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Chorionic gonadotropin

Human chorionic gonadotropin (hCG) is a peptide hormone produced in pregnancy, that is made by the embryo soon after conception and later by the trophoblast (part of the placenta). Its role is to prevent the disintegration of the corpus luteum of the ovary and thereby maintain progesterone production that is critical for a pregnancy in humans. hCG may have additional functions, for instance it is thought that it affects the immune tolerance of the pregnancy. Early pregnancy testing generally is based on the detection or measurement of hCG. more...

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The drugs Pregnyl®, Follutein®, and Ovidrel® use chorionic gonadoptropin as the active ingredient in their product. These preparations are used in assisted conception in lieu of luteinizing hormone to trigger ovulation.

Structure

hCG is a glycoprotein composed of 237 amino acids with a molecular mass of 36.7 kDa. It is heterodimeric, with an α (alpha) subunit identical to that of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH). Its β (beta) subunit is unique to hCG.

Function

hCG promotes the maintenance of the corpus luteum and causes it to secrete the hormone progesterone. Progesterone enriches the uterus with a thick lining of blood vessels and capillaries so that it can sustain the growing fetus.

Because of its similarity to LH and FSH, hCG can also be used clinically to induce ovulation in the ovaries as well as testosterone production in the testes. As the most abundant biological source is women who are presently pregnant, some organizations collect urine from gravidae to extract hCG for use in fertility treatment.

Pregnancy testing

Pregnancy tests measure the levels of hCG in the blood or urine to indicate the presence or absence of a fertilized egg. In particular, most pregnancy tests employ an antibody that is specific to the β-subunit of hCG (βhCG). This is important so that tests do not make false positives by confusing hCG with LH and FSH. (The latter two are always present at varying levels in the body, while hCG levels are negligible except during pregnancy.) The urine test is a chromatographic immunoassay that can detect levels of βhCG as low as 25-100 mIU/ml. The urine should be the first urine of the morning when hCG levels are highest. If the specific gravity of the urine is above 1.015, the urine should be diluted. The serum test, using 2-4 mL of venous blood, is a radioimmunoassay (RIA) that can detect βhCG levels as low as 5 mIU/ml and allows quantitation of the βhCG concentration. The ability to quantitate the βhCG level is useful in the evaluation of ectopic pregnancy and in monitoring germ cell and trophoblastic tumors.

Hydatiform moles ("molar pregnancy") may produce high levels of βhCG, despite the absence of an embryo. This can lead to false positive readings of pregnancy tests.

Tumor marker

βhCG is also secreted by some cancers including teratomas, choriocarcinomas and islet cell tumors. When a patient is suspected of harboring a teratoma (often found in the testes and ovaries but also in the brain as a dysgerminoma), a physician may consider measuring βhCG. Elevated levels cannot prove the presence of a tumor, and low levels do not rule it out (an exception is in males who do not naturally produce βhCG). Nevertheless, elevated βhCG levels fall after successful treatment (e.g. surgical intervention or chemotherapy), and a recurrence can often be detected by the finding of rising levels.

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The Pregnancy That Never Was—Beta Human Chorionic Gonadotropin Secreting Primary Lung Cancer - Abstract
From CHEST, 10/1/00 by Jennifer Anne LaRosa

Jennifer Anne LaRosa, MD; TB Pustilnik, MD; PJ O'Reilly, MD; MR Waldrum, MD; SM Harding, MD; MF Carcelen, MD--The University of Alabama at Birmingham, Birmingham, Alabama, USA

Introduction: Primary choriocarcinoma of the lung is an extremely rare form of non-small cell lung cancer. It has a predilection for young women who more commonly present with gestational trophoblastic disease.

Case Presentation: DP was a 33 year old African-American female who presented to her primary provider with 2-3 months of malaise, weight loss, nausea and vomiting, abdominal pain, exertional dyspnea, and productive cough. Chest roentgenogram showed a right upper lobe consolidation and sputum cultures were positive for Mycobacterium Tuberculosis. She was started on anti-tuberculous therapy but her symptoms worsened. She was then noted to have an umbilical hernia for which she underwent surgical repair. Intraoperative biopsy of an umbilical node revealed poorly differentiated metastatic carcinoma and a B-hCG level was noted to be 691 ng/ml.

