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

Abstract

OBJECTIVE There is conflicting evidence concerning the role of human chorionic gonadotrophin (hCG) in the aetiology of hyperemesis gravidarum (HG); particular isoforms of hCG may be the critical factor. Ethnic differences in HG prevalence and putative thyrotrophic effects of hCG may also relate to differences in hCG isoform profiles. To address these issues we examined the relationship of hCG isoforms to HG and thyroid function tests in two groups of women from ethnic backgrounds with significantly different HG prevalence 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-isoform profiles by chromatofocusing and measured the serum concentrations of total hCG, oestradiol (E2), thyrotrophin (TSH) and free thyroxine (FT4). RESULTS The mean serum total hCG levels were highest in the Samoan hyperemetics (176 268 IU/l), and overall higher in hyperemetics compared with controls (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 E2 levels did not differ between the four groups, but correlated with the hCG concentration between pH 5.2 and 4.01. Mean serum TSH levels 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 and gestational thyrotoxicosis. Minor ethnic differences in hCG isoform profiles were observed, but the relationship of acidic hCG isoforms to HG and serum thyroid hormone levels was largely independent of the patients' ethnicity. The mechanisms by which acidic isoforms might provoke nausea remain uncertain, but do not seem to involve E2, while the longer half-life of acidic hCG isoforms may result in increased in vivo TSH receptor cross-talk with resultant thyrotrophic effects.