SERUM LEVELS OF INTACT HUMAN CHORIONIC-GONADOTROPIN (HCG) AND ITS FREE-ALPHA AND BETA-SUBUNITS, IN RELATION TO MATERNAL THYROID-STIMULATIONDURING NORMAL-PREGNANCY

The main objective of the present study was to present additional evid ence of the potentially important thyrotropic role of hCG to regulate the maternal thyroid gland during normal pregnancy. Sequential determi nations (first and last trimesters) of intact hCG, free alpha and beta -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 gesta tion low TSH levels (less-than-or-equal-to 0.20 mU/L), and compared to 276 pregnant women with normal TSH levels. The prevalence of having l ow 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 co mparison to control subjects, women with a suppressed serum TSH had si gnificantly and markedly higher intact hCG and free beta-hCG subunit c oncentrations. The results suggest that TSH reduction may result from a relative oversecretion of both intact hCG and free beta-hCG subunits , compatible with three hypotheses: a) transient overexpression of the beta-hCG gene, leading to enhanced production of hCG heterodimer; b) increased glycosylation of circulating hCG, with in turn a prolonged h alf life; c) larger syncytiotrophoblast mass with increased hCG produc tion. 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 trime ster 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 thyroi d volume. During the last trimester and at term, most parameters of th yroid function were similar in both groups. In conclusion, a partial o r total serum TSH suppression is a frequent finding during normal preg nancy, usually occurring as a transient feature near the end of the fi rst 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 beta-hCG subunit and intact hCG leve ls, perhaps resulting from an imbalanced production of hCG. In approxi mately one percent of pregnancies, excessive thyroidal stimulation may lead to gestational transient thyrotoxicosis during the first trimest er. The present studies confirm the role of hCG as an important thyroi dal regulator during normal pregnancy.