Ovarian hematoma in an 11-year-old Thoroughbred-Hanovarian mare

Abstract

An aggressive mare, presented for prebreeding examination, was found to have a significantly enlarged ovary (soccer ball size). A granulosa thecal cell tumor was initially suspected. Following laboratory and repeated clinical examination, the mare was diagnosed with an ovarian hematoma, which regressed with treatment.

In October 2000, a new client purchased an 11-year-old Thoroughbred-Hanovarian mare as a beginner level show and jumping prospect. The 16.1-hand gray mare had a history of unpredictable behavior, including aggression, and was initially examined in February 2001 for injuries incurred when she ran through a wooden fence. At that time, the mare was very difficult to sedate and treat. In March 2001, when the mare was diagnosed with a strained left hind suspensory ligament and arthritis in the left hind fetlock, the owners decided to breed her.

On day 1, a prebreeding uterine swab was collected under sedation. Romifidine (Sedivet; Boehringer Ingelheim, Burlington, Ontario), 0.04 mg/kg BW, and butorphanol (Torbugesic; Ayerst Veterinary Laboratories, Guelph, Ontario), 0.02 mg/kg BW, were administered IV. The cervix was noted to be very puckered, firm, and closed. It was suspected that the mare was already pregnant because of her history of running fences and the fact that there were several mature stallions stabled on the farm. On transrectal examination, the cervix was firm and displaced cranially. The uterine body and horns were considered to be normal in size and with good tone; they were also displaced cranially. The left ovary was small and firm and had a 2.0-cm follicle on its cranial aspect. The right ovary was very firm, large (22 × 22 × 35 cm), and oblong in the sagittal plane. Ultrasonography revealed that the mass was capsulated and echodense with a very uniform internal appearance. The mare was not pregnant. Due to the abnormal ovarian findings, a uterine swab was not collected. Based on the mare's aggressive, unpredictable behavior and the clinical findings, a presumptive diagnosis of granulosa thecal cell tumor was made.

On day 8, a human chorionic gonadotropin (HCG) stimulation test was performed. A baseline blood sample (time 0) was collected to measure progesterone, total estrogens, and testosterone, then HCG (A.P.L.; Ayerst Veterinary Laboratories), 10 000 IU, was administered IV. Blood samples were taken at 1 h and 2 h postinjection and submitted for analysis of progesterone, total estrogens, and testosterone (BET Reproductive Laboratories, Lexington, Kentucky, USA).

Baseline progesterone was 0.05 ng/mL. The low progesterone value suggested the absence of luteal tissue. The total estrogen values for time 0 and the 1- and 2-hour postinjection samples remained constant at 3.6 ng/mL, and the testosterone values remained constant at 11.6 pg/mL (reference range for normally cycling mare, 20 to 45 pg/mL (1)). The sample of serum, collected at time 0, was submitted to the Endocrinology Laboratory (University of California, Davis, California, USA) for an inhibin assay. The inhibin value was 0.63 ng/mL, which is near the upper limit of normal for a nonpregnant mare (reference range, 0.1 to 0.7 ng/mL).

The differential diagnoses for an abnormally enlarged ovary in a mare include ovarian hematoma, ovarian neoplasia, and ovarian abscess. On the basis of the clinical examination, granulosa thecal cell tumor was considered to be the most likely neoplastic lesion. It is the most common equine ovarian neoplasm, and the mare had displayed aggressive, abnormal behavior (1,2). However, laboratory results indicated that the mass was unlikely to be a granulosa thecal cell tumor. An ovarian abscess was also an unlikely diagnosis, because it is rare and usually diagnosed concurrently with a history of ovariocentesis (2).

When the mare was reexamined on day 30, the owner reported an improvement in disposition, and she was significantly easier to handle. The left ovary was larger (5 × 5 × 7 cm) than when previously examined and active, with palpable follicles that were confirmed by ultrasonography. The right ovary was in a more caudal position than on the previous examination and was also softer and smaller (18 × 18 × 30 cm). Ultrasonography of the right ovary showed significant changes from the original presentation. The mass still had a hyperechoic capsule; however, the body of the mass was no longer of uniform consistency, rather it was mottled with areas of variable density.

On the basis of the normal progesterone, estrogen, and testosterone values after the HCG stimulation test, the normal inhibin values, the improved behavior of the mare, the decreasing size of the right ovarian mass, and the normal cyclicity of the mare, a final diagnosis of right ovarian hematoma was made.

