Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-22T08:37:24.876Z Has data issue: false hasContentIssue false

Chapter 9 - Nonpregnant and False-Positive Causes of β-hCG Elevation

Published online by Cambridge University Press:  23 October 2024

By
Timothy N. Dunn  and
Denise R. Nebgen
Edited by
Laurie J. Mckenzie  and
Denise R. Nebgen
Laurie J. Mckenzie
Affiliation:
University of Texas MD Anderson Cancer Center, Houston
Denise R. Nebgen
Affiliation:
University of Texas MD Anderson Cancer Center, Houston
Get access

Summary

Positive serum β-human chorionic gonadotropin (β-hCG) testing in reproductive-age women generally indicates a pregnancy and to a lesser extent gestational trophoblastic disease (GTD) or a germ cell tumor (GCT). Other non-pregnant or false-positive causes of serum β-hCG testing include pituitary hormone production in perimenopausal or postmenopausal women, heterophilic antibody interference, chronic renal disease, familial β-hCG, and exogenous hCG administration for assisted reproductive technology. Non-gynecologic cancer can be associated with positive β-hCG results. We review the general physiology of the β-hCG molecule and typical approaches to β-hCG testing. We present an algorithm to help guide clinicians in evaluating the non-pregnant or false-positive causes of positive β-hCG test results.

Keywords

β-hCGheterophilic antibody interferencepituitary production of β-hCGfamilial β-hCGinjectable hCGnon-gynecologic cancergestational trophoblastic diseasegerm cell tumornon-pregnant causes of β-hCGfalse-positive causes of β-hCG
Type
Chapter
Information
Caring for the Female Cancer Patient
Gynecologic Considerations
 , pp. 132 - 146
Publisher: Cambridge University Press
Print publication year: 2024

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Martin, S. K., Cifu, A. S. Routine preoperative laboratory tests for elective surgery. JAMA. 2017;318(6):567–8.CrossRefGoogle ScholarPubMed
Anesthesiologists Committee on Quality Management and Departmental Administration. Pregnancy Testing Prior to Anesthesia and Surgery. 2021.Google Scholar
Herkert, D., Meljen, V., Muasher, L., et al. Human chorionic gonadotropin: A review of the literature. Obstet Gynecol Surv. 2022;77(9):539–46.CrossRefGoogle ScholarPubMed
Cole, L. A. The hCG assay or pregnancy test. Clin Chem Lab Med. 2012;50(4):617–30.CrossRefGoogle ScholarPubMed
Choi, J., Smitz, J. Luteinizing hormone and human chorionic gonadotropin: origins of difference. Mol Cell Endocrinol. 2014;383(1–2):203–13.CrossRefGoogle ScholarPubMed
Cole, L. A. hCG, the wonder of today’s science. Reprod Biol Endocrinol. 2012;10:24.CrossRefGoogle ScholarPubMed
Harvey, R. Human chorionic gonadotropin: biochemistry and measurement in pregnancy and disease. 2022.Google Scholar
ACOG Committee Opinion No. 191. Tubal ectopic pregnancy. Obstet Gynecol. 2018;131(2):e65–e77.CrossRefGoogle Scholar
Carusi, D. Pregnancy of unknown location: Evaluation and management. Semin Perinatol. 2019;43(2):95–100.CrossRefGoogle ScholarPubMed
Chard, T. Pregnancy tests: A review. Hum Reprod. 1992;7(5):701–10.CrossRefGoogle ScholarPubMed
Knight, A. K., Bingemann, T., Cole, L., Cunningham-Rundles, C. Frequent false positive beta human chorionic gonadotropin tests in immunoglobulin A deficiency. Clin Exp Immunol. 2005;141(2):333–7.CrossRefGoogle ScholarPubMed
Bolstad, N., Warren, D. J., Nustad, K. Heterophilic antibody interference in immunometric assays. Best Pract Res Clin Endocrinol Metab. 2013;27(5):647–61.CrossRefGoogle ScholarPubMed
