Inhibin A, Tumor Marker, Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Inhibins are heterodimeric protein hormones secreted by granulosa cells of the ovary in the female and Sertoli cells of the testis in the male. They selectively suppress the secretion of pituitary follicle stimulating hormone (FSH) and also have local paracrine actions in the gonads. The inhibins consist of a dimer of 2 homologous subunits, an alpha subunit and either a beta A or beta B subunit, to form inhibin A and inhibin B, respectively.
In females, inhibin A is primarily produced by the dominant follicle and corpus luteum: whereas inhibin B is predominantly produced by small developing follicles. Serum inhibin A and B levels fluctuate during the menstrual cycle. At menopause, with the depletion of ovarian follicles, serum inhibin A and B decrease to very low or undetectable levels.
Ovarian cancer is classified into 3 types: epithelial, stromal sex cord, and germ cell tumors. Epithelial ovarian tumors account for 90% of cases and are further subdivided into: serous (70%), mucinous (10%-15%), and endometrioid (10%-15%) types. Granulosa cell tumors represent the majority of the stromal sex cord tumors, which account for 2% to 5% of all ovarian tumors.
Elevations of serum inhibin A and/or B are detected in some patients with granulosa cell tumors. Inhibin A elevations have been reported in approximately 70% of granulosa cell tumors. In these patients, inhibin A levels tend to show a 6-fold to 7-fold increase over the reference range value. The frequency of elevated levels varies amongst studies, likely due to the different specificities of the antibodies used in the immunoassays.
Inhibin A also appears to be suitable markers for epithelial tumors of the mucinous type with about 20% of cases having elevated inhibin A levels. In contrast, inhibin is not a very good marker in nonmucinous epithelial tumors. At best, total inhibin is elevated in 15% to 35% of nonmucinous epithelial ovarian cancer cases.
Inhibin seems to be a complementary to cancer antigen 125 (CA 125) as an ovarian cancer marker. CA 125 is not as good of a tumor marker for mucinous and granulosa ovarian cell tumors. Inhibin shows a better performance in those 2 types of ovarian cancer.
The majority of the studies for inhibin A and B as an ovarian cancer marker have been limited to postmenopausal women where the levels for both proteins are normally very low. Inhibin A has limited utility as an ovarian cancer marker in premenopausal women, where circulating levels are higher and fluctuate throughout the menstrual cycle and, therefore, are difficult to interpret.
An aid in the diagnosis of patients with granulosa cell tumors of the ovary when used in combination with inhibin B
Monitoring of patients with granulosa cell tumors and epithelial mucinous-type tumors of the ovary known to secrete inhibin A
Inhibin A levels are elevated in approximately 70% of patients with granulosa cell tumors and in approximately 20% of patients with epithelial ovarian tumors. A normal inhibin A level does not rule-out a mucinous or granulosa ovarian cell tumor. Testing for inhibin B in these cases might be informative as a higher proportion of mucinous or granulosa ovarian cell tumors will have an elevated inhibin B level. Consider ordering INHAB / Inhibin A and B, Tumor Marker, Serum.
For monitoring of patients with known ovarian cancer, inhibin A levels decrease shortly after surgery. Elevations of inhibin A after treatment are suggestive of residual, recurrent, or progressive disease. In patients with recurrent disease, inhibin A elevation seems to be present earlier than clinical symptoms. Patients in remission show normal levels of inhibin A.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Do not interpret serum inhibin levels as absolute evidence of the presence or the absence of malignant disease. Use results in conjunction with information from the clinical evaluation of the patient and other diagnostic procedures.
Inhibin values fluctuate during the menstrual cycle. Inhibin levels in premenopausal women should be interpreted with caution.
Some patients who have been exposed to animal antigens, either in the environment or as part of treatment or imaging procedures, may have circulating antianimal antibodies present. These antibodies may interfere with the assay reagents to produce unreliable results.
Tumor markers are not specific for malignancy and values may vary by testing methodology. The same method should be used to serially monitor patients.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Males: <2.0 pg/mL
<11 years: <4.7 pg/mL
11-17 years: <97.5 pg/mL
Premenopausal: <97.5 pg/mL
Postmenopausal: <2.1 pg/mL
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Mom CH, Engelen MJ, Willemse PH, et al: Granulosa cell tumors of the ovary: the clinical value of serum inhibin A and B levels in a large single center cohort. Gynecol Oncol 2007 May;105(2):365-372
2. Robertson DM, Pruysers E, Jobling T: Inhibin as a diagnostic marker for ovarian cancer. Cancer Lett 2007; 249:14-17
3. Jamieson S, Fuller PJ: Management of granulosa cell tumour of the ovary. Curr Opin Oncol 2008;20(5):560-564