Serum levels of intact human chorionic gonadotropin (HCG) and its free a and β subunits, in relation to maternal thyroid stimulation during normal pregnancy

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Abstract
The main objective of the present study was to present additional evidence of the potentially important thyrotropic role of hCG to regulate the maternal thyroid gland during normal pregnancy. Sequential determinations (first and last trimesters) of intact hCG, free α and β-hCG subunits concentrations (using monoclonal IRMAs), and assessment of parameters of thyroid function and thyroid volume were carried out in 62 pregnant women who exhibited during the first trimester of gestation low TSH levels (≤0.20 mU/L), and compared to 276 pregnant women with normal TSH levels. The prevalence of having low serum TSH represented 18% of all pregnancies, with almost one half of cases who transiently had undetectable TSH levels. Lowering of TSH was associated with high hCG levels, and occurred primarily during the first trimester. About 10% of women with low TSH presented transient gestational thyrotoxicosis, frequently associated with vomiting. In comparison to control subjects, women with a suppressed serum TSH had significantly and markedly higher intact hCG and free β-hCG subunit concentrations. The results suggest that TSH reduction may result from a relative oversecretion of both intact hCG and free β-hCG subunits, compatible with three hypotheses: a) transient overexpression of the β-hCG gene, leading to enhanced production of hCG heterodimer; b) increased glycosylation of circulating hCG, with in turn a prolonged half life; c) larger syncytiotrophoblast mass with increased hCG production. Increased hCG in women with low TSH was clearly associated with thyroidal stimulation: comparing women with or without low TSH, it was shown that high hCG production was accompanied during the first trimester by a 20% mean increase in free T4 levels and a parallel increase in the TBG saturation levels by T4. Furthermore, thyroidal stimulation during the first trimester was associated with a larger median thyroid volume. During the last trimester and at term, most parameters of thyroid function were similar in both groups. In conclusion, a partial or total serum TSH suppression is a frequent finding during normal pregnancy, usually occurring as a transient feature near the end of the first trimester, in association with high serum hCG levels. The present data indicate for the first time that in these women, circulating hCG is characterized by elevated free β-hCG subunit and intact hCG levels, perhaps resulting from an imbalanced production of hCG. In approximately one percent of pregnancies, excessive thyroidal stimulation may lead to gestational transient thyrotoxicosis during the first trimester. The present studies confirm the role of hCG as an important thyroidal regulator during normal pregnancy.