ACOG Committee Opinion No. 278. Avoiding inappropriate clinical decisions based on false-positive human chorionic gonadotropin test results. Obstet Gynecol. 2002;100(5):1057–9.Google Scholar
Rotmensch, S., Cole, L. A. False diagnosis and needless therapy of presumed malignant disease in women with false-positive human chorionic gonadotropin concentrations. The Lancet. 2000;355(9205):712–15.CrossRefGoogle ScholarPubMed
Heijboer, A. C., Martens, F., Mulder, S. D., Schats, R., Blankenstein, M. A. Interference in human chorionic gonadotropin (hCG) analysis by macro-hCG. Clin Chim Acta. 2011;412(23–4):2349–50.CrossRefGoogle ScholarPubMed
Snyder, J. A., Haymond, S., Parvin, C. A., Gronowski, A. M., Grenache, D. G. Diagnostic considerations in the measurement of human chorionic gonadotropin in aging women. Clin Chem. 2005;51(10):1830–5.CrossRefGoogle ScholarPubMed
Patel, K. K., Qavi, A. J., Hock, K. G., Gronowski, A. M. Establishing reference intervals for hCG in postmenopausal women. Clinical Biochemistry. 2017;50(4–5):234–7.CrossRefGoogle ScholarPubMed
Haninger-Vacariu, N., Herkner, H., Lorenz, M., et al. Exclusion of pregnancy in dialysis patients: Diagnostic performance of human chorionic gonadotropin. BMC Nephrol. 2020;21(1):70.CrossRefGoogle ScholarPubMed
Cole, L. A. Familial HCG syndrome. J Reprod Immunol. 2012;93(1):52–7.CrossRefGoogle ScholarPubMed
Cole, L. A., Butler, S. Familial hCG syndrome: Production of variable, degraded or mutant forms of hCG. J Reprod Med. 2014;59(9–10):435–42.Google ScholarPubMed
Lijesen, G. K., Theeuwen, I., Assendelft, W. J., Van Der Wal, G . The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by means of the Simeons therapy: A criteria-based meta-analysis. Br J Clin Pharmacol. 1995;40(3):237–43.CrossRefGoogle ScholarPubMed
Damewood, M. D., Shen, W., Zacur, H. A., Schlaff, W. D., Rock, J. A., Wallach, E. E. Disappearance of exogenously administered human chorionic gonadotropin. Fertility and Sterility. 1989;52(3):398–400.CrossRefGoogle ScholarPubMed
Horowitz, N. S., Eskander, R. N., Adelman, M. R., Burke, W. Epidemiology, diagnosis, and treatment of gestational trophoblastic disease: A Society of Gynecologic Oncology evidenced-based review and recommendation. Gynecol Oncol. 2021;163(3):605–13.CrossRefGoogle ScholarPubMed
Pectasides, D., Pectasides, E., Kassanos, D. Germ cell tumors of the ovary. Cancer Treat Rev. 2008;34(5):427–41.Google ScholarPubMed
Fujiwara, Y., Okamoto, K., Ninomiya, I., Saito, H., Yamaguchi, T., Terai, S, et al. Surgically resected primary esophageal choriocarcinoma accompanied with Barrett’s adenocarcinoma: A case report. Surg Case Rep. 2020;6(1):227.CrossRefGoogle ScholarPubMed
Gasparri, R., Sedda, G., Brambilla, D., et al. When a differential diagnosis is fundamental: Choriocarcinoma mimicking lung carcinoma. J Clin Med. 2019;8(11).CrossRefGoogle Scholar
Guo, N., Yin, R., Li, Q., Song, L., Wang, D. Postmenopausal choriocarcinoma: A rare case report and review of the literature. Menopause. 2018;25(2):239–41.Google ScholarPubMed
Schrader, E., Stephens, A. J., Shroff, S., Ahmad, S., Holloway, R. W. Widespread choriocarcinoma metastases from de-differentiated gastro-esophageal junction primary adenocarcinoma: A case report with literature review. Gynecol Oncol Rep. 2020;31:100513.CrossRefGoogle ScholarPubMed
Xiao, P., Guo, T., Luo, Y., Zhang, M., Yin, R. Real-world data of 14 cases of brain metastases from gestational trophoblastic neoplasia and a literature review. Arch Gynecol Obstet. 2022;305(4):929–35.CrossRefGoogle ScholarPubMed
