We reported that gestational
thyrotoxicosis is induced by thyroid-stimulating activity (
TSA) of circulating hCG. However, the serum immunological hCG concentration did not correlate to
TSA. To elucidate this, we examined the relation of
carbohydrate moieties of hCG to bioactivity in 79 early pregnant women, divided into 4 groups: no
emesis, mild
emesis, hyperemesis, and gestational
thyrotoxicosis with hyperemesis. Serum free T4 (FT4) and free T3 (FT3) levels were significantly higher and TSH was lower in the hyperemesis (FT4, 23.42 +/- 5.02 pmol/L; FT3, 6.26 +/- 1.80 pmol/L; TSH, 0.30 +/- 0.44 mU/L) and in gestational
thyrotoxicosis (FT4, 48.65 +/- 14.80 pmol/L; FT3, 14.71 +/- 3.47 pmol/L; TSH, < 0.04 mU/L) groups than in the no
emesis group (FT4, 16.99 +/- 2.48 pmol/L; FT3, 5.51 +/- 0.75 pmol/L; TSH, 1.37 +/- 1.23 mU/L; P < 0.0005).
TSA was also significantly higher in the hyperemesis (566 +/- 187%) and gestational
thyrotoxicosis (832 +/- 168%) groups than in the no
emesis group (321 +/- 135%). We found no significant difference among serum hCG concentrations measured by immunoassay in the four groups. To characterize the
carbohydrate chains, serum hCG was fractionated by
Concanavalin-A and
ricin lectin affinity chromatography. The fraction firmly bound to Con-canavalin-A, which contains hCG with high
mannose and hybrid-type
carbohydrate chains, was significantly higher in the hyperemesis group (91.07 +/- 2.06%; n = 15) than in the no
emesis group (89.61 +/- 2.38%; n = 24; P < 0.04). The fraction firmly bound to
ricin column, which contains hCG with asialo-
carbohydrate chains, was significantly increased in the gestational
thyrotoxicosis group (3.44 +/- 1.70%; n = 5) compared with that in the no
emesis group (1.77 +/- 0.49%; n = 24; P < 0.03). Serum FT4 positively correlated to the hCG fraction firmly bound to
ricin column (r = 0.61; P < 0.001). We conclude that
thyrotoxicosis with hyperemesis may be caused by circulating
asialo-hCG with higher thyrotropic bioactivity.