Acidic isoforms of chorionic gonadotrophin in European and Samoan women are associated with hyperemesis gravidarum and may be thyrotrophic

OBJECTIVE There is conflicting evidence concerning the role of human chorio nic gonadotrophin (hCG) in the aetiology of hyperemesis gravidarum (HG); pa rticular isoforms of hCG may be the critical factor. Ethnic differences in HG prevalence and putative thyrotrophic effects of hCG may also relate to d ifferences in I ICG isoform profiles. To address these issues we examined t he relationship of hCG isoforms to HG and thyroid function tests in two gro ups of women from ethnic backgrounds with significantly different HG preval ence rates. PATIENTS AND DESIGN We enrolled 10 European and 10 Samoan women with HG and an equally sized non-hyperemetic, gestational stage matched control group. MEASUREMENTS We administered a questionnaire, generated serum hCG charge-is oform profiles by chromatofocusing and measured the serum concentrations of total hCG, oestradiol (E-2), thyrotrophin (TSH) and free thyroxine (FT4), RESULTS The mean serum total hCG levels were highest in the Samoan hypereme tics (176 268 IU/l), and overall higher in hyperemetics compared with contr ols (159 770 IU/l vs, 86 420 IU/l, P< 0.001). When compared with controls, hyperemetics displayed increased hCG concentrations in the more acidic half (pH<4) of the chromatofocusing pH range (89 843 IU/l vs. 41 146 IU/l, P<0. 003). Serum E-2 levels did not differ between the four groups, but correlat ed with the hCG concentration between pH 5.2 and 4.01. Mean serum TSH level s were significantly lower in hyperemetics than in controls (0.33 mIU/l vs. 1.19 mIU/l, P<0.001) and correlated with the hCG concentration between pH 4.6 and 2.8, while serum FT4 correlated with the hCG concentration below pH 4.0. CONCLUSIONS Acidic isoforms of hCG may play a role in the aetiology of HG a nd gestational thyrotoxicosis. Minor ethnic differences in hCG isoform prof iles were observed, but the relationship of acidic hCG isoforms to HG and s erum thyroid hormone levels was largely independent of the patients' ethnic ity. The mechanisms by which acidic isoforms might provoke nausea remain un certain, but do not seem to involve Eg, while the longer half-life of acidi c hCG isoforms may result in increased in vivo TSH receptor cross-talk with resultant thyrotrophic effects.