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Commentary

Department of Clinical Chemistry, Helsinki University Central Hospital, Biomedicum, PB 700, FIN-00029, Helsinki, Finland. e-mail ulf-hakan.stenman{at}helsinki.fi.

The article by McCudden et al. (1) published in this issue of Clinical Chemistry describes the clinical work-up of a patient with low-positive human chorionic gonatodtropin (hCG) due to pituitary or heterophile antibody interference. In addressing this case it is also worthwhile to discuss additional confounding factors that affect hCG measurement.

assay calibration

In previous studies cited by McCudden et al. (2)(3), hCG concentrations up to 16 IU/L were observed in postmenopausal women. When serum hCG is measured by a highly sensitive and specific method (PerkinElmer Wallac AutoDELFIA®), the upper reference limit for postmenopausal women is 5 IU/L (15.5 pmol/L), and the highest concentration that we have observed is 11 IU/L (4). These disparate findings are likely attributable to differences in assay calibration and the contribution of free hCGβ. Thus, hCG concentrations are assay dependent, necessitating the establishment of assay-specific reference intervals.

HCG isoforms

Approximately 30%–70% of patients with various nontrophoblastic cancers produce hCGβ. The concentrations are usually low, but in 5%–10% of cases they are high enough to increase the concentration of total hCG to above the upper reference limit. This hCGβ is distinguishable from pituitary hCG because hCGβ is not suppressed by estrogen-replacement therapy. A moderately increased hCG concentration in a cancer patient, however, may be caused by a combination of hCG and hCGβ, and in such cases the concentration of total hCG will be partially suppressed by estrogen-replacement, thereby confounding interpretation of the measured values. In these situations, specific determination of each form of hCG is very useful, but very few assays specific for hCGβ are available (5).

hypogonadism

No systematic studies on hCG concentrations in hypogonadal men are available, but we recently observed hCG concentrations increasing from <0.5 to 4.5 IU/L after withdrawal of testosterone in a hypogonadal patient who had been treated for testicular cancer. This finding caused suspicion of a relapse, a diagnosis that was excluded on the basis of assay results for luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and the suppression of hCG with testosterone replacement (6). This case shows that increased hCG associated with hypogonadism can also occur in men.

Hypogonadism can also be caused by intensive chemotherapy, which may lead to increased serum hCG similar to that seen in menopausal women. Such cases may cause confusion, especially when serum hCG is used to monitor the effectiveness of chemotherapy. It is important to differentiate increased hCG caused by a relapse from that induced by chemotherapy; this can be done by measurement of LH and FSH (5).

Acknowledgments

Grant/funding Support: Finnish Academy of Sciences.

Financial Disclosures: None declared.

References

1. McCudden CR, Willis SM, Grenache DG. Persistent low concentration of human chorionic gonatodtropin in a nonpregnant female. Clin Chem 2008;54:209-213.[Free Full Text]
2. Snyder JA, Haymond S, Parvin CA, Gronowski AM, Grenache DG. Diagnostic considerations in the measurement of human chorionic gonadotropin in aging women. Clin Chem 2005;51:1830-1835.[Abstract/Free Full Text]
3. Cole LA, Sasaki Y, Muller CY. Normal production of human chorionic gonadotropin in menopause. N Engl J Med 2007;356:1184-1186.[Free Full Text]
4. Alfthan H, Haglund C, Dabek J, Stenman U-H. Concentrations of human chorionic gonadotropin, its β-subunit and the core fragment of the β-subunit in serum and urine of men and nonpregnant women. Clin Chem 1992;38:1981-1987.[Abstract]
5. Stenman UH, Tiitinen A, Alfthan H, Valmu L. The classification, functions and clinical use of different isoforms of HCG. Hum Reprod Update 2006;12:769-784.[Abstract/Free Full Text]
6. Lempiainen A, Hotakainen K, Blomqvist C, Alfthan H, Stenman UH. Increased human chorionic gonadotropin due to hypogonadism after treatment of a testicular seminoma. Clin Chem 2007;53:1560-1561.[Free Full Text]

This Article Extract Full Text (PDF) Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Stenman, U.-H. PubMed Articles by Stenman, U.-H. Related Collections Clinical Case Studies