Treatment for ovarian hematoma was initiated on day 30, with the objective of suppressing estrus to allow time for resorption and regression of the hematoma. If it is desirable to breed a mare with an ovarian hematoma during the same season, therefore requiring a rapid return to cyclicity, daily injections of progesterone (150 mg) and estradiol-17β (10 mg), each for 10 d, are recommended (3). Injections of prostaglandin F₂α may be given on the first and last days. This treatment protocol was considered inappropriate for this mare because of the difficulty of administering daily injections and the late season of the year for breeding.

The mare was prescribed altrenogest (Regu-mate Solution 0.22%; Intervet, Whitby, Ontario), 0.044 mg/kg BW, PO, for 15 d, in order to suppress the estrous cycle (3). The mare was reexamined on day 120, when the ovarian mass had moved caudally into a more normal location and had decreased in size (15 × 15 × 25 cm). There was a marked improvement in the mare's behavior at this time.

Ovarian hematoma is one the most common causes of abnormal ovarian enlargement in the mare (1). Differentiation of ovarian hematoma from granulosa thecal cell tumor is usually based on physical examination and circulating endocrine hormone levels. In a mare with an ovarian hematoma, the contralateral ovary continues to cycle normally, because there is no interference from increased inhibin values that commonly occur with granulosa thecal cell tumors. Inhibin, a polypeptide hormone produced by the granulosa cells of the ovary, inhibits the secretion of follicle stimulating hormone (FSH) (2,4,5,6). In a mare with a granulosa thecal cell tumor, increased production of inhibin and decreased secretion of FSH may potentially decrease the recruitment, maturation, ovulation, and luteinization of follicles, and thereby suppress the estrous cycle (2,5).

In this case, the contralateral ovary was small yet active, suggesting ovarian hematoma rather than granulosa thecal cell tumor. Inhibin is a valuable tumor marker for granulosa thecal cell tumors in humans (4). The equine granulosa thecal cell tumor produces inhibin, which can be measured in serum, allowing differentiation of ovarian neoplasia from other ovarian abnormalities, such as ovarian hematomas, (5,7,8). Christman et al (7) and Bailey et al (8) demonstrated that inhibin α- and β-subunit proteins are present in equine neoplastic granulosa cells and that the granulosa thecal cell tumor is therefore a potential source of increased inhibin production. Studies have also shown that in approximately 85% to 87% of mares with granulosa thecal cell tumors, the inhibin value is increased significantly above normal (1,6,7,9). The inhibin concentration for this mare was within normal range and thus provided evidence that a granulosa thecal cell tumor was not present.

This mare's aggressive and consistently abnormal behavior was suggestive of endocrine neoplasia. When abnormal behavior, such as aggression and virilism, has been noted in association with granulosa thecal cell tumor, serum testosterone has usually been > 100 pg/mL (1,2). However, serum testosterone is increased in only 40% to 50% of mares with granulosa thecal cell tumors, whether or not they display abnormal behavior (1,6,9). In this case, the low serum testosterone value suggested that the ovarian mass was not an endocrine-producing neoplasm. As well, the mare's disposition improved as the size of the ovarian mass decreased, suggesting that the enlarged ovary may have been a source of pain, which caused an increase in aggressive tendencies.

Human chorionic gonadotropin is produced by the cytotrophoblasts of the chorionic villi of the human placenta (2). It is chemically different from luteinizing hormone (LH); however, it has a primarily LH-like activity and has some similarities to the activity of FSH (2). It is commonly used to shorten estrus by mimicking the actions of FSH and LH and stimulating the formation of a corpus luteum. Receptors for LH and FSH are found on granulosa and thecal cells of ovarian follicles. If neoplastic granulosa cells are present when the HCG stimulation test is performed, an endocrine abnormality, such as an increase in serum progesterone, estrogen, or testosterone level, may be noted (2). In this case, all endocrine values were within the normal range after HCG stimulation, suggesting the absence of neoplastic ovarian tissue.

It is suspected that ovarian hematomas are formed when the follicular cavity overfills with blood postovulation (1,2). On day 1, ultrasonography revealed an echodense uniform mass. Granulosa thecal cell tumors are usually described as having a multicystic, honeycomb appearance; however, they may also have a uniform appearance (1,10). On days 30 and 120, ultrasonographically the mass appeared smaller and less uniform than on day 1, which is consistent with the breakdown of a blood clot and the regression of a hematoma. It is unlikely that a neoplastic mass would change in size and consistency in this manner.

In this case, a granulosa thecal cell tumor was suspected. Although the laboratory results did not support this diagnosis, it was possible that the laboratory results were false-negative. However, when the mare was reexamined, the improved behavior, normal cyclicity, and decrease in size of the ovary further supported the laboratory results and the diagnosis of an ovarian hematoma. A definitive diagnosis could have been established by surgical ovariectomy and histology. However, the owners chose to treat the mare with oral progesterone and to allow time for regression of the ovarian mass.