Chen, H., Ni, M., Xu, Y., Zhong, L. Y. Precocious puberty due to intracranial germ cell tumors: A case-control study. Endocr Relat Cancer. 2022;29(10):581–8.CrossRefGoogle ScholarPubMed
Parra Villasmil, M. G., Kim, C., Sato, M., Kanner, L. A. Rapidly progressive precocious puberty with an elevated testosterone level in a 5-year-old boy with a beta-human chorionic gonadotropin-secreting intracranial germ cell tumor in the pineal gland. AACE Clin Case Rep. 2022;8(4):174–8.Google Scholar
Butler, S. A., Ikram, M. S., Mathieu, S., Iles, R. K. The increase in bladder carcinoma cell population induced by the free beta subunit of human chorionic gonadotrophin is a result of an anti-apoptosis effect and not cell proliferation. Br J Cancer. 2000;82(9):1553–6.Google Scholar
Li, J., Yin, M., Song, W., et al. B subunit of human chorionic gonadotropin promotes tumor invasion and predicts poor prognosis of early-stage colorectal cancer. Cell Physiol Biochem. 2018;45(1):237–49.CrossRefGoogle ScholarPubMed
Hotakainen, K., Ljungberg, B., Paju, A., et al. The free beta-subunit of human chorionic gonadotropin as a prognostic factor in renal cell carcinoma. Br J Cancer. 2002;86(2):185–9.CrossRefGoogle ScholarPubMed
Douglas, J., Sharp, A., Chau, C., et al. Serum total hCGbeta level is an independent prognostic factor in transitional cell carcinoma of the urothelial tract. Br J Cancer. 2014;110(7):1759–66.CrossRefGoogle ScholarPubMed
Sjoblom, A., Carpen, T., Stenman, U. H., et al. The role of human chorionic gonadotropin beta (hCGbeta) in HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma. Cancer (Basel). 2022;14(12).CrossRefGoogle ScholarPubMed
Pelosof, L. C., Gerber, D. E. Paraneoplastic syndromes: An approach to diagnosis and treatment. Mayo Clin Proc. 2010;85(9):838–54.CrossRefGoogle ScholarPubMed
Gu, H., Sui, S., Cui, X., et al. Thyroid carcinoma producing beta-human chorionic gonadotropin shows different clinical behavior. Pathol Int. 2018;68(4):207–13.CrossRefGoogle ScholarPubMed
Alikhan, M., Koshy, A., Hyjek, E., et al. Discrepant serum and urine beta-hCG results due to production of beta-hCG by a cribriform-morular variant of thyroid papillary carcinoma. Clin Chim Acta. 2015;438:181–5.CrossRefGoogle ScholarPubMed
Glass, R., Asirvatham, J. R., Kahn, L., Aziz, M. Beta-human chorionic gonadotropin producing osteosarcoma of the sacrum in a 26-year-old woman: A case report and review of the literature. Case Rep Pathol. 2015;2015:897230.Google Scholar
Harrold, E., McMahon, E., McGing, P., Higgins, M. betahCG-secreting osteosarcoma. BMJ Case Rep. 2017;2017.CrossRefGoogle Scholar
Lee, A. F., Pawel, B. R., Sullivan, L. M. Significant immunohistochemical expression of human chorionic gonadotropin in high-grade osteosarcoma is rare, but may be associated with clinically elevated serum levels. Pediatr Dev Pathol. 2014;17(4):278–85.CrossRefGoogle ScholarPubMed
Masrouha, K. Z., Khattab, R., Tawil, A., et al. A preliminary investigation of Beta-hCG expression in patients with osteosarcoma. J Bone Joint Surg Br. 2012;94(3):419–24.Google ScholarPubMed
Blank, A. T., Khalighi, M., Randall, R. L., Jones, K. B. Don’t cancel the surgery just yet! A case report of positive preoperative pregnancy test due to a soft tissue sarcoma production of ectopic beta human chorionic gonadotropin. Rare Tumors. 2018;10:2036361318789727.CrossRefGoogle Scholar
