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Offsite Research:
Human chorionic gonadotropin and hyperemesis gravidarum
Goodwin, TM
Associate Professor, Division of Maternal Foetal Medicine, Department of Obstetrics and Gynaecology, University of Southern California, U.S.A.
Nausea and Vomiting of Pregnancy: State of the Art 2000 Conference
There are a number of reasons for considering the association of human chorionic gonadotropin (hCG) with hyperemesis gravidarum. The temporal relationship between peak hCG levels and the most common time of nausea and vomiting has long been noted. More recently, the relationship of hCG to transient hyperthyroidism of hyperemesis gravidarum (THHG) has been described. Several experiments of nature have suggested that hCG plays a role.
Thyroid function in patients with hyperemesis gravidarum
Bouillon R, Naesens M, Van Assche FA, De Keyser L, De Moor P, Renaer M, De Vos P, De Roo M.
Am J Obstet Gynecol 1982 Aug 15;143(8):922-6
An increased free thyroxine (T4) index was observed in 73% of 33 consecutive pregnancies complicated by severe hyperemesis gravidarum. The free triiodothyronine (T3) index was increased in only four of 11 hyperthyroxinemic patients. In five hyperthyroxinemic patients tested, no increase in serum thyrotropin was observed after the injection of thyrotropin-releasing hormone (THR). Goiter, exophthalmos, or previous history of hyperthyroidism was absent in all patients. The thyroxinemia returned to normal in one to several weeks, whether or not it was treated with antithyroid drugs. The thyroid function during the period of hyperemesis had no influence on the subsequent rate of abortion or duration of pregnancy. A lower birth weight, however, was observed in children born to hyperthyroxinemic mothers. Hyperemesis gravidarum should be included in the differential diagnosis of elevations in free T4 index during pregnancy and included in the differential diagnosis of hyperthyroidism.
The role of chorionic gonadotropin in transient hyperthyroidism of
hyperemesis gravidarum.
Goodwin TM, Montoro M, Mestman JH, Perkary AE,
Hershman JM.
The Journal of Clinical Endocrinology and
Metabolism 1992;75:1333-7.
Biochemical evidence of hyperthyroidism is frequently encountered in
hyperemesis gravidarum, but its relationship to the cause of hyperemesis is
unknown. TSH was suppressed in 60% of hyperemesis patients and 9% of
controls. hCG correlated directly with free T4(r = 0.45, P < 0.001) and
inversely with TSH (r = -0.48, P < 0.001). Hyperemesis patients had
significantly greater mean serum hCG, free T4, total T3, and estradiol, and
lesser serum TSH compared to controls. Hyperemesis patients with suppressed
TSH had significantly greater free T4 and hCG compared to those with TSH in
the normal range. The degree of biochemical hyperthyroidism and hCG
concentration varied directly with the severity of vomiting. These data show
that biochemical hyperthyroidism is a common finding in patients with
hyperemesis gravidarum and suggest that hCG is the thyroid stimulator in
this state. The increased estradiol concentration in patients with
hyperemesis gravidarum may be attributed to the effects of hCG on
steroidogenesis.
Morning sickness and thyroid function in normal pregnancy.
Mori M,
Amino N, Tamaki H, Miyai K, Tanizaw A.
Obstetrics and
Gynecology 1988;72:355-9.
The increased free T4 and hCG and decreased TSH correlated with the severity
of morning sickness, and these changes were especially marked in subjects
with nausea and vomiting. The individual serum levels of hCG in the pregnant
group correlated significantly, directly with the levels of free T4 and
inversely with those of TSH. The increased free T4 and decreased TSH in
subjects with emesis returned to the normal ranges of non-pregnant controls
after improvement of emesis. These data indicate that the thyroid gland is
physiologically activated in early pregnancy, possibly by hCG or a related
substance, which may induce gestational emesis.
Pathogenic role of asialo human chorionic gonadotropin in
gestational thyrotoxicosis.
Tsuruta E, Tada H, Tamaki H, Kashiwai T, Asahi
K, Takeoka K, Mitsuda N, Amino N.
The Journal of Clinical Endocrinology and
Metabolism 1995;80:350-5.
We reported that gestational thyrotoxicosis is induced by
thyroid-stimulating activity (TSA) of circulating hCG. Serum free T4 (FT4)
and free T3 (FT3) levels were significantly higher and TSH was lower in the
hyperemesis (FT4, 23.42 +/- 5.02 pmol/L; FT3, 6.26 +/- 1.80 pmol/L; TSH,
0.30 +/- 0.44 mU/L) and in gestational thyrotoxicosis (FT4, 48.65 +/- 14.80
pmol/L; FT3, 14.71 +/- 3.47 pmol/L; TSH, < 0.04 mU/L) groups than in the no
emesis group (FT4, 16.99 +/- 2.48 pmol/L; FT3, 5.51 +/- 0.75 pmol/L; TSH,
1.37 +/- 1.23 mU/L; P < 0.0005). TSA was also significantly higher in the
hyperemesis (566 +/- 187%) and gestational thyrotoxicosis (832 +/- 168%)
groups than in the no emesis group (321 +/- 135%). We conclude that
thyrotoxicosis with hyperemesis may be caused by circulating asialo-hCG with
higher thyrotropic bioactivity.
Thyrotropic activity of basic isoelectric forms of human chorionic
gonadotropin extracted from hydatidiform mole tissues.
Yoshimura M, Pekary
AE, Pang XP, Berg L, Goodwin TM, Hershman JM.
The Journal of Clinical
Endocrinology and Metabolism 1994;78:862-6.
These results indicate that isoforms of hCG with more thyrotropic activity
were produced by trophoblastic tissues in patients with hydatidiform mole.
We speculate that these isoforms of hCG may be responsible for the
hyperthyroidism in some patients with hydatidiform moles.
Increased concentration of the free beta-subunit of human chorionic
gonadotropin in hyperemesis gravidarum.
Goodwin TM, Hershman JM, Cole L.
Acta Obstetricia et Gynecologica Scandinavica 1994;73:770-2.
The amount of free beta subunit hCG (free beta) has been reported to be
increased in trophoblast disease and Down's syndrome, conditions also
associated with high total hCG. The concentration of hCG was greater in
hyperemesis patients (9237 +/- 3613 ng/ml, mean +/- s.d.) compared to
controls (5543 +/- 2290, p < 0.005) as was the concentration of free beta
hCG (101 +/- 70 ng/ml vs. 31 + 31, p < 0.001). A percent free beta greater
than 0.6 was found in 33/39 hyperemesis patients (85%) compared to 5/23
controls (22%), p < 0.001. Increased free beta hCG is found in hyperemesis
gravidarum. This finding strengthens the association of hyperemesis with
abnormal metabolism of hCG.
Familial gestational hyperthyroidism caused by a mutant thyrotropin
receptor hypersensitive to human chorionic gonadotropin.
Rodien P, Bremont
C, Sanson ML, Parma J, Van Sande J, Costagliola S, Luton JP, Vassart G,
Duprez L.
New England Journal of Medicine 1998;339:1823-6.
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