Hyperreactio luteinalis in a spontaneously conceived singleton pregnancy

Abstract

Hyperreactio luteinalis is a rare condition in pregnancy that is caused by high β-human chorionic gonadotropin (β-hCG) levels or abnormal sensitivity of the β-hCG receptor. It is mostly seen in patients with trophoblastic disease, multiple pregnancy or after fertility treatment. We describe our imaging findings and management of a case of hyperreactio luteinalis diagnosed in a singleton spontaneously conceived pregnancy. A 28-year-old primigravida was referred to the gynecological ultrasound department of the University Hospitals, Leuven, for the evaluation of bilateral adnexal masses at 14 weeks' gestation. Her pregnancy had been spontaneously conceived and she had no personal or family history of ovarian, breast or colon cancer. There was no history of subfertility and the patient did not use any kind of medication. The adnexal masses were first visualized in a regional hospital when she presented to the emergency room with abdominal pain. Vaginal examination revealed large mobile bilateral masses that filled the pouch of Douglas. Transabdominal and transvaginal gray-scale and color Doppler ultrasound examination was performed using a GE Voluson E8 Expert scanner (4–8-MHz transabdominal transducer and 6–12-MHz transvaginal transducer (GE Healthcare Technologies, Milwaukee, WI, USA)). Large bilateral multilocular masses measuring 141 × 134 × 103 mm (volume, 1019 cm3) in the left ovary and 127 × 120 × 87 mm (volume, 694 cm3) in the right ovary were visualized. Both masses contained more than 10 locules with rather thick (>3 mm) septa and anechoic cyst fluid. The cyst wall was regular (Figure 1) and the color score was 3 (moderately vascularized) in both masses. The fetus was normal in size for gestational age and no structural abnormalities were visualized. There was a small quantity of free fluid in the pouch of Douglas (30 × 22 mm) but no ascites. Both ultrasound examination and an X-ray of the chest were negative for metastases and pleural effusion. Blood analysis showed no abnormalities but a raised level of serum CA-125 of 442 kU/L. Gray-scale ultrasound images using the extended field of view imaging mode, showing one of the large multilocular adnexal masses and uterus containing a 14-week fetus in the sagittal (a) and axial (b) views in a case of hyperreactio luteinalis. Owing to the progressive growth and the size of the masses, reaching the level of the diaphragm, and the large number of locules, the masses were suspected to be mucinous borderline tumors of the intestinal type and the patient was referred for surgery. Surgery was performed at 18 weeks of gestation using a midline incision. The right mass reached the level of the liver and the left mass filled the entire paracolic area (Figure 2). There was no ascites and no macroscopic signs of metastases. A right adnexectomy was performed and, on frozen section, the intraoperative diagnosis was hyperreactio luteinalis (Figure 3). The left mass was punctured but left in situ. Postoperative recovery and the subsequent course of the pregnancy were uneventful. The patient had a spontaneous vaginal delivery of a 3800-g girl at 40 weeks. At 9 weeks' postpartum, the patient was asymptomatic and ultrasound examination showed that the left adnexa was normal and contained a hemorrhagic corpus luteum cyst. Intraoperative findings in the case of hyperreactio luteinalis, showing the large left adnexal mass and fundus uteri. Microscopic findings of adnexal mass leading to the diagnosis of hyperreactio luteinalis (original magnification × 250). Hyperreactio luteinalis is a rare condition that can occur at any stage of pregnancy, but is typically seen in the third trimester1. In almost all cases it is triggered by very high endogenous or exogenous β-hCG stimulation2. Therefore most publications report on the presence of hyperreactio luteinalis in a multiple or molar pregnancy, in association with choriocarcinoma and fetal hydrops, or after fertility treatment. An abnormally rapid rise in β-hCG in the first trimester or abnormal sensitivity of the hCG receptor due to a gene mutation can lead to the exceptional case of hyperreactio luteinalis in a spontaneous singleton pregnancy3. Burger described the first case of hyperreactio luteinalis not associated with trophoblastic disease, since when a few cases have been reported in spontaneous singleton pregnancies4-6. Depending on the size of the masses either patients are asymptomatic or they present with pain due to intra-abdominal pressure, torsion or intracystic hemorrhage. Virilization due to hyperandrogenism can occur in as many as 25% of affected patients7, 8. Symptoms of hyperemesis gravidarum or hyperthyroidism have been reported and are usually not related to hyperreactio luteinalis but are provoked by the underlying problem that is causing the high β-hCG level (trophoblastic disease, multiple pregnancy). The prognosis of this benign condition is good and in the postpartum period theca lutein cysts usually regress spontaneously7. The raised and sustained high β-hCG level or abnormal sensitivity to β-hCG induces the development of theca lutein cysts. Hypertrophy and luteinization of the granulosa and theca interna layer are the most typical microscopic features (Figure 3)9. On ultrasound examination hyperreactio luteinalis is characterized by large adnexal masses that consist of many thin-walled small theca lutein cysts, giving it the appearance of a ‘spoke wheel’. Ascites can be present. Owing to their large size and morphology they are hard to distinguish from ovarian hyperstimulation syndrome (OHSS)4, 5, 7, 8, 10. OHSS almost exclusively occurs in patients following fertility treatment although, very rarely, it can occur in spontaneous singleton pregnancies. By contrast with hyperreactio luteinalis, OHSS presents at the beginning of the first trimester and is associated with more severe symptoms involving acute fluid imbalances that impair the natural pregnancy course5. With their large number of locules, hyperreactio luteinalis can even mimic a malignancy, in particular a mucinous borderline tumor of the intestinal type, and lead to unnecessary surgery8. However, when compared with hyperreactio luteinalis, mucinous intestinal borderline tumors have smaller thin-walled locules that are not as round and tend to have less solid tissue than in cases of hyperreactio luteinalis. Frédéric Amant is a clinical researcher for Research Fund–Flanders (FWO–Vlaanderen).