To Be or Not to Be: Pregnant or Not

Background: Beta Human chorionic gonadotropin (β-hCG) is used for diagnosing pregnancy. Differential diagnosis for elevated β-hCG includes false positive test due to antibody interference, gestational trophoblastic disease (GTD), pituitary production of β-hCG or non-gestational malignancies including hepatic, neuroendocrine, breast, ovarian, pancreatic, cervical, and gastric cancers. We are presenting a case of a menopausal woman noted to have persistently positive serum pregnancy test. Case: 42-year-old female (G3 P2 A1) with a history of thyroid nodules and hypothyroidism was referred to endocrinology clinic for persistently positive serum pregnancy test without being pregnant. Last C-section delivery was 13 yrs ago. Last menstrual period was more than one year ago. Prior to that, her menstruation had always been irregular. Patient denied any spotting, pelvic discomfort/pain or weight loss in last few months. Seven months ago, POCT urine UCG test was done as per radiology protocol prior to CT abdomen for flank pain, and came back positive. Serum β-hCG was mildly positive at 4.3 (0.0 - 2.4 mIU/ml). Pelvic ultrasound did not show presence of a gestational sac. Repeat serum β-hCG level a week later was 3.8 mIU/ml. Patient was told she had early miscarriage. However, about 6 months later, PCP repeated serum β-hCG level and was elevated at 6.2 mIU/ml and thus patient was referred to endocrinology. Further work up showed FSH 61.3 (post-menopausal: 13.1-86.5 mIU/ml), prolactin 12.6 (3.0-18.6 ng/mL), TSH 9.41(0.47 - 4.70 uIU/ml) and estradiol level <15 pg/ml. β-hCG by dilution was ordered but was cancelled by lab for unknown reason. Patient was then also seen by OB-GYN who advised patient that she is menopausal and started her on estrogen-progesterone (E/P) therapy. About 4 weeks after starting E/P therapy, urine UCG came back negative. Hyper- glycosylated hCG (H-hCG) was not elevated. Patient was explained that false positive pregnancy test was due to pituitary production of β-hCG. Discussion: We propose considering following aspects when approaching a case of elevated β-hCG in absence of pregnancy. 1) Hook effect can mask very high level of β-hCG, repeating test after dilution will rule out hook effect. 2) Many case studies have shown pituitary production of β-hCG in perimenopausal women. Perimenopausal women 41-55 years of age with mildly elevated serum β-hCG levels (5.0-14.0 mIU/ml) and concomitant FSH level over 45.0 mIU/ml are likely to have pituitary production of β-hCG(1). If we can suppress β-hCG with two weeks of E/P therapy, this supports pituitary production of β-hCG. 3) If above testing is equivocal then one can consider checking H-hCG which is predominately secreted by the more invasive cytotrophoblastic cells, and supports diagnosis of GTD. References: 1) Gronowski AM, et al. Use of serum FSH to identify perimenopausal women with pituitary hCG. Clinical Chemistry. 2008. 54:4. 652-6.