human chorionic gonadotropin

**Structure:** Heterodimeric glycoprotein. The α subunit is identical to that of LH, FSH, and TSH; the β subunit is unique (confers specificity, so pregnancy tests detect β-hCG). hCG's β subunit is structurally similar to LH's, so hCG binds the LH receptor.

**Source:** Syncytiotrophoblast of the placenta (not cytotrophoblast). Secretion begins shortly after implantation.

**Physiology:** - Maintains the corpus luteum → continued progesterone (and estrogen) production until the placenta takes over (luteal-placental shift) at ~8–10 weeks. - Levels double roughly every 48 hours in early normal pregnancy, peak at ~8–10 weeks (end of the first trimester), then decline and plateau. - Stimulates fetal testicular Leydig cells to make testosterone (male sexual differentiation) before fetal pituitary LH is active. - Weak TSH-like activity: at peak levels can cause transient gestational hyperthyroidism (low TSH, high free T4) and contributes to hyperemesis gravidarum. - Cross-reactivity with the LH receptor underlies theca-lutein cyst formation when levels are very high.

**Clinical significance:** - *Pregnancy testing:* Urine/serum qualitative and quantitative assays. Serum β-hCG is detectable ~8–11 days after conception. - *Elevated hCG (higher than expected for dates):* Multiple gestation, hydatidiform (molar) pregnancy (very high, e.g., >100,000 mIU/mL, with "snowstorm" ultrasound, uterus large for dates, hyperemesis, early preeclampsia, theca-lutein cysts, hyperthyroidism), choriocarcinoma, Down syndrome (trisomy 21; quad screen: ↑hCG, ↑inhibin A, ↓AFP, ↓unconjugated estriol), and Rh alloimmunization/hydrops. - *Low or slowly rising hCG:* Ectopic pregnancy (rises <53–66% in 48 h; hCG above the discriminatory zone ~1,500–3,500 mIU/mL with no intrauterine gestational sac on transvaginal US is concerning), impending or incomplete miscarriage, blighted ovum. Also low in Edwards (trisomy 18) and Patau (trisomy 13) syndromes (↓hCG, ↓AFP, ↓estriol, ↓inhibin A). - *Tumor marker:* Gestational trophoblastic disease (hydatidiform mole, choriocarcinoma) and germ cell tumors (choriocarcinoma component of testicular tumors, dysgerminoma/mixed). Used to follow treatment response (methotrexate/dactinomycin) after mole evacuation. Choriocarcinoma is hematogenous to lung; it is hCG-secreting and chemosensitive. - *Men:* Elevated hCG with testicular mass suggests germ cell tumor (choriocarcinoma, seminoma with syncytiotrophoblasts); may cause gynecomastia, hyperthyroidism. - *Therapeutic use:* Ovulation induction (LH-surge mimic) in infertility treatment/IVF; treatment of cryptorchidism and hypogonadotropic hypogonadism in males. - *False positives:* Heterophile antibodies, pituitary hCG (perimenopausal women), and certain tumors; *false negatives:* "Hook effect" with extremely high hCG (dilute sample to resolve).

**Memory aids:** "hCG = Holds Corpus luteum Going." α subunit shared with FSH/LH/TSH; β subunit is specific. Hyperemesis + hyperthyroid + big uterus + very high hCG = molar pregnancy.