On physical exam, she was a thin female in no distress. Vital signs: Temperature: 101.0; Heart rate 100; Respiratory rate 20, Blood pressure 114/58, Room air oxygen saturation 96%. Head and neck: poor dentition. Cardiovascular: 3/6-holosystolic murmur. Pulmonary: diminished breath sounds over the right upper lobe. Abdomen: diffuse lower abdominal tenderness, subcutaneous flank nodule. Pelvic: no masses.

Abnormal labs: white blood cell 15,200/[mm.sup.3] (76 segmented neutrophils, 22 lymphocytes, 2 eosinophils), hemoglobin 9.3 g/dl, B-hCG 3502 ng/ml, total bilirubin 1.4 mg/dl, alkaline phosphatase 127 IU/L, gamma-gluyamyltranspeptidase 197 IU/L, lactate dehydrogenase 515 IU/L, albumin 2.3 g/dl. Chest roentgenogram showed complete opacification of the right upper lobe. CT scan of the thorax demonstrated an occlusive right upper lobe endobronchial lesion with central necrosis, aortopulmonary and bilateral paratracheal and subcarinal lymphadenopathy. CT scan of the abdomen/pelvis showed diffuse metastatic disease (adrenal glands, pancreas, left kidney, superficial musculature, and retropefitoneal lymph nodes); no adnexal or uterine abnormalities. Pelvic ultrasound was negative for intrauterine or ectopic pregnancy.

Bronchoscopy revealed a large fleshy tumor originating from the right upper lobe and obstructing [is greater than] 80% of the right mainstem bronchus. Bronchial brushings and endobronchial biopsies showed poorly differentiated non-small cell lung carcinoma which stained positive for B-hCG. Shortly after chemotherapy was begun, the patient vomited, aspirated, and was transferred to the intensive care unit (ICU) for severe respiratory distress. Over the next 10 days, the patient's condition deteriorated rapidly and she died from multi-organ system failure.

Discussion: This patient was diagnosed with pulmonary choriocarcinoma on the basis of presentation, elevated B-hCG levels, tissue obtained from primary and metastatic biopsies, and the absence of gynecologic pathology. Although pulmonary choriocarcinoma is rare, the presentation was not unusual. The tumor is extremely aggressive and tends to metastasize early, as exemplified by our patient's diffuse systemic involvement. Unfortunately, this patient's disease was diagnosed at a markedly advanced stage and she succumbed to infection and multiorgan system failure before appropriate treatment could be completed.

Conclusion: Fewer than 20 cases of pulmonary choriocarcinoma are reported in the literature. It is an extremely aggressive tumor that occurs in young women. This presents a significant diagnostic dilemma as many such female patients may often be misdiagnosed as being pregnant or having a, primary gynecologic neoplasm. This is unfortunate because the tumor is highly responsive to combination chemotherapy and relapses can be easily detected by following B-hCG levels. The origin of pulmonary choriocarcinoma is widely debated and conclusions are difficult to make because of the paucity of cases. Theories include the following: 1. pulmonary metastases with a gonadal primary undergoing spontaneous regression, 2. pulmonary embolic satellite lesions from abnormal products of gestation, 3. germ cell origin, 4. primary non-small cell lung carcinoma which undergoes embryonic metaplasia. A higher index of suspicion and more frequent reporting of such cases would enable us not only to study this neoplasm more thoroughly; it would also identify patients at earlier stages of disease who could potentially achieve disease remission.

References

[1] Aparicio, J, Okra, A, Martinez-Moragon, E, et al. Extragonadal nongestational choriocarcinoma involving the lung: A report of three cases. Respiration 1996; 63:251-253

[2] Pushchak, MJ, Farhi, DC, Primary choriocarcinoma of the lung. Arch Pathol Lab Med 1989; 113:82-83

[3] Tanimura, A, Natsuyama, H, Kawano, M, et al. Primary choriocarcinoma of the lung. Human Pathology 1985; 16:1281-1284

COPYRIGHT 2000 American College of Chest Physicians
COPYRIGHT 2001 Gale Group

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