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Angiotensin-converting Enzyme (ACE)

CPT: 82164
Updated on 08/3/2021
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Expected Turnaround Time

2 - 3 days

1 - 3 days

2 - 3 days


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Specimen Requirements


Specimen

Serum


Volume

0.5 mL


Minimum Volume

0.2 mL


Container

Red-top tube or gel-barrier tube


Collection

Separate serum from cells at the time of collection.


Storage Instructions

Room temperature


Stability Requirements

Temperature

Period

Room temperature

7 days

Refrigerated

7 days

Frozen

3 days

Freeze/thaw cycles

Stable x3


Patient Preparation

Stop administration of captopril, enalapril, or lisinopril for 12 hours prior to venipuncture (reduces ACE activity).


Causes for Rejection

Captopril, enalapril, or lisinopril administration; hemolyzed or icteric specimen; whole blood, cerebrospinal fluid (CSF), or EDTA plasma specimen received


Test Details


Use

High in sarcoidosis, more often when the disease is active. Of value in assessing the response of sarcoidosis to corticosteroid therapy. Changes in serum ACE correlate with clinical status and results of gallium scans (which reflect presence and activity of inflammatory granulomatous lesions). Falling ACE level is a favorable prognostic sign. Rising levels may reflect activity uncontrolled by therapy.


Limitations

Elevations have been reported in about 35% to 80% of cases of sarcoidosis. ACE levels are less likely to be increased with chronic sarcoidosis. Different admixtures of acute and chronic cases may explain some of the apparent variation in reported incidence of elevation in sarcoidosis. Elevations have been found in patients with diabetes mellitus, Gaucher disease, and leprosy. Twenty-five percent of 86 patients with acute histoplasmosis had elevated levels.3 Increased in some patients with primary biliary cirrhosis, amyloidosis, myeloma, some alpha1-antitrypsin variants, Melkersson-Rosenthal syndrome, and hyperthyroidism. It has been found increased in some cases of hyperparathyroidism and in some instances of oncogenic hypercalcemia. Thus, it is not a specific marker for the diagnosis of sarcoidosis.4 Positives are also reported in patients with extrinsic allergic alveolitis, coccidioidomycosis, beryllium disease, asbestosis, silicosis, and alcoholic liver disease.5 ACE activity is decreased during starvation, independent of the level of thyroid activity (as monitored by T3 levels).6


Methodology

Kinetic


Reference Interval

Pediatric1,2 and adults:

• 0 to 2 years: 18−95 units/L

• 3 to 14 years: 22−108 units/L

• 15 years or older: 14−82 units/L


Additional Information

Other abnormalities found in some sarcoidosis patients include elevations of serum alkaline phosphatase, calcium, gamma globulin with polyclonal gammopathy, and hypercalciuria. Serum angiotensin converting enzyme is elevated in 50% of cases of sarcoidosis but not in cases of active tuberculosis or Hodgkin disease. Increases are less frequent when sarcoidosis is inactive.6 Some 80% to 90% of patients with demonstrably active sarcoidosis have elevated serum ACE. Angiotensin converting enzyme activity is also increased in sarcoid lymph node homogenate. The diagnosis of sarcoidosis is an histopathologic/clinical complex. Noncaseating granulomas must be proven not to be caused by tuberculosis, histoplasmosis, or other microbiologic entities. Berylliosis is a very rare cause of such granulomas.

ACE is a dipeptidyl carboxypeptidase. It functions to split dipeptides from the free carboxy end of a variety of polypeptides including angiotensin I and bradykinin. It is especially known for its generation of the octapeptide angiotensin II by releasing the dipeptide histidyl-leucine from angiotensin I. The major site of ACE production is the pulmonary bed of endothelial cells.