Maryamchik, E., Lyapichev, K. A., Halliday, B., Rosenberg, A. E. Dedifferentiated liposarcoma with rhabdomyosarcomatous differentiation producing HCG: A case report of a diagnostic pitfall. Int J Surg Pathol. 2018;26(5):448–52.CrossRefGoogle ScholarPubMed
Russell, M. J., Flynt, F. L., Harroff, A. L., Fadare, O. Dedifferentiated liposarcoma of the retroperitoneum with extensive leiomyosarcomatous differentiation and beta-human chorionic gonadotropin production. Sarcoma. 2008;2008:658090.CrossRefGoogle ScholarPubMed
Birkenfeld, S., Noiman, G., Krispin, M., Schwartz, S., Zakut, H. The incidence and significance of serum hCG and CEA in patients with gastrointestinal malignant tumors. Eur J Surg Oncol. 1989;15(2):103–8.Google ScholarPubMed
Kang, S., Zaidi, A. J., Shokouh-Amiri, M., Wiley, E., Venepalli, N. K. A case report of paraneoplastic syndrome in beta-hCG-secreting duodenal adenocarcinoma. J Gastrointest Oncol. 2019;10(6):1151–6.CrossRefGoogle ScholarPubMed
Kutty, G., Gupta, S., Yap, J. E., McDunn, S. Advanced esophageal carcinoma expressing beta-HCG: A case report. American Journal of Gastroenterology. 2013;108:S217–S8.CrossRefGoogle Scholar
Leostic, A., Tran, P. L., Fagot, H., Boukerrou, M. Elevated human chorionic gonadotrophin without pregnancy: A case of gallbladder carcinoma. J Gynecol Obstet Hum Reprod. 2018;47(3):141–3.CrossRefGoogle ScholarPubMed
Li, D. M., Li, S. S., Zhang, Y. H., Zhang, H. J., Gao, D. L., Wang, Y. X. Expression of human chorionic gonadotropin, CD44v6 and CD44v4/5 in esophageal squamous cell carcinoma. World J Gastroenterol. 2005;11(47):7401–4.CrossRefGoogle ScholarPubMed
Trias, I., Campo, E., Benasco, C., Palacín, A., Cardesa, A. Human chorionic gonadotropin in esophageal carcinomas: An immunohistochemical study. Pathology – Research and Practice. 1991;187(4):503–7.Google ScholarPubMed
Dinis de, Sousa M., Barata, M., Miranda, A. R., et al. Beta-HCG secretion by a pulmonary pleomorphic carcinoma: A case report. Respir Med Case Rep. 2021;34:101528.Google Scholar
Groza, D., Duerr, D., Schmid, M., Boesch, B. When cancer patients suddenly have a positive pregnancy test. BMJ Case Rep. 2017;2017.CrossRefGoogle Scholar
Khattri, S., Vivekanandarajah, A., Varma, S., Kong, F. Secretion of beta-human chorionic gonadotropin by non-small cell lung cancer: A case report. J Med Case Rep. 2011;5:19.CrossRefGoogle ScholarPubMed
Kugasia, I. R., Alkayem, M., Patel, J. B. A rare case of beta-hCG production by a solitary fibrous tumor of the pleura. Am J Case Rep. 2014;15:518–22.Google ScholarPubMed
Peng, J., Lv, S., Liu, L., Feng, S., Xing, N. Lung neoplasm mimicking as ectopic pregnancy due to paraneoplastic secretion of human chorionic gonadotropin:A case report and literature review. Arch Gynecol Obstet. 2021;303(3):607–14.CrossRefGoogle ScholarPubMed
Wong, Y. P., Tan, G. C., Aziz, S., Pongprakyun, S., Ismail, F. Beta-human chorionic gonadotropin-secreting lung adenocarcinoma. Malays J Med Sci. 2015;22(4):76–80.Google ScholarPubMed
Chou, Y. C., Wu, Y. Y., Hung, S. P., et al. Treatment of primary central nervous system germinomas with short-course induction chemotherapy followed by low-dose radiotherapy without a tumor bed boost: Prognostic impact of human chorionic gonadotropin. J Pediatr Hematol Oncol. 2021;43(7):e907–e12.CrossRefGoogle ScholarPubMed
Maeyama, T., Ichikawa, C., Okada, Y., et al. Beta-human chorionic gonadotropin-producing neuroblastoma: An unrecognized cause of gonadotropin-independent precocious puberty. Endocr J. 2022;69(3):313–18.CrossRefGoogle ScholarPubMed
