A Case of Hyperreactio Luteinalis Complicated With Biochemical Hyperandrogenism, Symptomatic Hyperthyroidism and Preeclampsia

Abstract

Background: Hyperreactio luteinalis (HL) describes the development of multiple large ovarian cysts during pregnancy, which regress post-partum. We report a case of HL complicated with preeclampsia, biochemical hyperandrogenism and hyperthyroidism. Clinical Case: A 31-year-old non-obese Chinese woman presented at 14-week gestation for lower abdominal pain. USG showed a single fetus, multiple ovarian cysts with largest measured 39.5ml. She complained of hand tremor, palpitation but no vomiting. She had no goiter, orbitopathy or family history of thyroid disease. fT4 was 23.1pmol/L (normal: 9.8-19.8pmol/L) and TSH was <0.01mIU/L. Anti-TG, anti-TPO and anti-TSHR antibodies were negative. She had history of silent miscarriage at 6-week gestation in her first pregnancy 2 years ago, USG showed normal ovaries at that time. Carbimazole was started at 16-week gestation for fT4 26.6pmol/L (normal: 9.4-18.5pmol/L). The largest ovarian cyst increased to 130ml at 19-week gestation. Serum β-hCG was 251926IU/L (normal: 4060-165400IU/L). HL with hCG-mediated hyperthyroidism was suspected. Serum total testosterone was 22.9nmol/L (normal: 2.2-10.7nmol/L) and serum androstenedione was 70.5nmol/L (normal: 0.28-9.81nmol/L). Ferriham Gallwey score was 4. fT4 fell to 13.8pmol/L (normal: 8.8-17.0pmol/L) but TSH remained suppressed. Carbimazole was stopped at 22-week gestation with no rebound in fT4 level. She developed preeclampsia and GDM at 27-week gestation. IUGR was evident despite decreasing β-hCG level and ovarian cyst shrinkage. She had emergency LSCS for severe preeclampsia at 33-week gestation. A 1510g female baby with normal genitalia was delivered. Placenta pathology was normal. 2 days after delivery, β-hCG fell to 7081IU/L; fT4 was 9.9pmol/L (normal: 9-19pmol/L) and TSH was 0.25mIU/L (normal: 0.35-4.5mIU/L). Clinical Lessons: 1) hCG stimulates growth of ovarian stroma and androgen secretion, results in virilization in 30% of HL patients. However, only 5% of patients had hyperthyroidism. LH and hCG are structurally similar and bind to the same receptor. In contrast, hCG is a weak agonist of TSH receptor: a hCG level of more than 100000IU/L is required to cause clinical thyrotoxicosis. Since 30% of HL patients have normal hCG level, this may explain the lower incidence of hyperthyroidism than hyperandrogenism. 2) Degree of maternal virilization does not correlate with testosterone level. Study by Condic et al. found significant overlap of testosterone levels in women with (13.7-197.5nmol/l) and without (6.2-37.3nmol/l) virilization. Genetic polymorphism of androgen receptor may account for the different clinical manifestation. Fetal virilization is rare, due to protective role of placental aromatase. 3) Elevated hCG in apparently “normal” singleton pregnancy may be due to poor placentation in early gestation and is a risk factor for preeclampsia and IUGR in HL patients.