PATHOGENIC ROLE OF ASIALO HUMAN CHORIONIC-GONADOTROPIN IN GESTATIONALTHYROTOXICOSIS

We reported that gestational thyrotoxicosis is induced by thyroid-stim ulating activity (TSA) of circulating hCG. However, the serum immunolo gical hCG concentration did not correlate to TSA. To elucidate this, w e examined the relation of carbohydrate moieties of hCG to bioactivity in 79 early pregnant women, divided into 4 groups: no emesis, mild em esis, hyperemesis, and gestational thyrotoxicosis with hyperemesis. Se rum free T-4 (FT4) and free T-3 (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 th yrotoxicosis (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 (FT3, 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 +/- 1 87%) and gestational thyrotoxicosis (832 +/- 168%) groups than in the no emesis group (321 +/- 135%). We found no significant difference amo ng 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 fracti on firmly bound to Concanavalin-A, which contains hCG with high mannos e and hybrid-type carbohydrate chains, was significantly higher in the hyperemesis group (91.07 +/- 2.06%; n = 15) than in the no emesis gro up (89.61 +/- 2.38%; n = 24; P < 0.04). The fraction firmly bound to r icin column, which contains hCG with asialo-carbohydrate chains, was s ignificantly 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 fr action firmly bound to ricin column (r = 0.61; P < 0.001). We conclude that thyrotoxicosis with hyperemesis may be caused by circulating asi alo-hCG with higher thyrotropic bioactivity.