Serum Human Chorionic Gonadotropin Concentrations Greater than 400,000 IU/L Are Invariably Associated with Suppressed Serum Thyrotropin Concentrations

Background: During pregnancy, when human chorionic gonadotropin (hCG) concentrations are highest, there is a transient suppression of serum thyrotropin (TSH). In normal pregnancy, TSH concentrations generally remain within nonpregnant reference intervals; however, in some patients TSH is suppressed. Here we sought to extend previous studies to examine the relationship between very high serum concentrations of hCG (> 200,000 IU/L) and the thyroid hormones TSH and free thyroxine (FT4). The objective of this study was to determine: 1) if there is an hCG concentration above which TSH concentrations are suppressed (<= 0.2 mu IU/mL); 2) how thyroid hormone concentrations change in response to changes in hCG concentrations; and 3) the clinical symptoms in patients with such extremely elevated hCG concentrations. Methods: Residual specimens sent to the laboratories for physician-ordered hCG testing were utilized. Over 26 months, 15,597 physician-ordered hCG tests were performed. Sixty-nine specimens from 63 women with hCG concentrations > 200,000 IU/L were identified, and TSH and FT4 concentrations were measured. Medical records were reviewed for clinical information. Results: Thirty-seven percent of subjects had hyperemesis gravidarum (HG) and 19% had gestational trophoblastic disease (GTD). TSH was suppressed (<= 0.2 mu IU/mL) in 67% of the specimens with hCG concentrations > 200,000 IU/L and 100% of specimens with hCG concentrations > 400,000 IU/L. FT4 concentrations were elevated above the reference interval (1.8 ng/dL) in 32% of specimens with hCG concentrations > 200,000 IU/L and in 80% of specimens with hCG concentrations > 400,000 IU/L. Only four subjects had documented signs of hyperthyroidism. Women with GTD had a median hCG concentration twofold higher than women with HG and a median TSH concentration one half that of women with HG. Conclusions: 1) At hCG concentrations > 400,000 IU/L, TSH is consistently suppressed; 2) serum FT4 and TSH respond to changes in serum hCG concentrations; and 3) most patients with hCG concentrations > 200,000 IU/L lack overt hyperthyroid symptoms.