Correspondence

Quantitative human chorionic gonadotropin measurement in urine using the Access immunoassay

To the Editor,

Human chorionic gonadotropin (hCG) is a glycoprotein composed of 2 dissimilar subunits, ?- and ?-subunit, held together by charge interaction. Both subunits are needed for biological activity and are common to other hormones (eg, thyroid stimulating hormone, luteinizing hormone, and follicle stimulating hormone); however, the ?-subunit determines the specificity of the biological action of the hormones containing these subunits [1]. In urine, how- ever, a large fraction of the immunoreactivity of hCG is due to a metabolic breakdown product of hCG, for example, regular, intact hCG; nicked hCG; hyperglycosy- lated hCG; free ?-hCG; and a significant amount of ?-core fragment [2].

A number of preanalytical conditions, other than pregnancy, including trophoblastic disease and certain nontrophoblastic neoplasms (eg, testicular tumors, prostate cancer, breast cancer, and cervical cancer), can cause elevated serum levels of hCG that are then excreted into urine [3-5]. False-positive urine hCG results have also been reported in patients with nephritic-range proteinuria and Tubo-ovarian abscess [6,7]. Analytical causes of false- positive or false-negative urine hCG tests also include human or technical error in the performance of tests and/or the interpretation of test results.

Determination of pregnancy status is important in the work-up of a patient presenting with Vaginal bleeding or lower abdominal pain. Women with these symptoms should be screened for pregnancy using a urine pregnancy test, especially before undergoing an x-ray procedure. Clinical decisions regarding additional diagnostic testing should be based on the results of the urine pregnancy test. Although the methods for quantifying hCG in serum are well established, automated quantitative urine assays are not available yet. Bedside qualitative urine pregnancy testing was performed by using the ACON urine hCG One Step Pregnancy Device (Beckman Coulter, Fullerton, CA) (Format: FHC-102), an assay that uses a combination of antibodies including a monoclonal hCG antibody to selectively detect elevated hCG. Positive specimens react with the specific antibody-hCG-colored conjugate to form a colored line at the test line region of the membrane. Absence of this colored line suggests a negative result. It detects the presence of hCG in the Urine sample at a sensitivity of 20 IU/L. Occasionally, undetermined results (trace) will also occur. Recently, quantitative hCG measurement in urine has been reported using the Modular Analytics E170 module (Roche) and Abbott AxSYM [8,9]. In the present study, we performed the Access total ?-hCG (Beckman Coulter, Inc, Fullerton, Ca) for quantitative determination of urinary concentration of hCG. It is approved by the Food and Drug Administration only for serum use, not urine.

In fact, the most noticeable difference between serum and urine samples is the protein contents, an important issue with

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Table 1 Detection values of quantitative serum ?-hCG and estimated values of quantitative serum ?-hCG

104 Correspondence

respect to antigen-antibody interactions. Therefore, we analyzed the “matrix effect” by diluting 3 different concentrations of serum sample (low, medium, high) into various concentrations (1:2, 1:4, 1:6, 1:8, and 1:10 dilutions) with urine (negative for hCG) (Table 1). We observed a very strong correlation (r² = 0.99) between the expected values and the hCG concentration measured in the dilutions. We supposed that there was no particular matrix interference in the quantitative determination of urine hCG using the Access immunoassay.

Although numerous rapid bedside hCG assays are available and used in the ED as Screening tests for pregnancy [10], quantitative determination of urine hCG using the results of the urine pregnancy test. Access immunoassay may provide an adequate confirmation results of urine pregnancy test.