Thyroid hormone may modulate ACE activity. Both patients with low T3 levels (and clinical hypothyroidism) and patients with anorexia nervosa with associated findings of hypothyroidism may have low serum ACE activity.7,8 Monitoring of ACE levels may have application in assessing risk of pulmonary damage due to use of some antineoplastic agents, in particular bleomycin.9 Serum ACE is decreased in some patients with bronchogenic carcinoma. With response to chemotherapy/radiation therapy the ACE level has been noted to normalize.10 Cerebrospinal fluid ACE is useful in patients with neurosarcoidosis.

Elevated serum ACE levels in a case of the uncommon entity, Melkersson-Rosenthal syndrome, probably relate to the sarcoid-like noncaseating granulomas that are found in this condition. ACE levels normalized after successful (clinical management) therapy with methotrexate.11

Serum ACE abnormality has been reported in 20% to 30% of alpha1-antitrypsin variants (MZ, ZZ, and MS Pi types) but in only about 1% of individuals with normal MM Pi type.12 There is evidence that paraquat poisoning (because of its effect on pulmonary capillary endothelium) is associated with elevated serum ACE.13


Footnotes

1. Tietz NW, ed. Clinical Guide to Laboratory Tests. 3rd ed. Philadelphia, Pa: WB Saunders Co;1995: 54.
2. Lieberman J. Elevation of serum angiotensin-converting enzyme (ACE) level in sarcoidosis. Am J Med. 1975; 59(3):365-372. 169692
3. Ryder KW, Jay SJ, Kiblawi SO, Hull MT. Serum angiotensin converting enzyme activity in patients with histoplasmosis. JAMA. 1983 Apr; 249(14):1888-1889. 6300475
4. Lufkin EG, DeRemee RA, Rohrbach MS. The predictive value of serum angiotensin-converting enzyme activity in the differential diagnosis of hypercalcemia. Mayo Clin Proc. 1983; 58(7):447-451. 6306358
5. Studdy PR, Lapworth R, Bird R. Angiotensin-converting enzyme and its clinical significance−A review. J Clin Pathol. 1983; 36(8):938-947 (review). 6308066
6. Butkus NE, Burman KD, Smallridge RC. Angiotensin-converting enzyme activity decreases during fasting. Horm Metab Res. 1987; 19(2):76-79. 3030914
7. Matsubayashi S, Tamai H, Kobayashi N, et al. Angiotensin-converting enzyme and anorexia nervosa. Horm Metab Res. 1988; 20(12):761-764. 2851517
8. Smallridge RC, Rogers J, Verma PS. Serum angiotensin-converting enzyme: Alterations in hyperthyroidism, hypothyroidism, and subacute thyroiditis. JAMA. 1983; 250(18):2489-2493. 6313976
9. Nussinovitch N, Peleg E, Yaron A, Ratt P, Rosenthal T. Angiotensin converting enzyme in bleomycin-treated patients. Int J Clin Pharmacol Ther Toxicol. 1988 Jun; 26(6):310-313. 2457562
10. Schweisfurth H, Schmidt M, Brugger E, et al. Alterations of serum carboxypeptidases N and angiotensin-I-converting enzyme in malignant diseases. Clin Biochem. 1985; 18(4):242-246. 2994905
11. Leicht S, Youngberg G, Modica L. Melkersson-Rosenthal syndrome: Elevations in serum angiotensin converting enzyme and results of treatment with methotrexate. South Med J. 1989; 82(1):74-76. 2536197
12. Lieberman J, Sastre A. Serum angiotensin converting enzyme levels in patients with alpha1-antitrypsin variants. Am J Med. 1986; 81(5):821-824. 3022587
13. Hollinger MA, Potwell SW, Zuckerman JE, Gorin AB, Parsons G, Giri SN. Effect of paraquat on serum angiotensin converting enzyme. Am Rev Respir Dis. 1980 May; 121(5):795-798. 6250433

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
010116 Angiotensin-Converting Enzyme 2742-5 010117 ACE, Serum U/L 2742-5

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