Isolated β-Human Chorionic Gonadotropin Elevation-From Pregnancy to Fragile X-associated Premature Ovarian...

Elevated β-human chorionic gonadotropin (β-HCG) in a young female usually suggests pregnancy, gestational trophoblastic disease or germ cell tumor. We describe β-HCG elevation in a young female using intrauterine device (IUD), ultimately diagnosed with Fragile X-associated premature ovarian insufficiency (FXPOI).

A 31-year-old woman with Hashimoto's hypothyroidism and a levonorgesterel IUD presented to the emergency room for hematemesis. She had a positive urine and serum pregnancy test. Ultrasound showed no evidence of intrauterine gestation with a normally centered IUD. After removal of the IUD and methotrexate therapy for presumed ectopic pregnancy in an unknown location, β-HCG level remained elevated. Heterophile antibody interference was ruled out. Over the next 2 months, further testing confirmed FXPOI (follicle-stimulating hormone 174.58 mIU/mL, luteinizing hormone 70.61 mIU/mL, undetectable estradiol, undetectable progesterone, undetectable anti-mullerian hormone, and one FMR1 premutation allele). Hormone therapy with oral estradiol 2 mg daily and cyclic oral micronized progesterone 200 mg on 12 days of each month was initiated.

In menopause, decreased estradiol and progesterone lead to mildly elevated β-HCG through luteinizing hormone-mediated β-HCG production in the pituitary gland. This may be confused with pregnancy and could delay diagnosis of premature menopause due to premature ovarian insufficiency (POI), especially in young females. In young patients with normal karyotype, Fragile X premutation is the most common genetic cause of POI.

After pregnancy has been ruled out, less common causes of β-HCG elevations like gestational trophoblastic disease, germ cell tumors, POI associated menopause, and heterophile antibody interference, should be evaluated. FXPOI should be considered in young patients with β-HCG elevation.