Tze-Kiong Er¹

Graduate Institute of Medicine Faculty of Medicine, College of Medicine Kaohsiung Medical University, Kaohsiung, Taiwan Department of Laboratory Medicine

Kaohsiung Medical university hospital, Kaohsiung, Taiwan

E-mail address: [email protected]

Li-Yu Tsai PhD¹

Faculty of Biomedical Laboratory Science

College of Health Sciences Kaohsiung, 807 Taiwan, ROC

Miguel Angel Ruiz Gines MD Department of Pathology and Laboratory Medicine Hospital Virgen de la Salud (Toledo), Spain

Bai-Hsiun Chen MD Department of Laboratory Medicine Kaohsiung Medical University Hospital Kaohsiung 807, Taiwan, ROC

Jan-Gowth Chang MD Yuh-Jyh Jong MD

Graduate Institute of Medicine Department of Laboratory Medicine Kaohsiung Medical University Kaohsiung 807 Taiwan, ROC

College of Medicine Kaohsiung Medical University Kaohsiung 807, Taiwan, ROC

doi:10.1016/j.ajem.2007.07.003

¹ The first two authors contribute equally to this paper.

References

1. Wu J, Nakamura R. Human circulating tumor markers. Current concepts and clinical applications. Chicago Am Soc Clin Pathol 1997: 127-76.
2. Cole LA. Immunoassay of human chorionic gonadotrophin, its free subunits, and metabolites. Clin Chem 1997;43:2233-43.
3. Er TK, Jong JY, Tsai EM, Huang CL, Chou HW, Zheng BH, et al. False-negative pregnancy test in hydatidiform mole. Clin Chem 2006; 52:1616-8.
4. Braunstein GD, Vaitukaitis JL, Carbone PP, et al. Ectopic production of human chorionic gonadotrophin by neoplasms. Ann Intern Med 1973;78:39-45.
5. Er TK, Jong YJ, Tsai LY, Cheng HJ, Chen BH. Urine pregnancy testing in two women with cancer. LabMedicine 2007;38:280-1.
6. Levsky ME, Handle JA, Suarez RD, et al. False-positive urine beta- hCG in a women with a tubo-ovarian abscess. J Emerg Med 2001;2: 407-9.
7. Kountz DS, Kolander SA, Rozovsky A. False positive pregnancy test in the nephritic syndrome. N Engl J Med 1989;321:1416.
8. Ajubi NE, Nine N, Albert W. Quantitative automated human chorionic gonadotropin measurement in urine using the Modular Analytics E170 module. Clin Chem Lab Med 2005;43:68-70.
9. Carayannopoulos MO, Grenache DG, Gronowski AM. Total b-human chorionic gonadotropin measured in urine by an automated method. Clin Chem 2002;48:1796-7.
10. Bustler SA, Khanlian SA, Cole LA. Detection of early pregnancy forms of human chorionic gonadotrophin by home pregnancy test devices. Clin Chem 2001;47:2131-6.

?-agonists for patients with chronic obstructive pulmonary disease and heart disease?

To the Editor,

Because chronic obstructive pulmonary disease (COPD) and coronary artery disease coexist in many elderly patients, we explored whether ?-agonist aerosols might contribute to coronary events in hospitalized patients with COPD. At the 2007 International Conference of the American Thoracic Society, we presented preliminary data [1] demonstrating that only 4 of 92 patients discharged with a primary diagnosis of COPD over a 9-month period had a secondary diagnosis of MI. All received ?-agonist aerosols during hospitalization, and all 4 MIs occurred more than 48 hours after hospital admission. We reasoned that MI, whether the primary reason for admission or a complication, may take precedence as the primary discharge diagnosis for such patients with COPD, resulting in artificially low rates of MI in the previous cohort. In a second cohort of 94 patients whose primary discharge diagnosis was MI (with a secondary diagnosis of COPD), 27 presented with dyspnea and without chest pain. Of 27 (29%), 26 had troponin T elevations in the first 24 hours of their hospital stays; 16 (62%) received ?-agonist aerosols for dyspnea in the emergency department (ED). Of 44 (30%) with chest pain as a presenting symptom, 13 received ?-agonist inhalers.

Previous investigators have demonstrated that 1 in 5 patients with obstructive lung disease who present with