE
- Organ-Specific Complications from Elevated ACE Conditions: Pulmonary fibrosis with progressive respiratory failure, hypercalcemia and kidney stones (from calcitriol production by granulomas), granulomatous nephritis and renal insufficiency, cardiac arrhythmias and congestive heart failure from cardiac granulomas, neurological manifestations including neurosarcoidosis, and ocular involvement with uveitis
- Liver Involvement: ACE is metabolized and inactivated in the lungs and liver; hepatic granulomas can affect this metabolism and contribute to systemic ACE elevation
Follow-up Tests
- Serum Calcium and Serum Albumin-Adjusted Calcium: To detect hypercalcemia resulting from granulomar production of calcitriol (active vitamin D), a common complication in sarcoidosis
- 24-Hour Urine Calcium: To assess for hypercalciuria and risk of nephrolithiasis (kidney stones) in patients with elevated ACE and sarcoidosis
- Renal Function Tests (Creatinine, eGFR, BUN): To evaluate for granulomatous nephritis and renal involvement, crucial for monitoring patients on ACE-inhibitors or angiotensin antagonists
- Chest X-Ray: First-line imaging to assess pulmonary involvement, granuloma distribution, and staging of sarcoidosis in patients with elevated ACE
- High-Resolution CT (HRCT) of the Chest: Detailed assessment of pulmonary parenchyma, mediastinal lymphadenopathy, and evaluation for early fibrosis in suspected sarcoidosis
- Pulmonary Function Tests (PFTs): To assess lung function (FVC, FEV1, DLCO), detect restrictive or obstructive patterns, and monitor disease progression in pulmonary sarcoidosis
- Tissue Biopsy (Lung, Liver, Skin): Histopathological confirmation of non-caseating granulomas essential for definitive sarcoidosis diagnosis in patients with elevated ACE
- Angiotensin-Converting Enzyme Inhibitor (ACEi) Challenge: Repeat ACE testing after initiation or escalation of ACE inhibitors to assess drug efficacy and inflammatory response
- Tuberculosis Screening (TB Skin Test or IGRA): Mandatory to exclude tuberculosis in patients with elevated ACE and granulomatous findings on imaging or biopsy
- Fungal Serologies and Cultures: Histoplasma, Coccidioides, and Cryptococcus testing to rule out endemic fungal infections presenting with elevated ACE in appropriate geographic/exposure contexts
- Cardiac Evaluation (ECG, Echocardiogram): To assess for cardiac granulomas, conduction abnormalities, and ventricular dysfunction in patients with elevated ACE and sarcoidosis
- Ophthalmologic Examination: Slit-lamp examination and fundoscopy to detect uveitis and other ocular manifestations in patients with elevated ACE and sarcoidosis
- Serial ACE Measurements: Every 3-6 months during active disease monitoring or following treatment changes. Decreasing levels indicate response to therapy; rising levels suggest disease progression or treatment failure requiring intervention
- Lysozyme and Angiotensin-Converting Enzyme in Cerebrospinal Fluid (CSF): If neurosarcoidosis is suspected based on neurological symptoms
Fasting Required?
- Fasting: NO - Fasting is not required for ACE testing. The test can be performed at any time of day without dietary restrictions
- Sample Collection: Simple blood draw (venipuncture) into a standard serum separator or plain tube. No special preparation or patient positioning required
- Medications to Avoid: ACE-inhibitor medications (lisinopril, enalapril, ramipril, etc.) can suppress ACE levels and may cause false-negative results. If possible, ACE inhibitors should be discontinued 4 weeks before testing, though this must be coordinated with the prescribing physician as these medications may be essential for patient's cardiac or renal health. Angiotensin II receptor blockers (ARBs) do not typically suppress ACE levels
- Other Preparations: No fluid restrictions or activity limitations. Patient may eat and drink normally. Can be tested any time without regard to time of day or meals
- Specimen Handling: Sample should be allowed to clot if in a serum separator tube, then centrifuged within 1 hour. Rapid transport to laboratory at room temperature is preferred. Prolonged storage may affect results
- Timing Considerations: Results are typically available within 1-3 days. For baseline testing, results are reported as single values. For monitoring, previous results should be available for comparison to assess for trends (rising, stable, or declining levels)
- Pre-Test Consultation: Inform laboratory staff of all current medications, especially ACE inhibitors or angiotensin antagonists. Report any recent infections, fever, or immunosuppressive therapy that may affect results. Document smoking status as it may influence ACE levels

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