Weinberg, B. D., Newell, K. L., Wang, F. A case of a beta-human chorionic gonadotropin secreting sinonasal teratocarcinosarcoma. J Neurol Surg Rep. 2014;75(1):e103–7.Google ScholarPubMed
Wenneker, E., Xu, Y., Hernandez, D. J. Two cases of beta-human chorionic gonadotropin-positive oral tongue cancer resulting in false-positive pregnancy tests. Otolaryngol Head Neck Surg. 2022:1945998221095391.CrossRefGoogle Scholar
Lawless, M. E., Jour, G., Hoch, B. L., Rendi, M. H. Beta-human chorionic gonadotropin expression in recurrent and metastatic giant cell tumors of bone: A potential mimicker of germ cell tumor. Int J Surg Pathol. 2014;22(7):617–22.CrossRefGoogle Scholar
Morris, C. D., Hameed, M. R., Agaram, N. P., Hwang, S. Elevated beta-hCG associated with aggressive Osteoblastoma. Skeletal Radiol. 2017;46(9):1187–92.CrossRefGoogle ScholarPubMed
Pokharel, K., Gilbar, P. J., Mansfield, S. K., Nair, L. M., So, A. Elevated beta human chorionic gonadotropin in a non-pregnant female diagnosed with anal squamous cell carcinoma. J Oncol Pharm Pract. 2020;26(5):1266–9.CrossRefGoogle Scholar
Michalski, W., Poniatowska, G. M., Jońska-Gmyrek, J. G., et al. hCG-secreting malignancies: Diagnostic pitfalls. Oncology in Clinical Practice. 2020;15(6):331–5.CrossRefGoogle Scholar
Ben, Kridis W., Ben, Hassena R., Charfi, S., et al. Gastric signet-ring cell carcinoma with hypersecretion of β-Human chorionic gonadotropin and review of the literature. Experimental Oncology. 2018;40(2):144–8.Google Scholar
Brown, J., Barrett-Campbell, O., David, Y., Luhrs, C., McFarlane, S. I. An unexpected pregnancy test result leading to the diagnosis of advanced gastric cancer. Am J Med Case Rep. 2019;7(7):148–50.Google Scholar
Kafka, M., Woll, E., Brunhuber, T., et al. A presumed extragonadal germ cell tumor that turned out to be a gastric cancer: A case report. Transl Androl Urol. 2021;10(6):2528–33.CrossRefGoogle ScholarPubMed
Daniel, M., Das, K. An atypical cause for a positive urine pregnancy test. Gastroenterology. 2022;162(6):e6–e7.CrossRefGoogle ScholarPubMed
Fenichel, P., Rouzier, C., Butori, C., et al. Extragestational betaHCG secretion due to an isolated lung epithelioid trophoblastic tumor: microsatellite genotyping of tumoral cells confirmed their placental origin and oriented specific chemotherapy. J Clin Endocrinol Metab. 2014;99(10):3515–20.CrossRefGoogle Scholar
Becker, N., Chernock, R. D., Nussenbaum, B., Lewis, J. S., Jr. Prognostic significance of beta-human chorionic gonadotropin and PAX8 expression in anaplastic thyroid carcinoma. Thyroid. 2014;24(2):319–26.CrossRefGoogle ScholarPubMed
Puco, K., Bierner, J., Muller, S., et al. Abstract 481: Utility of hCG as a biomarker of treatment response in advanced urothelial cancer: A population based series at Akershus University Hospital, Norway. Cancer Research. 2021;81.CrossRefGoogle Scholar
Gupta, A. K., Charlton, A., Prelog, K., Kellie, S. J. beta-HCG Elevation in Wilms Tumor: An Uncommon Presentation. Pediatr Blood Cancer. 2016;63(6):1105–6.CrossRefGoogle ScholarPubMed
Goldstein, J., Pandey, P., Fleming, N., Westin, S., Piha-Paul, S. A non-pregnant woman with elevated beta-HCG: A case of para-neoplastic syndrome in ovarian cancer. Gynecol Oncol Rep. 2016;17:49–52.CrossRefGoogle ScholarPubMed
Mustafa, A., Bozdağ, Z., Tepe, N. B., Ozcan, H. C. An unexpected reason for elevated human chorionic gonadotropin in a young woman Cervical squamous carcinoma. Saudi Medical Journal. 2016;37(8):905–7.CrossRefGoogle Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×