SERUM LEVELS OF INTACT HUMAN CHORIONIC-GONADOTROPIN (HCG) AND ITS FREE-ALPHA AND BETA-SUBUNITS, IN RELATION TO MATERNAL THYROID-STIMULATIONDURING NORMAL-PREGNANCY
D. Glinoer et al., SERUM LEVELS OF INTACT HUMAN CHORIONIC-GONADOTROPIN (HCG) AND ITS FREE-ALPHA AND BETA-SUBUNITS, IN RELATION TO MATERNAL THYROID-STIMULATIONDURING NORMAL-PREGNANCY, Journal of endocrinological investigation, 16(11), 1993, pp. 881-888
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.